Family of retrovirus-associated DNA sequences (myc) originally isolated from an avian myelocytomatosis virus. The proto-oncogene myc (c-myc) codes for a nuclear protein which is involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Truncation of the first exon, which appears to regulate c-myc expression, is crucial for tumorigenicity. The human c-myc gene is located at 8q24 on the long arm of chromosome 8.
Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.
Methods to identify and characterize cancer in the early stages of disease and predict tumor behavior.
Tumors or cancer of the PROSTATE.
Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.
Tumors or cancer of the human BREAST.
Tumors or cancer of the LUNG.
Tumors or cancer of the STOMACH.
Tumors or cancer of the COLON.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.
Ability of neoplasms to infiltrate and actively destroy surrounding tissue.
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
Vaccines or candidate vaccines designed to prevent or treat cancer. Vaccines are produced using the patient's own whole tumor cells as the source of antigens, or using tumor-specific antigens, often recombinantly produced.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
A cell line derived from cultured tumor cells.
A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.
Tumors or cancer of the UTERINE CERVIX.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.
A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.
A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for "cancer." (From Dorland, 27th ed)
The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)
A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.
Tumors or cancer of the URINARY BLADDER.
Component of the NATIONAL INSTITUTES OF HEALTH. Through basic and clinical biomedical research and training, it conducts and supports research with the objective of cancer prevention, early stage identification and elimination. This Institute was established in 1937.
The probability that an event will occur. It encompasses a variety of measures of the probability of a generally unfavorable outcome.
Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.
Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.
Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.
Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.
Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important.
In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.
The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers.
Transforming protein coded by myc oncogenes. The v-myc protein has been found in several replication-defective avian retrovirus isolates which induce a broad spectrum of malignancies.
Methods which attempt to express in replicable terms the extent of the neoplasm in the patient.
A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of ADENOCARCINOMAS. It has extensive homology to and heterodimerizes with the EGF RECEPTOR, the ERBB-3 RECEPTOR, and the ERBB-4 RECEPTOR. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member.
Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
DNA present in neoplastic tissue.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Persons who have experienced a prolonged survival after serious disease or who continue to live with a usually life-threatening condition as well as family members, significant others, or individuals surviving traumatic life events.
Experimental transplantation of neoplasms in laboratory animals for research purposes.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
The local recurrence of a neoplasm following treatment. It arises from microscopic cells of the original neoplasm that have escaped therapeutic intervention and later become clinically visible at the original site.
The qualitative or quantitative estimation of the likelihood of adverse effects that may result from exposure to specified health hazards or from the absence of beneficial influences. (Last, Dictionary of Epidemiology, 1988)
Tumors or cancer of the RECTUM.
Period after successful treatment in which there is no appearance of the symptoms or effects of the disease.
The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, RADIOIMMUNOTHERAPY, chemoradiotherapy, cryochemotherapy, and SALVAGE THERAPY are seen most frequently, but their combinations with each other and surgery are also used.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
A family of transcription factors that contain regions rich in basic residues, LEUCINE ZIPPER domains, and HELIX-LOOP-HELIX MOTIFS.
Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time.
Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.
Tumors or cancer of ENDOMETRIUM, the mucous lining of the UTERUS. These neoplasms can be benign or malignant. Their classification and grading are based on the various cell types and the percent of undifferentiated cells.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.
The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM.
Transplantation between animals of different species.
Drug therapy given to augment or stimulate some other form of treatment such as surgery or radiation therapy. Adjuvant chemotherapy is commonly used in the therapy of cancer and can be administered before or after the primary treatment.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Inhaling and exhaling the smoke of burning TOBACCO.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS.
Tumors or cancer of the ESOPHAGUS.
A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.
A subspecialty of internal medicine concerned with the study of neoplasms.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
Specific proteins found in or on cells of progesterone target tissues that specifically combine with progesterone. The cytosol progesterone-receptor complex then associates with the nucleic acids to initiate protein synthesis. There are two kinds of progesterone receptors, A and B. Both are induced by estrogen and have short half-lives.
Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)
An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
A malignant epithelial tumor with a glandular organization.
In humans, one of the paired regions in the anterior portion of the THORAX. The breasts consist of the MAMMARY GLANDS, the SKIN, the MUSCLES, the ADIPOSE TISSUE, and the CONNECTIVE TISSUES.
A nonparametric method of compiling LIFE TABLES or survival tables. It combines calculated probabilities of survival and estimates to allow for observations occurring beyond a measurement threshold, which are assumed to occur randomly. Time intervals are defined as ending each time an event occurs and are therefore unequal. (From Last, A Dictionary of Epidemiology, 1995)
A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human CHROMOSOME 17 at locus 17q21. Mutations of this gene are associated with the formation of HEREDITARY BREAST AND OVARIAN CANCER SYNDROME. It encodes a large nuclear protein that is a component of DNA repair pathways.
Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.
Tumors or cancer of the LIVER.
Radiographic examination of the breast.
Antineoplastic agents that are used to treat hormone-sensitive tumors. Hormone-sensitive tumors may be hormone-dependent, hormone-responsive, or both. A hormone-dependent tumor regresses on removal of the hormonal stimulus, by surgery or pharmacological block. Hormone-responsive tumors may regress when pharmacologic amounts of hormones are administered regardless of whether previous signs of hormone sensitivity were observed. The major hormone-responsive cancers include carcinomas of the breast, prostate, and endometrium; lymphomas; and certain leukemias. (From AMA Drug Evaluations Annual 1994, p2079)
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.
An anaplastic, highly malignant, and usually bronchogenic carcinoma composed of small ovoid cells with scanty neoplasm. It is characterized by a dominant, deeply basophilic nucleus, and absent or indistinct nucleoli. (From Stedman, 25th ed; Holland et al., Cancer Medicine, 3d ed, p1286-7)
A class of EUKARYOTA (traditionally algae), characterized by biflagellated cells and found in both freshwater and marine environments. Pigmentation varies but only one CHLOROPLAST is present. Unique structures include a nucleomorph and ejectosomes.
A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables.
Treatments with drugs which interact with or block synthesis of specific cellular components characteristic of the individual's disease in order to stop or interrupt the specific biochemical dysfunction involved in progression of the disease.
The total amount (cell number, weight, size or volume) of tumor cells or tissue in the body.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Certain tumors that 1, arise in organs that are normally dependent on specific hormones and 2, are stimulated or caused to regress by manipulation of the endocrine environment.
Predetermined sets of questions used to collect data - clinical data, social status, occupational group, etc. The term is often applied to a self-completed survey instrument.
A cancer registry mandated under the National Cancer Act of 1971 to operate and maintain a population-based cancer reporting system, reporting periodically estimates of cancer incidence and mortality in the United States. The Surveillance, Epidemiology, and End Results (SEER) Program is a continuing project of the National Cancer Institute of the National Institutes of Health. Among its goals, in addition to assembling and reporting cancer statistics, are the monitoring of annual cancer incident trends and the promoting of studies designed to identify factors amenable to cancer control interventions. (From National Cancer Institute, NIH Publication No. 91-3074, October 1990)
Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)
Interruption or suppression of the expression of a gene at transcriptional or translational levels.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Agents that reduce the frequency or rate of spontaneous or induced tumors independently of the mechanism involved.
Tumors or cancer of the MOUTH.
A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.
The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.
The simultaneous analysis of multiple samples of TISSUES or CELLS from BIOPSY or in vitro culture that have been arranged in an array format on slides or microchips.
Tumors, cancer or other neoplasms produced by exposure to ionizing or non-ionizing radiation.
Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries.
A gland in males that surrounds the neck of the URINARY BLADDER and the URETHRA. It secretes a substance that liquefies coagulated semen. It is situated in the pelvic cavity behind the lower part of the PUBIC SYMPHYSIS, above the deep layer of the triangular ligament, and rests upon the RECTUM.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.
Tumors or cancer located in bone tissue or specific BONES.
A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication.
A voluntary organization concerned with the prevention and treatment of cancer through education and research.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Pathological processes that tend eventually to become malignant. (From Dorland, 27th ed)
Established cell cultures that have the potential to propagate indefinitely.
RNA present in neoplastic tissue.
Antibodies produced by a single clone of cells.
A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Abnormal growths of tissue that follow a previous neoplasm but are not metastases of the latter. The second neoplasm may have the same or different histological type and can occur in the same or different organs as the previous neoplasm but in all cases arises from an independent oncogenic event. The development of the second neoplasm may or may not be related to the treatment for the previous neoplasm since genetic risk or predisposing factors may actually be the cause.
Genes whose abnormal expression, or MUTATION are associated with the development, growth, or progression of NEOPLASMS.
Tumors or cancer of the SKIN.
In screening and diagnostic tests, the probability that a person with a positive test is a true positive (i.e., has the disease), is referred to as the predictive value of a positive test; whereas, the predictive value of a negative test is the probability that the person with a negative test does not have the disease. Predictive value is related to the sensitivity and specificity of the test.
The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.
Neoplasms composed of glandular tissue, an aggregation of epithelial cells that elaborate secretions, and of any type of epithelium itself. The concept does not refer to neoplasms located in the various glands or in epithelial tissue.
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.
Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor.
Any detectable and heritable alteration in the lineage of germ cells. Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.
Tumor or cancer of the female reproductive tract (GENITALIA, FEMALE).
The use of IONIZING RADIATION to treat malignant NEOPLASMS and some benign conditions.
Methods which attempt to express in replicable terms the level of CELL DIFFERENTIATION in neoplasms as increasing ANAPLASIA correlates with the aggressiveness of the neoplasm.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment; the overall condition of a human life.
Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.
Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Tumors or cancer of the GASTROINTESTINAL TRACT, from the MOUTH to the ANAL CANAL.
A range of values for a variable of interest, e.g., a rate, constructed so that this range has a specified probability of including the true value of the variable.
A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.
An estrogen responsive cell line derived from a patient with metastatic human breast ADENOCARCINOMA (at the Michigan Cancer Foundation.)
Antimetabolites that are useful in cancer chemotherapy.
Proteins, generally found in the CYTOPLASM, that specifically bind ANDROGENS and mediate their cellular actions. The complex of the androgen and receptor migrates to the CELL NUCLEUS where it induces transcription of specific segments of DNA.
The physiological period following the MENOPAUSE, the permanent cessation of the menstrual life.
A group of diterpenoid CYCLODECANES named for the taxanes that were discovered in the TAXUS tree. The action on MICROTUBULES has made some of them useful as ANTINEOPLASTIC AGENTS.
Tumors or cancer of the THYROID GLAND.
A large superfamily of transcription factors that contain a region rich in BASIC AMINO ACID residues followed by a LEUCINE ZIPPER domain.
A country spanning from central Asia to the Pacific Ocean.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
Regular course of eating and drinking adopted by a person or animal.
Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.
A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human chromosome 13 at locus 13q12.3. Mutations in this gene predispose humans to breast and ovarian cancer. It encodes a large, nuclear protein that is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev 2000;14(11):1400-6)
A large, nuclear protein, encoded by the BRCA2 gene (GENE, BRCA2). Mutations in this gene predispose humans to breast and ovarian cancer. The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev. 2000;14(11):1400-6)
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells such as the GOBLET CELLS.
The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from PREVALENCE, which refers to all cases, new or old, in the population at a given time.
Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.
Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.
Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.
Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.
Compounds that interact with ANDROGEN RECEPTORS in target tissues to bring about the effects similar to those of TESTOSTERONE. Depending on the target tissues, androgenic effects can be on SEX DIFFERENTIATION; male reproductive organs, SPERMATOGENESIS; secondary male SEX CHARACTERISTICS; LIBIDO; development of muscle mass, strength, and power.
Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Tumors or cancer of the PHARYNX.
Care alleviating symptoms without curing the underlying disease. (Stedman, 25th ed)
Mädge B, Geisen C, Möröy T, Schwab M (2003). "Yaf2 inhibits Myc biological function". Cancer Lett. 193 (2): 171-6. doi:10.1016/ ... 2002). "A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells". Science. 296 (5570): 1132- ...
Several diseases, especially cancer, have been suspected of selectively turning genes on or off, thereby resulting in a ... Li Y, Casey SC, Felsher DW (July 2014). "Inactivation of MYC reverses tumorigenesis". Journal of Internal Medicine. 276 (1): 52 ... The role of epigenetics in cancer has been the subject of intensive study. For the purposes of epigenetic therapy, the two key ... Many diseases, including cancer, heart disease, diabetes, and mental illnesses are influenced by epigenetic mechanisms. ...
"Intrachromosomal rearrangements fusing L-myc and rlf in small-cell lung cancer". Mol Cell Biol. 11 (8): 4015-21. doi:10.1128/ ... "Entrez Gene: RLF rearranged L-myc fusion". Olsen JV; Blagoev B; Gnad F; et al. (2006). "Global, in vivo, and site-specific ... 1996). "The rearranged L-myc fusion gene (RLF) encodes a Zn-15 related zinc finger protein". Oncogene. 11 (12): 2699-704. PMID ...
She believes that inhibition of Myc can force the immune system to wake up, and kill cancer from the inside and outside. ... Her research considers the Myc oncoprotein, a protein that cancer cells appear to depend on, which had long been considered too ... She has demonstrated that inhibition of Myc can have a dramatic therapeutic index in mouse models of cancer, causing minimal ... Her publications include: Soucek, Laura (2020). "Blocking Myc to Treat Cancer: Reflecting on Two Decades of Omomyc". Cells. 9 ( ...
Almeida MI, Reis RM, Calin GA (2010). "MYC-microRNA-9-metastasis connection in breast cancer". Cell Res. 20 (6): 603-4. doi: ... a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis". Nat Cell Biol. 12 (3): 247-56. doi:10.1038/ncb2024 ... "Potential role of miR-9 and miR-223 in recurrent ovarian cancer". Mol Cancer. 7 (1): 35. doi:10.1186/1476-4598-7-35. PMC ... Guo LM, Pu Y, Han Z, Liu T, Li YX, Liu M, Li X, Tang H (2009). "MicroRNA-9 inhibits ovarian cancer cell growth through ...
"Distinct Thresholds Govern Myc's Biological Output in Vivo". Cancer Cell. 14 (6): 447-457. doi:10.1016/j.ccr.2008.10.018. PMC ... "Modelling Myc inhibition as a cancer therapy". Nature. 455 (7213): 679-683. Bibcode:2008Natur.455..679S. doi:10.1038/ ... "Gerard Evan : Cancer Research UK". Archived from the original on 17 June 2013. List of publications from Microsoft Academic ... Sodir, N. M.; Swigart, L. B.; Karnezis, A. N.; Hanahan, D.; Evan, G. I.; Soucek, L. (2011). "Endogenous Myc maintains the tumor ...
Cancer Research. 62 (23): 6820-2. PMID 12460892. Gery S, Koeffler HP (May 2003). "Repression of the TMEFF2 promoter by c-Myc". ... and HPP1 in human cancers". British Journal of Cancer. 93 (9): 1029-37. doi:10.1038/sj.bjc.6602837. PMC 2361683. PMID 16234815 ... Cancer Research. 62 (20): 5637-40. PMID 12384516. Sato F, Shibata D, Harpaz N, Xu Y, Yin J, Mori Y, Wang S, Olaru A, Deacu E, ... Cancer Research. 60 (17): 4907-12. PMID 10987305. Young J, Biden KG, Simms LA, Huggard P, Karamatic R, Eyre HJ, Sutherland GR, ...
... also targets Myc Binding Protein (MYCBP). This prevents transcription of c-Myc target genes by silencing c-MYCBP. ... Mir-22 was found to be over-expressed in prostate cancer but down-regulated in breast cancer, cholangiocarcinoma, multiple ... "Tumor-suppressive microRNA-22 inhibits the transcription of E-box-containing c-Myc target genes by silencing c-Myc binding ... a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients". Breast Cancer ...
... pancreatic cancer where the NEDD4 directly targets the respective oncoproteins N-Myc and c-Myc associated with these cancers ... Ye X, Wang L, Shang B, Wang Z, Wei W (2014). "NEDD4: a promising target for cancer therapy". Curr Cancer Drug Targets. 14 (6): ... Chen C, Matesic LE (2007). "The Nedd4-like family of E3 ubiquitin ligases and cancer". Cancer Metastasis Rev. 26 (3-4): 587-604 ... However, in other in vivo models, and in many human cancer cell lines, NEDD4 does appear responsible for the degradation of ...
Ruggero, D (1 December 2009). "The role of Myc-induced protein synthesis in cancer". Cancer Research. 69 (23): 8839-43. doi: ... In cancer, Myc driven transcriptional amplification is posited to help tumor cells overcome rate-limiting constraints in growth ... "The spliceosome is a therapeutic vulnerability in MYC-driven cancer". Nature. 525 (7569): 384-8. doi:10.1038/nature14985. PMC ... "Targeting transcriptional addictions in small cell lung cancer with a covalent CDK7 inhibitor". Cancer Cell. 26 (6): 909-22. ...
Sharma VM, Draheim KM, Kelliher MA (Apr 2007). "The Notch1/c-Myc pathway in T cell leukemia". Cell Cycle. 6 (8): 927-30. doi: ... Bolós V, Grego-Bessa J, de la Pompa JL (May 2007). "Notch signaling in development and cancer". Endocrine Reviews. 28 (3): 339- ... In the context of T-ALL, Notch activity cooperates with additional oncogenic lesions such as c-MYC to activate anabolic ... Bagley, Katherine (2009-11-11). "New drug target for cancer". The Scientist. Retrieved 2009-11-11. Bhandari DR, Seo KW, Roh KH ...
"Targeting MYC dependence in cancer by inhibiting BET bromodomains". Proceedings of the National Academy of Sciences of the ... Blood Cancer Journal. 3 (7): e126. doi:10.1038/bcj.2013.24. PMC 3730202. PMID 23872705. "Jay Bradner: Open-source cancer ... In many cases, expression of the growth promoting transcription factor Myc is blocked by BET inhibitors. BRD2 and BRD3 are ... Interest in using BET inhibitors in cancer began with the observation that chromosomal translocations involving BET genes BRD3 ...
"Commonly occurring loss and mutation of the MXI1 gene in prostate cancer". Genes Chromosomes Cancer. 22 (4): 295-304. doi: ... Benson LQ, Coon MR, Krueger LM, Han GC, Sarnaik AA, Wechsler DS (1999). "Expression of MXI1, a Myc antagonist, is regulated by ... J. Cancer. 86 (3): 477-84. doi:10.1038/sj.bjc.6600065. PMC 2375210. PMID 11875718. Ariyanayagam-Baksh SM, Baksh FK, Swalsky PA ... Eagle LR, Yin X, Brothman AR, Williams BJ, Atkin NB, Prochownik EV (1995). "Mutation of the MXI1 gene in prostate cancer". Nat ...
Myc A, Majoros IJ, Thomas TP, Baker JR (January 2007). "Dendrimer-based targeted delivery of an apoptotic sensor in cancer ... Majoros IJ, Myc A, Thomas T, Mehta CB, Baker JR (February 2006). "PAMAM dendrimer-based multifunctional conjugate for cancer ... Malik N, Evagorou EG, Duncan R (September 1999). "Dendrimer-platinate: a novel approach to cancer chemotherapy". Anti-Cancer ... "Nanoparticle targeting of anticancer drug improves therapeutic response in animal model of human epithelial cancer". Cancer ...
... a rare pediatric cancer. Both forms of brain cancer are characterized by Myc overexpression. The first Phase 1b clinical trial ... Myc overexpression is a known factor in many cancers, with 80 percent of glioblastomas characterized by this property. ... August 2014). "Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis". Nature ... "FDA grants orphan drug designation to zotiraciclib for the treatment of glioma". NIH National Cancer Institute. Cancer Research ...
"PEG10 is a c-MYC target gene in cancer cells". Cancer Research. 66 (2): 665-72. doi:10.1158/0008-5472.CAN-05-1553. PMID ... Cancer Research. 63 (12): 3043-8. PMID 12810624. Tsou AP, Chuang YC, Su JY, Yang CW, Liao YL, Liu WK, Chiu JH, Chou CK (2004 ... Cancer Research. 63 (12): 3043-8. PMID 12810624. Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (Apr 1996). "A " ...
2003). "N-Myc downstream-regulated gene 2 (NDRG2) inhibits glioblastoma cell proliferation". Int. J. Cancer. 106 (3): 342-7. ... "N-Myc downstream-regulated gene 2 (NDRG2) inhibits glioblastoma cell proliferation". Int. J. Cancer. 106 (3): 342-7. doi: ... 2003). "Expression and regulation of NDRG2 (N-myc downstream regulated gene 2) during the differentiation of dendritic cells". ... 2005). "NDRG2 expression and mutation in human liver and pancreatic cancers". World J. Gastroenterol. 10 (23): 3518-21. doi: ...
"Insertional mutagenesis reveals progression genes and checkpoints in MYC/Runx2 lymphomas". Cancer Research. 67 (11): 5126-33. ... Later, another study also showed that JDP2 can substitute Oct4 to generate iPSCs with Klf4, Sox2 and Myc (KSM) or KS[ ... JDP2-transgenic mice display potentiation of liver cancer, higher mortality and increase number and size of tumors, especially ... Cancer. 47 (6): 500-9. doi:10.1002/gcc.20551. PMID 18314910. Yuanhong X, Feng X, Qingchang L, Jianpeng F, Zhe L, Kejian G (2009 ...
This gene was identified as a c-Myc responsive gene, and behaves as a direct c-Myc target gene. Overexpression of this gene is ... Walker MG (Aug 2002). "Drug target discovery by gene expression analysis: cell cycle genes". Curr Cancer Drug Targets. 1 (1): ... 2005). "The Myc target gene JPO1/CDCA7 is frequently overexpressed in human tumors and has limited transforming activity in ... "A novel c-Myc-responsive gene, JPO1, participates in neoplastic transformation". J Biol Chem. 276 (51): 48276-84. doi:10.1074/ ...
"FOXO6 promotes gastric cancer cell tumorigenicity via upregulation of C-myc". FEBS Letters. 587 (14): 2105-11. doi:10.1016/j. ...
"Evaluation of the 8q24 prostate cancer risk locus and MYC expression". Cancer Res. 69 (13): 5568-74. doi:10.1158/0008-5472.CAN- ... "Variation at 8q24 and 9p24 and risk of epithelial ovarian cancer". Twin Res Hum Genet. 13 (1): 43-56. doi:10.1375/twin.13.1.43 ...
The glutamine analog DON has also been seen to act as an irreversible inhibitor, and has been used as an anti-cancer agent. CTP ... CTP synthase levels have been shown to be dependent on levels of the transcription factor Myc. In turn, CTP synthase activity ... Aughey GN, Grice SJ, Liu JL (February 2016). "The Interplay between Myc and CTP Synthase in Drosophila". PLOS Genetics. 12 (2 ... Ahluwalia GS, Grem JL, Hao Z, Cooney DA (1990). "Metabolism and action of amino acid analog anti-cancer agents". Pharmacology ...
