Cell Line, Tumor: A cell line derived from cultured tumor cells.Tumor Cells, Cultured: 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.Tumor Markers, Biological: 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.Neoplasms, Experimental: Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.Tumor Burden: The total amount (cell number, weight, size or volume) of tumor cells or tissue in the body.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Neoplasms: 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.Neoplasm Metastasis: The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.Carcinoma, Ehrlich Tumor: A transplantable, poorly differentiated malignant tumor which appeared originally as a spontaneous breast carcinoma in a mouse. It grows in both solid and ascitic forms.Tumor Suppressor Protein p53: 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.Mammary Neoplasms, Experimental: Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS.Wilms Tumor: A malignant kidney tumor, caused by the uncontrolled multiplication of renal stem (blastemal), stromal (STROMAL CELLS), and epithelial (EPITHELIAL CELLS) elements. However, not all three are present in every case. Several genes or chromosomal areas have been associated with Wilms tumor which is usually found in childhood as a firm lump in a child's side or ABDOMEN.Genes, Tumor Suppressor: 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.Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.Neoplasm Transplantation: Experimental transplantation of neoplasms in laboratory animals for research purposes.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Mice, Nude: 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.Antigens, Neoplasm: 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.Neoplastic Cells, Circulating: Exfoliate neoplastic cells circulating in the blood and associated with metastasizing tumors.Tumor Microenvironment: The milieu surrounding neoplasms consisting of cells, vessels, soluble factors, and molecules, that can influence and be influenced by, the neoplasm's growth.Neovascularization, Pathologic: A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Carcinoid Tumor: A usually small, slow-growing neoplasm composed of islands of rounded, oxyphilic, or spindle-shaped cells of medium size, with moderately small vesicular nuclei, and covered by intact mucosa with a yellow cut surface. The tumor can occur anywhere in the gastrointestinal tract (and in the lungs and other sites); approximately 90% arise in the appendix. It is now established that these tumors are of neuroendocrine origin and derive from a primitive stem cell. (From Stedman, 25th ed & Holland et al., Cancer Medicine, 3d ed, p1182)Transplantation, Heterologous: Transplantation between animals of different species.Adenocarcinoma: A malignant epithelial tumor with a glandular organization.Fibrosarcoma: A sarcoma derived from deep fibrous tissue, characterized by bundles of immature proliferating fibroblasts with variable collagen formation, which tends to invade locally and metastasize by the bloodstream. (Stedman, 25th ed)Xenograft Model Antitumor Assays: 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.Mice, Inbred BALB CNeoplasm Proteins: 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.Tumor Suppressor Proteins: Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.Neuroendocrine Tumors: Tumors whose cells possess secretory granules and originate from the neuroectoderm, i.e., the cells of the ectoblast or epiblast that program the neuroendocrine system. Common properties across most neuroendocrine tumors include ectopic hormone production (often via APUD CELLS), the presence of tumor-associated antigens, and isozyme composition.Colonic Neoplasms: Tumors or cancer of the COLON.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Cell Survival: 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.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Breast Neoplasms: Tumors or cancer of the human BREAST.Apoptosis: 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.Sarcoma, Experimental: Experimentally induced neoplasms of CONNECTIVE TISSUE in animals to provide a model for studying human SARCOMA.Melanoma, Experimental: Experimentally induced tumor that produces MELANIN in animals to provide a model for studying human MELANOMA.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.RNA, Messenger: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Mice, SCID: 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.Signal Transduction: 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.Mice, Inbred C57BLDNA, Neoplasm: DNA present in neoplastic tissue.Cell Transformation, Neoplastic: 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.Ovarian Neoplasms: 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.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Glioma: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)Transfection: 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.Reverse Transcriptase Polymerase Chain Reaction: 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.Liver Neoplasms: Tumors or cancer of the LIVER.Kidney Neoplasms: Tumors or cancers of the KIDNEY.Flow Cytometry: 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.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Skin Neoplasms: Tumors or cancer of the SKIN.Cytotoxicity, Immunologic: The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.Lung Neoplasms: Tumors or cancer of the LUNG.Pancreatic 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).Carcinoma, Squamous Cell: 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)Time Factors: Elements of limited time intervals, contributing to particular results or situations.Mammary Neoplasms, Animal: Tumors or cancer of the MAMMARY GLAND in animals (MAMMARY GLANDS, ANIMAL).Gastrointestinal Stromal Tumors: All tumors in the GASTROINTESTINAL TRACT arising from mesenchymal cells (MESODERM) except those of smooth muscle cells (LEIOMYOMA) or Schwann cells (SCHWANNOMA).Blotting, Western: 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.Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.Neoplasm Staging: Methods which attempt to express in replicable terms the extent of the neoplasm in the patient.Disease Progression: 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.Cancer Vaccines: 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.Molecular Sequence Data: 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.Tumor Stem Cell Assay: A cytologic technique for measuring the functional capacity of tumor stem cells by assaying their activity. It is used primarily for the in vitro testing of antineoplastic agents.Mutation: 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.Bone Neoplasms: Tumors or cancer located in bone tissue or specific BONES.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.RNA, Small Interfering: 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.RNA, Neoplasm: RNA present in neoplastic tissue.Cell Cycle: 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.Leydig Cell Tumor: Gonadal interstitial or stromal cell neoplasm composed of only LEYDIG CELLS. These tumors may produce one or more of the steroid hormones such as ANDROGENS; ESTROGENS; and CORTICOSTEROIDS. Clinical symptoms include testicular swelling, GYNECOMASTIA, sexual precocity in children, or virilization (VIRILISM) in females.Cell Growth Processes: Processes required for CELL ENLARGEMENT and CELL PROLIFERATION.Immunoenzyme Techniques: 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.Cell Adhesion: Adherence of cells to surfaces or to other cells.Genetic Therapy: Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.Down-Regulation: 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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Liver Neoplasms, Experimental: Experimentally induced tumors of the LIVER.Carcinoma, Hepatocellular: A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Lymphatic Metastasis: Transfer of a neoplasm from its primary site to lymph nodes or to distant parts of the body by way of the lymphatic system.Rhabdoid Tumor: A rare but highly lethal childhood tumor found almost exclusively in infants. Histopathologically, it resembles RHABDOMYOSARCOMA but the tumor cells are not of myogenic origin. Although it arises primarily in the kidney, it may be found in other parts of the body. The rhabdoid cytomorphology is believed to be the expression of a very primitive malignant cell. (From Holland et al., Cancer Medicine, 3d ed, p2210)Neoplasm Invasiveness: Ability of neoplasms to infiltrate and actively destroy surrounding tissue.Up-Regulation: 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.Neoplastic Stem Cells: Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS.Treatment Outcome: 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.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Polymerase Chain Reaction: 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.Neuroblastoma: A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)Carcinoma 256, Walker: A transplantable carcinoma of the rat that originally appeared spontaneously in the mammary gland of a pregnant albino rat, and which now resembles a carcinoma in young transplants and a sarcoma in older transplants. (Stedman, 25th ed)Granulosa Cell Tumor: A neoplasm composed entirely of GRANULOSA CELLS, occurring mostly in the OVARY. In the adult form, it may contain some THECA CELLS. This tumor often produces ESTRADIOL and INHIBIN. The excess estrogen exposure can lead to other malignancies in women and PRECOCIOUS PUBERTY in girls. In rare cases, granulosa cell tumors have been identified in the TESTES.Combined Modality Therapy: 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.Melanoma: A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)Lymphocytes, Tumor-Infiltrating: Lymphocytes that show specificity for autologous tumor cells. Ex vivo isolation and culturing of TIL with interleukin-2, followed by reinfusion into the patient, is one form of adoptive immunotherapy of cancer.Neoplasm Recurrence, Local: 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.Urinary Bladder Neoplasms: Tumors or cancer of the URINARY BLADDER.Cell Hypoxia: A condition of decreased oxygen content at the cellular level.Astrocytoma: Neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors. Fibrillary astrocytomas are the most common type and may be classified in order of increasing malignancy (grades I through IV). In the first two decades of life, astrocytomas tend to originate in the cerebellar hemispheres; in adults, they most frequently arise in the cerebrum and frequently undergo malignant transformation. (From Devita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2013-7; Holland et al., Cancer Medicine, 3d ed, p1082)Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.Angiogenesis Inhibitors: Agents and endogenous substances that antagonize or inhibit the development of new blood vessels.Carcinoma, Lewis Lung: A carcinoma discovered by Dr. Margaret R. Lewis of the Wistar Institute in 1951. This tumor originated spontaneously as a carcinoma of the lung of a C57BL mouse. The tumor does not appear to be grossly hemorrhagic and the majority of the tumor tissue is a semifirm homogeneous mass. (From Cancer Chemother Rep 2 1972 Nov;(3)1:325) It is also called 3LL and LLC and is used as a transplantable malignancy.Killer Cells, Natural: Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.Genes, p53: Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Mast-Cell Sarcoma: A unifocal malignant tumor that consists of atypical pathological MAST CELLS without systemic involvement. It causes local destructive growth in organs other than in skin or bone marrow.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Carcinoma, Renal Cell: A heterogeneous group of sporadic or hereditary carcinoma derived from cells of the KIDNEYS. There are several subtypes including the clear cells, the papillary, the chromophobe, the collecting duct, the spindle cells (sarcomatoid), or mixed cell-type carcinoma.Genetic Vectors: DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.Radiation-Sensitizing Agents: Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells.Pituitary Neoplasms: Neoplasms which arise from or metastasize to the PITUITARY GLAND. The majority of pituitary neoplasms are adenomas, which are divided into non-secreting and secreting forms. Hormone producing forms are further classified by the type of hormone they secrete. Pituitary adenomas may also be characterized by their staining properties (see ADENOMA, BASOPHIL; ADENOMA, ACIDOPHIL; and ADENOMA, CHROMOPHOBE). Pituitary tumors may compress adjacent structures, including the HYPOTHALAMUS, several CRANIAL NERVES, and the OPTIC CHIASM. Chiasmal compression may result in bitemporal HEMIANOPSIA.Osteosarcoma: A sarcoma originating in bone-forming cells, affecting the ends of long bones. It is the most common and most malignant of sarcomas of the bones, and occurs chiefly among 10- to 25-year-old youths. (From Stedman, 25th ed)Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Proto-Oncogene Proteins: 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.Survival Analysis: 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.Ki-67 Antigen: A CELL CYCLE and tumor growth marker which can be readily detected using IMMUNOCYTOCHEMISTRY methods. Ki-67 is a nuclear antigen present only in the nuclei of cycling cells.Prognosis: 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.Adenoviridae: A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases.Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.Promoter Regions, Genetic: 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.Head and Neck Neoplasms: 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)Models, Biological: 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.Stomach Neoplasms: Tumors or cancer of the STOMACH.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.DNA-Binding Proteins: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Gastrointestinal Neoplasms: Tumors or cancer of the GASTROINTESTINAL TRACT, from the MOUTH to the ANAL CANAL.Adenoma: A benign epithelial tumor with a glandular organization.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.HT29 Cells: Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells such as the GOBLET CELLS.Drug Screening Assays, Antitumor: 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.Radiation Tolerance: The ability of some cells or tissues to survive lethal doses of IONIZING RADIATION. Tolerance depends on the species, cell type, and physical and chemical variables, including RADIATION-PROTECTIVE AGENTS and RADIATION-SENSITIZING AGENTS.Genes, ras: 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.Receptors, Tumor Necrosis Factor, Type I: A tumor necrosis factor receptor subtype that has specificity for TUMOR NECROSIS FACTOR ALPHA and LYMPHOTOXIN ALPHA. It is constitutively expressed in most tissues and is a key mediator of tumor necrosis factor signaling in the vast majority of cells. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.Survival Rate: 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.Clone Cells: A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant.Antibiotics, Antineoplastic: Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.Neuroectodermal Tumors, Primitive: A group of malignant tumors of the nervous system that feature primitive cells with elements of neuronal and/or glial differentiation. Use of this term is limited by some authors to central nervous system tumors and others include neoplasms of similar origin which arise extracranially (i.e., NEUROECTODERMAL TUMORS, PRIMITIVE, PERIPHERAL). This term is also occasionally used as a synonym for MEDULLOBLASTOMA. In general, these tumors arise in the first decade of life and tend to be highly malignant. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2059)Interferon-gamma: The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.Tomography, X-Ray Computed: Tomography using x-ray transmission and a computer algorithm to reconstruct the image.Cisplatin: 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.Testicular Neoplasms: Tumors or cancer of the TESTIS. Germ cell tumors (GERMINOMA) of the testis constitute 95% of all testicular neoplasms.HCT116 Cells: Human COLORECTAL CARCINOMA cell line.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Phyllodes Tumor: A type of connective tissue neoplasm typically arising from intralobular stroma of the breast. It is characterized by the rapid enlargement of an asymmetric firm mobile mass. Histologically, its leaf-like stromal clefts are lined by EPITHELIAL CELLS. Rare phyllodes tumor of the prostate is also known.Rats, Inbred F344Mice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.Immunotherapy, Adoptive: Form of adoptive transfer where cells with antitumor activity are transferred to the tumor-bearing host in order to mediate tumor regression. The lymphoid cells commonly used are lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). This is usually considered a form of passive immunotherapy. (From DeVita, et al., Cancer, 1993, pp.305-7, 314)Meningioma: A relatively common neoplasm of the CENTRAL NERVOUS SYSTEM that arises from arachnoidal cells. The majority are well differentiated vascular tumors which grow slowly and have a low potential to be invasive, although malignant subtypes occur. Meningiomas have a predilection to arise from the parasagittal region, cerebral convexity, sphenoidal ridge, olfactory groove, and SPINAL CANAL. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2056-7)Antineoplastic Combined Chemotherapy Protocols: 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.RNA Interference: 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.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Oligonucleotide Array Sequence Analysis: 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.Glomus Tumor: A blue-red, extremely painful vascular neoplasm involving a glomeriform arteriovenous anastomosis (glomus body), which may be found anywhere in the skin, most often in the distal portion of the fingers and toes, especially beneath the nail. It is composed of specialized pericytes (sometimes termed glomus cells), usually in single encapsulated nodular masses which may be several millimeters in diameter (From Stedman, 27th ed). CHEMODECTOMA, a tumor of NEURAL CREST origin, is also sometimes called a glomus tumor.Retrospective Studies: 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.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Proto-Oncogene Proteins c-bcl-2: Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.Carcinogens: 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.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Rhabdomyosarcoma: A malignant solid tumor arising from mesenchymal tissues which normally differentiate to form striated muscle. It can occur in a wide variety of sites. It is divided into four distinct types: pleomorphic, predominantly in male adults; alveolar (RHABDOMYOSARCOMA, ALVEOLAR), mainly in adolescents and young adults; embryonal (RHABDOMYOSARCOMA, EMBRYONAL), predominantly in infants and children; and botryoidal, also in young children. It is one of the most frequently occurring soft tissue sarcomas and the most common in children under 15. (From Dorland, 27th ed; Holland et al., Cancer Medicine, 3d ed, p2186; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, pp1647-9)Tumor Virus Infections: Infections produced by oncogenic viruses. The infections caused by DNA viruses are less numerous but more diverse than those caused by the RNA oncogenic viruses.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels.Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Keratins: A class of fibrous proteins or scleroproteins that represents the principal constituent of EPIDERMIS; HAIR; NAILS; horny tissues, and the organic matrix of tooth ENAMEL. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of TYPE I KERATIN and a TYPE II KERATIN, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. alpha-Keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to GENE DUPLICATION.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Drug Delivery Systems: Systems for the delivery of drugs to target sites of pharmacological actions. Technologies employed include those concerning drug preparation, route of administration, site targeting, metabolism, and toxicity.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Carcinoembryonic Antigen: A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment.Giant Cell Tumors: Tumors of bone tissue or synovial or other soft tissue characterized by the presence of giant cells. The most common are giant cell tumor of tendon sheath and GIANT CELL TUMOR OF BONE.Coculture Techniques: A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere.Radiopharmaceuticals: Compounds that are used in medicine as sources of radiation for radiotherapy and for diagnostic purposes. They have numerous uses in research and industry. (Martindale, The Extra Pharmacopoeia, 30th ed, p1161)Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques.Injections, Intralesional: Injections introduced directly into localized lesions.Giant Cell Tumor of Bone: A bone tumor composed of cellular spindle-cell stroma containing scattered multinucleated giant cells resembling osteoclasts. The tumors range from benign to frankly malignant lesions. The tumor occurs most frequently in an end of a long tubular bone in young adults. (From Dorland, 27th ed; Stedman, 25th ed)Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair, resulting in abnormal HEMIZYGOSITY. It is detected when heterozygous markers for a locus appear monomorphic because one of the ALLELES was deleted.Medulloblastoma: A malignant neoplasm that may be classified either as a glioma or as a primitive neuroectodermal tumor of childhood (see NEUROECTODERMAL TUMOR, PRIMITIVE). The tumor occurs most frequently in the first decade of life with the most typical location being the cerebellar vermis. Histologic features include a high degree of cellularity, frequent mitotic figures, and a tendency for the cells to organize into sheets or form rosettes. Medulloblastoma have a high propensity to spread throughout the craniospinal intradural axis. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2060-1)Necrosis: The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.Neuroectodermal Tumors: Malignant neoplasms arising in the neuroectoderm, the portion of the ectoderm of the early embryo that gives rise to the central and peripheral nervous systems, including some glial cells.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.Lymph Nodes: They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.DNA Methylation: Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.Apoptosis Regulatory Proteins: A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.Sensitivity and Specificity: 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)Spheroids, Cellular: Spherical, heterogeneous aggregates of proliferating, quiescent, and necrotic cells in culture that retain three-dimensional architecture and tissue-specific functions. The ability to form spheroids is a characteristic trait of CULTURED TUMOR CELLS derived from solid TUMORS. Cells from normal tissues can also form spheroids. They represent an in-vitro model for studies of the biology of both normal and malignant cells. (From Bjerkvig, Spheroid Culture in Cancer Research, 1992, p4)