... has been shown to be down-regulated in breast cancer. miR-145 is also involved in colon cancer and acute myeloid ... Sachdeva M, Zhu S, Wu F, Wu H, Walia V, Kumar S, Elble R, Watabe K, Mo YY (Mar 2009). "p53 represses c-Myc through induction of ... "The functional significance of microRNA-145 in prostate cancer". British Journal of Cancer. 103 (2): 256-64. doi:10.1038/sj.bjc ... and angiogenesis of gastric cancer cells". Molecular Cancer Research. 11 (2): 182-93. doi:10.1158/1541-7786.MCR-12-0534. PMID ...
Cancer Research. 63 (5): 980-6. PMID 12615712. Zhou B, Liu X, Mo X, Xue L, Darwish D, Qiu W, Shih J, Hwu EB, Luh F, Yen Y ( ... "Inhibitory effect of c-Myc on p53-induced apoptosis in leukemia cells. Microarray analysis reveals defective induction of p53 ... Cancer Research. 63 (20): 6583-94. PMID 14583450. Shao J, Zhou B, Zhu L, Qiu W, Yuan YC, Xi B, Yen Y (January 2004). "In vitro ... Cancer Letters. 190 (2): 233-43. doi:10.1016/S0304-3835(02)00588-8. PMID 12565178. Xue L, Zhou B, Liu X, Qiu W, Jin Z, Yen Y ( ...
Induction of resistance to Aplidin in a human ovarian cancer cell line related to MDR expression. Cancer Biol Ther (2005) 4: ... Multiple effects of paclitaxel are modulated by high c-myc amplification level. Exp Cell Res (2003) 290:49-59. Erba E, Serafini ... "Induction of resistance to Aplidin in a human ovarian cancer cell line related to MDR expression". Cancer Biology & Therapy. 4 ... Cancer Chem Pharm (2004) 53:89-90. Bottone MG, Soldani C, Tognon G, Gorrini C, Lazzè MC, Brison O, Ciomei M, Pellicciari C, ...
2009). "Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells". BMC Cancer. 9 ... AP2-gamma also suppresses genes such as MYC and C/EBP alpha. It also represses CD44 expression, which is a cell marker for some ... and activator protein 2gamma expression levels correlate with basal phenotype in breast cancer". Cancer. 115 (4): 899-908. doi: ... Cancer Res. 13 (20): 6115-21. doi:10.1158/1078-0432.CCR-07-1282. PMID 17947476. Kotani T, Iwase A, Ino K, et al. (2009). " ...
Shachaf CM.and Felsher D. W.Tumor dormancy and MYC inactivation: pushing cancer to the brink of normalcy. Cancer Res. 2005 June ... Shachaf CM.and Felsher D. W.Tumor dormancy and MYC inactivation: pushing cancer to the brink of normalcy. Cancer Res. 2005 June ... Systematic molecular analysis of a MYC overexpressing tumor cell following MYC inactivation. Cancer Res. 2008 Jul 1;68(13):5132 ... Jul 2008). "Systematic molecular analysis of a MYC overexpressing tumor cell following MYC inactivation". Cancer Res. 68 (13): ...
Implication in Cancer Treatments[edit]. If a cancer cell's capacity to repair DNA damage were incapacitated, cancer treatments ... Wang Q, Zhang H, Kajino K, Greene MI (Oct 1998). "BRCA1 binds c-Myc and inhibits its transcriptional and transforming activity ... Cancer. 6 (5): 382-91. doi:10.1038/nrc1878. PMID 16633366.. *^ a b c d Ryser S, Dizin E, Jefford CE, Delaval B, Gagos S, ... cancer-associated BARD1beta scaffolds Aurora B and BRCA2". Cancer Research. 69 (3): 1125-34. doi:10.1158/0008-5472.CAN-08-2134 ...
... "hsa-mir-210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer". Cancer. 116 (9): 2148-58. doi: ... "MicroRNA miR-210 modulates cellular response to hypoxia through the MYC antagonist MNT". Cell Cycle. 8 (17): 2756-68. doi: ... J. Cancer. 126 (1): 73-80. doi:10.1002/ijc.24687. PMID 19551852. Zhang Z, Sun H, Dai H, Walsh RM, Imakura M, Schelter J, ... "MicroRNA-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulfur ...
The JUN protein binds to the USP28 promoter in colorectal cancer cells and is involved in the activation of these cancer cells ... Transcription factors affected are glucocorticoid responsive elements and E2F-myc cell cycle regulars. There are eleven common ... American Association of Cancer Research Annual Meeting 2016. New Orleans LA, USA. doi:10.13140/rg.2.2.23237.65765. "C18orf63 ... Kuruc M (April 2016). The Commonality of the Cancer Serum Proteome Phenotype as analyzed by LC-MS/MS, and Its Application to ...
... c-Myc 발현을 제거함으로써 안전성을 향상시킬 수 있는 잠재적 전략은 세포의 줄기세포능을 보존하기 어려울 것이다. 그러나, N-Myc 및 L-Myc은 c-Myc 대신에 유도만능줄기세포를 유사한 효율로 유도하는 것으로 확인되었다 ... "Cancer Research》 24: 1544-1551. ISSN 0008-5472. PMID 14234000.. *↑ Andrews, P. W.; Matin, M. M.; Bahrami, A. R.; Damjanov, I.; ... 배아줄기세포는 유전적으로 암과 관련된 c-Myc 같은 유전자로 변형되지 않기 때문에, 본질적으로 유도만능줄기세포보다 안전할 것으로 예측된다. 그럼에도 불구하고, 배아줄기세포는 매우 높은 수준의 유도만능줄기세포 유도 유전자를 ... "c-Myc is dispensable for direct reprogramming of mouse fibroblasts". 》Cell Stem Cell》 2 (1): 10-12. ISSN 1875-9777. PMID ...
2007). "Gonadal mosaicism and familial adenomatous polyposis". Familial Cancer. 7 (2): 173-7. doi:10.1007/s10689-007-9169-1. ... Burkitt's lymphoma t(8 MYC;14 IGH). *Follicular lymphoma t(14 IGH;18 BCL2) ... cancer research has shown that somatic mutations are increasingly present throughout a lifetime and are responsible for most ... "Detectable Clonal Mosaicism and Its Relationship to Aging and Cancer". Nature Genetics. 44 (6): 651-U668. doi:10.1038/ng.2270 ...
Cancer 2 (10): 764-76. PMID 12360279. doi:10.1038/nrc904. *Nilsson JA, Cleveland JL (2004). "Myc pathways provoking cell ... Myc (c-Myc) je regulatorni gen koji kodira transkripcioni faktor. Mutirane verzije Myc gena su nađene u mnoštvu tipova kancera ... Dang CV, O'donnell KA, Juopperi T (2005). "The great MYC escape in tumorigenesis". Cancer Cell 8 (3): 177-8. PMID 16169462. doi ... V-myc mielocitomatozni viralni onkogenski homolog. Struktura c-Myc (crveno) u kompleksu sa Max (plavo) i DNK (1nkp). Oba ...
Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, ... Adams J (April 2003). "Potential for proteasome inhibition in the treatment of cancer". Drug Discovery Today. 8 (7): 307-15. ... Hershko's year-long sabbatical in the laboratory of Irwin Rose at the Fox Chase Cancer Center provided key conceptual insights ... UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of ...
"Increased androgen receptor activity and altered c-myc expression in prostate cancer cells after long-term androgen deprivation ... "Prostate Cancer". National Cancer Institute. Retrieved 12 October 2014. *↑ ۲٫۰ ۲٫۱ ۲٫۲ ۲٫۳ ۲٫۴ ۲٫۵ ۲٫۶ World Cancer Report 2014 ... Prostate cancer is the development of cancer in the prostate, a gland in the male reproductive system.[6] Most prostate cancers ... "Cancer of the Prostate - Cancer Stat Facts". Archived from the original on 18 March 2017. Retrieved 11 April ...
Metastatic cancerEdit. IL-15 has been shown to enhance the anti-tumor immunity of CD8+ T cells in pre-clinical models.[27][28] ... c-Myc and NF-κB.[13] ... cancer cells or fibroblasts, this cytokine is produced as a ... ALT-803 was given fast track status by the FDA in 2017 and at that time, Phase III trials in bladder cancer were being prepared ... Xu X, Sun Q, Yu X, Zhao L (April 2017). "Rescue of nonlytic Newcastle Disease Virus (NDV) expressing IL-15 for cancer ...
"National Cancer Institute. 8 December 2017. Retrieved 20 December 2017.. *^ a b c d e f g h i j k l m n o p q r s Hunger SP, ... An example of this includes the translocation of C-MYC, a gene that encodes a transcription factor that leads to increased cell ... "Acute Lymphocytic Leukemia - Cancer Stat Facts". SEER. Retrieved 20 December 2017.. *^ a b Tubergen DG, Bleyer A, Ritchey AK ( ... Bethesda, MD: National Cancer Institute, SEER Program.. *^ a b Shapira T, Pereg D, Lishner M (September 2008). "How I treat ...
"p21 is necessary for the p53-mediated G1 arrest in human cancer cells." Cancer research 55.22 (1995): 5187-5190. ... "Nature Reviews Cancer. 9 (6): 400-414. doi:10.1038/nrc2657. PMC 2722839. PMID 19440234.. ... Almond JB, Cohen GM (April 2002). "The proteasome: a novel target for cancer chemotherapy". Leukemia. 16 (4): 433-43. doi: ... Gartel AL, Radhakrishnan SK (May 2005). "Lost in transcription: p21 repression, mechanisms, and consequences". Cancer Res. 65 ( ...
2006). "Transcriptome analysis of human gastric cancer.". Mamm. Genome. 16 (12): 942-54. PMID 16341674. doi:10.1007/s00335-005- ...
Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation In National Cancer Institute Fact Sheet web site. ... c-Myc ir Klf4 transkripcijos faktorius.[50] Kinų kilmės JAV mokslininkas Džunjing Ju (Junying Yu), Jamesas Thomsonas ir jų ...
... of bladder cancers, 88% of stomach cancers, 74% of thyroid cancers, 40%-90% of colorectal cancers and 50% of brain cancers. ... "c-MYC Generates Repair Errors via Increased Transcription of Alternative-NHEJ Factors, LIG3 and PARP1, in Tyrosine Kinase- ... Promoter hypermethylation of NEIL1 occurs in 62% of head and neck cancers and in 42% of non-small-cell lung cancers. Promoter ... Promoter CpG hyper/hypo-methylation in cancer[edit]. In cancers, loss of expression of genes occurs about 10 times more ...
The BCR-ABL oncogene has been found to be involved in the development of cancer in humans. c-Myc is involved in the regulation ... Unlike other cancer genes, which promote cancer by stimulating cell proliferation, BCL2 promoted cancer by stopping lymphoma ... Kaczanowski, S. Apoptosis: its origin, history, maintenance and the medical implications for cancer and aging. Phys Biol 13, ... infection and cancer. A critical regulator of autophagy induction is the kinase mTOR, which when activated, suppresses ...
These cells proliferate abnormally rapidly, even compared to other cancer cells. Like many other cancer cells,[36] HeLa cells ... Dual-color FISH with a c-MYC probe mapping to 8q24 revealed colocalization with HPV18 at all integration sites, indicating that ... HeLa cells are rapidly dividing cancer cells, and the number of chromosomes varied during cancer formation and cell culture. ... as well as in in vitro cancer research using cell lines.[33] Further HeLa cells have also been used to define cancer markers in ...
... and c-Myc inhibits c-Myc-induced human telomerase reverse transcriptase gene (hTERT) promoter activity in breast cancer (PDF), ... La proteina Myc appartiene alla famiglia Myc di fattori di trascrizione, che include anche i geni N-Myc e L-Myc. I fattori di ... Pelengaris S, Khan M, Evan G, c-MYC: more than just a matter of life and death, in Nat. Rev. Cancer, vol. 2, nº 10, ottobre ... Nilsson JA, Cleveland JL, Myc pathways provoking cell suicide and cancer (PDF), in Oncogene, vol. 22, nº 56, 8 dicembre 2003, ...
"British Journal of Cancer. 107 (2): 375-81. PMC 3394973. . PMID 22644305. doi:10.1038/bjc.2012.231. الوسيط ,السنة=. تم تجاهله ( ...
British Journal of Cancer. 81 (1): 144-151 [146, 149]. doi:10.1038/sj.bjc.6690664. PMC 2374359. PMID 10487626.. ... Burkitt's lymphoma t(8 MYC;14 IGH). *Follicular lymphoma t(14 IGH;18 BCL2) ... "British Journal of Cancer. 88 (3): 382-7. doi:10.1038/sj.bjc.6600748. PMC 2747537. PMID 12569380.. ... Paternal smoking use has also been linked to an increased risk of birth defects and childhood cancer for the offspring, where ...
Controlling the chromatin remodeling process within cancer cells may provide a novel drug target for cancer research.[30] ... PCAF has also been observed to acetylate c-MYC, GATA-2, retinoblastoma (Rb), Ku70, and E1A adenovirus protein.[19] It can also ... Klein G, Vande Woude GF (2002). Advances in Cancer Research, Volume 86. Boston: Academic Press. ISBN 0-12-006686-6.. ... radiosensitizes cancer cells by inhibiting non-homologous end joining". Int. J. Radiat. Oncol. Biol. Phys. 84 (3): 815-21. doi: ...
... and many forms of cancer including non-Hodgkin's lymphoma,[62] colorectal cancer, head and neck cancer and breast cancer.[63] ... "Class switching and Myc translocation: how does DNA break?". Nat. Immunol. 5 (11): 1101-1103. doi:10.1038/ni1104-1101. PMC ... antibody-secreting lymphocytes are isolated from the animal and immortalized by fusing them with a cancer cell line. The fused ... this process may explain the efficacy of monoclonal antibodies used in biological therapies against cancer. The Fc receptors ...
Cancer[edit]. Hsp70 is overexpressed in malignant melanoma[17] and underexpressed in renal cell cancer.[18][19] ... c-myc and HLA-DR expression in patients with malignant melanoma". European Journal of Surgical Oncology. 27 (1): 88-93. doi: ... Sherman M, Multhoff G (October 2007). "Heat shock proteins in cancer". Annals of the New York Academy of Sciences. 1113 (1): ...
Hajra KM, Chen DY, Fearon ER (March 2002). "The SLUG zinc-finger protein represses E-cadherin in breast cancer". Cancer ... Cancer. 9 (4): 265-73. doi:10.1038/nrc2620. PMID 19262571.. *^ Berx G, Cleton-Jansen AM, Nollet F, de Leeuw WJ, van de Vijver M ... a cause of loss of intercellular adhesiveness in human cancer cell lines". Cancer Research. 54 (23): 6282-7. PMID 7954478.. ... Cadherin-1 and cancer[edit]. Cadherin-1 in metastasis[edit]. Transitions between epithelial and mesenchymal states play ...
"British Journal of Cancer. 81 (1): 144-151 [146, 149]. doi:10.1038/sj.bjc.6690664. PMC 2374359. PMID 10487626.. ... Burkitt's lymphoma t(8 MYC;14 IGH). *Follicular lymphoma t(14 IGH;18 BCL2) ... "British Journal of Cancer. 88 (3): 382-7. doi:10.1038/sj.bjc.6600748. PMC 2747537. PMID 12569380.. ... "JNCI Journal of the National Cancer Institute. 89 (3): 238-243. doi:10.1093/jnci/89.3.238. PMID 9017004.. ...
"Cancer Research. 63 (4): 831-37. PMID 12591734.. *^ Vlahopoulos SA (August 2017). "Aberrant control of NF-κB in cancer permits ... ras or c-myc) are mutated or inactivated in diseased cells, and further genes (such as bcl-2) also modify their expression in ... In cancer, the apoptosis cell-division ratio is altered. Cancer treatment by chemotherapy and irradiation kills target cells ... "Finding Cancer's Self-Destruct Button". CR magazine (Spring 2007). Article on apoptosis and cancer. ...
... polymerase 1 in BRCA-mutated serous ovarian cancer". BMC Cancer 13: 90. PMC 3599366. PMID 23442605. doi:10.1186/1471-2407-13-90 ... "c-MYC Generates Repair Errors via Increased Transcription of Alternative-NHEJ Factors, LIG3 and PARP1, in Tyrosine Kinase- ... 21,0 21,1 Bernstein C, Prasad AR, Nfonsam V, Bernstein H. (2013). DNA Damage, DNA Repair and Cancer, New Research Directions in ... Bernstein H, Payne CM, Bernstein C, Garewal H, Dvorak K (2008). Cancer and aging as consequences of un-repaired DNA damage. In ...
New strategies in lung cancer: epigenetic therapy for non-small cell lung cancer. Clinical Cancer Research. May 2014, 20 (9): ... 呼吸道上皮细胞需长时间暴露于促癌物质下并逐渐积累多种基因突变才能成为腫瘤。刺激细胞生长(K-ras, MYC)的基因突变逐渐导致生长因子受体(EGFR,HER2/neu)信号异常,抑制凋亡(BCL-2),引起异常细胞增殖。此外,肿瘤抑制基因的突变(p53 ... 肺癌(英語:Lung cancer[7])是惡性的肺
... which results in increased activity of MYC, a central player in colorectal cancer.[44] ... Colorectal cancer (CRC), also known as bowel cancer and colon cancer, is the development of cancer from the colon or rectum ( ... "Bowel cancer , About bowel cancer , Cancer Research UK". Archived from the original on March 9, 2017 ... The polyp to cancer progression sequence is the classical model of colorectal cancer pathogenesis.[48] The polyp to cancer ...
... and c-Myc inhibits c-Myc-induced human telomerase reverse transcriptase gene (hTERT) promoter activity in breast cancer". J. ... Cancer chemotherapyEdit. Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. At diagnosis, ... of breast cancers), HER2+ (15%-30% of breast cancers), ER+/PR+ (about 70% of breast cancers), and Invasive lobular carcinoma ( ... "The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers". BMC Cancer. 7: 152. doi:10.1186/ ...
"The PRMT5 arginine methyltransferase: many roles in development, cancer and beyond". Cellular and Molecular Life Sciences. 72 ... "mSin3A/histone deacetylase 2- and PRMT5-containing Brg1 complex is involved in transcriptional repression of the Myc target ...
In 1978, Weintraub joined the Fred Hutchinson Cancer Research Center (FHCRC), established in 1971 as an independent affiliate ... "MyoD is a sequence-specific DNA binding protein requiring a region of myc homology to bind to the muscle creatine kinase ... "Weintraub Graduate Student Award". Fred Hutchinson Cancer Research Center: Basic Sciences Division. Retrieved 21 January 2015 ... 4, 5". Fred Hutchinson Cancer Research Center: Hutch News. Retrieved November 28, 2014. ...
... a TAT-fused protein was delivered into mitochondria of breast cancer cells and decreased the survival of breast cancer cells, ... a delivery vector for decoy oligonucleotides targeting the Myc protein". Journal of Controlled Release. 110 (1): 189-201. doi: ... In vivo studies show that QD are able to selectively label cancer cells, and they accumulate at tumor sites. Tumor cells ... These contrast agents are able to label the tumor cells, making the compounds important tools in cancer diagnosis; they are ...
Other approaches to halt Myc on the path to cancer involve targeting Myc-Max dimerization or Myc-induced microRNA expression. ... Upon activation of MYC and elevated levels of Myc, mass action favors the binding of Myc-Max to E-box genes to regulate ... MYC on the path to cancer.. Dang CV1.. Author information. 1. Division of Hematology-Oncology, Department of Medicine, Abramson ... The MYC oncogene contributes to the genesis of many human cancers. Recent insights into its expression and function have led to ...
A) Representative light microscopy images of control (pLKO) and MYC knockdown (MYC HP1) MDA-MB-231 breast cancer cells ... cancer signatures. In addition, functional inactivation of MYC in human breast cancer cells specifically inhibits distant ... MYC regulation of a "poor-prognosis" metastatic cancer cell state.. Wolfer A1, Wittner BS, Irimia D, Flavin RJ, Lupien M, ... D) Representative light microscopy images of pLKO and MYC HP1 MDA-MB-231 breast cancer cells migrating through collagen IV- ...
Their studies were performed in mouse cancer models and in human cell cultures.. "While MYC has a definite role in cancer, MYC ... Too much DLX5, they found, led to too much MYC. When they knocked out expression of DLX5 in lung cancer cells, it resulted in ... From this, Testa and Xu were able to gain a broader understanding of how cancers involving AKT2, DLX5 and MYC might develop. A ... Studies in both cells and a mouse model for cancer showed that they could promote the expression of MYC by transfecting cells ...
Destruction of Myc by ubiquitin-mediated proteolysis: cancer-associated and transforming mutations stabilize Myc. EMBO J 1999; ... An important future goal will be to study the parallels between the effects of E1A on Myc versus the tumor-derived Myc cancer ... Cancer Research Online ISSN: 1538-7445. Cancer Research Print ISSN: 0008-5472. Journal of Cancer Research ISSN: 0099-7013. ... E1A may also stabilize Myc by activation of ERK. As it is likely that some cancer-associated Myc mutants are stabilized by ...
Exceeds Gold-Standard For Treatment Of MYC-Driven Cancer - read this article along with other careers information, tips and ... Exceeds Gold-Standard For Treatment Of MYC-Driven Cancer. Published: Nov 16, 2015 ... We are encouraged by the high hit rate so far and are confident that a larger pool of specific MYC inhibitors will emerge once ... a broader set of MYC inhibitors we will then choose the highest quality candidates for analysis in animal models of cancer." ...
... pathway through multiple molecular mechanisms in a variety of c-Myc- and N-Myc-dependent cancers. In particular, Myc- ... Myc activation is a primary oncogenic event in many human cancers; however, these transcription factors are difficult to ... IRE1α RNase-dependent lipid homeostasis promotes survival in Myc-transformed cancers. ... IRE1α RNase-dependent lipid homeostasis promotes survival in Myc-transformed cancers. ...
D) GSEA for the Myc-bound gene sets comparing gene expression profiles for Eμ-Myc and Eμ-Myc Dpy30+/- B cells. Myc targets that ... C-MYC, N-MYC, and L-MYC) (Supplemental Figure 3A). Therefore, the association between MYC and DPY30 overexpression is not tumor ... 5 Eμ-Myc Dpy30+/- cells. For bone marrow: n = 4 WT; n = 7 Dpy30+/-; n = 5 Eμ-Myc; and n = 5 Eμ-Myc Dpy30+/- cells. (F) Annexin ... 8 Eμ-Myc Dpy30+/- cells. For bone marrow: n = 8 WT; n = 11 Dpy30+/-; n = 14 Eμ-Myc; and n = 10 Eμ-Myc Dpy30+/- cells. Data ...
These examine important topics in molecular biology, genetics, development, virology, neurobiology, immunology and cancer ... Neuroblastoma and MYCN. Miller Huang and William A. Weiss. MYC Association with Cancer Risk and a New Model of MYC-Mediated ... Cellular MYCro Economics: Balancing MYC Function with MYC Expression. David Levens. MYC and Transcription Elongation. Peter B. ... MYC and the Pathway to Cancer. Subject Area(s): Molecular Biology; Genetics; Cancer Biology. Edited by Chi V. Dang, University ...