Transformation mediated by RhoA requires activity of ROCK kinases. (1/52805)

BACKGROUND: The Ras-related GTPase RhoA controls signalling processes required for cytoskeletal reorganisation, transcriptional regulation, and transformation. The ability of RhoA mutants to transform cells correlates not with transcription but with their ability to bind ROCK-I, an effector kinase involved in cytoskeletal reorganisation. We used a recently developed specific ROCK inhibitor, Y-27632, and ROCK truncation mutants to investigate the role of ROCK kinases in transcriptional activation and transformation. RESULTS: In NIH3T3 cells, Y-27632 did not prevent the activation of serum response factor, transcription of c-fos or cell cycle re-entry following serum stimulation. Repeated treatment of NIH3T3 cells with Y-27632, however, substantially disrupted their actin fibre network but did not affect their growth rate. Y-27632 blocked focus formation by RhoA and its guanine-nucleotide exchange factors Dbl and mNET1. It did not affect the growth rate of cells transformed by Dbl and mNET1, but restored normal growth control at confluence and prevented their growth in soft agar. Y-27632 also significantly inhibited focus formation by Ras, but had no effect on the establishment or maintenance of transformation by Src. Furthermore, it significantly inhibited anchorage-independent growth of two out of four colorectal tumour cell lines. Consistent with these data, a truncated ROCK derivative exhibited weak ability to cooperate with activated Raf in focus formation assays. CONCLUSIONS: ROCK signalling is required for both the establishment and maintenance of transformation by constitutive activation of RhoA, and contributes to the Ras-transformed phenotype. These observations provide a potential explanation for the requirement for Rho in Ras-mediated transformation. Moreover, the inhibition of ROCK kinases may be of therapeutic use.  (+info)

Caspase-mediated cleavage of p21Waf1/Cip1 converts cancer cells from growth arrest to undergoing apoptosis. (2/52805)

The cyclin-dependent kinase inhibitor p21waf1/Cip1 is a downstream effector of the p53-dependent cell growth arrest. We report herein that p21 was cleaved by caspase-3/CPP32 at the site of DHVD112L during the DNA damage-induced apoptosis of cancer cells. The cleaved p21 fragment could no more arrest the cells in G1 phase nor suppress the cells undergoing apoptosis because it failed to bind to the proliferating cell nuclear antigen (PCNA) and lost its capability to localize in the nucleus. Thus, caspase-3-mediated cleavage and inactivation of p21 protein may convert cancer cells from growth arrest to undergoing apoptosis, leading to the acceleration of chemotherapy-induced apoptotic process in cancer cells.  (+info)

Decreased expression of the pro-apoptotic protein Par-4 in renal cell carcinoma. (3/52805)

Par-4 is a widely expressed leucine zipper protein that confers sensitization to apoptosis induced by exogenous insults. Because the expression of genes that promote apoptosis may be down-regulated during tumorigenesis, we sought to examine the expression of Par-4 in human tumors. We present here evidence that Par-4 protein levels were severely decreased in human renal cell carcinoma specimens relative to normal tubular cells. Replenishment of Par-4 protein levels in renal cell carcinoma cell lines conferred sensitivity to apoptosis. Because apoptosis may serve as a defense mechanism against malignant transformation or progression, decreased expression of Par-4 may contribute to the pathophysiology of renal cell carcinoma.  (+info)

Activation of Src in human breast tumor cell lines: elevated levels of phosphotyrosine phosphatase activity that preferentially recognizes the Src carboxy terminal negative regulatory tyrosine 530. (4/52805)

Elevated levels of Src kinase activity have been reported in a number of human cancers, including colon and breast cancer. We have analysed four human breast tumor cell lines that exhibit high levels of Src kinase activity, and have determined that these cell lines also exhibit a high level of a phosphotyrosine phosphatase activity that recognizes the Src carboxy-terminal P-Tyr530 negative regulatory site. Total Src kinase activity in these cell lines is elevated as much as 30-fold over activity in normal control cells and specific activity is elevated as much as 5.6-fold. When the breast tumor cells were grown in the presence of the tyrosine phosphatase inhibitor vanadate, Src kinase activity was reduced in all four breast tumor cell lines, suggesting that Src was being activated by a phosphatase which could recognize the Tyr530 negative regulatory site. In fractionated cell extracts from the breast tumor cells, we found elevated levels of a membrane associated tyrosine phosphatase activity that preferentially dephosphorylated a Src family carboxy-terminal phosphopeptide containing the regulatory tyrosine 530 site. Src was hypophosphorylated in vivo at tyrosine 530 in at least two of the tumor cell lines, further suggesting that Src was being activated by a phosphatase in these cells. In preliminary immunoprecipitation and antibody depletion experiments, we were unable to correlate the major portion of this phosphatase activity with several known phosphatases.  (+info)

Caspase 3 inactivation to suppress Fas-mediated apoptosis: identification of binding domain with p21 and ILP and inactivation machinery by p21. (5/52805)

The death mediator caspase acts as the dominant regulator during cell death induction. The CPP32 subfamily, including caspase 3 (CPP32/Yama/Apopain), is essential for the cell death signaling. We recently reported that activation of caspase 3 is regulated by complex formation with p21 or ILP. In the present study, we investigated the binding domain with p21 and ILP to further characterize the caspase 3 inactivation machinery. Our results show that caspase 3 contains p21 binding domain in the N-terminus and ILP binding domain in the active site. Further, the caspase 3 binding domain in p21 was independent of the Cdk- or PCNA-binding domain. We also found caspase 3 protection by p21 from the p3-site cleavage serineproteinase contributes to the suppression machinery. Here, we propose the caspase 3 inactivation system by p21 and ILP as new essential system in the regulation of cell death.  (+info)

Phenotypic analysis of human glioma cells expressing the MMAC1 tumor suppressor phosphatase. (6/52805)

MMAC1, also known as PTEN or TEP-1, was recently identified as a gene commonly mutated in a variety of human neoplasias. Sequence analysis revealed that MMAC1 harbored sequences similar to those found in several protein phosphatases. Subsequent studies demonstrated that MMAC1 possessed in vitro enzymatic activity similar to that exhibited by dual specificity phosphatases. To characterize the potential cellular functions of MMAC1, we expressed wild-type and several mutant variants of MMAC1 in the human glioma cell line, U373, that lacks endogenous expression. While expression of wild-type MMAC1 in these cells significantly reduced their growth rate and saturation density, expression of enzymatically inactive MMAC1 significantly enhanced growth in soft agar. Our observations indicate that while wild-type MMAC1 exhibits activities compatible with its proposed role as a tumor suppressor, cellular expression of MMAC1 containing mutations in the catalytic domain may yield protein products that enhance transformation characteristics.  (+info)

Detailed methylation analysis of the glutathione S-transferase pi (GSTP1) gene in prostate cancer. (7/52805)

Glutathione-S-Transferases (GSTs) comprise a family of isoenzymes that provide protection to mammalian cells against electrophilic metabolites of carcinogens and reactive oxygen species. Previous studies have shown that the CpG-rich promoter region of the pi-class gene GSTP1 is methylated at single restriction sites in the majority of prostate cancers. In order to understand the nature of abnormal methylation of the GSTP1 gene in prostate cancer we undertook a detailed analysis of methylation at 131 CpG sites spanning the promoter and body of the gene. Our results show that DNA methylation is not confined to specific CpG sites in the promoter region of the GSTP1 gene but is extensive throughout the CpG island in prostate cancer cells. Furthermore we found that both alleles are abnormally methylated in this region. In normal prostate tissue, the entire CpG island was unmethylated, but extensive methylation was found outside the island in the body of the gene. Loss of GSTP1 expression correlated with DNA methylation of the CpG island in both prostate cancer cell lines and cancer tissues whereas methylation outside the CpG island in normal prostate tissue appeared to have no effect on gene expression.  (+info)

Growth inhibition of breast cancer cells by Grb2 downregulation is correlated with inactivation of mitogen-activated protein kinase in EGFR, but not in ErbB2, cells. (8/52805)

Increased breast cancer growth has been associated with increased expression of epidermal growth factor receptor (EGFR) and ErbB2 receptor tyrosine kinases (RTKs). Upon activation, RTKs may transmit their oncogenic signals by binding to the growth factor receptor bound protein-2 (Grb2), which in turn binds to SOS and activates the Ras/Raf/MEK/mitogen-activated protein (MAP) kinase pathway. Grb2 is important for the transformation of fibroblasts by EGFR and ErbB2; however, whether Grb2 is also important for the proliferation of breast cancer cells expressing these RTKs is unclear. We have used liposomes to deliver nuclease-resistant antisense oligodeoxynucleotides (oligos) specific for the GRB2 mRNA to breast cancer cells. Grb2 protein downregulation could inhibit breast cancer cell growth; the degree of growth inhibition was dependent upon the activation and/or endogenous levels of the RTKs. Grb2 inhibition led to MAP kinase inactivation in EGFR, but not in ErbB2, breast cancer cells, suggesting that different pathways might be used by EGFR and ErbB2 to regulate breast cancer growth.  (+info)