One gene that has been implicated in many cancers is c-Myc. One cancer, a common liver cancer in children, didnt appear to ... However, in cancer cells that undergo rapid division and metabolism, c-Myc is required. c-Mycs role may be to allow cells to ... Given c-Mycs involvement in a number of cancers, why is this news? "Our findings indicate that even tumors which do not ... When c-Myc is overexpressed in cancers, it effectively signals to turn on other genes at levels higher than normal. The ...
The iMYC trial is screening oesophagogastric tumours for MYC amplification in order to investigate a novel biomarker-driven ... Gastrointestinal Cancers. Rectal Cancer • Biliary cancer • Gastric cancer • Oesophageal cancerCancer of the pancreas • ... Genitourinary Cancers. Testicular Germ Cell CancerCancer of the Prostate • Bladder Cancer • Renal Cell Carcinoma • Penile ... Metastatic colorectal cancer • Anal cancer • Early colon cancer • Familial risk colorectal cancer • Hepatocellular carcinoma ...
Analysis of the Cancer Genome Atlas (TCGA) database of endometrial tumors identified an inverse correlation between PR and Myc ... We established that PR is a negative transcriptional regulator of Myc in endometrial cancer in the presence or absence of ERα, ... Inverse Relationship between Progesterone Receptor and Myc in Endometrial Cancer.. [Tamar Kavlashvili, Yichen Jia, Donghai Dai ... First, estrogen stimulation augmented PR expression and decreased Myc in endometrial cancer cell lines. Second, progesterone ...
Recent developments have produced a new drug-class that inhibits MYC. These ‘MYC inhibitors can kill lymphomas but some ... Some of the worst lymphomas are caused by a gene called ‘MYC. ... Lymphomas are cancers of the white blood cells. ... Cancer Types. Cancer is a disease of the cells, which are the ... Lymphomas are cancers of the white blood cells. Some of the worst lymphomas are caused by a gene called MYC. Recent ...
As c-Myc, N-Myc, and L-Myc are highly conserved ( 45), it is tempting to postulate that the region of c-Myc between amino acid ... Myc-driven murine prostate cancer shares molecular features with human prostate tumors. Cancer Cell 2003; 4: 223-38. ... 2007 American Association for Cancer Research.. References. *↵ Prochownik EV. c-Myc as a therapeutic target in cancer. Expert ... Destruction of Myc by ubiquitin-mediated proteolysis: cancer-associated and transforming mutations stabilize Myc. EMBO J 1999; ...
... mortality by cervical cancer is the first cause of mortality by cancer in women (Parkin et al., 1984), and continues to ... Alterations of C-Ha-ras Gene are Associated with c-myc Activation in Human Cervical Cancers. ... In underdeveloped countries, mortality by cervical cancer is the first cause of mortality by cancer in women (Parkin et al., ... Présence de génomes de papillomavirus et amplification des oncogènes c-myc et c-Ha-ras dans des cancers envahissants du col de ...
HIF and c-Myc: sibling rivals for control of cancer cell metabolism and proliferation. Cancer Cell 2007;12:108-13. ... The action mechanism of the Myc inhibitor termed Omomyc may give clues on how to target Myc for cancer therapy. PLoS One 2011;6 ... MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Res 2007;67:9762-70. ... MYC-induced cancer cell energy metabolism and therapeutic opportunities. Clin Cancer Res 2009;15:6479-83. ...
As the c-Myc oncoprotein has recognized roles in normal stem cell biology, we hypothesized that c-Myc may contribute to cancer ... c-Myc is required for maintenance of glioma cancer stem cells.. [Jialiang Wang, Hui Wang, Zhizhong Li, Qiulian Wu, Justin D ... Further, glioma cancer stem cells with decreased c-Myc levels failed to form neurospheres in vitro or tumors when ... Here we report that c-Myc is highly expressed in glioma cancer stem cells relative to non-stem glioma cells. To interrogate the ...
Ironing Out MYC in Prostate Cancer Message Subject. (Your Name) has forwarded a page to you from Science Translational Medicine ... Myc is a growth-promoting protein implicated in the formation of several malignancies, including prostate cancer. Activation of ... Numerous cancers express TFRC on the cell surface, and many investigators have attempted to target TFRC as a mechanism for ... J. P. Holland et al., Annotating MYC status with 89Zr-transferrin imaging. Nat. Med. 18, 1586-1592 (2012). [PubMed] ...
Kessler, JD, Hasegawa, H, Brun, SN, Yang, ZJ, Dutton, JW, Wang, F and Wechsler-Reya, RJ N-myc alters the fate of preneoplastic ... Early cancer intervention relies on identifying the molecular signals that transform precancerous cells into tumors. ... They also found that N-myc promotes tumor progression and might be a key determinant of tumorigenesis. ...
We evaluated copy numbers and expression of all three MYC family members (MYC, MYCN, and MYCL1) and nine signatures of MYC ... Alternative strategies target MYC through epigenetic modulation of MYC transcription itself or of MYC target genes (13, 14). In ... However, some samples without MYC amplification had high expression of MYC or of other genes upregulated by MYC. This ... C, left, correlation of MYC activation scores with copy numbers of MYC isoforms and correlation of MYC activation scores with ...
We studied the effect of tamoxifen on RNA levels of these oncogenes in 19 breast cancer patients treated for 3 weeks prior to ... The c-myc, c-erbB-2, hst and int-2 oncogenes are frequently amplified and/or overexpressed in human breast carcinomas. ... Decrease of c-erbB-2 and c-myc RNA levels in tamoxifen-treated breast cancer Oncogene. 1991 Mar;6(3):431-7. ... These results suggest that in vivo tamoxifen decreases c-myc and c-erbB-2 RNA levels in breast cancer cells via two different ...
MYC-Generated Osteosarcoma Kicked Cancer Habit After Key Oncogene Switched Two Ways ...
... commonly found at high levels inside cancer cells, fuels the disease by allowing cells to override their in-built self-destruct ... Provided by Cancer Research UK Citation: Researchers show Myc protein is cancers volume control (2012, October 1) retrieved ... by Cancer Research UK (Medical Xpress)-A protein called Myc, commonly found at high levels inside cancer cells, fuels the ... Dr Victoria Cowling, a Cancer Research UK-funded expert on Myc from the University of Dundee, said: "Myc increases the rate at ...
E) Levels of c-Myc and phospho-c-MycSer62/Thr58 were determined by Western blotting. (F) Expression of c-Myc was examined by ... These results suggest a significant link between sLex/a expression and EMT in colon cancer cells and a pivotal role of c-Myc ... Transcription factors c-Myc and CDX2 mediate E-selectin ligand expression in colon cancer cells undergoing EGF/bFGF-induced ... Transcription factors c-Myc and CDX2 mediate E-selectin ligand expression in colon cancer cells undergoing EGF/bFGF-induced ...
We have examined c-MYC for its ability to induce metastasis in a C-RAF-driven mouse model for non-small-cell lung cancer. c-MYC ... MYC is a metastasis gene for non-small-cell lung cancer. In: PLOS ONE 4(6), e6029 ... NSCLC is the most lethal human cancer due to its high rate of metastasis. Lack of a suitable animal model has so far hampered ... Thus we have generated the first conditional model for metastasis of NSCLC and identified a gene, c-MYC that is able to ...
High level MYC expression is associated with almost all human cancers. JQ1, a chemical compound that inhibits MYC expression is ... "Regulation of MYC Expression and Differential JQ1 Sensitivity in Cancer Cells." PLoS ONE 9 (1): e87003. doi:10.1371/journal. ... Our study demonstrates that the regulation of high levels of MYC expression in different cancer cells is driven by unique ... The BL cells showed a ∼90% decrease in MYC transcription upon treatment with JQ1, however, no corresponding reduction was seen ...
MYC overexpression, and amplification of MYC gene upon analysis of circulating tumor DNA. We have observed significant intra- ... Planned analyses include: 1) correlation of gallium citrate uptake on PET with MYC copy number and expression levels, and 2) ... a class of therapies known to downregulate MYC expression. Study accrual is ongoing and interim analysis is planned within the ... which is likely reflective of the underlying biological heterogeneity of metastatic castration resistant prostate cancer. We ...
... Sheng, Xia; Nenseth, Hatice Zeynep; Qu, Su; Kuzu, ... XBP1s is necessary for optimal c-MYC mRNA and protein expression, establishing, for the first time, a direct link between UPR ... Here, we report that an IRE1α RNase-specific inhibitor, MKC8866, strongly inhibits prostate cancer (PCa) tumor growth as ... Interestingly, global transcriptomic analysis reveal that IRE1α-XBP1s pathway activity is required for c-MYC signaling, one of ...
The transcription factor c-Myc plays critical roles in cancer development and progression through regulating expression of ... Effects of c-Myc-LDHA axis on aerobic glycolysis in pancreatic cancer cells in vitro. a The protein level of c-Myc and LDHA was ... Effects of c-Myc-LDHA axis on aerobic glycolysis in pancreatic cancer cells in vitro. To demonstrate the effect of c-Myc-LDHA ... Vita M, Henriksson M. The Myc oncoprotein as a therapeutic target for human cancer. Semin Cancer Biol. 2006;16(4):318-30. doi: ...
Colon cancer is the second leading cause of cancer related deaths in the USA. Cancer stem cells (CSCs) have the ability to ... J. Wang, H. Wang, Z. Li et al., "c-Myc is required for maintenance of glioma cancer stem cells," PLoS ONE, vol. 3, no. 11, ... D. J. Liao, A. Thakur, J. Wu, H. Biliran, and F. H. Sarkar, "Perspectives on c-myc, cyclin D1, and their interaction in cancer ... B. J. Chen, Y. L. Wu, Y. Tanaka, and W. Zhang, "Small molecules targeting c-Myc oncogene: promising anti-cancer therapeutics," ...
Colon cancer is the second leading cause of cancer related deaths in the USA. Cancer stem cells (CSCs) have the ability to ... Triphala Extract Suppresses Proliferation and Induces Apoptosis in Human Colon Cancer Stem Cells via Suppressing c-Myc/Cyclin ... on HCT116 colon cancer cells and human colon cancer stem cells (HCCSCs). The total phenolic content, antioxidant activity, and ... Therefore, strategies that target CSCs could be effective against colon cancer and in reducing the risk of relapse and ...
  • A . The MYC protooncogene is depicted downstream of receptor signal transduction pathways, which elicit positive or negative regulation of the MYC gene. (
  • B . When MYC is deregulated, by gene amplication, chromosomal translocation or loss of upstream regulators, such as APC, acute sustained oncogenic MYC expression results in checkpoint activation p53 or Arf. (
  • B . Myc-Max also mediates gene repression. (
  • DLX5, a gene crucial for embryonic development, promotes cancer by activating the expression of the known oncogene, MYC, according to researchers from Fox Chase Cancer Center. (
  • Since the DLX5 gene is inactive in normal adults, it may be an ideal target for future anti-cancer drugs, they reason. (
  • Previously the researchers found that a chromosomal inversion "" a genetic misalignment, where part of the chromosome containing the DLX5 gene gets flipped around during cell division "" cooperates with another known oncogene, AKT2, to drive cancer in mice. (
  • In the current paper, the researchers discover that DLX5 binds to and actively promotes the activity of a gene known as MYC, which evidence has demonstrated is a potent factor in numerous cancers, including lymphoma, lung and pancreatic cancer. (
  • After their previous studies demonstrated that expression of the protein encoded by the DLX5 gene correlated with that of the MYC gene, Testa and Jinfei Xu, PhD, a research associate in the laboratory, used a luciferase assay "" developed from the luciferase enzyme fireflies use to make light "" to see exactly where DLX5 protein binds to the promoter region of the MYC gene. (
  • One of the targets of DLX5 is the MYC gene itself, causing the cells to produce many copies of the MYC oncoprotein. (
  • Although adenovirus is not thought to cause cancer in humans, its early gene products are particularly effective at transforming mammalian cells in vitro . (
  • The MYC gene family plays essential roles in normal development and in multiple cellular functions. (
  • Moreover aberrant MYC gene activation is profoundly involved in the etiology of a wide range of cancers. (
  • This book is essential reading for all cancer biologists, as well as researchers studying the regulation of gene expression. (
  • One gene that has been implicated in many cancers is c-Myc. (
  • IMAGE PROVIDED BY EDWARD PROCHOWNIK The c-Myc gene encodes a transcription factor, which is a protein that binds to DNA and promotes the expression of particular genes. (
  • They used mice genetically engineered to lack the c-Myc gene in their livers and then used beta-catenin and YAP to induce hepatoblastoma formation. (
  • At the same time, c-Myc overexpression results in coordinated changes in level of expression of gene families which result in increased cellular proliferation. (
  • Although c-Myc may play a primary oncogenic role in tumors such as Burkitt lymphoma in which it is translocated under the promoter regions of the heavy- or light-chain immunoglobulin genes ( 5 ), it is more commonly a downstream "early-response" gene, which responds to activation of many diverse signaling pathways. (
  • To our knowledge this is the first evidence of in vivo down regulation of a gene by tamoxifen in ER- breast cancer cells. (
  • Cancer Research UK's Dr Cowling said: "Rather than switching a specific set of gene targets on or off, Myc could be more like a volume control that amplifies the levels of all genes that are already active in cells. (
  • MYC is a metastasis gene for non-small-cell lung cancer. (
  • Thus we have generated the first conditional model for metastasis of NSCLC and identified a gene, c-MYC that is able to orchestrate all steps of this process. (
  • Our preliminary results to date demonstrate that gallium citrate PET can feasibly detect metastatic lesions in patients with advanced prostate cancer, and that there are early signals that uptake on PET scan is associated with histologic evidence of small cell/neuroendocrine differentiation, MYC overexpression, and amplification of MYC gene upon analysis of circulating tumor DNA. (
  • Prior work has shown that the cancer gene MYCN and its protein product N-Myc are highly expressed in NEPC. (
  • We show that the introduction of N-Myc and a second cancer gene AKT1 is sufficient to convert normal human prostate cells to NEPC with properties of rapid growth, high invasive potential, and molecular signatures of aggressive prostate cancer. (
  • C-Myc is a widely expressed transcription factor, regulating cellular differentiation , proliferation, cell cycle progression and pro-apoptotic gene expression. (
  • However, in cancer cells genetic aberrations cause the gene to be expressed in an uncontrolled fashion. (
  • Around 100,000 cancer deaths a year can be attributed to the c-Myc gene in the US alone. (
  • In a recent study with gene expression profiles from 21 breast cancer data sets and 587 TNBC cases, TNBC was classified into 6 subtypes, including two basal-like, an immunomodulatory, a mesenchymal, a mesenchymal stem-like, and a luminal androgen receptor subtype [ 2 ]. (
  • Increased Myc gene copy number is observed in human prostate cancer. (
  • This module includes the Pim-1 kinase, a gene known to cooperate with Myc in tumorigenesis, and defines a subset of human, "Myc-like" human cancers. (
  • Dr. Gene 'Lee' Bidwell is working on a new drug delivery system that can preferentially deliver chemotherapeutics to cancer cells, concentrating the toxic effects at the tumor site, sparing normal cells, and reducing treatment side effects. (
  • Similarly, Aurora-A and N-Myc bind each other and together drive an oncogenic gene expression program in neuroendocrine prostate tumors. (
  • Previous studies have shown that MYC gene is amplified in many types of cancer including head and neck squamous cell carcinoma (HNSCC). (
  • The aim of this study was to investigate the relationship between c-Myc protein and CT120 gene. (
  • We show that CT120 gene is a target of c-Myc and it contributes to cancer progression in HNSCC. (
  • Although mutations in the gene encoding the RNA splicing factor SF3B1 are frequent in multiple cancers, their functional effects and therapeutic dependencies are poorly understood. (
  • Here, we identify that mutations in SF3B1 , the most commonly mutated splicing factor gene across cancers, alter splicing of a specific subunit of the PP2A serine/threonine phosphatase complex to confer post-translational MYC and BCL2 activation, which is therapeutically intervenable using an FDA-approved drug. (
  • These molecular events are similar to the initial changes in cyclin gene expression, CDK complex formation and CDK activity seen after antiestrogen (ICI 182780)-mediated growth inhibition of MCF-7 cells, which suggests that the down-regulation of c-Myc by ICI 182780 is a primary event that culminates in cell cycle arrest. (
  • Bartram CR, Berthold F (1987) Amplification and expression of the N-myc gene in neuroblastoma. (
  • This is usually not due to Myc gene mutation but results from upstream mutations affecting other oncogenes or tumor suppressors. (
  • The results of bioinformatics analysis combined with qRT-PCR and Western blot demonstrated that Myc might be the target gene of miR-4282 in breast cancer. (
  • The distal BRCA1 promoter region is associated with c-Myc and contributes to BRCA1 gene activation. (
  • The human breast cancer susceptibility gene 1 product, BRCA1 is involved in important cellular processes, including DNA repair, and loss of BRCA1 can result in genomic instability. (
  • Four independent regions within 8q24 near the MYC gene are associated with risk for prostate cancer (Pca). (
  • Here, we investigated allelic imbalance (AI) at 8q24 risk variants and MYC gene DNA copy number (CN) in 27 primary Pcas. (
  • No AI was observed in tumors, which did not reveal increased MYC gene CN. (
  • Higher Gleason score was associated with tumors exhibiting AI (P=0.04) and also with increased MYC gene CN (P=0.02). (
  • Our results suggest that AI at 8q24 and increased MYC gene CN may both be related to high Gleason score in Pca. (
  • N-myc downstream regulated gene 1 (NDRG1), also known as differentiation related gene 1, was previously identified as an up-regulated gene upon cellular differentiation. (
  • The development of prostate cancer is considered to be dependent on a number of gene abnormalities, and in this manner, the molecular biology research in this field is obvious and essential. (
  • In this study, NDRG1, a proliferation related gene, was investigated in order to clarify its functionality in human prostate cancer cells. (
  • N-myc downstream regulated gene 1 (NDRG1), which is mapped to the human chromosome 8q24.2, was initially identified by differential display as up-regulated gene in cellular differentiation [1]. (
  • The nuclear transcription factor c-Myc is a member of the Myc gene family with multiple functions and located on band q24.1 of chromosome 8. (
  • The c-Myc gene is activated by chromosomal translocation, rearrangement, and amplification. (
  • Aberrant expression of c-Myc is likely to ascribable to direct gene alteration, which associates with tumorigenesis and sustained tumor growth [ 2 - 4 ]. (
  • A schematic diagram of human c-Myc gene structure. (
  • Human telomerase reverse transcriptase (hTERT) underlies cancer cell immortalization, and the expression of hTERT is regulated strictly at the gene transcription. (
  • Here, we report that transcription factor Ets2 is required for hTERT gene expression and breast cancer cell proliferation. (
  • Silencing Ets2 induces a decrease of hTERT gene expression and increase in human breast cancer cell death. (
  • Thus, hTERT gene expression is maintained by a mechanism involving Ets2 interactions with the c-Myc transcription factor and the hTERT gene promoter, a protein-DNA complex critical for hTERT gene expression and breast cancer cell proliferation. (
  • Here, we briefly review the current understanding of how lncRNAs regulate chromatin structure and gene transcription, and then focus on the new developments in the emerging field exploring the lncRNA-MYC network in cancer. (
  • Myc ( c-Myc ) is a regulator gene that codes for a transcription factor . (
  • This means that in addition to its role as a classical transcription factor, Myc also functions to regulate global chromatin structure by regulating histone acetylation both in gene-rich regions and at sites far from any known gene. (
  • Myc gene was first discovered in Burkitt lymphoma patients. (
  • Cloning the break-point of the fusion chromosomes revealed a gene that was similar to myelocytomatosis viral oncogene (v-Myc). (
  • Thus, the newfound cellular gene was named c-Myc. (
  • Myc overexpression stimulates gene amplification, [12] presumably through DNA over-replication. (
  • c-Myc induces MTDH (AEG-1) gene expression and in turn itself requires AEG-1 oncogene for its expression. (
  • The object of this study is to explore the influence of SAM on the status of methylation at the promoter of the oncogenes c-myc , H-ras and tumor-suppressor gene p16 (INK4a), as well as its inhibitory effect on cancer cells. (
  • N-myc downstream-regulated gene1 ( NDRG1 ) has been identified as a potent tumor suppressor gene. (
  • Then, the effects of over-expression and depletion of NDRG1 gene on apoptosis of colorectal cancer were tested in vitro and in vivo . (
  • The Larson research group uses high-throughput imaging and analysis to quantify how MYC changes gene expression at the single cell level. (
  • Pictured are a population of human lung cells that are labeled for their nuclei (blue), and the RNA transcripts of MYC (red) and a downstream gene (green). (
  • Before we design new therapies that inactivate a gene product, which is an approach being considered for c-myc in cancer, we need to be very sure that we are not going to be also destroying a vital role in a normal process such as the body's immune system. (
  • Intra-tumor heterogeneity is a potential cause for failure of targeted therapy in gastric cancer, but the extent of heterogeneity of established (HER2) or potential (EGFR, CCND1) target genes and prognostic gene alterations (MYC) had not been systematically studied. (
  • Gene amplification is a prime mechanism of cancer cells for overexpressing genes that are critical for their survival and expansion. (
  • Mad1 (encoded by the gene mxd1 ), a member of the Myc/Mad/Max family known as bHLH/LZip proteins ( 1 , 2 ), is recognized as an important cellular antagonist of Myc ( 1 , 2 ). (
  • Feng's research focuses on the gene MYC , often called the "cancer gene from hell," because it is altered in nearly all human cancers. (
  • Feng, whose work is supported by BU's Shamim and Ashraf Dahod Breast Cancer Research Center , the National Institutes of Health , and a number of private foundations, including the Leukemia Research Foundation and the Mary Kay Foundation , says that many different cancers, seemingly caused by many different gene mutations, all eventually lead back to MYC . (
  • MYC 's ubiquity made the gene a particularly attractive target for Feng. (
  • N-myc proto-oncogene protein also known as N-Myc or basic helix-loop-helix protein 37 (bHLHe37), is a protein that in humans is encoded by the MYCN gene. (
  • The MYCN gene is a member of the MYC family of transcription factors and encodes a protein with a basic helix-loop-helix (bHLH) domain. (
  • Excess N-Myc is associated with a variety of tumors, most notably neuroblastomas where patients with amplification of the N-Myc gene tend to have poor outcomes. (
  • The Myc gene family is uniquely situated to synergize upstream pathways into downstream cell cycle control. (
  • Mice engineered to have just one copy of the gene Myc live longer, healthier lives than wild-type animals. (
  • In patients, hyper-activation of c-myc is associated with the most aggressive cancer types, with 20-40 percent of all cancers having an activated myc gene. (
  • To identify genes involved in coping with this stress, Westbrook and his colleague Dr. Stephen Elledge of Harvard Medical School used a special RNA interference screen to disrupt the function of each gene in the genome and identify the genes required to allow the cancer cell to tolerate the stress of the myc oncogene. (
  • N-myc-interactor also known as N-myc and STAT interactor is a protein that in humans is encoded by the NMI gene. (
  • Blocking the expression of the Myc gene in these cases causes the complete regression of tumors in animals. (
  • Forskere har opdaget en sammenhæng mellem nedregulering af genet, N-myc Downstream Regulated Gene 2 (NDRG2), og udvikling af cancer. (
  • Gene set enrichment analysis showed Myc target pathways are highly induced in mutant cells. (
  • We demonstrate for the first time in pancreatic cancer that these agents increase the expression of the growth and metastasis suppressor N-myc downstream-regulated gene 1 and its phosphorylation at Ser330 and Thr346 that is important for its activity against this tumor. (
  • A Ludwig Cancer Research study has uncovered a novel vulnerability in tumors that are driven by a common cancer gene known as MYC. (