  • Cells grown in vitro from neoplastic tissue. (nih.gov)
  • We have investigated eosinophils as potential anti-cancer effector cells, and have reported the ability of their toxic granular proteins (MBP, EPO, ECP, EDN) to inhibit prostate tumor cell growth in vitro . (scirp.org)
  • 14. The formulation of claim 13, wherein said dendritic cells are selected from the group consisting of cutaneous epidermal Langerhans cells, dermal dendritic cells, lymph node dendritic cells, spleen dendritic cells and dendritic cells derived through in vitro culture of precursors. (freepatentsonline.com)
  • Overexpression of ABCG2 in cancer cell lines in vitro has been shown to confer MDR to a variety of anticancer drugs including mitoxantrone, irinotecan, methotrexate, flavopiridol, and anthracyclines [ 1 ]. (hindawi.com)
  • In addition, treatment with IL-6 resulted in a reduction of monocyte in vitro cytotoxicity for tumor target cells. (jimmunol.org)
  • Malignant hematopoietic cell lines: in vitro models for double-hit B-cell lymphomas. (dsmz.de)
  • Drexler HG, Ehrentraut S, Nagel S, Eberth S, MacLeod R: Malignant hematopoietic cell lines: In vitro models for the study of primary mediastinal B-cell lymphomas. (dsmz.de)
  • As such, we sought to identify small-molecule inhibitors which sensitize tumor cells to glucose starvation by high-throughput drug screening in vitro. (mdpi.com)
  • The effectiveness of these derivatives in causing photo-killing of tumor cells in vitro, as determined by colony forming assay, correlated well with their singlet oxygen yields indicating that this is likely to be the main mechanism for the photocytotoxicity. (spie.org)
  • Tumor necrosis factor (TNF), a potent inflammatory mediator secreted by monocytes during inflammation, was shown to significantly increase the adherence of Staphylococcus aureus to cultured human umbilical vein endothelial cells in vitro. (asm.org)
  • Reproducible three-dimensional in vitro systems for exploring interactions of the stroma with pancreatic cancer cells have not previously been available, prompting us to develop such a model. (nih.gov)
  • In conclusion, pancreatic organotypic culture offers a reproducible, bio-mimetic, three-dimensional in vitro model that allows examination of the interactions between stromal elements and pancreatic cancer cells. (nih.gov)
  • ccRCC primary cultures are a reliable in vitro model, well-reproducing original tumor genetics and phenotype, potentially useful for future functional approaches aimed to study genes or pathways involved in ccRCC etiopathogenesis and to identify novel clinical markers or therapeutic targets. (biomedcentral.com)
  • DMP1 was isolated in a yeast two-hybrid interactive screen performed with cyclin D2 as bait, and the protein binds to any of the three D-type cyclins, but not to cyclins A, B, C, or H in vitro or when expressed with them in insect Sf9 or mammalian cells ( 26 , 27 ). (pnas.org)
  • In this study, we examined the effects of echinatin on growth, chemosensitivity, and metastatic potential of ESCC cells in vitro and in vivo. (nature.com)
  • To assess this effect of KLF5, we knocked down KLF5 in prostate cancer cells and found that KLF5 knockdown promoted invasive ability of prostate cancer cells in vitro and in vivo. (nature.com)
  • As linear correlations exist between expression levels of angiogenic factors under normoxic and hypoxic conditions in vitro , we propose that explanted primary cells may be used to probe the in vivo hypoxic environment. (biomedcentral.com)
  • In vitro studies have shown that stromal cells cultured in hypoxic growth conditions secrete higher levels of critical angiogenesis-inducing factors than cells cultured in normoxic conditions [ 3 ]. (biomedcentral.com)
  • found hypoxia induced a 13-fold increase in the number of KDR receptors per endothelial cell in vitro , which may be the mechanism of action for the pronounced effect of hypoxia and VEGF in vivo [ 12 ]. (biomedcentral.com)
  • In vitro sensitization (IVS) and expansion assays of PBMC demonstrated that immunization with the modified peptide was superior to the parental (pa) g209-217 peptide in the induction of CTL reactivity against the 209-pa epitope and HLA-A2 + melanoma cells. (jimmunol.org)
  • Interestingly, 209-2M immunization combined with the systemic administration of high dose bolus IL-2 resulted in clinical tumor regression in 13 of 31 patients (42%), but only 3 of 19 (16%) patients demonstrated peripheral blood reactivity in the in vitro sensitization assay. (jimmunol.org)
  • In an attempt to reconcile the dichotomy observed between in vitro generated PBMC reactivity and in vivo tumor regression, we developed a sensitive molecular assay to directly detect specific low precursor CTL reactivity in bulk PBMC and in the local tumor microenvironment. (jimmunol.org)
  • In previous studies involving the immunization of cancer patients, monitoring of immune reactivity has involved single or multiple in vitro restimulation of PBMC to generate cultures with detectable reactivity ( 5 , 6 ). (jimmunol.org)
  • This study indicates that inhibitors influence lymphocyte blastogenic responses to tumor cells in vitro and suggests that such factors may influence host response to tumors. (elsevier.com)
  • After culture in the presence of IL-2, NKT cells can mediate lysis through TCR, NK1.1, or CD16, and kill classical NK-sensitive targets such as YAC-1 in vitro ( 23 )( 24 ). (rupress.org)
  • 9,10 Previous in vitro evidence showed that carvedilol, as an oxidant scavenger, could inhibit cardiomyocyte membrane lipid peroxidation and protect cells from oxidant injury. (ahajournals.org)
  • 9,12 Recently, carvedilol was shown to reduce low-density lipoprotein oxidation in vitro 13,14 and inhibit smooth muscle cell migration, proliferation, or neointimal formation after vascular injury in vivo. (ahajournals.org)
  • We then tested the hypothesis that carvedilol may reduce tumor necrosis factor-α (TNF-α)-induced intracellular ROS production, redox-sensitive transcription pathway activation, and adhesion molecules expression, resulting in the inhibition of endothelial adhesiveness to human MNCs in vitro-an early sign of atherogenesis. (ahajournals.org)
  • The suitability of in vitro bladder tumor culture models to study complex biological phenomena such as malignancy and invasion is discussed. (nih.gov)
  • We also confirmed that miR-17 exerted this function by directly targeting RND3 in vitro , and that the expression of miR-17 was negatively correlated with that of RND3 in CRC tissues and CRC cells. (portlandpress.com)
  • Further in vitro migration assays were performed to confirm cancer cells conditioned medium dependent MSC and doxorubicin (DOX) treated MSC migration. (medsci.org)
  • MSCs were loaded with DOX, and their therapeutic effects against the cancer cells were studied in vitro . (medsci.org)
  • ectopic S1PR2 expression induces apoptosis in DLBCL cells in vitro and prevents tumor growth. (bloodjournal.org)
  • We found that in vitro Notch pathway blockade in glioblastoma (GBM) cells using a gammasecretase inhibitor (GSI) led to increased activity in two other pathways important for neural development-Wnt and Hedgehog. (aacrjournals.org)
  • Inhibition of both Notch and Hedgehog in vitro dramatically decreased the growth of GBM cell lines and low-passage neurospheres derived from primary human tumors. (aacrjournals.org)
  • In the present study, tumour cell lines: A549 (lung), HCT116 (colon) and MCF-7 (breast), were treated with various concentrations of the chemotherapeutic drugs cyclophosphamide, gemcitabine (GEM) and oxaliplatin (OXP) for 24 hours in vitro. (sgul.ac.uk)
  • In vitro drug assays testing doxorubicin and selumetinib assessed drug penetration and toxicity after 48 hours using imaging and the CellTiter-Glo 3D Cell Viability Assay. (arvojournals.org)
  • In vitro drug assays showed varying penetrations into UM cell line spheroids, with doxorubicin passing into the spheroid core and selumetinib having an effect largely on peripheral cells. (arvojournals.org)
  • The increasing use of three-dimensional (3D) in vitro cell cultures in cancer is contributing to the development of more physiologically relevant models of tumor biology than standard two-dimensional (2D) cultures. (arvojournals.org)
  • This finding was also confirmed in vitro as PC3 PCa cells express Robo 4 on mRNA as well as protein level. (medsci.org)
  • tumour hypoxia induces metastasis-associated genes. (nih.gov)
  • Poly-α2,8-sialic acid (PSA) has been implicated in numerous normal and pathological processes, including development, neuronal plasticity, and tumor metastasis. (sciencemag.org)
  • Taken together, our results indicate that KLF5 could be an important suppressor of prostate cancer invasion and metastasis, because KLF5 could suppress the transcription of IGF1, a tumor cell autocrine cytokine, and its downstream cell signaling to inhibit cell invasive ability, and reveal a novel mechanism for STAT3 activation in prostate cancer. (nature.com)
  • Although a majority of patients with localized tumor responds to the initial treatment, nearly 20-30% of treated patients inevitably progress to castration-resistant PCa followed by cancer metastasis 2 , leading to poor prognosis and mortality 3 . (nature.com)
  • Most PCa metastases were positive for p-STAT3 staining and STAT3 inhibitor galiellalactone effectively decreased metastatic tumor spread in a mouse model of PCa 15 , indicating that STAT3 activation may be a crucial promotor in PCa invasion and metastasis. (nature.com)
  • Gene-targeted and lymphocyte subset-depleted mice were used to establish the relative importance of natural killer (NK) and NK1.1 + T (NKT) cells in protection from tumor initiation and metastasis. (rupress.org)
  • In the models examined, CD3 − NK cells were responsible for tumor rejection and protection from metastasis in models where control of major histocompatibility complex class I-deficient tumors was independent of IL-12. (rupress.org)
  • Although it is likely that endogenously produced IL-12 may also stimulate NKT cells to produce IFN-γ and activate NKT cell cytolytic function, no study to date has evaluated the natural ability (i.e., not exogenously activated by IL-12 or α-GalCer) of NKT cells to reject tumor growth or metastasis. (rupress.org)
  • Both the positivity rate and the number of CTCs were significantly correlated with tumor size, portal vein tumor thrombus, differentiation status, and the disease extent as classified by the TNM (tumor-node-metastasis) classification and the Milan criteria. (aacrjournals.org)
  • Hepatocyte growth factor (HGF) is found in tumor microenvironments, and interaction with its tyrosine kinase receptor Met triggers cell invasion and metastasis. (biologists.org)
  • Treated prostate tumor cell lines trended toward apoptosis-induction, as evident in bcl-xl/bax ratios (scirp.org)
  • Figure 2: Induction of apoptosis in diffuse large B-cell lymphoma cell line U-2932 by etoposide treatment. (dsmz.de)