  • Myc is a transcription factor that can both activate and repress gene transcription and thus influences many potential targets that might contribute to regulation of apoptosis. (
  • At least in certain cell types, the new results indicate that transcription of the BCL2 gene is the essential target regulated through c-MYC and MIZ-1, thus providing a mechanistic explanation for the observed cooperation of BCL-2 and c-MYC in tumorigenesis. (
  • Nevertheless, the molecular mechanism by which the c- myc gene product, the transcription factor c-Myc, triggers the cell death program remains unknown. (
  • Further gene expression profiling analysis revealed that p62 was positively correlated with MYC expression level, which mediated the function of p62 in promoting breast cancer stem-like properties. (
  • The MYC oncogene contributes to the genesis of many human cancers. (
  • These results suggest that MYC oncogene activity (as marked by "poor-prognosis" signature expression) may be necessary for the translocation of poor-outcome human breast tumors to distant sites. (
  • Our studies also revealed that HDACi treatment results in marked downregulation of the oncogene Myc. (
  • Together, these data reveal a previously unanticipated inverse relationship between the tumor suppressor PR and the oncogene Myc in endometrial cancer. (
  • The c-Myc oncogene is a "master regulator" which controls many aspects of both of these processes. (
  • The effects induced by c-Myc can occur either as a "primary oncogene" which is activated by amplification or translocation or as a downstream effect of other activated oncogenes. (
  • It has also become clear that the multifaceted oncogene, c-Myc, plays important regulatory roles in many aspects of transformation ( 1-4 ). (
  • XBP1s is necessary for optimal c-MYC mRNA and protein expression, establishing, for the first time, a direct link between UPR and oncogene activation. (
  • The transcription factor c-Myc amplifies the transcription of many growth-related genes in cancer cells, but its role as an oncogene is not fully understood. (
  • Background: The proto-oncogene MYC is implicated in prostate cancer progression. (
  • c-Myc, an oncogene regulated by hypoxia inducible factors (HIFs), plays a critical role in cell proliferation and metabolism. (
  • The proto-oncogene c-myc is up-regulated by estrogen stimulation of hormone-dependent breast cancer cells and is frequently overexpressed in breast and other cancers. (
  • Alitalo K, Schwab M, Lin CC, Varmus H, Bishop JM (1983) Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma. (
  • Mechanism studies revealed that TIM upregulated the expression and the trans-activity of the well-known oncogene MYC. (
  • The focus of the present review, c-Myc (hereafter referred to as Myc), is the cellular homolog of the avian retroviral oncogene v- myc and, together with N- myc and L- myc , comprises the family of myc proto-oncogenes. (
  • Chen BJ, Wu YL, Tanaka Y, Zhang W. Small Molecules Targeting c-Myc Oncogene: Promising Anti-Cancer Therapeutics. (
  • In this minireview, we summarize unique characteristics of c-Myc and therapeutic strategies against cancer using small molecules targeting the oncogene, and discuss the prospects in the development of agents targeting c-Myc, in particular G-quadruplexes formed in c-Myc promoter and c-Myc/Max dimerization. (
  • Some 20 years ago, c-Myc was discovered in human Burkitt's lymphoma, as a celluar homologue of the viral oncogene v-Myc which was isolated from an avian retrovirus [ 7 , 8 ]. (
  • Overexpression of oncogene c-Myc is one of the most frequently encountered events present in ovarian carcinoma. (
  • The human proto‐oncogene c‐ myc encodes a highly unstable transcription factor that promotes cell proliferation. (
  • The c‐ myc proto‐oncogene encodes a basic helix-loop-helix transcription factor that features prominently in the regulation of cell proliferation (reviewed by Henriksson and Luscher, 1996 ). (
  • HOTAIR was previously shown to be an oncogene and negative prognostic factor in a variety of cancers. (
  • Ribosome biogenesis and protein synthesis are dysregulated in many cancers, with those driven by the proto-oncogene c-MYC characterized by elevated Pol I-mediated ribosomal rDNA transcription and mTORC1/eIF4E-driven mRNA translation. (
  • Metformin targets c-MYC oncogene to prevent prostate cancer. (
  • Metformin, an old antidiabetes drug, may inhibit prostate intraepithelial neoplasia transforming to cancer lesion via reducing c-MYC, an 'old' overexpressed oncogene. (
  • 1982) Isolation and characterization of c-myc, a cellular homolog of the oncogene (v-myc) of avian myelocytomatosis virus strain 29. (
  • Myc is a very strong proto-oncogene and it is very often found to be upregulated in many types of cancers. (
  • By analyzing genetically engineered mouse models with reduced c-myc, reduced IL-15 or absent IL-15, we discovered that it's actually c-myc, which is known primarily as an oncogene, that acts downstream of the IL-15 signaling pathway to regulate T memory cell homeostasis. (
  • DCR-MYC targets the driver oncogene MYC, which is central to the growth of many tumor types, including HCC. (
  • Patients with HCC frequently show amplification of the MYC oncogene, suggesting an important role for MYC activity in a significant portion of people with the disease. (
  • One classical example of an oncogene that creates such a delicate balance is c-myc. (
  • For 30 years, scientists have tried to attack the oncogene myc," said Dr. Thomas Westbrook , assistant professor of molecular and human genetics and biochemistry and molecular biology at BCM and a senior author of the report. (
  • Now we have to take advantage of the stresses the oncogene puts on the cancer cell and determine if we can ramp those up to kill the tumor. (
  • NMYC interactor (NMI) interacts with NMYC and CMYC (two members of the oncogene Myc family), and other transcription factors containing a Zip, HLH, or HLH-Zip motif. (
  • NBs often express high levels of N-myc, a proto-oncogene that can potently activate key components of the cell cycle machinery. (
  • The Myc oncogene is mutated or misregulated in over half of all human cancers. (
  • Bacterial degradation of the MYC oncogene: A new cancer treatment strategy? (
  • Scientists at Lund University have discovered how E. coli bacteria target and degrade the well-known oncogene MYC, which is involved in many forms of cancer. (
  • The pleiotropic transcription factor MYC has been named "the quintessential oncogene" and is hyperactive in the majority of human cancers. (
  • Most human tumors have genetic alterations in myc proto-oncogene family members that result in deregulation of myc expression ( 1 ). (
  • On the surface, c-Myc generally doesn't appear to be involved in the formation of hepatoblastoma, although it has been seen at high levels in some tumors. (
  • Our findings indicate that even tumors which do not superficially appear to involve c-Myc deregulation, such as hepatoblastomas, are nevertheless highly dependent on it," explains Prochownik. (
  • Therefore, we modeled advanced endometrial tumors that have lost both ERα and PR expression by generating ERα-null endometrial cancer cell lines. (
  • Analysis of the Cancer Genome Atlas (TCGA) database of endometrial tumors identified an inverse correlation between PR and Myc mRNA levels, with a corresponding inverse correlation between PR and Myc downstream transcriptional targets SRD5A1, CDK2 and CCNB1. (
  • Degrasyn reduced c-Myc levels in A375 melanoma cells and in A375 tumors in nude mice, and this activity correlated with tumor growth inhibition. (
  • Loss of control of c-Myc expression and stability occurs in many human cancers ( 7 , 8 ) and is associated with highly aggressive, poorly differentiated tumors with poor patient prognosis. (
  • Recent studies support the existence of cancer stem cells in gliomas that are functionally defined by their capacity for extensive self-renewal and formation of secondary tumors that phenocopy the original tumors. (
  • Further, glioma cancer stem cells with decreased c-Myc levels failed to form neurospheres in vitro or tumors when xenotransplanted into the brains of immunocompromised mice. (
  • They then injected the 89 Zr-DFO-labeled transferrin tracer into mice harboring subcutaneous tumors or spontaneous prostate cancers expressing Myc and found that both mouse models demonstrated significant uptake and retention of the tracer within the tumors. (
  • In the tumors tested in this study, the rise in TFRC was driven by Myc activation, suggesting that the effects of important cancer pathways can be noninvasively tracked by monitoring downstream reporters, such as TFRC. (
  • Early cancer intervention relies on identifying the molecular signals that transform precancerous cells into tumors. (
  • Metastasis is a process by which cancer cells learn to form satellite tumors in distant organs and represents the principle cause of death of patients with solid tumors. (
  • The tumors require the expression of N-Myc and disruption of N-Myc levels by genetic and drug targeting leads to increased cell death and a reduction in tumor burden. (
  • The c-Myc antibody is widely used in cancer research , as a number of human tumors have been attributed to altered c-Myc expression. (
  • C-Myc antibody studies have revealed abnormal expression of the protein in 90% of gynecological cancers and 80% of breast tumors . (
  • Results: MYC nuclear protein expression was present in 97% of tumors. (
  • Further, we showed that the thermally targeted anti-cancer peptide can greatly reduce the progression (75 percent reduction relative to untreated tumors) of these tumors. (
  • An increased c‑MYC expression was observed in 28 pairs of primary and metastatic tumors from patients treated with TAM, and the clinical remission rate of cisplatin‑based chemotherapy was significantly higher compared with other chemotherapy‑based regimens in 122 patients with TAM resistant breast cancer. (
  • Multiple proof-of-principle experiments suggest that targeting members of the Myc family of oncoproteins will have significant therapeutic benefit in human tumors. (
  • Here, we characterize 98 tumors and 12 isogenic cell lines harboring SF3B1 hotspot mutations, identifying hundreds of cryptic 3′ splice sites common and specific to different cancer types. (
  • Myc activity thus appears to be required for development and maintenance of the majority of tumors, even when initiated by other causes. (
  • In tumors induced by Myc upregulation in transgenic mice, even brief Myc de-activation triggers tumor regression accompanied by growth arrest, differentiation, and collapse of the tumor vascular system [5] . (
  • The results showed that miR-4282 was down-regulated in human breast cancer tissues and was particularly in invasive and metastatic tumors. (
  • Although data associating obesity and prostate cancer risk have been inconclusive ( 1, 2 ), studies have shown increased risk of biochemical failure and metastasis, as well as poorer survival among obese patients with prostate cancer with androgen-dependent tumors, especially those who experienced rapid weight gain ( 3 ). (
  • The abnormal over-expression of c-Myc is frequently observed in some tumors, including carcinomas of the breast, colon, and cervix, as well as small-cell lung cancer, osteosarcomas, glioblastomas, and myeloid leukemias, therefore making it a possible target for anticancer therapy. (
  • N-Myc overexpression, whatever in PCA or in CPRC stage, shuts down AR signaling that is required for prostate cancer growth, and as a consequence should benefit the N-Myc overexpressed prostate tumors to AR-targeted therapies. (
  • However, the N-Myc overexpressed prostate tumors are resistant to AR-targeted therapies, including ADT and Enzalutamide, indicating that N-Myc re-establishes other AR-independent pro-survival mechanisms/pathways to drive the disease progression and therapeutic resistance development. (
  • This new trial expands the development program for DCR-MYC, which is also being studied in a Phase 1 clinical trial in patients with solid tumors and hematological malignancies. (
  • Intra-tumor heterogeneity was found in the primary tumors of 9 of 19 (47.3%) cancers with HER2, 8 of 17 (47.0%) cancers with CCND1, 5 of 7 (71.4%) cancers with EGFR, and 23 of 27 (85.2%) cancers with MYC amplification. (
  • In addition, myc drives many others kinds of cancers and he anticipates that inhibiting this enzyme in these tumors may have the same effect. (
  • We are working to identify lung cancers that are dependent on MYC, determine their oncogenotype and molecular properties, and identify "acquired vulnerabilities" that would provide both novel therapeutic targets as well as biomarkers to identify patients with MYC-dependent tumors. (
  • Moreover, chromatin immunoprecipitation showed constitutive, fulvestrant-resistant, recruitment of ERα mutants to the Myc enhancer region, resulting in estrogen-independent Myc overexpression in mutant cells and tumors. (
  • For example, the oncoprotein c-MYC, an important contributor to human tumors, acts both to increase proliferation and to promote cell death. (
  • These data highlight that aminotransferases and mitochondrial ROS might be attractive targets for cancer therapy in MYC -driven tumors. (
  • Miz-1 is shown tethered to the INR element to regulate transcription of target genes, which could be silenced by Myc displacement of NPM, a Miz-1 cofactor, or by Myc induction of the ribosomal protein RPL23, which retains NPM in the nucleolus, keeping it away from Miz-1. (
  • Myc-Max is shown bound to E-box driven genes, which could also be regulated by other E-box transcription factors, such as the carbohydrate response element binding protein (ChREBP), sterol response element binding protein (SREBP), nuclear respiratory factor 1 (NRF1), circadian transcription factor Clock (and Bmal), and hypoxia inducible factor (HIF). (
  • A ) Western blot for MYC protein after stable, lentiviral-mediated knockdown with two different MYC hairpins (HP1 and HP2) compared with pLKO empty vector control after serial passage in MDA-MB-231 cells. (
  • Here, we show that Myc overexpression induces endoplasmic reticulum (ER) stress and engages the inositol-requiring enzyme 1α (IRE1α)/X-box binding protein 1 (XBP1) pathway through multiple molecular mechanisms in a variety of c-Myc- and N-Myc-dependent cancers. (
  • While the genomic binding of MYC protein correlates with active epigenetic marks on chromatin, it remains largely unclear how major epigenetic mechanisms functionally impact the tumorigenic potential of MYC. (
  • The contributors discuss its normal functions in the control of cell growth, cell competition, pluripotency, and development, as well as the molecular basis for the effects of the MYC protein on transcription. (
  • The apparent role for c-Myc in supporting tumor growth was its ability to maximize certain crucial metabolic processes, such as protein synthesis and glucose uptake," says Prochownik. (
  • c-Myc is possibly the most frequently deregulated protein in human cancer, making it a good target for therapeutics. (
  • Second, progesterone increased PR activity yet blunted Myc mRNA and protein expression. (
  • Degrasyn, a small synthetic molecule, induces rapid degradation of c-Myc protein in MM-1 multiple myeloma and other tumor cell lines. (
  • Degrasyn-induced degradation of c-Myc depends on proteasomes but is independent of the degron regions previously shown to be important for ubiquitin-mediated targeting and proteasomal destruction of the protein. (
  • Degrasyn-dependent c-Myc proteolysis is not mediated by any previously identified c-Myc regulatory mechanism, does not require new protein synthesis, and does not depend on the nuclear localization of c-Myc. (
  • Ubiquitin-mediated proteolysis ( 9 ), a specific multistep process that results in the target protein being rapidly destroyed by the 20S proteasome, plays an important role in c-Myc degradation and is responsible for its short half-life ( 10 - 16 ). (
  • c-Myc protein levels are regulated by a NH 2 -terminal "degron" that signals c-Myc ubiquitination and a COOH-terminal "stabilon" that stabilizes c-Myc by enabling it to associate with the POZ domain protein Miz or to be sequestered into a stabilizing subnuclear compartment ( 12 , 17 ). (
  • A second F-box protein (Skp2) along with its associated E3 ligase SCF complex (Skp/Cul1/F-box) interact with c-Myc and mediate the destabilization of the protein ( 21 , 22 ). (
  • Myc is a growth-promoting protein implicated in the formation of several malignancies, including prostate cancer. (
  • Medical Xpress)-A protein called Myc, commonly found at high levels inside cancer cells, fuels the disease by allowing cells to override their in-built self-destruct mechanisms, according to two new studies by US scientists. (
  • The researchers - from the Whitehead Institute and the National Institutes of Health - say their findings explain the wide range effects the Myc protein has been linked to. (
  • Activation of endoplasmic reticulum (ER) stress/the unfolded protein response (UPR) has been linked to cancer, but the molecular mechanisms are poorly understood and there is a paucity of reagents to translate this for cancer therapy. (
  • Knockdown of c-Myc reduced the protein expression of LDHA, lactate production and glucose consumption, and silencing of LDHA mimicked this effect. (
  • Western blotting data suggested that MET suppressed protein levels of c-Myc and cyclin D1, key proteins involved in proliferation, and induced apoptosis through elevation of Bax/Bcl-2 ratio. (
  • C-Myc is a basic helix-loop-helix-leucine zipper (b-HLH-LZ) protein. (
  • In contrast, c-Myc mRNA and protein expression was up-regulated in the basal-like breast cancer cell lines. (
  • In addition, CDKN1A mRNA and p21 protein expression were significantly increased in all breast cancer cell lines upon β-catenin silencing. (
  • Whether MYC tumor expression at the protein or mRNA level is associated with poorer prognosis has not been well studied. (
  • MYC protein expression was evaluated using immunohistochemistry, and we used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of its association with lethal prostate cancer (distant metastases/prostate cancer death). (
  • There were no significant associations between MYC protein expression and stage, grade or PSA level at diagnosis. (
  • The multivariable HR for lethal prostate cancer among men in the top versus bottom quartile of MYC protein expression was 1.09 (95% CI: 0.50-2.35). (
  • Conclusion: Neither MYC protein overexpression nor MYC mRNA overexpression are strong prognostic markers in men treated with radical prostatectomy for prostate cancer. (
  • Impact: This is the largest study to examine the prognostic role of MYC protein and mRNA expression in prostate cancer. (
  • The agent we are working with now is specific for a protein that is often over-produced by cancer cells. (
  • Inhibiting this cancer-specific protein, therefore, will have a greater effect on the cancer cells and tend to spare normal cells of the body. (
  • However, directly targeting MYC paralog has proven challenging due to the unique protein structures of the different paralogs ( 20 ). (
  • In conclusion, the studies suggested that diclofenac inhibited cell glycolysis and suppressed TNBC cell growth by decreasing GLUT1 protein expression and HK activity through the c‑Myc pathway. (
  • SF3B1 mutations promote decay of transcripts encoding the protein phosphatase 2A (PP2A) subunit PPP2R5A, increasing MYC S62 and BCL2 S70 phosphorylation which, in turn, promotes MYC protein stability and impair apoptosis, respectively. (
  • We demonstrate that c-Myc mRNA and protein levels in colon cancer cells are induced within 2 h of hypoxic stress (1% O2) but are then significantly downregulated when exposed to prolonged hypoxia. (
  • In the present study, we found that MAZ protein is highly expressed in human ulcerative colitis and colon cancer. (
  • Blackwood EM, Eisenman RN (1991) Max: A helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. (
  • This molecule - instead - appears to cause an edge-specific perturbation that destroys some protein interactions of the Myc node and keeps others intact, with the result of reshaping the Myc transcriptome. (
  • Omomyc selectively targets Myc protein interactions: it binds c- and N-Myc, Max and Miz-1, but does not bind Mad or select HLH proteins. (
  • Myc operates within a highly interconnected interactome network and a possible strategy for targeting Myc oncogenic function is dominant interference of Myc protein interactions. (
  • Depletion of c-Myc was found to be correlated with reduced expression levels of BRCA1 mRNA and BRCA1 protein. (
  • Heat shock protein 90 (Hsp90) is a kind of stress proteins and is known to be overexpressed in a variety of cancers. (
  • The half-lives of Myc mRNA and protein are short, allowing for tight and rapid regulation of Myc levels, which occurs via numerous transcription factors (TFs) and signaling pathways. (
  • TFs that occupy or regulate the myc promoter without specific binding sites include p53, CCAAT/enhancer binding protein beta, and Stat5. (
  • The Myc protein is a basic helix-loop-helix TF that must heterodimerize with the abundantly expressed Max to regulate transcription. (
  • As a vital transcription regulator, c-Myc plays an essential role in the regulation of many physiological processes including cell cycle control, apoptosis, protein synthesis, and cell adhesion [ 1 ]. (
  • The response to 10058-F4 was independent the level of c-Myc protein over-expression in primary cultures of ovarian carcinoma. (
  • Recent studies have provided strong evidence that c-Myc proteins combine with Max, a common Myc partner protein, to form heterodimers that can both bind to DNA and induce transactivation. (
  • We show that Myc is destroyed by ubiquitin‐mediated proteolysis, and define two elements in Myc that oppositely regulate its stability: a transcriptional activation domain that promotes Myc destruction, and a region required for association with the POZ domain protein Miz‐1 that stabilizes Myc. (
  • Our data reveal a complex network of interactions regulating Myc destruction, and imply that enhanced protein stability contributes to oncogenic transformation by mutant Myc proteins. (
  • The expression and activity of Myc are tightly regulated at many levels, including transcription, mRNA stability, translation and protein stability ( Spencer and Groudine, 1991 ). (
  • Indeed, Myc is a highly unstable protein, with a typical half‐life of 30 min ( Hann and Eisenman, 1984 ). (
  • Here, we demonstrate that coordinated targeting of rDNA transcription and PI3K-AKT-mTORC1-dependent ribosome biogenesis and protein synthesis provides a remarkable improvement in survival in MYC-driven B lymphoma. (
  • Myc protein belongs to Myc family of transcription factors, which also includes N-Myc and L-Myc genes. (
  • Myc mRNA contains an IRES (internal ribosome entry site) that allows the RNA to be translated into protein when 5' cap -dependent translation is inhibited, such as during viral infection. (
  • Myc protein is a transcription factor that activates expression of many genes through binding enhancer box sequences ( E-boxes ) and recruiting histone acetyltransferases (HATs). (
  • The levels of Mad1 protein are generally low in many human cancers, and Mad1 protein has a very short half-life. (
  • The half-life of Mad1 protein, like that of Myc protein, is very short ( 1 ), and the levels of Mad1 are tightly regulated during cell proliferation and differentiation ( 2 ). (
  • Therefore, because both Myc and Mad1 compete for Max ( 1 ), the availability of Max to Myc is profoundly dependent on the expression levels of Mad1 protein (and vice versa). (
  • Usually, alterations push MYC into overdrive, and because it codes for a transcription factor-a protein that turns genes on or off-hyperactive MYC can lead to runaway expression of many genes, and cancer. (
  • The N-myc-induced cell cycle entry, but not enhanced survival, was inhibited by coexpression of a constitutively hypophosphorylated form of the retinoblastoma tumor suppressor protein, suggesting that these two effects of N-myc are mediated by separate pathways. (
  • Taken along our conclusions show MTBP functions with MYC in promoting malignancy distinguishing this necessary protein as a new general healing target in human tumor. (
  • Collectively our data show MTBP is an oncogenic protein and a novel regulator of MYC. (
  • The Myc protein, depicted here, is mutated in more than half of all human cancers. (
  • A cancer-associated protein called Myc directly controls the expression of two molecules known to protect tumor cells from the host's immune system, according to a study by researchers at the Stanford University School of Medicine . (
  • One of the molecules is the CD47 protein, which researchers in the Stanford laboratory of Irving Weissman , MD, have discovered serves as a "don't eat me" signal to ward off cancer-gobbling immune cells called macrophages. (
  • Nearly all human cancers express high levels of CD47 on their surfaces, and an antibody targeting the CD47 protein is currently in phase-1 clinical trials for a variety of human cancers. (