  • Western blot analysis was performed to study Boswellia sacra essential oil-regulated proteins involved in apoptosis, signaling pathways, and cell cycle regulation. (biomedcentral.com)
  • Boswellia sacra essential oil hydrodistilled at 100 o C was more potent than the essential oil prepared at 78 o C in inducing cancer cell death, preventing the cellular network formation (MDA-MB-231) cells on Matrigel, causing the breakdown of multicellular tumor spheroids (T47D cells), and regulating molecules involved in apoptosis, signal transduction, and cell cycle progression. (biomedcentral.com)
  • The number of colonies in the clonogenic assay, the foci formation of RAD51 and γH2AX, and the induction of apoptosis were not affected by PTEN introduction in the HEC-6 PTEN + cells. (biomedcentral.com)
  • Unlike genes such as Myc , adenovirus E1A , and E2F-1, which, when overexpressed, activate the ARF-p53 pathway and trigger apoptosis, DMP1, like ARF itself, does not induce programmed cell death. (pnas.org)
  • Therefore, apart from its recently recognized role in protecting cells from potentially oncogenic signals, ARF can be induced in response to antiproliferative stimuli that do not obligatorily lead to apoptosis. (pnas.org)
  • In its role as a transcription factor, it activates a series of genes that can restrict cell cycle progression and trigger apoptosis. (pnas.org)
  • It encodes two distinct tumor suppressor proteins: p16 INK4a , which inhibits the phosphorylation of the retinoblastoma protein by cyclin D-dependent kinases ( 13 ), and p19 ARF ( 14 ), which stabilizes and activates p53 to promote either cell cycle arrest or apoptosis (reviewed in ref. 15 ). (pnas.org)
  • Confocal fluorescence microscopy data showed that echinatin significantly induced autophagy in ESCC cells, and autophagy inhibitor bafilomycinA1 attenuated the suppressive effects of echinatin on cell viability and apoptosis. (nature.com)
  • 11. The isolated stem cell of claim 8, wherein said polypeptide is tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). (freepatentsonline.com)
  • Down regulation of c-FLIP L could increase the tumor apoptosis and enhance the antitumor response of T cells in the lymphocyte tumor cells co-culture system. (frontiersin.org)
  • As a result, activated tumor-infiltrating lymphocytes can induce apoptosis of tumor cells ( 8 ). (frontiersin.org)
  • Increased expression of c-FLIP can block the expression of Caspase-8, thus making cells resistant to receptor-mediated apoptosis ( 10 ). (frontiersin.org)
  • Ectopic expression of wild-type S1PR2, but not a point mutant incapable of activating downstream signaling pathways, induces apoptosis in DLBCL cells and restricts tumor growth in subcutaneous and orthotopic models of the disease. (bloodjournal.org)
  • Targeting Notch and Hedgehog simultaneously induced apoptosis, decreased cell growth, and inhibited colony-forming ability more dramatically than monotherapy. (aacrjournals.org)
  • Cell viability, apoptosis, and related factors were determined using cell counting kit-8 (CCK-8), Annexin-V/PI (propidium) assay, enzyme-linked immunosorbnent assay (ELISA), RT-qPCR, and Western blot assays after miR-218 mimics has been transfected to HeLa cervical cancer cells. (springer.com)
  • MiR-218 overexpression was found to inhibit cell viability and promoted apoptosis via activating the expression of Cleaved-Caspase-3 and to inhibit the expression of Survivin, immune factors (TGF-β, VEGF, IL-6, PGE2, COX-2), and JAK2/STAT3 pathway. (springer.com)
  • The p53 tumor suppressor can restrict malignant transformation by triggering cell-autonomous programs of cell cycle arrest or apoptosis. (pubmedcentralcanada.ca)
  • Cis -diamminedichloroplatinum(II) (cisplatin)-induced renal proximal tubular apoptosis is known to be preceded by actin cytoskeleton reorganization, in conjunction with disruption of cell-matrix and cell-cell adhesion. (aspetjournals.org)
  • In the present study, we show that the proinflammatory cytokine tumor necrosis factor α (TNF- α ) aggravated these cisplatin-induced F-actin and cell adhesion changes, which was associated with enhanced cisplatin-induced apoptosis of immortalized proximal tubular epithelial cells. (aspetjournals.org)
  • Pharmacological inhibition of Rho kinase signaling re-established the synergistic apoptosis induced by combined cisplatin/TNF- α treatment of shRelB cells. (aspetjournals.org)
  • In conclusion, our study shows for the first time that RelB is required for the cisplatin/TNF- α -induced cytoskeletal reorganization and apoptosis in renal cells by controlling a Rho kinase-dependent signaling network. (aspetjournals.org)
  • Once delivered, granzymes are able to induce apoptosis and cause target cell death. (wikipedia.org)
  • Working with human prostate cancer cells in tissue culture, Hughes-Fulford and her fellow researchers identified for the first time a direct chain of causation: When introduced into prostate tumor cells in culture, omega-6 fatty acid causes the production of cPLA2, which then causes the production of the enzyme COX2. (ucsf.edu)
  • Oxygen status and tissue dimensionality are critical determinants of tumor angiogenesis, a hallmark of cancer and an enduring target for therapeutic intervention. (sigmaaldrich.com)
  • The production of vascular endothelial growth factor (VEGF) and other hypoxia-induced angiogenic cytokines to promote increase tissue vascularization, and the metabolic switch from oxidative to glycolytic metabolism represent the two major adaptive responses to enhance cell survival under tumor hypoxic condition. (hindawi.com)
  • Lung colony formation by elutriated B16a cells (i.e., cells freshly isolated from tumor tissue) was consistently inhibited by CGS14854, whereas inhibition of lung colony formation by cultured B16a cells was dependent upon culture conditions. (rti.org)
  • Objective: To collect high quality, representative tissue material from tumors and manage its distribution to different laboratories. (scirp.org)
  • To improve this complex procedure, we developed a workflow allowing for rapid and flexible tissue preparation for subsequent derivation of primary tumor cell cultures using our novel Pancreas TumorMACS™ Medium. (miltenyibiotec.com)
  • The gentleMACS™ Dissociator in combination with the Tumor Dissociation Kit, human ensures rapid and standardized dissociation of tissue samples into single-cell suspensions. (miltenyibiotec.com)
  • Single-cell suspensions from human melanoma tissue were prepared using the Tumor Dissociation Kit in combination with the gentleMACS™ Dissociator. (miltenyibiotec.com)
  • Finally, viability amounted to 86% at a yield of 5.8×10⁷ cells per gram of tissue. (miltenyibiotec.com)
  • Get more information on storage and dissociation of tumor tissue here. (miltenyibiotec.com)
  • The method gently arranges cells in a suspension into a single aggregate in each well of the microplate and, by this, nucleates 3D tissue-like cell growth for culture times between two and seven days. (diva-portal.org)
  • The ultrasound-based method itself is generic and can meet any demand from applications where it is advantageous to monitor cell culture from production to analysis of 3D tissue or tumor models using microscopy in one single microplate device. (diva-portal.org)
  • Global concordance for each culture/tissue pair was assayed evaluating the correlations between whole-genome CN profiles and SNP allelic calls. (biomedcentral.com)
  • A very good overlap between the CNAs of each culture and corresponding tissue was observed. (biomedcentral.com)
  • The finding, reinforced by high whole-genome CN correlations and SNP call concordances, provided evidence that each culture was derived from its corresponding tissue and maintained the genomic alterations of parental tumor. (biomedcentral.com)
  • These cells have been confirmed as maintaining the characteristics of the original tumor tissue through genomic, gene expression, and histological analyses. (essenbioscience.com)
  • Intriguingly, miRNA expression profiling has shown that miRNAs are globally down-regulated in tumors relative to normal tissue ( 10 ). (pnas.org)
  • Tissue microarray analysis with 91 HGG tumors demonstrates that the proportion of MELK (+) cells is a statistically significant indicator of postsurgical survival periods. (wiley.com)
  • As a tumor grows, the existing blood supply becomes inefficient at supporting the tissue, and areas of the tumor become hypoxic. (biomedcentral.com)
  • Methods Primary cultures were established from human breast tumour and adjacent non-tumour tissue. (lenus.ie)
  • The Vitamin D receptor (VDR) expressed in normal breast tissue and breast tumors has been suggested as a new prognostic biomarker in breast cancer (BC). (mdpi.com)
  • As one of the nuclear receptor (NR) members, VDR is found in both normal breast tissue and breast tumors [ 9 , 10 ]. (mdpi.com)
  • ATCC has designed tumor cell panels based on the tissue of tumor origin, each annotated with details regarding known mutations - enabling more intelligent choices when selecting cell-based research models. (atcc.org)
  • Here, we reported that the expression of TET1 in glioma tissue was significantly lower than the corresponding non-tumour normal tissues, and the concentration of TET1 is negatively correlated with the glioma WHO classification. (portlandpress.com)
  • Elevated glutathione (GSH) levels have been detected in many tumors compared with the healthy, surrounding tissue. (aspetjournals.org)
  • Because quantitative and/or qualitative biochemical differences exist between tumors and the healthy surrounding tissue, it may be possible to selectively deliver drugs to the tumor by designing prodrugs that are metabolized more rapidly or in greater quantities in the tumor than in the surrounding tissue ( Dubowchik and Walker, 1999 ). (aspetjournals.org)
  • Recent evidence has assigned distinct features and functions to tissue-specific NK cells ( 2 ). (aacrjournals.org)
  • To put cells into culture, the tissue of interest is exposed to enzymes that dissociate the tissue to release the component cells. (encyclopedia.com)
  • The general process of cell culture has been used extensively since the early 1900s for research on tissue growth and development, virus biology, properties of cancer cells, studies relating to aging, genetics, and gene therapy. (encyclopedia.com)
  • British biologist who developed ways to grow cells outside the body ("tissue culture") in order to more closely study the cells and the effects of hormones, vitamins, and other chemicals. (encyclopedia.com)
  • In the 1960s, biologists found that normal human fibroblasts, cells derived from connective tissue , had a predictable limit in their ability to proliferate in culture. (encyclopedia.com)
  • RESULTS: We found that the expression of both connective tissue growth factor (CTGF/CCN2) and type I collagen was negatively regulated in CCD-1068SK fibroblast cells under direct co-culture conditions. (uct.ac.za)
  • In this tissue, tumor initiation is often preceded by hepatic fibrosis resulting from liver damage produced by chronic hepatitis, alcohol or chemical insults. (pubmedcentralcanada.ca)
  • The EGFR is also frequently overexpressed in human colorectal tumors when compared with normal intestinal tissue, and this is associated with increased metastatic potential and poor prognosis [ 5-7 ]. (pubmedcentralcanada.ca)
  • ATCC tumor cell panels group authenticated, reliable tumor cell lines according to tissue type or gene mutation to generate powerful platforms for cancer research. (atcc.org)
  • Metastatic HNSCC cells lines were found to have vasculogenic properties similar to HUVEC cell lines when compared to cell lines from their corresponding primary tumour. (biomedsearch.com)
  • The present study was undertaken to investigate the factors involved in determining the metastatic potential of cultured cells derived from solid tumors. (rti.org)
  • Metastatic Merkel Cell carcinoma (MCC) is a highly unusual and aggressive skin cancer that presents as a small, pink to violet skin lesion and metastasizes early in its growth. (scirp.org)
  • Metastatic MCC is generally treated with small cell lung cancer chemotherapy regimens, because the tumor consists of neuroendocrine cells, but patients generally do not have durable responses. (scirp.org)
  • Although this adoptive cell therapy (ACT) has been shown capable of mediating objective clinical responses in patients with metastatic melanoma, including patients who have previously been treated with aldesleukin or chemotherapy, the treatment is only available in the Surgery Branch, National Cancer Institute (NCI) and in just one or two other institutions in the United States. (knowcancer.com)
  • 1. Measurable metastatic melanoma with at least one lesion that is resectable for tumor infiltrating lymphocytes (TIL) generation. (knowcancer.com)
  • The cloning of cancer Ags recognized by T cells has provided potentially new tools to enhance immunity against metastatic cancer. (jimmunol.org)
  • The results of these molecular assays provide direct evidence that peptide immunization in humans can result in tumor-specific CTL that localize to metastatic sites. (jimmunol.org)
  • The existence of systemic and local CTL that recognize tumor Ags provides strong evidence that natural immune response can exist against metastatic cancer in humans. (jimmunol.org)
  • The ease by which melanoma-specific tumor-infiltrating lymphocytes can be isolated from metastatic deposits illustrates this awareness by the immune system ( 1 ). (jimmunol.org)
  • Besides, increasing evidence supports the view that the detection of circulating tumor cells (CTCs) predicts outcome in early and metastatic BC. (mdpi.com)
  • As an attempt to profile and subtype the CTCs of metastatic patients, we established an innovative fluorescence technique using nine BC cell lines to visualize, define, and compare their individual VDR status. (mdpi.com)
  • It is generally accepted that the host immune status, particularly natural immune responses, is essential in controlling the dissemination and growth of metastatic tumors. (rupress.org)
  • The question of how this molecule is regulated in invasive and metastatic processes of breast cancer cells is addressed in the present study. (rupress.org)
  • The development of metastatic foci, resulting from an invasive primary tumor, is the leading cause of cancer-associated deaths. (biologists.org)
  • 2016). While organ confined PCa is mostly cured by local therapies like radical prostatectomy (RPE), radiation therapy (plus anti-androgenic therapy in intermediate and high risk cancers) or focal therapy about 30% of prostate tumors are diagnosed in a locally advanced or primary metastatic stage. (medsci.org)
  • Prolonged culture resulted in a 10-fold decrease in the incidence of B16a lung colonies, whereas passage in vivo for 150 days did not affect lung colony formation by tumor cells isolated from enzymatic dispersates by centrifugal elutriation. (rti.org)
  • The results were validated and confirmed in vivo, with QNZ and papaverine exhibiting superior antitumor activity in a tumor xenograft model when combined with the VEGF inhibitor bevacizumab (avastin). (mdpi.com)
  • These results demonstrated that TEC maintain distinct biological differences from NEC as observed in tumor blood vessels in vivo. (plos.org)
  • Thus, elevated expression of c-FLIP is associated with tumor cells escaping from immune surveillance in vivo , correlates with a more aggressive tumor, and is also considered to be the main cause of immune escape ( 11 ). (frontiersin.org)
  • NK cells mediate spontaneous cytotoxicity against MHC class I-deficient tumor cells and their metastases ( 1 ), and they have long been known to participate in the innate immune response against transformed cells in vivo ( 1 )( 2 ). (rupress.org)
  • The in vivo antitumor activity of α-GalCer strongly resembles the antitumor activity mediated by IL-12 ( 9 )( 32 ), and indeed α-GalCer mediates its effects by inducing IL-12 production by dendritic cells (DCs) and IL-12 receptor and IFN-γ expression by NKT cells ( 33 ). (rupress.org)
  • A nticancer drug efficacy has been tested on circulating tumor cells ( CTC s) derived from patient blood samples after ex vivo expansion into CTC clusters. (nus.edu.sg)
  • In this study, we confirmed the migration of MSCs to tumor sites in cancer xenograft models using both in vivo and ex vivo BLI imaging. (medsci.org)
  • Tumor cells were shown to specifically denude the venules both in culture and in vivo, explaining the VSMC phenotype in the stroma. (jci.org)
  • IL-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice. (jimmunol.org)
  • This was followed by repeated selection for increasingly aggressive tumor formation from cells recovered from xenograft tumors in immuno-compromised mice, generating the MCF-10CA1a cell line. (biomedsearch.com)
  • When inoculated subcutaneously into the flanks of immuno-compromised mice, MCF-10AT cells occasionally form tumors, whereas MCF-10CA1a cells invariably form tumors with a shorter latency than MCF-10AT derived tumors. (biomedsearch.com)
  • At the same time, we examined xenografts of ACC2 in SCID mice and compared the nature of pseudocystic spaces formed in the transplants with that in the collagen gel cultures. (nii.ac.jp)
  • Transplants of ACC2 cells in SCID mice grew to form tumor messes in which pseudocysts were formed. (nii.ac.jp)
  • Publications] Munakata, R.: 'Pseudocyst tormation by adenoid cystic carcinoma cells collagen gel culture and in SCID mice' J Oral Pathol Med. (nii.ac.jp)
  • In B16F10-bearing C57BL/6 mice model, we found that murine IL-15 has antitumoral effect since the activation and expansion of CD8+ T cells with murine IL-15 treatment. (frontiersin.org)
  • But no enhanced or reduced tumor growth was observed in mice when human IL-15 was used. (frontiersin.org)
  • In particular, T cell receptor Jα281 gene-targeted mice confirmed a critical function for NKT cells in protection from spontaneous tumors initiated by the chemical carcinogen, methylcholanthrene. (rupress.org)
  • However, only a few studies have reported a prominent role for NK cells on the growth of primary tumors in mice without using biological response modifiers to magnify the response ( 2 )( 3 ). (rupress.org)
  • Transfer of purified polyclonal T cells from FBL (Friend MuLV-induced erythroleukemia cell line) vaccinated mice in naive animals can protect these mice against subsequent tumor challenge. (rupress.org)
  • FBL cells do not express MHC class II molecules, but CD4 + T cells can protect mice even in the absence of CD8 + T cells. (rupress.org)
  • These mice were rendered tolerant for env-specific Th responses and it was not possible to protect these mice against FBL tumors by vaccination. (rupress.org)
  • In addition, proteasome inhibitors have been shown to suppress human tumor growth in nude mice. (aacrjournals.org)
  • We show that STAT5 normally represses the transcription of VEGFA in NK cells, in both mice and humans. (aacrjournals.org)
  • When R26PR is mated to either of two Cre lines, Mx1-cre or MMTV-cre, mice develop early-onset T-cell acute lymphoblastic leukemia (T-ALL) with median overall survival of 41 and 64 days for R26PR;Mx1-cre and R26PR;MMTV-cre, respectively. (biologists.org)
  • The study also identifies a potential new molecular target for anti-tumor drugs: an enzyme known as cPLA2, which plays a key role in the chain leading from omega-6 fatty acids to prostate tumor cell growth. (ucsf.edu)
  • Prospective Randomized Comparative Study of Cell Transfer Therapy Using CD8+-Enriched Short-Term Cultured Anti-Tumor Autologous Lymphocytes Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen Compared to High-Dose Aldesleukin in M. (knowcancer.com)
  • We examined the anti-tumor activity of olaparib, a PARP inhibitor, and its correlation between the sensitivity and status of PTEN in endometrial cancer cell lines. (biomedcentral.com)
  • These cells become immunogenic, lose their tumorigenicity, and even induce protection against wild-type MHC class II negative tumors, indicating that direct MHC class II presentation of tumor expressed antigens can induce efficient anti-tumor responses. (rupress.org)
  • However, it is unclear how these microenvironmental conditions interact to promote neovascularization, due in part to a lack of comprehensive, unbiased data sets describing tumor cell gene expression as a function of oxygen levels within three-dimensional (3D) culture. (sigmaaldrich.com)
  • Microarray gene expression analysis of tumor cells cultured in 2D versus 3D under ambient or hypoxic conditions revealed striking interdependence between culture dimensionality and hypoxia response, which was mediated in part by pro-inflammatory signaling pathways. (sigmaaldrich.com)
  • Hypoxia induced ATF4 and the HIF1alpha target gene apelin in CTCs, but not in parental cells. (nih.gov)
  • D) Expression of ATF4 and its target gene ASNS in CTCs, compared with parental MDA-MB-231 cells. (nih.gov)
  • ABCG2 promoter luciferase reporter gene assay showing that the promoter region harboring the HIF-1α response element is required for the activation of ABCG2 in HCT‐116 human colon cancer cell line. (hindawi.com)
  • Vlad-Fiegen A, Freytag NV, Dorn S, Müller O, Eberth S. The Wnt pathway target gene CCND1 changes mitochondrial localization and decreases mitochondrial activity in colorectal cancer cell line SW480. (dsmz.de)
  • Cell lysis for Real Time PCR and quantification of gene expression of CX 43, 32 and E-cadherin in canine mast cells. (scirp.org)
  • For gene expression quantification of CX 43, 32 and E-cadherin in canine mast cell tumors (MCT), 95.5% of samples were considered to be of good quality. (scirp.org)
  • DMP1 binds to a single canonical recognition site in the ARF promoter to activate gene expression, and in turn, p19 ARF synthesis causes p53-dependent cell cycle arrest. (pnas.org)
  • The singularly most frequently disrupted gene in cancer is p53, whose loss of function occurs in more than half of human tumors ( 1 ). (pnas.org)