  • The other molecule is a "don't find me" protein called PD-L1, known to suppress the immune system during cancer and autoimmune diseases but also in normal pregnancy. (
  • Researchers in Felsher's laboratory have been studying the Myc protein for more than a decade. (
  • Immunohistochemistry (IHC) was performed to detect c-Myc and PRDX2 protein levels in CRC tissue samples (n = 97). (
  • In turn, miR-200b-3p disrupted the stability of c-Myc protein by inducing c-Myc protein threonine 58 (T58) phosphorylation and serine 62 (S62) dephosphorylation via AKT2/GSK3β pathway. (
  • In this review, we reconnoitre the two major pathways (intrinsic and extrinsic) targeted cancer therapeutics, steering toward chief modulators of these pathways, such as B-cell lymphoma 2 protein family members (pro- and antiapoptotic), inhibitor of apoptosis proteins, and the foremost thespian of extrinsic pathway regulator, tumour necrosis factor-related apoptosis-inducing agent. (
  • We have studied the histopathology and differential distribution of the c-myc protein (Myc) in human breast tissues including 17 cases of infiltrating mammary carcinoma, 4 cases of fibroadenoma, 5 cases with fibrocystic changes, and 1 case of reduction mammoplasty (as a control). (
  • Researchers at Lund University have made the surprising discovery that uropathogenic E. coli deplete c-MYC protein from infected cells and tissues as a result of accelerated c-MYC protein degradation and attenuated MYC expression. (
  • Regulation of expression of the antiapoptotic protein BCL2 links the c-MYC oncoprotein to control of cell death. (
  • Both MEF and S3T3 cells also expressed low but detectable amounts of CD95 ligand (CD95L) (Fig. 1 C). To examine any involvement of CD95 signaling in apoptosis induced by c-Myc, we used S3T3 cells that expressed a conditional 4-hydroxytamoxifen (OHT)-dependent c-Myc protein (S3T3 c-MycER) ( 7 ) and that die by apoptosis upon c-Myc activation in low serum concentration ( 8 ). (
  • Finally, overexpression of PR by adenoviral transduction in ERα-null endometrial cancer cells significantly decreased expression of Myc and Myc-regulated genes. (
  • The metabolic changes which occur in transformed cells, many of which are driven by c-Myc overexpression, are necessary to support the increased need for nucleic acids, proteins, and lipids necessary for rapid cellular proliferation. (
  • It remains unclear whether c-Myc overexpression is primarily responsible for the metabolic changes induced by transformation or whether its common overexpression may be a result of the complex metabolic changes which occur when cells become malignant. (
  • c-Myc overexpression and LDHA overexpression were correlated with TNM stage and tumor size and indicated poor prognosis in patients with pancreatic cancer. (
  • MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). (
  • Overexpression has also been reported in 70% of colon cancers and 50% of hepatic carcinomas, as well as a number of hematological cancers. (
  • Furthermore, overexpression of c-MYC or MYCL dramatically accelerated SCLC progression in genetically-engineered mouse models, which indicated that MYC paralogs promote oncogenesis in SCLC ( 18 , 19 ). (
  • Overexpression of c-Myc reversed the inhibition of cyclinD1, CDK4, and CDK6, which accelerated the G1/S phase transition under hypoxia and enhanced sensitivity to 5-FU. (
  • Overexpression of TIM dramatically enhanced, while knockdown of TIM suppressed the self-renewal of cancer stem cells (CSCs), cell invasion and migration abilities of breast cancer cells in vitro. (
  • Moreover, overexpression of TIM significantly augmented, while knockdown of TIM reduced the tumorigenicity of breast cancer cells in vivo. (
  • Overexpression of EZH2 by lentivirus transduction was used to study the role of EZH2 in the inhibiotroy effect of c-Myc and Bmi1 expression. (
  • Overexpression of EZH2 could overcome the inhibitory effect of 17-DMAG in suppression of Bmi1 and c-Myc expression. (
  • Based on the analysis so far, as many as 20% of human cancers can be associated with the overexpression of c-Myc. (
  • MYCN amplification or N-Myc overexpression is found in approximately 40% NEPC and up to 20% CRPC patients. (
  • N-Myc overexpression suppressed ATM expression through upregulating miR-421 in LNCaP cells. (
  • Surprisingly, N-Myc overexpression upregulated ATM expression in C4-2 cells and this upregulation promoted migration and invasion of prostate cancer cells. (
  • Our findings would offer a potential combination therapeutic strategy using ATM kinase inhibitor and Enzalutamide for the treatment of a subset of mCRPC with N-Myc overexpression that accounts for up to 20% CRPC patients. (
  • Amplification and overexpression of N-Myc can lead to tumorigenesis. (
  • Many cancers are driven by the overexpression of oncogenes. (
  • Aberrant p62 overexpression has been implicated in breast cancer development. (
  • Indeed, short-hairpin RNA (shRNA)-mediated knockdown of p62 impaired breast cancer cells from self-renewing under anchorage-independent conditions, whereas ectopic overexpression of p62 enhanced the self-renewal ability of breast cancer cells in vitro. (
  • MYC mRNA level was reduced upon p62 deletion by siRNA and increased with p62 overexpression in breast cancer cells, suggesting that p62 positively regulated MYC mRNA. (
  • abstract = "Background: Germline BRCA2 mutations are associated with poorer outcome prostate cancer ( PCa) compared with sporadic tumours but this association remains to be characterised. (
  • Mol Cancer Ther 2013;12(5 Suppl):Abstract nr IA13. (
  • MYC produces the transcription factor Myc, which dimerizes with Max and bind target DNA sequences or E-boxes (with the sequence 5′-CANNTG-3′) to regulate transcription of genes involved in cell growth and proliferation. (
  • A . The Myc-Max heterodimer is shown to interact with key co-factors such as TFIIH that triggers transcriptional elongation or TRRAP that recruits the GCN5, which acetylates histone, permitting transcription of target genes. (
  • To simplify the analysis, we first created two "metagenes" by separately averaging up-regulated and down-regulated genes from each multigene poor-outcome cancer signature (s1-s13). (
  • UP and DOWN poor-outcome signature genes with at least one MYC binding site within ± 5 kb of their transcription start site (orange) versus the same for all other genes on the tiling array (green). (
  • They found that there were two sites where DLX5 could bind to the MYC promoter, which is a section of DNA where certain proteins known as transcription factors attach in order to recruit the cellular machinery used to transcribe genes into messenger RNA and then proteins. (
  • Through its interaction with p400, E1A stabilizes Myc and promotes formation of Myc-p400 complexes on chromatin, leading to activation of Myc target genes. (
  • MYC encodes a transcriptional regulator that modulates expression of genes controlling cell growth, proliferation, metabolism, differentiation, and death. (
  • Cancers involve a diverse range of genes and proteins that aid in their formation, progression and maintenance. (
  • When c-Myc is overexpressed in cancers, it effectively signals to turn on other genes at levels higher than normal. (
  • The products of these genes then can promote cancer development and progression. (
  • In the new studies, researchers artificially increased the levels of Myc inside different types of cells, and then analysed the cells' DNA to find out where it 'stuck' - in other words which genes it had switched on. (
  • They found that Myc was able to bind to DNA at a wide variety of sites across the genome , and that where it bound was determined by which genes were already active. (
  • The transcription factor c-Myc plays critical roles in cancer development and progression through regulating expression of targeted genes. (
  • p53, one of the critical tumor suppressor genes, is mutated in 50−75% of colon cancer cases and marks transition to metastasis [ 2 - 4 ]. (
  • c-Myc and cyclin D1 are oncogenes, the key signatory genes of Wnt signaling, and both function in the stimulation of cell proliferation and in resistance to apoptosis. (
  • In other words, rather than increasing the transcription of a specific set of target genes, c-Myc increases the transcription of all active genes. (
  • Second, silent genes - genes that are expressed at very low levels or not at all - were generally not activated by elevated c-Myc levels. (
  • that c-Myc acts as an amplifier for the expression of active genes in P493-6 cells - could be confirmed. (
  • Virtually the same set of genes that was up-regulated in response to c-Myc in the original study was also up-regulated in the Replication Study for serum lot 2. (
  • Human prostate tumor databases revealed modules of human genes that varied in concert with the Myc prostate cancer signature. (
  • Integrative analysis of multiple RNA-seq data sets indicated that DNA damage response (DDR) genes involved in the replication stress response (RSR) and homologous recombination (HR) repair pathways were highly enriched in MYC paralog-addicted SCLC cell models and in human SCLC specimens. (
  • Myc can regulate expression of many genes by binding to E-boxes. (
  • Specifically, it prevents Myc binding to promoter E-boxes and transactivation of target genes while retaining Miz-1 dependent binding to promoters and transrepression. (
  • Given the extraordinary therapeutic impact of Omomyc in animal models, these data suggest that successfully targeting Myc for cancer therapy might require a similar twofold action, in order to prevent Myc/Max binding to E-boxes and, at the same time, keep repressing genes that would be repressed by Myc. (
  • Myc transcriptional regulators - c-, N- and L-Myc - are basic, helix-loop-helix, leucine zipper (bHLHZip) proteins that bind to an array of genomic sites to either induce or repress transcription of genes important for cell growth, metabolism and differentiation [1] - [4] . (
  • c-Myc can act as a transcriptional activator, regulating up to 15% of all genes in the human genome and results from a high throughput screen suggest that BRCA1 is one of its targets. (
  • As a result of synergistic or sequential damages of DNA, several proto-oncogenes such as c-Myc are activated and tumor suppressor genes are inactivated, leading to the alteration of DNA repair system and apoptosis regulation. (
  • Disrupting the function of c-Myc and its downstream target genes is a promising strategy for cancer therapy. (
  • The transcriptionally active c-Myc-Max dimer promotes proliferation, cell adhesion, apoptosis, and angiogenesis in cancer cells through its control on the transcription of Myc target genes [ 5 ],[ 6 ]. (
  • The concurrent disruption of c-Myc-Max heterotetramerization interferes with the function/expression of all subsequent downstream target genes, suggesting that the c-Myc-Max interaction is a promising molecular target for cancer therapeutics. (
  • Small-molecule c-Myc inhibitor, 10058-F4, is a cell-permeable thiazolidinone that specifically disrupts the formation and function of the c-Myc-Max heterodimer and prevents transactivation of c-Myc target genes [ 7 ]. (
  • Genome-wide studies have shown that MYC transcriptionally regulates many lncRNA genes. (
  • This leads to the unregulated expression of many genes, some of which are involved in cell proliferation , and results in the formation of cancer . (
  • In the human genome , Myc is located on chromosome 8 and is believed to regulate expression of 15% of all genes [8] through binding on enhancer box sequences ( E-boxes ) and recruiting histone acetyltransferases (HATs). (
  • [11] By modifying the expression of its target genes, Myc activation results in numerous biological effects. (
  • With no influence on the expression of the tumor suppressor genes, such as P16, SAM could be used as a potential drug for cancer therapy. (
  • To study heterogeneity of these genes in a large patient cohort, a heterogeneity tissue microarray was constructed containing 0.6 mm tissue cores from 9 different areas of the primary gastric cancers of 113 patients and matched lymph node metastases from 61 of these patients. (
  • For example, the phosphorylation of FoxO transcription factors by Akt has been shown to alleviate the inhibition of Myc target genes by FoxO transcriptional factors and to facilitate Myc-mediated transcription and cellular transformation ( 9 ). (
  • Scientists in her lab look for genes, biological pathways, and molecules that impair MYC -driven cancer cells, while leaving normal cells alone. (
  • However subsequent data demonstrated Mtbp HA130 manufacture does not regulate Mdm2 (14 15 Instead data suggested Mtbp may function in proliferation Lersivirine (UK-453061) supplier as Mtbp expression increased in response to pro-proliferative factors and siRNA knockdown of Mtbp reduced proliferation regardless of p53 status (15 16 Additionally we reported heterozygosity limited the ability of Myc to promote proliferation and activate transcription of pro-proliferative target genes. (
  • Functional studies are therefore an essential complement to these approaches, serving both to confirm the biological roles of candidate cancer genes, and also to identify other vulnerabilities that are acquired as a consequence of observed genetic alterations. (
  • Col1a1-tetO-OKSM mice have expression of the OKSM cassette consisting of four mouse reprogramming genes, Pou5f1 , Klf4 , Sox2 , and Myc , under the control of the bi-directional tet-responsive element ( tetO ) with CMV minimal enhancer-less promoter. (
  • Early studies identified oncogenes, genes that that normally control cell growth, but which can cause mutations responsible for the creation of cancer cells and explain their competitive advantage. (
  • DLX5, however, is not generally active in healthy adult cells, so it represents a much more 'druggable' target for cancer inhibition. (
  • Pharmacological and genetic XBP1 inhibition induces Myc-dependent apoptosis, which is alleviated by exogenous unsaturated fatty acids. (
  • Furthermore, IRE1α inhibition enhances the cytotoxic effects of standard chemotherapy drugs used to treat c-Myc-overexpressing Burkitt's lymphoma, suggesting that inhibiting the IRE1α/XBP1 pathway is a useful general strategy for treatment of Myc-driven cancers. (
  • On the basis of previous reports of a link between Jak/Stat inhibition and suppression of c-Myc ( 25 , 26 ), additional compounds were synthesized and screened for their ability to directly reduce c-Myc levels in the absence of Stat3 activation. (
  • In the ER+ population, the tamoxifen-treated group had significantly lower c-myc expression levels than the control group (P = 0.04) which is in agreement with the estrogen induction of c-myc in ER+ T47D cell line and its inhibition by antiestrogens. (
  • FGFR inhibition in FGFR-addicted cancer facilitated c-Myc degradation via phosphorylating c-Myc at threonine 58. (
  • Ectopic expression of undegradable c-Myc mutant conferred resistance to FGFR inhibition both in vitro and in vivo . (
  • c-Myc level alteration stringently determined the response to FGFR inhibitors, as demonstrated in FGFR-responsive cancer subset, as well as cancers bearing acquired or de novo resistance to FGFR inhibition. (
  • Further, N-Myc is required for tumor maintenance, and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. (
  • however, inhibition of β-catenin or over-expression of dominant-negative LEF1 had no effect on c-Myc promoter activity in basal-like breast cancer cell lines. (
  • Targeting the MYC paralog-PARP1 axis with concomitant BET and PARP inhibition resulted in synergistic effects in MYC paralog-activated SCLC. (
  • Furthermore, the TAM‑resistant cells were significantly more sensitive to cisplatin compared with the parent cells, and the silencing of c‑MYC expression desensitized the cells to cisplatin through the inhibition of the cell cycle. (
  • We show that the decreased cellular proliferation of MCF-7 cells after direct inhibition of c-Myc is a consequence of inhibition of cyclin D1 expression, subsequent redistribution of p21(WAF1/CIP1) from cyclin D1-Cdk4 to cyclin E-Cdk2 complexes, and a decline in cyclin E-Cdk2 enzymatic activity. (
  • Inhibition of MYC significantly blocked the effects of TIM on CSC population, cell invasion and anchor-independent cell growth. (
  • Thus, the inhibition of c-Myc has promise as a therapeutic strategy for human cancer [ 5 , 6 ]. (
  • Consistently, primary cultures of ovarian cancer treated with 10058-F4 showed induction of caspase-3 activity and inhibition of cell proliferation in 15 of 18 cases. (
  • We used 10058-F4 to inhibit the c-Myc-Max interaction in two ovarian cancer cell lines expressing c-Myc in order to determine if the inhibition of c-Myc-Max subsequently inhibits cellular proliferation. (
  • Resetting cancer stem cell regulatory nodes upon MYC inhibition. (
  • The results indicated that SAM treatment inhibited cell growth in gastric cancer cells and colon cancer cells, and the inhibition efficiency was significantly higher than that in the normal cells. (
  • Further, the N-Myc-induced ATM upregulation in C4-2 cells rendered the cells resistance to Enzalutamide, and inhibition of ATM by CRISPR-Cas9 knockout or ATM inhibitor Ku60019 re-sensitized them to Enzalutamide. (
  • Patel and McMahon extended earlier studies showing that binding of Myc to another transcription factor, MIZ-1, and inhibition of MIZ-1-dependent transcription were important for promotion of apoptosis by c-MYC. (
  • Indeed, expression of BCL2 was decreased by wild-type c-MYC but not by the c-MYCV394D mutant, and inhibition of expression of BCL2 by shRNA rescued the effect of c-MYCV394D to promote apoptosis. (
  • MUC16 knockdown leads to inhibition of mTOR activity and reduced expression of its downstream target c-MYC, a key player in cellular growth, proliferation and metabolism. (
  • Furthermore, inhibition of aminotransferases selectively diminished cell proliferation and survival of osteogenic sarcoma MYC -expressing cells. (
  • The WNT pathway is depicted with APC negatively regulating β-catenin, which upon nuclear translocation participates in the transactivation of MYC, such that loss of APC results in constitutive oncogenic MYC expression. (
  • Interestingly, global transcriptomic analysis reveal that IRE1α-XBP1s pathway activity is required for c-MYC signaling, one of the most highly activated oncogenic pathways in PCa. (
  • Treatment with 2-Deoxy- d -glucose, an inhibitor of anaerobic glycolysis, completely blocked the oncogenic roles of c-Myc-LDHA signaling. (
  • Lately, emerging evidence has suggested that oncogenic kinases are associated with specific downstream effectors to govern tumor growth, suggesting potential translational values in kinase-targeted cancer therapy. (
  • We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. (
  • In the presence of Omomyc, the Myc interactome is channeled to repression and its activity appears to switch from a pro-oncogenic to a tumor suppressive one. (
  • Consistent with its normal role in promoting cell growth, Myc can drive oncogenic transformation, and deregulated Myc expression is associated with a variety of human cancers (for review see Spencer and Groudine, 1991 ). (
  • Similarly, the emerging variety of interactions between lncRNAs and MYC, a well-known oncogenic transcription factor linked to most types of cancer, have caught the attention of many biomedical researchers. (
  • These findings are of particular interest because they suggest roles of lncRNAs as regulators of MYC oncogenic functions and the possibility that targeting lncRNAs could represent a novel avenue to cancer treatment. (
  • Here we determined Mtbp is HA130 manufacture oncogenic and identified novel interactions between Mtbp and Tip48 Myc and Tip49. (
  • however, if the damage is irreparable it will, or continue to, survive with the oncogenic mutations resulting in aberrant functions leading to various diseases like cancer. (
  • c-Myc is a central regulator of key cellular processes including differentiation, G 1 -S phase transition, proliferation, maintenance of cell size, redox state, genomic integrity, and apoptosis ( 1 - 3 ). (
  • Knockdown of c-Myc in glioma cancer stem cells reduced proliferation with concomitant cell cycle arrest in the G(0)/G(1) phase and increased apoptosis. (
  • Under normal circumstances, if levels of Myc get too high, cells immediately 'commit suicide' through a process called apoptosis . (
  • Interestingly, inhibiting β-catenin expression alone did not induce apoptosis in breast cancer cell lines despite c-Myc regulation, but we observed a modest increase of cells in the G1 phase of the cell cycle and decrease of cells in S phase upon β-catenin silencing. (
  • c-Myc is an important transcription factor modulating cell progression, apoptosis and cellular transformation. (
  • The non‑steroidal anti‑inflammatory drug diclofenac can inhibit glycolysis in melanoma cells and thereby promote apoptosis by downregulating c‑Myc and GLUT1. (
  • Recovery of miR-4282 expression in the cell could inhibit the proliferation of breast cancer cells, blocked G1-S phase and promoted breast cancer cell apoptosis, inhibited breast cancer cell migration and invasion. (
  • The accumulated findings of an association between high expression levels of the α6 integrin subunit and carcinoma cell invasion, metastatic capacity, apoptosis evasion and negative patient outcome [ 4 - 6 ] strongly argue in favor of a role for α6 containing integrins in human cancers. (
  • Using MTT assay, colony formation, flow cytometry and Annexin V FITC assays, we found that 10058-F4 significantly inhibited cell proliferation of both SKOV3 and Hey ovarian cancer cells in a dose dependent manner through induction of apoptosis and cell cycle G1 arrest. (
  • Myc proteins are key regulators of cell proliferation, apoptosis, and differentiation and are thus active across multiple cellular pathways [ 5 ]. (
  • McMahon SB (2014) MYC and the control of apoptosis. (
  • The purpose of this study was to investigate the role of NDRG1 in the apoptosis of colorectal cancer (CRC) cells. (
  • NDRG1 over-expression promoted apoptosis in colorectal cancer cells whereas depletion of NDRG1 resulted in resistance to oxaliplatin treatment. (
  • In conclusion,NDRG1 promotes oxaliplatin-triggered apoptosis in colorectal cancer. (
  • Specifically, these experiments demonstrate that expression of N-myc at levels similar to those in NBs caused sympathetic neurons to reenter S-phase, as monitored by 5-bromo-2-deoxyuridine incorporation and expression of cell cycle regulatory proteins, and rescued them from apoptosis induced by withdrawal of their obligate survival factor, nerve growth factor. (
  • Thus, N-myc both selectively causes sympathetic neurons to reenter the cell cycle and protects them from apoptosis, potentially contributing to their transformation to NBs. (
  • Through these associations Mtbp increased Myc-mediated transcription transformation and proliferation while inhibiting Myc-induced apoptosis. (
  • To allow for Myc-induced Lersivirine (UK-453061) supplier apoptosis cells were cultured under low serum (1%) conditions. (
  • Increased understanding of the molecular pathways underlying apoptosis has enabled scientists to establish unique approaches targeting apoptosis pathways in cancer therapeutics. (
  • Many therapeutic agents have been proposed with robust anticancer activity capable of inducing apoptosis in cancer cells, but the mechanisms defining their mode of action remain a mystery. (
  • Cancer is often caused by cells that show not only excessive proliferation but also resistance to apoptosis. (
  • Thus, deciphering the signaling pathways that are disrupted in transformed cells that become resistant to apoptosis may provide insights for the control of human cancer. (
  • In cultured human diploid fibroblasts, a form of c-MYC (c-MYCV394D) that fails to interact with MIZ-1 was also defective in inducing apoptosis. (
  • Furthermore, if expression of MIZ-1 was reduced in these cells by expression of short hairpin RNA (shRNA), the apoptotic effect of c-MYCV394D was restored, indicating that MIZ-1 is a key target of c-MYC in controlling apoptosis. (
  • J. H. Patel, S. B. McMahon, BCL2 is a downstream effector of MIZ-1 essential for blocking c-MYC-induced apoptosis. (
  • Induction of apoptosis by oncogenes like c- myc may be important in restraining the emergence of neoplasia. (
  • However, the mechanism by which c- myc induces apoptosis is unknown. (
  • c- myc -induced apoptosis was shown to require interaction on the cell surface between CD95 and its ligand. (
  • Moreover, IGF-I signaling and Bcl-2 suppress c- myc -induced apoptosis by also acting downstream of CD95. (
  • However, growth-promoting oncogenes like c- myc are also effective inducers of apoptosis, and this lethal attribute may both restrain inappropriate cell growth and maintain normal tissue homeostasis ( 2 ). (
  • We have recently reported that a critical downstream link of the E1A-p400 nexus is the oncoprotein transcription factor c-Myc. (
  • c-Myc is a highly unstable transcription factor whose deregulation and increased expression are associated with cancer. (
  • c-Myc is a transcription factor that is involved in a number of cellular processes. (