  • Using serial gene expression analysis, we report functional evidence of vaccine-induced CTL reactivity in fresh cells obtained directly from the peripheral blood of postimmunized patients. (jimmunol.org)
  • In this study, using molecular gene quantitation techniques, we report evidence of specific CTL reactivity in fresh cells obtained directly from the peripheral blood of patients immunized with the 209-2M peptide. (jimmunol.org)
  • The present invention relates to tumor tropic stem cells, and particularly to neural stem cells, and their use as delivery vehicles for therapeutic gene products to neoplastic foci. (freepatentsonline.com)
  • 5. The isolated stem cell of claim 1, wherein said isolated stem cell comprises a heterologous gene. (freepatentsonline.com)
  • 6. The isolated stem cell of claim 5, wherein said heterologous gene encodes a polypeptide of therapeutic use in the treatment of a disease condition. (freepatentsonline.com)
  • ATCC has created gene mutation lists based on the ATCC tumor cell line collection and known mutation information maintained in the Sanger Institute COSMIC database. (atcc.org)
  • We have combined chromatin immunoprecipitation and gene expression profiling after FOXP1 depletion with functional screening to identify targets of FOXP1 contributing to tumor cell survival. (bloodjournal.org)
  • Most colorectal tumors are initiated by inactivating mutations in the tumor suppressor gene APC [ 2 ]. (pubmedcentralcanada.ca)
  • The presence of activating mutations in the KRAS gene in these tumors is a reliable predictor of tumor resistance to anti-EGFR therapy [ 13,14 ]. (pubmedcentralcanada.ca)
  • This gene is located within chromosome 9 (9q32-33), a chromosomal region that frequently shows loss of heterozygosity in transitional cell carcinoma of the bladder. (wikipedia.org)
  • Nonetheless, it is suspected to act as a tumor suppressor gene. (wikipedia.org)
  • It is also believed to be a survival factor for cancer stem cells to drive tumor growth. (hindawi.com)
  • It may also contribute to the maintenance of stem or progenitor cells as a survival factor, ultimately driving tumor growth [ 4 ]. (hindawi.com)
  • Accordingly, tumor cells depend on cellular pathways promoting survival under such conditions. (mdpi.com)
  • Following failure of initial chemotherapy and radiation, effective palliation was achieved by using a sequence of electron-beam radiotherapy, low dose gemcitabine, and etoposide, resulting in significant periods of tumor regression and prolonged survival. (scirp.org)
  • Despite our reports of the objective regressions in patients receiving adoptive cell therapy (ACT), doubts have been raised concerning the possible influence of patient selection bias that may have accounted for the increase in survival using ACT compared to historical controls. (knowcancer.com)
  • The response to olaparib was evaluated using a clonogenic assay with SF50 values (concentration to inhibit cell survival to 50%) in 16 endometrial cancer cell lines. (biomedcentral.com)
  • The combined treatment reduced the survival of the resistant cells but in the gefitinib sensitive cells, the combined treatment increased survival, which was highly unexpected. (eurekaselect.com)
  • A limited number of astatine decays per cell gave low survival, which was expected. (eurekaselect.com)
  • In recent years, an increasing number of clinical studies have suggested that an optimal vitamin D status has a protective effect against BC development and that high Vitamin D receptor (VDR) expression in breast tumors is associated with a better survival rate [ 5 , 6 , 7 , 8 ]. (mdpi.com)
  • Interleukin 15 (IL-15) regulates the development, survival, and functions of multiple innate and adaptive immune cells and plays a dual role in promoting both tumor cell growth and antitumor immunity. (frontiersin.org)
  • We found that in chronic lymphocytic leukemia (CLL), HIF-1α is a novel regulator of the interaction of CLL cells with protective leukemia microenvironments and, in turn, is regulated by this interaction in a positive feedback loop that promotes leukemia survival and propagation. (bloodjournal.org)
  • The sphingosine-1-phosphate receptor 2 (S1PR2) is a novel tumor suppressor and survival prognosticator in the ABC subtype of DLBCL. (bloodjournal.org)
  • The forkhead box protein 1 (FOXP1) transcription factor is aberrantly expressed in the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) and represents a widely accepted biomarker for survival prognostication in DLBCL. (bloodjournal.org)
  • These findings demonstrate that Notch-targeted therapeutics can lead to alterations in other developmental signaling cascades that promote tumor survival, and suggest that combined treatment with Hedgehog pathway inhibitors may be able to increase the efficacy of GSIs in some cancer patients. (aacrjournals.org)
  • The antioxidant compound N -acetylcysteine blocked the curcumin-induced increased reactive oxygen species (ROS), sustained activation of ERK1/2, and decreased survival after IR in HeLa cells, implicating a ROS-dependent mechanism for curcumin radiosensitivity. (aspetjournals.org)
  • In this study, possible correlations of these properties to the uptake, retention and photosensitization activity of these oxazines were examined in a human bladder tumor cell line (MGH. (spie.org)
  • Researchers based at the Massachusetts General Hospital (MGH) Center for Engineering in Medicine and the MGH Cancer Center have created a microchip device, called the CTC-iChip, which can capture circulating tumor cells in order to track ongoing genetic mutation within a tumor. (oncologynurseadvisor.com)
  • Circulating tumor cells captured with a microchip-based device developed at the Massachusetts General Hospital (MGH) Center for Engineering in Medicine and the MGH Cancer Center can be cultured to establish cell lines for genetic analysis and drug testing. (oncologynurseadvisor.com)
  • To establish a sensitive and specific isolation and enumeration system for circulating tumor cells (CTC) in patients with hepatocellular carcinoma (HCC). (aacrjournals.org)
  • Detection of circulating tumor cells (CTC) has considerable clinical significance in predicting recurrence and monitoring treatment response in patients with hepatocellular carcinoma (HCC). (aacrjournals.org)
  • As hematogenous spread is the major route of HCC recurrence ( 5 ), detection of circulating tumor cells (CTC) undoubtedly has important clinical significance in predicting recurrence and monitoring therapeutic efficiency in HCC patients. (aacrjournals.org)
  • To better understand the interaction of HSV-1 with neoplastic cells, we inoculated three-dimensional (3D) cultures of human uveal melanoma cells with HSV-1. (asm.org)
  • Furthermore, our findings raise the possibility that HSV-1 infection of neoplastic cells during natural infections or vaccinations may promote the growth of tumors. (asm.org)
  • Similar to our previous observations in human bladder cancer cells, Boswellia sacra essential oil induces breast cancer cell-specific cytotoxicity. (biomedcentral.com)
  • Poly (ADP-ribose) polymerase (PARP) plays key roles in the repair of DNA single-strand breaks, and a PARP inhibitor induces synthetic lethality in cancer cells with HR deficiency. (biomedcentral.com)
  • Pro-oxidant treatment of human prostate carcinoma (DU145) induces autoschizis cell death: autophagosomes build up out of injured endomembranes and mitochondria. (semanticscholar.org)
  • RESULTS: There were observable differences in growth of the cells on laboratory plastic and collagen matrix. (biomedsearch.com)
  • The endothelial growth factor antibodies used did not inhibit or stimulate cell growth when compared to control but did discourage vascular mimicry. (biomedsearch.com)
  • A study conducted at the San Francisco VA Medical Center (SFVAMC) has demonstrated that omega-6 fatty acids such as the fat found in corn oil promote the growth of prostate tumor cells in the laboratory. (ucsf.edu)
  • The study was led by Millie Hughes-Fulford, PhD, director of the Laboratory of Cell Growth at SFVAMC and scientific advisor to the U.S. Undersecretary of Health for the Department of Veterans Affairs. (ucsf.edu)
  • In turn, COX2 stimulates the release of PGE2, a hormone-like molecule that promotes cell growth. (ucsf.edu)
  • Hughes-Fulford also found that flurbiprofen, a non-steroidal anti-inflammatory drug commonly prescribed for arthritis, blocked the production of cPLA2 and broke the chain leading to cell growth. (ucsf.edu)
  • COX2 has been implicated in the growth of many types of tumors," she notes. (ucsf.edu)
  • So if you can find a way to block that cascade in the tumor, starting with cPLA2, you might have a new way of modifying or slowing tumor growth. (ucsf.edu)
  • These drugs have been shown to be effective against tumor growth as well as in treating the pain associated with inflammatory conditions such as arthritis, but have been implicated in increased risk of cardiovascular problems in people who take them regularly. (ucsf.edu)
  • Hypoxia was further demonstrated to cause a more malignant anchorage-independent growth phenotype in the resistant cells, which can be abolished by knocking down ABCG2. (hindawi.com)
  • In addition, the cell models exhibit predictable growth rates and stable proteomic expression. (technologynetworks.com)
  • AMSBIO's extensive quality control process ensures stable growth rate for each lot of Cellaria cell models delivered. (technologynetworks.com)
  • 3D melanoma cultures were established by placing tumor cells on the surface of a Matrigel matrix, which was followed by the growth of tumor cells on the matrix surface and invasion of the Matrigel matrix by some tumor cells to form multicellular tumor spheroids within the matrix. (asm.org)
  • However, HSV-1 infection did not lead to a complete destruction of tumor cells in the 3D cultures during a 17-day observation period and, surprisingly, HSV-1 infection promoted the growth of some melanoma cells within the matrix as determined by the significantly increased size of residual viable multicellular tumor spheroids in virus-inoculated 3D cultures at 17 days after virus inoculation. (asm.org)
  • These findings suggest that although HSV-1 oncolytic virotherapy may cause extensive tumor cell killing, it may also be associated with the unintended promotion of the growth of some tumor cells. (asm.org)
  • Our observations reported here suggest that potential dangers of HSV-1 oncolytic therapy include promotion of growth of some tumor cells. (asm.org)
  • Our study indicates that HSV-1 infection of 3D tumor cell cultures provides an experimental platform in which mechanisms of HSV-1-mediated promotion of tumor cell growth can be effectively studied. (asm.org)
  • Interaction of tumor promoters and growth factors with cultured cells. (elsevier.com)
  • In tumor xenografts, we observed significant growth reduction of both murine and human non-small cell lung tumors when overexpression of let-7g was induced from lentiviral vectors. (pnas.org)