  • Glucose transporter 1 (GLUT1) is a transmembrane transporter necessary for the entry of glucose into tumor cells, hexokinase (HK) is a key enzyme in the glycolytic pathway, and both are targets of the transcription factor c‑Myc. (
  • Myc-associated zinc finger (MAZ) is a transcription factor highly upregulated in chronic inflammatory disease and several human cancers. (
  • Recent evidence points to Myc - a multifaceted bHLHZip transcription factor deregulated in the majority of human cancers - as a priority target for therapy. (
  • Through its bHLH DNA-binding motif, Myc interacts with DNA , while the leucine zipper TF-binding motif allows the dimerization with its partner Max, another bHLH transcription factor. (
  • Asparagine limitation in melanoma and pancreatic cancer cells activates receptor tyrosine kinase-MAPK signalling as part of a feedforward mechanism involving mammalian target of rapamycin complex 1 (mTORC1)-dependent increase in MAPK-interacting kinase 1 (MNK1) and eukaryotic translation initiation factor 4E (eIF4E), resulting in enhanced translation of activating transcription factor 4 ( ATF4 ) mRNA. (
  • When they knocked out expression of DLX5 in lung cancer cells, it resulted in decreased expression of MYC and reduced cell proliferation. (
  • Non-stem glioma cells displayed limited dependence on c-Myc expression for survival and proliferation. (
  • These findings support a central role of c-Myc in regulating proliferation and survival of glioma cancer stem cells. (
  • Another important role of sLe x/a in hematogenous metastasis is tumor angiogenesis ( 3 , 5 ), which can facilitate intravasation and postextravasational proliferation of cancer cells ( 6 ⇓ - 8 ). (
  • Disruption of c-Myc overrode the cell proliferation driven by constitutively active FGFR. (
  • C-Myc antibody research has revealed cellular proliferation and cell cycle progression may be controlled by phosphorylation at Thr58/Ser62, via glycogen synthase kinase 3, cyclin dependent kinase, ERK2 and JNK (C-Jun N terminal Kinase) interaction. (
  • Our findings suggest that the regulation of c-Myc in breast cancer cells is dependent on the molecular subtype, and that β-catenin-mediated regulation of c-Myc and p21 may control the balance of cell death and proliferation in breast cancer. (
  • In the present study, TAM‑resistant cells were shown to exhibit increased proliferation and invasion compared with the parent cells, and the increased expression of c‑MYC was demonstrated to play an important role in TAM resistance. (
  • Diclofenac significantly inhibited cell proliferation, downregulated GLUT1 and c‑Myc expression, and decreased HK activity in TNBC cells compared with non‑TNBC cells. (
  • Even though its sequence along with its expressional pattern in cancer cell lines are evident, the functional aspects concerning cell proliferation, viability, differentiation and cell cycle regulation of NDRG1 remains vague. (
  • Then, using forced expression experiments, we investigated the effect of α6A and α6B on the regulation of cell proliferation in a colon cancer cell line. (
  • The net result of this integrin mediated intracellular signalling is control of cellular functions such as proliferation, migration, invasion and survival, all of which are pivotal events in cancer progression [ 2 ]. (
  • The effects of HOTAIR and miRNA-130a on gallbladder cancer cell invasion and proliferation was tested using in vitro cell invasion and flow cytometric assays. (
  • A major effect of Myc is B cell proliferation. (
  • Migration, cell proliferation and colony formation assays were used to measure the cellular response after overexpressing N-Myc or perturbing the miR-421/ATM pathway. (
  • Accelerated glucose uptake and glycolysis are main characteristics of cancer cells that allow them for intensive growth and proliferation. (
  • Most early studies concerning cancer biology focused only on molecular alterations in signaling pathways that led to uncontrolled proliferation, while changes in cancer metabolism were treated as a secondary effect. (
  • The increased synthesis of nucleic acid and lipids promote proliferation and growth of cancer cells. (
  • The expression of Mad1 suppresses Myc-mediated cell proliferation and transformation. (
  • A number of observations suggest that Myc specifically cooperates with activated PI3K in deregulated cell proliferation and transformation. (
  • Our findings provide a novel mechanism by which the growth factor signaling pathways cooperate with Myc to promote proliferation and cellular transformation. (
  • There are three Mycs that are embedded within the Myc/Max/Mad network to regulate proliferation. (
  • We found that CAFs isolated from human endometrial cancer (EC) tissues secreted high levels of interleukin-6 (IL-6), which promotes EC cell proliferation in vitro. (
  • EC cell proliferation was dependent on c-Myc expression, as RNAi-mediated c-Myc down-regulation led to a significant 46% reduction in cell viability when compared with scrambled control. (
  • Interestingly, CAF-conditioned media failed to promote proliferation in EC cells with reduced c-Myc expression, suggesting that CAF-mediated cell proliferation was also dependent on c-Myc expression. (
  • Taken together, our data suggests that IL-6 secreted by CAF induces c-Myc expression to promote EC proliferation in vitro and in vivo. (
  • Elevated levels of nuclear Myc in tumor cells and subsets of benign tissue are consistent with a role for Myc in mammary cell proliferation and tumorigenesis. (
  • Knockdown and virus transduction showed Myc is necessary and sufficient for ligand-independent proliferation of the mutant cells but had no effect on metastasis-related phenotypes. (
  • Thus, Myc plays a key role in aggressive proliferation-related phenotypes exhibited by breast cancer cells expressing ERα mutations. (
  • Nevertheless, the mitochondrial-targeted antioxidant Mito-Vitamin E still diminished proliferation of MYC -dependent osteogenic sarcoma cells. (
  • We characterized c-Myc expression in matched tumor cell populations using real time PCR, immunoblotting, immunofluorescence and flow cytometry. (
  • And they suggest that altering this amplification effect could lead to new ways to treat cancer. (
  • Transcriptional Amplification in Tumor Cells with Elevated c-Myc, Cell , 151 (1) 67. (
  • Brodeur G, Seeger RC, Schwab M, Varmus HE, Bishop JM (1984) Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. (
  • Cohn SL, Herst CV, Maurer HS, Rosen ST (1987) N-myc amplification in an infant with stage IV-s neuroblastoma. (
  • Fong CT, Dracopoli NC, White PS, Merril PT, Griffith RC, Housman DE, Brodeur GM (1989) Loss of heterozygosity for the short arm of chromosome 1 in human neuroblastomas: Correlation with N-myc amplification. (
  • Dual color fluorescence in-situ hybridization was performed to assess amplification of HER2, EGFR, CCND1 and MYC using established thresholds (ratio ≥ 2.0). (
  • Amplification was found in 17.4% of 109 interpretable cases for HER2, 6.4% for EGFR, 17.4% for CCND1, and 24.8% for MYC. (
  • These early studies of the E1A-Rb connection thus revealed an important regulatory pathway that has subsequently been found to be deregulated in most human cancers. (
  • We previously reported that the Wnt pathway is preferentially activated in basal-like breast cancer. (
  • However, the mechanisms by which the Wnt pathway regulates down-stream targets in basal-like breast cancer, and the biological significance of this regulation, are poorly understood. (
  • Mutations of Wnt pathway components, such as APC, CTNNB1 and Axin are rare in breast cancer [ 12 - 14 ]. (
  • Our study identified a critical PARP1 regulatory pathway, and provided evidence for a rational combination treatment strategy for MYC paralog-activated SCLC. (
  • These results revealed that NDRG1 is functional in prostate cancer cells and able to induce expression of differentiation factors through p53 independent pathway. (
  • Our data demonstrated that 17-DMAG could suppress the self-renwal of BCSCs through EZH2/c-Myc/Bmi1 pathway. (
  • Myc is activated upon various mitogenic signals such as serum stimulation or by Wnt , Shh and EGF (via the MAPK/ERK pathway ). (
  • N-Myc differentially regulating miR-421/ATM pathway contributes to ADT resistance and Enzalutamide resistance development respectively. (
  • The potential of inhibiting the MYC pathway with DsiRNA therapeutics is very exciting and could be of tremendous therapeutic value for patients. (
  • Ser-145 phosphorylation of Mad1 accelerates the ubiquitination and degradation of Mad1 through the 26S proteasome pathway, which in turn promotes the transcriptional activity of Myc. (
  • However, no direct interaction of the PI3K pathway with Myc/Max/Mad family of proteins has been described. (
  • Cancer-associated fibroblasts promote endometrial cancer growth via activation of interleukin-6/STAT-3/c-Myc pathway. (
  • IL-6 pathway can be a potential target to disrupt tumor-stroma interaction in endometrial cancer progression. (
  • Western blot was used to quantify PRDX2, c-Myc, AKT2/GSK3β pathway-associated proteins and epithelial-mesenchymal transition (EMT)-related proteins in CRC cells. (
  • Potential of apoptotic pathway-targeted cancer therapeutic research: Where do we stand? (
  • cMyc-mediated activation of serine biosynthesis pathway is critical for cancer progression under nutrient deprivation conditions. (
  • Tumor growth can also be curbed by pharmacologically uncoupling bioenergetic pathways involving glucose or glutamine metabolism from Myc-induced cellular biomass accumulation. (
  • Our data suggest that pharmacologic approaches specifically targeting c-Myc or some of the pathways it regulates might be viable targets for novel therapeutic interventions," says Prochownik. (
  • Targeting core stem cell pathways may offer improved therapeutic approaches for advanced cancers. (
  • The molecular pathways leading to the development of basal-like breast cancer are not well understood. (
  • Further studies are required to clarify the intra cellular molecular pathways affecting NDRG1 function in human prostate cancer. (
  • Numerous signals and pathways converge on Myc, which in turn acts on a continuously growing number of identified targets, via transcriptional and nontranscriptional mechanisms. (
  • To provide some insight into the complexity of Myc regulation, we will mention a few of the factors and pathways that impact on its expression, many of which were shown to be essential during mammary gland development [ 4 ]. (
  • The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (
  • This paper reviews recent findings related to O -GlcNAc-dependent regulation of signaling pathways, transcription factors, enzymes, and epigenetic changes involved in metabolic reprograming of cancer. (
  • Our study provides a direct link between the growth factor signaling pathways regulated by PI3 kinase/Akt and MAP kinases with Myc-mediated transcription. (
  • These findings link two apoptotic pathways previously thought to be independent and establish the dependency of Myc on CD95 signaling for its killing activity. (
  • Other approaches to halt Myc on the path to cancer involve targeting Myc-Max dimerization or Myc-induced microRNA expression. (
  • Myc regulates a network of microRNAs through activation of the miR-17-92 cluster and repression of dozens of miRs including Let-7, which was recently shown to affect insulin signaling, miR-23a/b, which regulates glutaminase expression, and miR-34a, which was shown to regulate lactate dehydrogenase (LDHA) expression. (
  • We find that the c-MYC oncoprotein coordinately regulates the expression of 13 different "poor-outcome" cancer signatures. (
  • Studies in both cells and a mouse model for cancer showed that they could promote the expression of MYC by transfecting cells with DNA strands containing DLX5. (
  • First, estrogen stimulation augmented PR expression and decreased Myc in endometrial cancer cell lines. (
  • To interrogate the significance of c-Myc expression in glioma cancer stem cells, we targeted its expression using lentivirally transduced short hairpin RNA (shRNA). (
  • Activation of Myc has numerous effects within a cell, including increasing expression of the transferrin receptor 1 (TFRC). (
  • These results have potential implications for understanding multiple tumor types, including prostate cancer, in which TFRC expression is elevated. (
  • To address the association between sLe x/a expression and EMT, we assessed whether sLe x/a are highly expressed on colon cancer cells undergoing EMT. (
  • The contribution of c-Myc and CDX2 to the sLe x/a induction was proved to be significant by knockdown or forced expression experiments. (
  • Finally, immunohistological study indicated high E-selectin ligand expression on cancer cells undergoing EMT in vivo, supporting their coexistence observed in vitro. (
  • These results suggest a significant link between sLe x/a expression and EMT in colon cancer cells and a pivotal role of c-Myc and CDX2 in regulating sLe x/a expression during EMT. (
  • In line with these observations, high sLe x/a expression levels in colon cancer patients are correlated with poor prognosis ( 2 ). (
  • High level MYC expression is associated with almost all human cancers. (
  • JQ1, a chemical compound that inhibits MYC expression is therapeutically effective in preclinical animal models in midline carcinoma, and Burkitt's lymphoma (BL). (
  • Here we show that JQ1 does not inhibit MYC expression to a similar extent in all tumor cells. (
  • Our study demonstrates that the regulation of high levels of MYC expression in different cancer cells is driven by unique regulatory mechanisms and that such exclusive regulatory signatures in each cancer cells could be employed for targeted therapeutics. (
  • We have initiated paired gallium citrate PET imaging in patients being treated with BET bromodomain inhibitors, a class of therapies known to downregulate MYC expression. (
  • Planned analyses include: 1) correlation of gallium citrate uptake on PET with MYC copy number and expression levels, and 2) determination of the mean percent change from baseline in Ga-citrate uptake on PET upon treatment with BET bromodomain inhibitor treatment. (
  • In this study, we determined the expression pattern and clinical significance of c-Myc-LDHA axis in pancreatic cancer. (
  • However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. (
  • In normal tissue c-Myc expression is tightly regulated, only occurring when cells actively divide. (
  • After silencing β-catenin using siRNA, c-Myc expression was decreased in non-basal-like breast cancer cells. (
  • Microarray-based expression profiling identified a Myc prostate cancer expression signature, which included the putative human tumor suppressor NXK3.1. (
  • We assessed the association between MYC mRNA expression and lethal prostate cancer in a case-control study including 113 lethal cases and 291 indolent controls. (
  • There was no significant association between MYC mRNA expression and lethal prostate cancer. (
  • In this study, we showed that high PARP1 expression was associated with better overall survival (OS), and was positively correlated with the expression of MYC paralogs in patients with SCLC. (
  • We have shown previously that MYCN-amplified neuroblastoma cells depend on high levels of Aurora-A expression for maintaining N-Myc function. (
  • Expression of c-Myc was significantly higher in tumor tissues than in non-cancerous tissue samples. (
  • c‑Myc can promote aerobic glycolysis by upregulating GLUT1 expression and enhancing HK activity. (
  • GLUT1 and c‑Myc expression was measured by western blotting. (
  • Rogers S, Docherty SE, Slavin JL, Henderson MA and Best JD: Differential expression of GLUT12 in breast cancer and normal breast tissue. (
  • In summary, HIF-2α plays an important role in regulating the expression of c-Myc in chronic hypoxia, and consequently controls the sensitivity of colon cancer cells to 5-FU treatment in this environment. (
  • Moreover, MAZ expression increased tumorigenesis in an in vivo model of inflammation-induced colon cancer and was important for growth of human colon cancer cell lines in vitro and in vivo . (
  • Therapeutic interventions that inhibit c-Myc expression have been extensively investigated, including antisense oligonucleotides that have high specificity and potential clinical application. (
  • This investigation compared antiestrogen-mediated growth arrest with the molecular events after repression of c-Myc expression in MCF-7 breast cancer cells using an antisense oligonucleotide. (
  • Simultaneous repression of p21(WAF1/CIP1) can attenuate the growth-inhibitory effects of reduced c-Myc expression emphasizing the importance of this cyclin-dependent kinase (CDK) inhibitor in growth arrest. (
  • To investigate the expression and role of MicroRNA 4282 (miR-4282) in the development of breast cancer. (
  • In situ hybridization was performed to investigate the expression of miR-4282 in human breast cancer tissues. (
  • In addition, the expression of miR-4282 was related to the occurrence of metastasis and the clinical grade of breast cancer. (
  • Furthermore, breast cancer cells with reduced BRCA1 expression due to depletion of c-Myc exhibited impaired DNA repair activity. (
  • In the present study, we demonstrate that high expression of TIM contributes to maintenance of the CSC population, migration, invasion and tumorigenicity of breast cancer through activation of MYC. (
  • Furthermore, human cDNA of NDRG1 from normal placenta was cloned into a eukaryotic expression vector and transfected into the three cancer cell lines. (
  • The expression of Bmi1, c-Myc and EZH2 was determined by western blot. (
  • 17-DMAG inhibited the expression of c-Myc, suppressed the binding of c-Myc in Bmi1 promoter as well as the transcriptional activity of c-Myc. (
  • Taken together, these findings point out the importance of integrin variant expression in colon cancer cell biology. (
  • Insight has been gained into Myc's function in normal physiology, where its role appears to be organ specific, and in cancer where many mechanisms contribute to aberrant Myc expression. (
  • On the basis of the study of v-Myc in chicken, the expression of human c-Myc was found to be altered in cancer. (
  • Here using assays of chromatin conformation, allele-specific chromatin immunoprecipitation and genome editing, we show that HIF binding to this regulatory element is necessary to trans-activate MYC and PVT1 expression specifically in cells of renal tubular origins. (
  • The expression levels of HOTAIR, c-Myc and miRNA-130a were examined in 65 matched pairs of gallbladder cancer tissues. (
  • Conversely, recent reports identified lncRNAs that regulate MYC expression both at the transcriptional and post-transcriptional levels. (
  • Therefore, colorectal cancer patients can be stratified by the expression level of NDRG1. (
  • On the other hand, the expression of these oncogenes creates additional anti-growth cellular stresses, conflicts that the cancer cell must subvert in order to survive. (
  • The NMI mRNA has low expression levels in all human fetal and adult tissues tested except brain and has high expression in cancer cell line-myeloid leukemias. (
  • Casey and Felsher decided to see if there was a link between Myc expression and the levels of CD47 and PD-L1 proteins on the surface of cancer cells. (
  • To do so, they investigated what would happen if they actively turned off Myc expression in tumor cells from mice or humans. (
  • Mice injected with EC cells with down-regulated c-Myc expression, however, showed at least 2.5 times smaller tumor compared to those in control group. (
  • Further immunohistochemical staining on human tissues showed positive expression of IL-6 receptors, phosphorylated-STAT3 and c-Myc in human EC tissues with less signals in benign endometrium. (
  • Peroxiredoxin-2 (PRDX2), an important member of peroxiredoxin family, has been reported to be aberrant expression in various cancers and exerts dual roles in cancer progression. (
  • However, it is unknown whether some lung cancers are dependent on MYC expression for their survival and tumorigenic phenotype. (
  • The discovery was made after observing that children with acute pyelonephritis have decreased MYC expression. (
  • In addition, these agents increased expression of the cyclin-dependent kinase inhibitor p21 CIP1/WAF1 , whereas decreasing cyclin D1 in pancreatic cancer cells. (
  • Here, we found that p62 expression was elevated in breast cancer stem cells (BCSCs), including CD44+CD24− fractions, mammospheres, ALDH1+ populations and side population cells. (
  • Instead, p62 delayed the degradation of MYC mRNA by repressing the expression of let-7a and let-7b, thus promoting MYC mRNA stabilization at the post-transcriptional level. (
  • Ectopic expression of c-MYC in MUC16 knockdown pancreatic cancer cells restores the altered cellular physiology. (
  • We observed similar metabolic alterations that correlated with MUC16 expression in primary tumor tissue specimens from human pancreatic adenocarcinoma cancer patients. (
  • MDA-MB-231 primary tumorigenesis and metastasis in vivo with stable MYC knockdown. (
  • They also found that N-myc promotes tumor progression and might be a key determinant of tumorigenesis. (
  • MYC paralogs, including c-MYC , MYCL , and MYCN , play a pivotal role in tumorigenesis and tumor maintenance through regulation of a variety of cellular processes ( 12 - 15 ). (
  • BRCA1 inactivation contributes to breast cancer tumorigenesis. (
  • Normally MYC regulates many functions within the cell, including cell division. (
  • Our findings reveal that the c-Myc/miR-200b/PRDX2 loop regulates CRC progression and its disruption enhances tumor metastasis and chemotherapeutic resistance in CRC. (
  • The c-myc, c-erbB-2, hst and int-2 oncogenes are frequently amplified and/or overexpressed in human breast carcinomas. (
  • We studied the effect of tamoxifen on RNA levels of these oncogenes in 19 breast cancer patients treated for 3 weeks prior to surgery as compared with 22 control patients. (
  • A recent genome-wide association study on renal cancer susceptibility identified single-nucleotide polymorphisms (SNPs) in an intergenic region located between the oncogenes MYC and PVT1. (
  • Our findings describe an intimate, causal connection between how oncogenes like Myc cause cancer and how those cancer cells manage to evade the immune system," Felsher said. (
  • Oncogenes normally perform vital cellular functions, but when mutated or expressed incorrectly they become powerful cancer promoters. (
  • c-Myc binds to all E-boxes except E-box 5 on CT120 promoter. (
  • The association of c-Myc with the BRCA1 promoter in vivo was tested by a chromatin immunoprecipitation assay. (
  • We investigated the function of the c-Myc binding site in the BRCA1 promoter region by a promoter assay with nucleotide substitutions in the putative E boxes. (
  • Depletion of c-Myc decreased BRCA1 promoter activity, while ectopically expressed c-Myc increased BRCA1 promoter activity. (
  • In the distal BRCA1 promoter, DNA sequence analysis revealed two tandem clusters with high similarity, and each cluster contained a possible c-Myc binding site. (
  • Nucleotide substitutions in the c-Myc binding sites in these regions abrogated c-Myc-dependent promoter activation. (
  • Chromatin IP was used for study the binding of c-Myc to Bmi1 promoter. (
  • The myc promoter contains TF binding sites for Myc (auto-suppression), estrogen receptor (ER) alpha, T-cell factor (TCF) 4, Notch/C promoter-binding factor 1 (Cbf1), E2F, Fos/Jun, signal transducer and activator of transcription (Stat) 3, NF-κB, Smads and others. (
  • The association of c-Myc with the HOTAIR promoter in vivo was confirmed by chromatin immunoprecipitation assay and Electrophoretic mobility shift assay. (
  • Luciferase reporter assays were used to analyze the interaction between miR-200b-3p and 3′untranslated region (3′UTR) of PRDX2 mRNA and AKT2 mRNA as well as c-Myc and the miR-200b-3p promoter. (
  • Chromatin immunoprecipitation (ChIP) assay was used to evaluate binding of c-Myc to the miR-200b-3p promoter. (
  • Moreover, c-Myc bound to the promoter of miR-200b-3p and repressed its transcription. (
  • Interestingly, p62 did not transactivate MYC promoter. (
  • The authors also provide a detailed analysis of the role of MYC in tumor initiation and progression. (
  • But now, in a recent article selected as one of the Editors' Picks in in the Journal of Biological Chemistry , a team led by Edward Prochownik of the University of Pittsburgh has shown that hepatoblastomas are no different from most other cancers: Tumor progression requires c-Myc. (
  • There were more cellular building blocks that made increased growth and cancer progression possible. (
  • The work of Prochownik and colleagues indicates that c-Myc is involved in tumor progression but not initiation. (
  • However, little is known about the effects of c-Myc-LDHA axis in the progression of pancreatic cancer. (
  • Taken together, dysregulated c-Myc-LDHA signaling plays important roles in aerobic glycolysis and facilitates tumor progression of pancreatic cancer. (
  • We found that up-regulated c-Myc-LDHA axis is closely associated with tumor progression and indicates a poor prognosis in pancreatic cancer. (
  • Thus, cisplatin may be a preferred chemotherapeutic agent for the treatment of patients with TAM‑resistant breast cancer, particularly in patients where the rapid control of disease progression is required. (
  • However, the precise role for MAZ in the progression of colitis and colon cancer is not well defined. (
  • These data indicate an important functional role for MAZ in the inflammatory progression of colon cancer through regulation of STAT3 signaling and suggest that MAZ is a potential therapeutic target to dampen STAT3 signaling in colon cancer. (
  • Collectively, these findings suggest that enhanced growth factor (Akt/mTORC1 and STAT3) and inflammatory (NFκB and cytokines) signaling may play a role in dietary energy balance effects on prostate cancer progression in Hi-Myc mice. (
  • Epidemiologic evaluations of the independent role of energy intake in prostate cancer incidence, disease progression, or mortality are more limited. (
  • Several biologic mechanisms, similar to those of obesity per se , have been postulated to explain the role of energy intake and/or fat consumption in prostate cancer progression. (
  • In the current study, we have used the Hi-Myc transgenic mouse model ( 21 ) of prostate cancer to explore the effects of dietary energy balance manipulation, including a standard diet-induced obesity (DIO) regimen, a control diet regimen that results in an overweight phenotype, and a calorie restriction (CR) regimen that leads to a lean phenotype, on prostate cancer progression. (
  • Given that approximately 68% of the adult population in the United States is currently overweight ( 22 ), a comparison of the effects and underlying mechanisms of a lean, overweight, and obese phenotype on prostate cancer progression was therefore evaluated. (
  • TIMELESS (TIM), a circadian rhythm regulator, has been recently implicated in the progression of human cancer. (
  • However, the role of TIM in the progression of breast cancer has not been well-characterized. (
  • TIM plays an important role in promoting breast cancer progression and may represent a novel therapeutic target for breast cancer. (
  • However, the precise role of TIM in the progression of breast cancer has not been fully clarified. (
  • These findings reveal a key function for TIM in breast cancer progression, and may represent a novel target for breast cancer treatment. (
  • Integrins are known to be important contributors to cancer progression. (
  • N-Myc has been demonstrated to drive disease progression and hormonal therapeutic resistance of NEPC/CRPC. (
  • Because Myc and Mad1 have been shown to antagonistically regulate G 0 -S progression and the levels of Myc proteins are increased during G 0 -S transition ( 10 , 11 ), we examined the abundance of Mad1 during cell cycle reentry after starvation. (
  • Cancer-associated fibroblasts (CAFs) secrete various pro-tumorigenic cytokines, yet the role of these cytokines in the progression of endometrial cancer remains unclear. (
  • In addition, functional inactivation of MYC in human breast cancer cells specifically inhibits distant metastasis in vivo and invasive behavior in vitro of these cells. (
  • While MYC has a definite role in cancer, MYC also has an important place in the normal functioning of cells, so it may be difficult to target without killing healthy cells," says Joseph Testa, PhD, a Fox Chase professor and co-author of the study. (
  • By adding an overabundance of MYC, they found they could turn those cells cancerous again. (
  • With an overabundance of MYC, the cell may reproduce out of control, accumulating in each generation the further genetic damage that is the hallmark of cancer cells. (
  • Notably, two of these Phylogica candidates exhibit better killing activity in cancer cells than the previous gold-standard OmoMYC when fused to Phylogica's proprietary cell penetrating Phylomers. (
  • In particular, Myc-overexpressing cells require IRE1α/XBP1 signaling for sustained growth and survival in vitro and in vivo, dependent on elevated stearoyl-CoA-desaturase 1 (SCD1) activity. (
  • This was somewhat surprising, as recent work from the same laboratory has shown that c-Myc is not required for the long-term replacement and maintenance of normal noncancerous liver cells. (
  • c-Myc is largely dispensable in normal cells that have relatively slow and highly controlled growth. (
  • However, in cancer cells that undergo rapid division and metabolism, c-Myc is required. (
  • We established that PR is a negative transcriptional regulator of Myc in endometrial cancer in the presence or absence of ERα, which is in contrast to studies in breast cancer cells. (
  • Lymphomas are cancers of the white blood cells. (
  • These 'MYC inhibitors' can kill lymphomas but some cells survive and become resistant. (
  • Cancer is a disease of the cells, which are the body's basic building blocks. (
  • c-Myc is required for maintenance of glioma cancer stem cells. (
  • As the c-Myc oncoprotein has recognized roles in normal stem cell biology, we hypothesized that c-Myc may contribute to cancer stem cell biology as these cells share characteristics with normal stem cells. (
  • Based on previous methods that we and others have employed, tumor cell populations were enriched or depleted for cancer stem cells using the stem cell marker CD133 (Prominin-1). (
  • Here we report that c-Myc is highly expressed in glioma cancer stem cells relative to non-stem glioma cells. (
  • Numerous cancers express TFRC on the cell surface, and many investigators have attempted to target TFRC as a mechanism for imaging tumor cells. (
  • These results suggest that in vivo tamoxifen decreases c-myc and c-erbB-2 RNA levels in breast cancer cells via two different mechanisms. (
  • But cancer cells find a way to side-step the self-destruct process to survive. (
  • Dr Victoria Cowling, a Cancer Research UK-funded expert on Myc from the University of Dundee, said: "Myc increases the rate at which cells grow and divide, and when Myc levels increase it contributes to the development of almost all human tumour types. (
  • This comprehensive work confirms what other research has hinted at - that there may be a unifying explanation for the many effects Myc has in cancer cells . (
  • Sialyl Lewis x (sLe x ) and sialyl Lewis a (sLe a ) glycans are expressed on highly metastatic colon cancer cells. (
  • They promote extravasation of cancer cells and tumor angiogenesis via interacting with E-selectin on endothelial cells. (
  • Recently, epithelial-mesenchymal transition (EMT) has been noted as a critical phenotypic alteration in metastatic cancer cells. (
  • Sialyl Lewis x (sLe x ) and sialyl Lewis a (sLe a ) are E-selectin ligand glycans expressed on the surface of many types of cancer cells, including colorectal, pancreatic, gastric, breast, prostate, and lung cancer ( 2 , 3 ). (
  • The most established role is promoting extravasation of cancer cells: circulating cancer cells in blood flow arrest at distant sites by adhering to endothelial cells, which enables their movement out of the vasculature ( 2 , 3 ). (
  • Importantly, the interaction between sLe x/a and E-selectin exclusively mediates the adhesion of most epithelial cancer cells to endothelial cells, whereas sLe x/a -independent interaction with endothelial ICAM-1 and VCAM-1 mediates the adhesion of nonepithelial malignant cells, such as leukemia and some sarcoma cells, to endothelial cells ( 4 ). (
  • It is also notable that EMT is known to be associated with cancer stem cells ( 14 , 15 ). (
  • The BL cells showed a ∼90% decrease in MYC transcription upon treatment with JQ1, however, no corresponding reduction was seen in several non-BL cells. (
  • Suppression of c-Myc-LDHA axis caused reduced aerobic glycolysis and further contributed to growth arrest and inability of invasion in pancreatic cancer cells. (
  • Human pancreatic cancer cells including AsPC-1, BxPC-3, Capan-2, CFPAC-1, HPAC, PANC-1, MiaPaca2 and SW1990 were cultured in specific media supplemented with 10 % (v/v) fetal bovine serum (FBS), 100 U/mL, penicillin and 100 μg/mL streptomycin at 37 °C in a humidified incubator with 5 % CO 2 . (
  • Cancer stem cells (CSCs) have the ability to drive continued expansion of the population of malignant cells. (
  • In this study, we evaluated the antiproliferative and proapoptotic effects of triphala, a widely used formulation in Indian traditional medicine, on HCT116 colon cancer cells and human colon cancer stem cells (HCCSCs). (
  • Stem cells have the ability to self-renew for many generations, making them live long enough to acquire the mutations necessary to become cancer stem cells (CSCs) [ 7 ]. (
  • These cells can reproduce themselves and sustain the cancer [ 8 ]. (
  • The idea that a smaller population of stem cells primarily drives cancer has important implications. (
  • N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells. (
  • Home › About CIRM › Our Publications › Grantee publications › N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells. (
  • It is also known that high levels of c-Myc increase the likelihood of normal cells developing into tumor cells. (
  • However, several key questions about the role c-Myc in both normal and cancer cells remain unanswered. (
  • Using Affymetrix microarray-based technology to study all the mRNA transcripts produced by the P493-6 cells in the presence of low and high levels of c-Myc, Lin et al. (
  • Subsequent work by other researchers also explored the role of c-Myc in cancer cells. (
  • While the new lots of serum did not affect the induction of high levels of c-Myc in the cells, they had a clear affect on the steady-state levels of RNA that were measured in the cells 24 hours later. (
  • Triple‑negative breast cancer (TNBC) cells obtain energy mainly through aerobic glycolysis, and their glycolytic rate is significantly higher compared with that of non‑TNBC cells. (
  • Luo C, Wang Y, Wei C, Chen Y and Ji Z: The anti-migration and anti-invasion effects of Bruceine D in human triple-negative breast cancer MDA-MB-231 cells. (
  • Yin L, Qi XW, Liu XZ, Yang ZY, Cai RL, Cui HJ, Chen L and Yu SC: Icaritin enhances the efficacy of cetuximab against triple-negative breast cancer cells. (
  • Warburg O: On the origin of cancer cells. (
  • Regulatory network analysis revealed that the most common SF3B1 mutation activates MYC via effects conserved across human and mouse cells. (
  • Colorectal cancers (CRCs) invariably become hypoxic as they enlarge, and this places unique metabolic demands upon the tumor cells. (
  • Hypoxic stress can enhance the invasiveness of cancer cells and induce chemoresistance. (
  • In chronic hypoxia (over 8 h at 1% O2), HIF-2α but not HIF-1α gradually accumulated in colon cancer cells. (
  • In contrast, knockdown of c-Myc impaired 5-FU chemosensitivity in colon cancer cells. (
  • Moreover, MAZ was essential for cytokine- and bacterium-induced STAT3 signaling in colon cancer cells. (
  • Amler LC, Schwab M (1989) Amplified N-myc in human neuroblastoma cells is often arranged as clustered tandem repeats of differently recombined DNA. (
  • Amler LC, Schwab M (1992) Multiple amplicons of discrete sizes encompassing N-myc in neuroblastoma cells evolve through differential recombination from a large precursor DNA. (
  • How to target Myc is less clear, given its involvement in a variety of key functions in healthy cells. (
  • In this respect, Myc oligomerization domain - the bHLHZip region - proved to be capable of dominantly inhibiting Myc transforming ability in rat embryo fibroblast cells [6] , [7] . (
  • The effects of miR-4282 on the biological behavior of breast cancer cells were then explored in vitro. (
  • Besides, miR-4282 also significantly enhanced the sensitivity of breast cancer cells to paclitaxel. (
  • In this report, we used cultured breast cancer cells to examine the mechanisms of transcriptional activation of BRCA1 by c-Myc. (
  • c-Myc was depleted using c-Myc-specific siRNAs in cultured breast cancer cells. (
  • Mammosphere formation analysis and side population analysis were used to examine the effect of TIM on the self-renewal of breast cancer stem cells. (
  • Breast cancer stem cells (BCSCs) could be enriched by cell sorting according to cell surface markers (CD24-CD44+) or intracellular aldehyde dehydrogenase (ALDH) activity as well as by tumorsphere cultivation. (
  • We previously discovered that 17-demethoxygeldanamycin (17-DMAG), one of the Hsp90 inhibitors, could decrease ALDH+ population of human breast cancer cells. (
  • The self-renewal of human breast cancer cells including MDA-MB-231 and AS-B244 was determined by mammosphere formation assay. (
  • Additional studies in colon cancer cells showed that experimentally restoring the α6A/α6B balance in favor of α6B caused a decrease in cellular S-phase entry and repressed the activity of c-Myc. (
  • The findings that the α6Bβ4 integrin is expressed in quiescent normal colonic cells and is significantly down-regulated in colon cancer cells relative to its α6Aβ4 counterpart are consistent with the anti-proliferative influence and inhibitory effect on c-Myc activity identified for this α6Bβ4 integrin. (
  • Our objective was to evaluate the potential effects of small-molecule c-Myc inhibitor, 10058-F4, on ovarian carcinoma cells and the underlying mechanisms by which 10058-F4 exerts its actions. (
  • These novel findings suggest that the growth of ovarian cancer cells is dependent upon c-MYC activity and that targeting c-Myc-Max heterodimerization could be a potential therapeutic strategy for ovarian cancer. (
  • Although the extreme instability of Myc plays an important role in preventing its accumulation in normal cells, little is known about how Myc is targeted for rapid destruction. (
  • We demonstrate that HOTAIR is a direct target of c-Myc through interaction with putative c-Myc target response element (RE) in the upstream region of HOTAIR in gallbladder cancer cells. (
  • In Burkitt lymphoma, cancer cells show chromosomal translocations , in which chromosome 8 is frequently involved. (
  • Under standard growth conditions, C-myc and H-ras promoters were hypomethylated in gastric cancer cells and colon cancer cells. (
  • Luo J, Li YN, Wang F, Zhang WM, Geng X. S-Adenosylmethionine Inhibits the Growth of Cancer Cells by Reversing the Hypomethylation Status of c-myc and H-ras in Human Gastric Cancer and Colon Cancer. (
  • CRISPR-Cas9 was used to knock out ATM in C4-2 cells and MTS cell viability assay was used to evaluate the drug sensitivity of N-Myc overexpressing C4-2 cells in response to Enzalutamide and ATM inhibitor Ku60019 respectively or in combination. (
  • Combination treatment with ATM inhibitor re-sensitizes N-Myc overexpressed CRPC cells to Enzalutamide. (
  • Although the results were inconsistent, oxaliplatin was still a reasonable candidate for inclusion into neoadjuvant chemotherapy regimens, which was further evidenced by studies demonstrating that oxaliplatin was able to induce apoptotic cell death in colorectal cancer (CRC) cells [ 8 , 9 ]. (
  • However, the mechanisms by which oxaliplatin trigger death signal in cancer cells have not been fully defined yet. (
  • Immune cells called macrophages are supposed to serve and protect, but cancer has found ways to put them to sleep. (
  • FISH analysis is unaffected by the (unavoidable) admixture of normal cells to cancer tissues and FISH results are not altered by tissue processing variations. (
  • Cancer cells exhibit aberrant glucose metabolism characterized by aerobic glycolysis, a phenomenon known as Warburg effect. (
  • In cancer cells, oxidative phosphorylation is inhibited and cells use glycolysis to provide them with the necessary energy. (
  • Cancer cells preferentially use glycolysis even in the abundance of oxygen whereas normal cells use only when oxygen supply is limited ( 4 - 6 ). (
  • Cancer cells convert most glucose to lactate regardless of the availability of O 2 (the Warburg effect). (
  • It was originally hypothesized that these metabolic changes in cancer cells reflected damage to mitochondrial oxidative phosphorylation, suggesting that cancer cells are forced to use glycolysis instead of oxidative phosphorylation ( 1 - 3 ). (
  • For example, coexpression of c-Myc and PI3K was found to be sufficient to transform early passage human mammary epithelial cells and fibroblasts in vitro in the presence of hTERT and SV40 large T ( 8 ). (
  • Although it might seem odd to study breast cancer in an animal with no breasts, zebrafish do have lungs, hearts, brains, eyes, and blood vessels that respond to cancer cells much as human vasculature does. (
  • Feng's strategy is to combine observations and experiments in zebrafish with tests in human cells and analysis of human cancer genome databases. (
  • If you had a way of killing cancer cells or blocking the spread or metastasis of these cells," says Farb, "that could apply not just to triple-negative breast cancer, but to all cancers. (
  • N-Myc and MYCNOS are co-regulated both in normal development and in tumor cells, so it is possible that the two transcripts are functionally related. (
  • Regular chemotherapy takes advantage of this, but the drugs kill dividing cancer and normal cells. (
  • The fundamental question we asked was how are the stresses in cancer cells different from those in normal cells? (
  • That means that turning off SAE2 exacerbates the stress on cancer cells but not normal cells and thus be a great way to kill cancers without many of the side effects of traditional chemotherapies. (
  • The therapeutic value is that a drug targeting SAE will cause the cancer cell to no longer tolerate myc but will not be detrimental to normal cells. (
  • They found that a reduction in Myc caused a similar reduction in the levels of CD47 and PD-L1 proteins on the surface of mouse and human acute lymphoblastic leukemia cells, mouse and human liver cancer cells, human skin cancer cells, and human non-small-cell lung cancer cells. (
  • We found that miR-200b-3p was significantly downregulated, whereas c-Myc and PRDX2 were upregulated in metastatic CRC cells and CRC tissues compared to their counterparts. (
  • Here we demonstrate a role of translational reprogramming in the survival of asparagine-restricted cancer cells. (
  • Using a sensitive immunohistochemical method on frozen tissue sections, both a rabbit polyclonal anti-c-myc antibody and a mouse monoclonal anti-c-myc antibody, H51C116, produced high levels of Myc staining in the nuclei of epithelial cells of infiltrating mammary carcinomas (30-90% of cells stained). (
  • Cancer cells grow too fast, outcompete normal cells and spread to distant sites, where they cause metastases. (
  • Understanding what makes cancer cells so efficient and threatening is critically important and stopping them has always been the goal of cancer research. (
  • Surprisingly, the Lon protease was shown to mainly affect cells where MYC is overactive, suggesting limited toxicity. (
  • Ion beams are often used today in cancer treatment: this involves electrically charged atoms being fired at the tumor to destroy cancer cells. (
  • Many earlier studies of mouse models and of human tumor cells have shown that BCL2 and c-MYC appear to work together in promoting cancer. (
  • c-Myc acts downstream of the CD95 receptor by sensitizing cells to the CD95 death signal. (
  • In the current studies, we observed that MUC16 knockdown pancreatic cancer cells exhibit reduced glucose uptake and lactate secretion along with reduced migration and invasion potential, which can be restored by supplementing the culture media with lactate, an end product of aerobic glycolysis. (
  • Our LC-MS/MS based metabolomics studies indicate global metabolic alterations in MUC16 knockdown pancreatic cancer cells, as compared to the controls. (
  • Overall, our results demonstrate that MUC16 plays an important role in metabolic reprogramming of pancreatic cancer cells by increasing glycolysis and enhancing motility and invasiveness. (
  • Cancer cells engage in aerobic glycolysis and glutaminolysis to fulfill their biosynthetic and energetic demands in part by activating MYC . (
  • Previous reports have characterized metabolic changes in proliferating cells upon MYC loss or gain of function. (
  • However, metabolic differences between MYC -dependent cancer cells and their isogenic differentiated counterparts have not been characterized upon MYC suppression in vitro . (
  • Here we report metabolic changes between MYC -dependent mouse osteogenic sarcomas and differentiated osteoid cells induced upon MYC suppression. (
  • While osteogenic sarcoma cells increased oxygen consumption and spare respiratory capacity upon MYC suppression, they displayed minimal changes in glucose and glutamine consumption as well as their respective contribution to the citrate pool. (
  • This outcome is a testament to the power of the Phylomer platform which has unique potential to discover and deliver our own drugs against some of the highest value (but currently undruggable) targets in cancer. (
  • however, these transcription factors are difficult to inhibit pharmacologically, suggesting that Myc-dependent downstream effectors may be more tractable therapeutic targets. (
  • He added: "Now that we know the mechanism by which Myc acts, we can go after the components of that mechanism as potential drug targets. (
  • She said the new research is likely to focus attention back on potential therapies that block Myc itself rather than its targets. (
  • Triple negative breast cancer (TNBC, estrogen receptor-negative, progesterone receptor-negative and Her2/Neu-negative) is well known for its poor prognosis and lack of therapeutic targets [ 1 ]. (
  • Comprehending the molecular aspect of prostate cancer will aid in prevention, provide molecular markers for diagnosis, support the development of tumor staging along with classification, and shift towards novel therapeutic targets in the treatment for highly developed and metastasized cancers. (
  • Here, we aim to identify the molecular mechanisms underlying the N-Myc-driven therapeutic resistance and provide new therapeutic targets for those N-Myc overexpressed NEPC/CRPC. (
  • As our knowledge on the molecular biology of gastric cancer increases rapidly, it can be hoped, that the identification of molecular mechanisms driving cancer aggressiveness, influencing response to specific chemotherapies, and representing direct targets for therapeutic drugs will eventually enable a better treatment of our patients. (
  • By linking all three approaches, she hopes to pinpoint new drug targets and potential therapies for breast cancer. (
  • Pooled short hairpin RNAi screening is proving to be a powerful method by which loss-of-function studies can identify new cancer targets. (
  • Altered cellular metabolism is one of the most important hallmarks of cancer. (
  • The problem, though, is that MYC is also important in normal cell division and cellular metabolism, so simply shutting it off doesn't work. (
  • Mechanistic investigations suggested as a factor associations with TIP48/TIP49 along with MYC in MTBP function in cell phone transformation as well as the growth of people breast cancer cellular material. (
  • 2001) Function of the c-Myc oncoprotein in chromatin remodeling and transcription. (
  • Although our detailed understanding of cancer metabolism and growth regulation have evolved independently ( 6 ), these 2 areas of investigation have now merged. (
  • Li C, Li X, Li G, Sun L, Zhang W, Jiang J and Ge Q: Identification of a prognosis-associated signature associated with energy metabolism in triple-negative breast cancer. (
  • Long JP, Li XN and Zhang F: Targeting metabolism in breast cancer: How far we can go? (
  • Although cancer metabolism has received considerable attention over the past decade, our knowledge on its specifics is still fragmentary. (
  • Cancer cell metabolism is characterized by an enhanced uptake and utilization of glucose ( 2 - 6 ). (
  • Altman, B. J., Stine, Z. E. & Dang, C. V. From Krebs to clinic: glutamine metabolism to cancer therapy. (
  • MYC regulation of a "poor-prognosis" metastatic cancer cell state. (
  • Molecular regulation of 13 poor-outcome human cancer signatures. (
  • Together, these results suggest that degrasyn reduces the stability of c-Myc in vitro and in vivo through a unique signaling process that uses c-Myc domains not previously associated with c-Myc regulation. (
  • Current estimates suggest that c-Myc influences 5% to 15% of the human genome ( 4 ) and is finely regulated owing to its central role in cell regulation ( 5 , 6 ). (
  • c-MycS, a naturally occurring mutant of c-Myc, has a half-life similar to that of the full-length c-Myc despite missing the first 100 amino acids ( 18 ), suggesting that regions of c-Myc outside the degron are also important in its regulation. (
  • The synthetic small molecule degrasyn induces rapid down-regulation of c-Myc in several tumor cell types, including MM-1 multiple myeloma, HeLa cervical carcinoma, and A375 melanoma. (
  • Our current understanding of the Warburg effect and its implications for the regulation of cancer cell growth has been refined by several generations of tumor biologists and has had increasing clarity as the molecular biology of the malignant phenotype has been elucidated. (
  • This review will concentrate on Myc as a signaling mediator in the mammary gland, discussing its regulation and function during normal development, as well as its activation and roles in breast cancer. (
  • Xiang JF, Yang L, Chen LL (2015) The long noncoding RNA regulation at the MYC locus. (
  • Together, these findings unveiled a previously unappreciated role of p62 in the regulation of BCSCs, assigning p62 as a promising therapeutic target for breast cancer treatments. (
  • Max has been known to bind to certain Mad proteins, forming heterodimers which block c-Myc transcriptional activity in association with other proteins, including histone deacetylases and Sin3 . (
  • Mad1, a member of the Myc/Max/Mad family, suppresses Myc-mediated transcriptional activity by competing with Myc for heterodimerization with its obligatory partner, Max. (
  • This study explores chemopreventive efficacy of metformin in prostate cancer and its link to cMYC in vitro and in vivo. (
  • Indeed, these agents had significantly higher antiproliferative activity in vitro than the established treatments for pancreatic cancer, namely gemcitabine and 5-fluorouracil. (
  • Under normal growth conditions, c-Jun NH 2 -terminal kinase (JNK) associates with c-Myc in a region between amino acids 127 and 189 and mediates its ubiquitination and degradation ( 14 ). (
  • The Cdc42/Rac GTPase-controlled kinase PAK2 phosphorylates c-Myc at Thr 358 , Ser 373 , and Thr 400 , reducing its interaction with Max and preventing c-Myc-mediated transcription while increasing its degradation through a process that remains elusive ( 23 , 24 ). (
  • Although stabilization of N-Myc does not require the catalytic activity of Aurora-A, we found that two inhibitors of Aurora-A disrupt the Aurora-A/N-Myc complex and promote degradation of N-Myc via the Fbxw7 ubiquitin ligase. (
  • N-Myc is also stabilized by aurora A which protects it from degradation. (
  • By screening molecules released by the bacteria, Lon protease was identified as the main effector of MYC degradation, with selectivity for MYC. (
  • Similar to other cancers, current viewpoint suggests that colon cancer is a disease of aberrant stem cell populations [ 6 ]. (
  • Tyrosine kinase FGFR, which is aberrant in various cancer types, is one of the most investigated kinases in molecularly targeted cancer therapy. (
  • A range of assays was used to assess the role of c-Myc in FGFR aberrant cancers and its translational relevance in FGFR-targeted therapy, including assessment of drug sensitivity using cell viability assay, signaling transduction profiling using immunoblotting, and in vivo antitumor efficacy using cancer cell line-based xenografts and patient-derived xenografts models. (
  • We discovered that c-Myc functioned as the key downstream effector that preceded FGFR-MEK/ERK signaling in FGFR aberrant cancer. (
  • Once considered to be non-functional products of low-level aberrant transcription from non-coding regions of the genome, lncRNAs are now viewed as important epigenetic regulators and several lncRNAs have now been demonstrated to be critical players in the development and/or maintenance of cancer. (
  • Here, we show that in postmitotic sympathetic neurons, N-myc can induce S-phase entry while protecting neurons from death caused by aberrant cell cycle reentry. (
  • In our work, we asked whether c-Myc was required for beta-catenin and YAP to induce hepatoblastomas in mice," explains Prochownik. (
  • We have examined c-MYC for its ability to induce metastasis in a C-RAF-driven mouse model for non-small-cell lung cancer. (
  • Moreover, addition of c-MYC was sufficient to induce macrometastasis in liver and lymph nodes with short latency associated with lineage switch events. (
  • If you inhibit this enzyme in a non-myc driven breast cancer, nothing happens," said Westbrook. (
  • 2014) Dicer-microRNA-Myc circuit promotes transcription of hundreds of long noncoding RNAs. (
  • Our most recent studies show that PRDX2 promotes vasculogenic mimicry formation by activating VEGFR2 [ 16 ] and contributes to maintain colorectal cancer stem cell-like properties [ 17 ], suggesting a possible implication of PRDX2 in regulating CRC invasion and metastasis. (
  • The investigators asked if the two proteins lead to cancer by themselves or if they also need c-Myc. (
  • Moreover since Myc has proven difficult to directly target therapeutically identifying proteins that regulate Myc HA130 manufacture function could provide novel therapeutic approaches for the treatment of cancers that rely on MYC. (
  • The finding is the first to link two critical steps in the development of a successful tumor: uncontrolled cell growth - when mutated or misregulated, Myc causes an increase in the levels of proteins that promote cell division - and an ability to outwit the immune molecules meant to stop it. (
  • Here we report on the action mechanism of the Myc interfering molecule termed Omomyc, which demonstrated astounding therapeutic efficacy in transgenic mouse cancer models in vivo . (
  • c-Myc bound to these regions in vivo . (
  • Studies in vivo demonstrated that a novel thiosemicarbazone, namely di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone hydrochloride, completely inhibited the growth of pancreatic cancer xenografts with no evidence of marked alterations in normal tissue histology. (
  • proceeded to test whether the earliest precursor to prostate cancer, prostatic intraepithelial neoplasia (PIN), could also be visualized with 89 Zr-DFO-labeled transferrin. (
  • In transgenic mice that always develop prostate cancer, the authors detected PIN lesions via PET imaging even before enlargement of the prostate had occurred. (
  • A new imaging approach may be able to better detect some prostate cancers. (
  • We have observed significant intra- and inter-patient heterogeneity of gallium citrate uptake on PET scan, which is likely reflective of the underlying biological heterogeneity of metastatic castration resistant prostate cancer. (
  • Here, we report that an IRE1α RNase-specific inhibitor, MKC8866, strongly inhibits prostate cancer (PCa) tumor growth as monotherapy in multiple preclinical models in mice and shows synergistic antitumor effects with current PCa drugs. (
  • Neuroendocrine prostate cancer (NEPC) is a highly aggressive subtype of prostate cancer that is found in up to 20% of those who succumb to advanced disease. (
  • However, the role of N-Myc in initiating prostate cancer and promoting NEPC has not been established. (
  • We use this defined model system to demonstrate that NEPC and the most common type of prostate cancer, prostate adenocarcinoma, can both arise from the same prostate cell. (
  • To define Myc's functional role, we generated transgenic mice expressing human c-Myc in the mouse prostate. (
  • Methods: We conducted a cohort study including 634 men from the Physicians' Health Study and Health Professionals Follow-up Study treated with radical prostatectomy for prostate cancer in 1983-2004 and followed-up for a median of 13.7 years. (
  • Men with low-volume prostate cancer have a lower body mass index (BMI), less body fat, and a smaller waist-to-hip ratio than men with high-volume prostate cancer, which agrees with other reported findings ( 10, 11 ). (
  • High total energy intake, independent of BMI, was associated with a statistically significant increased risk of fatal prostate cancer in the Health Professionals Follow-Up Study Cohort ( 15 ). (
  • Fat, the most calorically dense component of total energy intake, has been the focus of most prostate cancer dietary epidemiologic investigations. (
  • High consumption of fat, especially saturated fat ( 17-19 ), is associated with advanced-stage prostate cancer and mortality ( 17 , 20 ). (
  • Prostate Cancer and Prostatic Diseases , 13 (3), 238-243. (
  • The aim of the present study was to elucidate the functional role of NDRG1 in human prostate cancer. (
  • Prostate cancer emerges as a central problem of male's public health in recent years, as it develops mainly in elderly men making its incidence to be continuously growing in an era characterized with ageing of the population. (
  • Thus, identification of the critical molecules that regulate self-renewal of CSCs may help to develop novel therapeutic strategies for breast cancer metastasis and recurrence. (
  • but regions of Myc that regulate its destruction have not been characterized. (
  • The functions of Myc-nick are currently under investigation, but this new Myc family member was found to regulate cell morphology, at least in part, by interacting with acetyl transferases to promote the acetylation of α-tubulin . (
  • Thus, much of what we take for granted in modern-day molecular biology and cancer research has come from studying DNA tumor viruses. (
  • The researchers used metabolic and molecular profiling to understand why the mice without c-Myc survived longer. (
  • Thank you for sharing this Molecular Cancer Therapeutics article. (
  • Message Body (Your Name) thought you would be interested in this article in Molecular Cancer Therapeutics. (
  • However, even if molecular methods work at the highest level of precision, diagnostic errors will occur in heterogeneous cancers. (
  • Such information will not always reflect the molecular situation of the entire (heterogeneous) cancer mass. (
  • Molecular heterogeneity may not only lead to clones with different aggressiveness within one cancer but also to subpopulations with varying response to anti-cancer drugs and thus be of utmost clinical significance. (
  • The clinical success of targeted therapies along with technological advances in genome-wide profiling have spurred large-scale efforts to systematically map the molecular landscape of human cancers. (
  • Together, our studies have identified molecular effectors of a novel and potent antitumor agent that could be useful for pancreatic cancer treatment. (
  • Although early detection, increased awareness, and developments in treatment have increased complete cure rates especially in some advanced countries, distant metastasis is still a critical event that makes colon cancer a lethal disease. (
  • Recently, epithelial-mesenchymal transition (EMT) has been noted as a critical event in the early step of cancer metastasis ( 12 , 13 ). (
  • NSCLC is the most lethal human cancer due to its high rate of metastasis. (
  • Meanwhile, reduced c-Myc-LDHA signaling resulted in decreased tumor growth and metastasis in pancreatic cancer. (
  • Therefore, strategies that target CSCs could be effective against colon cancer and in reducing the risk of relapse and metastasis. (
  • Tumor metastasis and relapse are the main reasons for the high mortality rate in cancer. (
  • Because of the involvement of BCSCs in tumor initiation, drug resistance or metastasis, to target BCSCs is considered as the key for successful breast cancer therapy. (
  • And finally-especially useful for studying cancer-the fish are transparent during development, and mutants like Casper are transparent as adults, so scientists can easily monitor tumor growth and metastasis. (
  • Metastasis is a major threat to colorectal cancer (CRC) patients. (
  • Richard Hopkins, Phylogica's CEO said "We're delighted to have identified at least two proprietary Phylomers that represent the most potent inhibitors of MYC yet described. (
  • We are encouraged by the high hit rate so far and are confident that a larger pool of specific MYC inhibitors will emerge once the functional screens are completed early next year. (
  • Once we have identified a broader set of MYC inhibitors we will then choose the highest quality candidates for analysis in animal models of cancer. (
  • Hsp90 inhibitors such as 17-DMAG may serve as effective agents in breast cancer treatment. (
  • Still, finding c-MYC inhibitors for therapeutic use has been problematic and MYC itself has long been viewed as undruggable. (
  • Thus, by studying these viruses over the years, researchers have been able to probe mechanisms of cancer initiation as well as expose the underlying biological events. (
  • Here, we have investigated mechanisms regulating the stability of Myc. (
  • Their studies were performed in mouse cancer models and in human cell cultures. (
  • Phylogica's CSO, Dr Paul Watt, commented "To date we've assayed less than 20% of the hits identified in the primary screens against MYC as fusions to our cell penetrating Phylomers. (
  • Phylogica's differentiation in the field of intracellular drug delivery now extends from best in class cell penetrating Phylomers for drug delivery to best in class active biologics drug compounds active against MYC. (
  • In this study, we found that c-Myc and LDHA are concomitantly overexpressed in pancreatic cancer cell lines and clinical specimens. (
  • However, the precise role of c-Myc-LDHA axis in aerobic glycolysis and tumor cell phenotype of pancreatic cancer remains unclear. (
  • Poly (ADP-ribose) polymerase 1 (PARP1) is highly expressed in small cell lung cancer (SCLC) and has emerged as an attractive target for treatment of SCLC. (
  • Small cell lung cancer is a high-grade neuroendocrine carcinoma that accounts for over 250,000 annual cases worldwide ( 1 , 2 ). (
  • 8 Department of Pathology and Cell Biology, and the Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York. (
  • A wound healing assay and a Transwell assay were used to determine the role of TIM in breast cancer cell migration and invasion. (
  • TIM levels in both breast cancer cell lines and tissues were significantly upregulated. (
  • Loss of sensitivity to p21 cell cycle control may be associated with prostatic cancer behavior. (
  • c-Myc is deregulated in a wide range of malignancies, such as mammary carcinoma, colon carcinoma, cervical carcinoma, myeloid leukaemia, melanoma osteosarcoma, glioblastoma, and small-cell lung carcinoma [ 8 ]. (
  • In the present study, we aimed to elucidate the specific role of 10058-F4 in ovarian cancer cell growth. (
  • MYC deregulation is common in human cancer and has a role in sustaining the aggressive cancer stem cell populations. (
  • Bretones G, Delgado MD, Leon J (2015) Myc and cell cycle control. (
  • N-Myc overexpressing stable cell lines for LNCaP and C4-2 were generated by lentivirus infection. (
  • If we find something in the fish, we go to the human patient cancer cell and ask: is this true for human cancer or not? (
  • We will summarize the recently published work describing the early and late effects of N-Myc and L-Myc on hair cell formation and maintenance. (
  • Experts think that special programs within the cancer cell allow it to cope with the stress as it grows and divides (mitosis). (
  • Westbrook, Elledge, and colleagues showed that SUMO-activating enzyme, the first step in the process, is required for myc-driven cancers to go through cell division. (
  • Weissman is the Virginia and D.K. Ludwig Professor for Clinical Investigation in Cancer Research and the director of Stanford's Institute for Stem Cell Biology and Regenerative Medicine . (
  • An antibody that binds to PD-L1 has been approved by the U.S. Food and Drug Administration to treat bladder and non-small-cell lung cancer, but it has been shown to be effective in the treatment of many cancers. (
  • Underneath the intricacy of every cancer lies mysterious events that impel the tumour cell and its posterity into abnormal growth and tissue invasion. (
  • In 2014, an estimated 71,830 men and 65,000 women were diagnosed with colorectal cancer, while 26,270 men and 24,040 women died due to the disease [ 1 ]. (
  • Colorectal cancer (CRC) is the second most common malignancy worldwide in females and the third in males, and one of the main causes of cancer death [ 1 ]. (
  • Approximately 30% of metastatic breast cancers harbor estrogen receptor α (ERα) mutations associated with resistance to endocrine therapy and reduced survival. (
  • We also show that Myc is stabilized by cancer‐associated and transforming mutations within its transcriptional activation domain. (
  • They observed that the mice lacking c-Myc in their livers survived much longer than mice with intact c-Myc. (
  • Male Hi-Myc mice were placed on three dietary regimens [30% calorie restriction (CR), overweight control (modified AIN76A with 10 kcal% fat), and a diet-induced obesity regimen (DIO) 60 kcal% fat]. (
  • Combining an inhibitor of rDNA transcription (CX-5461) with the mTORC1 inhibitor everolimus more than doubled survival of Eμ-Myc lymphoma-bearing mice. (
  • We demonstrate that combining pharmacologic targeting of ribosome biogenesis and mTORC1-dependent translation provides a remarkable therapeutic benefit to Eμ-Myc lymphoma-bearing mice. (
  • heterozygosity also delayed Myc-induced lymphomagenesis in mice (15). (
  • Disruption of the Aurora-A/N-Myc complex inhibits N-Myc-dependent transcription, correlating with tumor regression and prolonged survival in a mouse model of MYCN-driven neuroblastoma, suggesting that Aurora-A is an accessible target that makes destabilization of N-Myc a viable therapeutic strategy. (
  • Thus, inhibiting SAE could be a therapeutic strategy for myc-cancers. (
  • Basal-like breast cancer constitutes one of the most challenging subtypes of breast cancers. (
  • Although it only accounts for about 10-15% of breast cancer cases, basal-like breast cancer is responsible for a disproportionate number of breast cancer deaths [ 4 ]. (
  • However, the role of Wnt/β-catenin in breast cancer is not as clear as it is in colon cancer and hepatocarcinoma. (
  • What have you accomplished so far and what is the next step to bringing your research closer to helping breast cancer patients? (
  • With our DoD BCRP funding, we were able to validate our thermal targeting approach in an estrogen receptor-positive mouse model of breast cancer. (
  • The next step is to test this thermally targeted anti-cancer peptide in other models of breast cancer to define what patient population(s) might benefit from treatment with this agent. (
  • How did this award help advance your research and your career as a breast cancer researcher? (
  • Is the Subject Area "Breast cancer" applicable to this article? (
  • Tamoxifen (TAM) resistance is a major challenge in the treatment of estrogen receptor‑positive (ER+) breast cancer. (
  • To date, to the best of our knowledge, there are only a few studies available examining the response of patients with TAM‑resistant breast cancer to chemotherapy, and the guidelines do not specify recommended drugs for these patients. (
  • Taken together, the data of the present study demonstrated that although c‑MYC was involved in TAM resistance, it increased the sensitivity of ER+ breast cancer to cisplatin. (
  • Foulkes WD, Smith IE and Reis-Filho JS: Triple-negative breast cancer. (
  • Shen L, O'Shea JM, Kaadige MR, Cunha S, Wilde BR, Cohen AL, Welm AL and Ayer DE: Metabolic reprogramming in triple-negative breast cancer through Myc suppression of TXNIP. (
  • miR-4282 inhibited the occurrence and development of breast cancer by regulating Myc, which made it a new target for clinical diagnosis and treatment of breast cancer. (
  • Breast cancer is the most common malignancy and the leading cause of cancer death among women. (
  • Immunohistochemistry (IHC) staining was used to examine TIM levels in breast cancer specimens. (
  • These marvelous mutants, and others, are under the charge of Hui Feng, director of BU's Lab of Zebrafish Genetics and Cancer Therapeutics , and they may hold clues to treating breast cancer. (
  • And MYC is disproportionately elevated in triple-negative breast cancer, or TNBC, which lacks hormone receptors and therefore doesn't respond to hormone therapy. (
  • While TNBC often responds well to chemotherapy, it can grow quickly, spread aggressively, and is more likely to recur than other types of breast cancer, according to the Susan G. Komen Breast Cancer Foundation. (
  • To test this, they turned off the SAE enzyme in a form of myc-driven breast cancer. (
  • The findings in this report have particular importance for an aggressive form of breast cancer called triple negative breast cancer (TNBC). (
  • Through techniques including RNA sequencing and mitochondrial analysis, they observed a role for c-Myc in supporting tumor growth. (
  • c-MYC alone induced frank tumor growth only after long latency at which time secondary mutations in K-Ras or LKB1 were detected reminiscent of human NSCLC. (
  • Lactate dehydrogenase A (LDHA), which catalyzes the conversion of l -lactate to pyruvate in the final step of anaerobic glycolysis, is frequently upregulated in pancreatic cancer. (
  • The disappointing survival rate and poor prognosis of pancreatic cancer indicate the aggressive nature of this disease. (
  • The most successful agent for pancreatic cancer treatment is gemcitabine, although the overall effect in terms of patient survival remains very poor. (
  • This study was initiated to evaluate a novel class of anticancer agents against pancreatic cancer. (
  • These findings point to an important role for p400 in Myc function and reveal that E1A drives oncogenesis by tapping into two important transcriptional networks: those of E2F and Myc. (
  • Our findings establish N-Myc as a driver of NEPC and a target for future therapies. (
  • Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention. (
  • Similarly, PRDX2 is epigenetically silenced and inhibits c-Myc-induced leukemogenesis in acute myeloid leukemia (AML) [ 5 ]. (
  • Understand more about the role genetics has in cancer risk and how to find out more if you are concerned about a family history of cancer. (
  • This interesting duality of c-Myc effects places it in the mainstream of transformational changes and gives it a very important role in regulating the "transformed phenotype. (
  • In either case, it appears that c-Myc plays a central role in sustaining the changes which occur with transformation. (
  • To date, however, there are only a few studies on the physiological role of Myc in the mammary gland. (
  • A summary of the discussion on the role of Myc in normal development is shown in Figure 1 . (
  • c-Myc also plays a critical role in malignant transformation. (
  • In addition, myc has a direct role in the control of DNA replication. (
  • Here we review structural and functional features of c-Myc and highlight to discuss possible small molecule modulators of c-Myc as promising anti-cancer therapeutics. (
  • Cambridge, Mass., February 2, 2015 - Dicerna Pharmaceuticals, Inc. (NASDAQ: DRNA), a leader in the development of RNAi therapeutics, today announced that the first patient has been dosed in a global Phase 1b/2 clinical trial of DCR-MYC, an investigational Dicer substrate short interfering RNA (DsiRNA) therapeutic, in patients with advanced hepatocellular carcinoma (HCC). (
  • Relative frequency of select mutations or alterations found in lung cancer. (
  • A personalized approach to cancer treatment has become more common over the last several decades, with numerous targeted drugs approved to treat particular tumor types with specific mutations or patterns. (
  • MYC was overexpressed in 68% of the tumor tissue samples compared to normal tissues. (
  • A positive correlation between c-Myc and HOTAIR mRNA levels was observed in gallbladder cancer tissues. (
  • Researchers at Baylor College of Medicine and Harvard Medical School have developed ways to exploit the addictions of cancers to kill them without harming normal tissues. (
  • Here the richness of our understanding of MYC is reviewed, highlighting new biological insights and opportunities for cancer therapies. (
  • Its involvement in cancers such as medulloblastoma, neuroblastoma, and Burkitt's lymphoma is examined, as are the prospects for anti-MYC therapies in cancer treatment. (
  • Mount Sinai researchers have found a new type of therapy to be effective for patients with a particular type of bone marrow cancer that is resistant to several standard therapies, according to results of a clinical trial published in The New England Journal of Medicine in August. (
  • Thus, targeting the network controlling the synthesis and function of ribosomes at multiple points provides a potential new strategy to treat MYC-driven malignancies. (
  • Treatment options for the high proportion of cancers driven by MYC are limited. (
  • These results establish a rationale for targeting ribosome biogenesis and function to treat MYC-driven cancer. (
  • This subtype is often driven by myc, and there are currently no effective treatments for these patients. (
  • Perth, Australia, 16 November 2015: Phylogica Limited (ASX:PYC) has successfully identified multiple proprietary Phylomer candidates with confirmed ability to bind and block intracellular MYC activity. (
  • Myc-Max dimers bind to hexameric DNA sequences (E-box) and activate transcription by recruiting multiple coactivators [ 1 ]. (
  • Located within MB I are two key amino acid residues (Thr 58 and Ser 62 ) whose pattern of phosphorylation determines c-Myc stability. (
  • We provide evidence that ST3GAL1 / 3 / 4 and FUT3 are transcriptionally up-regulated by c-Myc with probable involvement of Ser62 phosphorylation, and that FUT2 is transcriptionally down-regulated through the attenuation of CDX2. (
  • Novus Biologicals offers both polyclonal ( NB600-1271 ) and monoclonal ( NB110-57173 ) c-Myc antibodies specific to phosphorylation at residues threonine 58 and serine 62. (
  • MYCN can also be activated in neuroblastoma and other cancers through somatic mutation. (