  • A localized hypoxic environment occurs during tumor growth necessitating an angiogenic response or tumor necrosis results. (biomedcentral.com)
  • However, the presence of melanoma-specific killer cells does not arrest tumor growth. (jimmunol.org)
  • Furthermore, we found that human IL-15 mediated insulin-like growth factor-1 production in CD215+ myeloid cells and blocking IGF-1 reduced the tumor-promoting effect of IL-15. (frontiersin.org)
  • These data indicate that the soft-agar culture technique can be successfully used to investigate the endocrine mechanisms affecting the growth of individual experimental mammary cancers. (elsevier.com)
  • The data also suggest an important role of polyamines in mediating the growth of this mammary tumor model. (elsevier.com)
  • We recently developed a simple but unique microfluidics-based culture approach that requires minimal preprocessing (~30 min) and does not require prior enrichment of CTC s or depend on the use of growth factor supplements. (nus.edu.sg)
  • Cell culture describes the laboratory growth of cells derived from plants or animals. (encyclopedia.com)
  • Dispersed cells are then transferred to a suitable growth medium and allowed to attach to the surface of culture flasks. (encyclopedia.com)
  • Cell culture requires careful attention to the growth medium to ensure cells are given all the components they require to grow. (encyclopedia.com)
  • Often the culture medium requires growth factors or hormones to stimulate growth. (encyclopedia.com)
  • Media used to propagate cells are rich in nutrients and, therefore, support growth of a multitude of organisms. (encyclopedia.com)
  • The ability to culture cells allowed the laboratory growth of polio virus to produce vaccines that nearly eliminated polio as a disease. (encyclopedia.com)
  • Ongoing genomic instability in cells such as CICs can subsequently allow for outgrowth of unique subclones, which acquire additional driver mutations that endow them with a selective growth advantage ( Hanahan and Weinberg, 2011 ). (biologists.org)
  • BACKGROUND: Recent studies have revealed that interactions between tumour cells and the surrounding stroma play an important role in facilitating tumour growth and invasion. (uct.ac.za)
  • The tumor cells secrete immunosuppressive factors, to name a few, transforming growth factor-β(TGF-β). (springer.com)
  • Professor Przyborski is developing new and innovative ways to manage the growth and function of cultured cells. (smi-online.co.uk)
  • Adequate T helper cell activation is essential in the initiation of an immune reaction. (rupress.org)
  • Although tumor cells can directly present endogenously processed antigenic peptide in surface MHC class I molecules to CD8 + CTL precursors, initiation of tumor-specific CTL responses is likely to involve indirect presentation of tumor antigens by specialized APCs. (rupress.org)
  • however, aberrant expression is associated with tumor initiation in a wide variety of human cancers, including breast cancer and leukemia. (biologists.org)
  • A novel circulating tumor cell (CTC) culture assay was performed on four separate clinic visits during the treatment period. (scirp.org)
  • The effects of PTEN on the sensitivity to olaparib and ionizing radiation (IR) exposure were compared between parental HEC-6 (PTEN-null) and HEC-6 PTEN + (stably expressing wild-type PTEN) cells by clonogenic assay, foci formation of RAD51 and γH2AX, and induction of cleaved PARP. (biomedcentral.com)
  • Interlaboratory studies with the chinese hamster v79 cell metabolic cooperation assay to detect tumor-promoting agents. (cdc.gov)
  • The authors conclude that several characteristics of the assay may limit its usefulness for screening broad classes of chemicals for potential activity as tumor promoters. (cdc.gov)
  • The establishment of this assay and clarification of the origin of these cells pave the way for further analysis of the mechanisms of conversion, and of the consequence of such heterogeneity for diagnosis and treatment. (jci.org)
  • The recent identification and cloning of melanoma-associated Ags recognized by T cells ( 2 , 3 ) have provided potentially new tools to enhance natural immunity by the same approach that has been successful in the immunization against foreign pathogens. (jimmunol.org)
  • For development and evaluation of systems through which tumor immunity might be evaluated in man, allogeneic tumor cell-lymphocyte interactions were studied with the one-way mixed culture technique. (elsevier.com)
  • PD-1 and its ligand PD-L1 signaling pathway are important mechanisms that tumors use to escape antitumor immunity. (frontiersin.org)
  • In order to help understanding the tumor immune response and designing the immunotherapy, Daniel S proposed the concept of "cancer-immunity cycle," referring to seven key links initiated in the anticancer immune response which could lead to effective killing of cancerous cells ( 5 ). (frontiersin.org)
  • Perhaps the strongest implication for a role for NKT cells in Th1 immunity is in tumor rejection responses after exogenous IL-12 ( 9 )( 28 )( 29 )( 30 ) or α-GalCer ( 11 )( 31 ) administration. (rupress.org)
  • This study shows that induction of tumor-specific CD4 + T cells by vaccination with a specific viral T helper epitope, contained within a synthetic peptide, results in protective immunity against major histocompatibility complex (MHC) class II negative, virus-induced tumor cells. (rupress.org)
  • These results indicate the crucial role of T helper cells for optimal induction of protective immunity against MHC class II negative tumor cells. (rupress.org)
  • The inability to control tumor outgrowth can be due to inadequate T helper responses underlying poor tumor-specific immunity. (rupress.org)
  • Evidence for a role of T helper cell-mediated immunity comes from studies with genetically modified tumor cells. (rupress.org)
  • As of early 2016, there are three families belonging to the MACPF superfamily: 1.C.12 - The Thiol-activated Cholesterol-dependent Cytolysin (CDC) Family 1.C.39 - The Membrane Attack Complex/Perforin (MACPF) Family 1.C.97 - The Pleurotolysin Pore-forming (Pleurotolysin) Family Proteins containing MACPF domains play key roles in vertebrate immunity, embryonic development, and neural-cell migration. (wikipedia.org)
  • We investigated whether brain tumors show resistance to therapies against Notch, and whether targeting multiple pathways simultaneously would kill brain tumor cells more effectively than monotherapy. (aacrjournals.org)
  • Here, we adapted a microfluidic device to deplete hematopoietic cells from blood specimens of patients with GBM, uncovering evidence of circulating brain tumor cells (CTC). (aacrjournals.org)
  • Mechanistic studies indicated that LD/LP tumor cells induced aggregation of homologous platelets, whereas HD/HP B16a cells failed to induce significant platelet aggregation. (rti.org)
  • Recombinant human tumor necrosis factor alpha promotes adherence of Staphylococcus aureus to cultured human endothelial cells. (asm.org)
  • The ability of TNF-alpha to augment staphylococcal adherence to endothelial cells was contingent upon the presence of plasma factors. (asm.org)
  • Thus, the complex interaction among cytokines (such as TNF), plasma factor(s), and the endothelium serves to modulate bacterial adherence to endothelial cells. (asm.org)
  • Such a marked suppression by TNF-α was not observed in confluent bovine aortic endothelial cells and human fibroblastic IMR-90 cells. (elsevier.com)
  • Increasing evidence indicates that tumor endothelial cells (TEC) differ from normal endothelial cells (NEC). (plos.org)
  • Furthermore, there are many differences at the molecular and functional levels between tumor endothelial cells (TEC) and normal EC (NEC) , . (plos.org)
  • Compared with control condition, pretreatment of carvedilol (10 μmol/L for 18 hours) or probucol (5 μmol/L for 18 hours), but not propanolol, prazosin, or both propanolol and prazosin significantly decreased TNF-α-stimulated adhesiveness of cultured human aortic endothelial cells (HAECs) to MNCs. (ahajournals.org)
  • In the early phase of atherogenesis, cell surface adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and endothelial cell selectin (E-selectin) could express on endothelial cells to recruit circulating mononuclear cells (MNCs), mainly monocytes, and facilitate their binding to endothelium and migrating to subendothelial space. (ahajournals.org)
  • 1-3 Reactive oxygen species (ROS) may serve as a common intracellular messenger for various redox-sensitive transcription pathways that lead to adhesion molecule expression in vascular endothelial cells. (ahajournals.org)
  • Briefly, granular proteins were differentially extracted from GRC.014.22 and GRC.014.24, eosinophilic cell lines established in our laboratory from a patient with moderate asthma. (scirp.org)
  • Basic proteins and polyamino acids are taken up by mammalian cells at rates up to 3000 times greater than serum albumin. (sciencemag.org)
  • Hypoxia induced lower levels of carbonic anhydrase IX (CAIX), GLUT1 and BCL2/adenovirus E1B 19-KD protein-interacting protein 3 (BNIP3) proteins in CTCs than in parental cells, supporting an altered hypoxia response. (nih.gov)
  • PS-1 cells were confirmed as stellate based on the expression of key cytoskeletal proteins and lipid vesicles. (nih.gov)
  • The infected human cells expressed, upon cultivation with dexamethasone, MMTV structural proteins and released spiked B-type virions, the infectivity of which could be neutralized by anti-MMTV antibody. (biomedcentral.com)
  • The cognate human and mouse proteins are 95% identical, and hDMP1 on human chromosome 7q21 is frequently deleted in myeloid leukemia, connoting a possible role for DMP1 as a tumor suppressor ( 28 ). (pnas.org)
  • Tumor-derived MVs (TMV) contain bioactive molecules such as microRNAs (miRNA), mRNAs, and/or proteins inside themselves . (plos.org)
  • Comparison of the IEF 2-D gel protein profiles of fresh tumors and their primary cultures showed that the overall expression profiles were strikingly similar, although differing significantly in the levels of several proteins whose rate of synthesis was differentially regulated in at least 85% of the tumor/culture pairs as a result of the short-term culturing. (nih.gov)
  • Most of the proteins affected by culturing were upregulated and among them we identified components of the cytoskeleton (keratin 18, gelsolin and tropomyosin 3), a molecular chaperone (hsp 28), aldose reductase, GST pi, metastasin, synuclein, the calreticulin precursor and three polypeptides of unknown identity. (nih.gov)
  • The MACPF domain is structurally similar to pore-forming cholesterol-dependent cytolysins from gram-positive bacteria, suggesting that MACPF proteins create pores and disrupt cell membranes similar to cytolysin. (wikipedia.org)
  • 15. The formulation of claim 13, wherein said tumor cells are selected from the group consisting of melanoma cells, lung carcinoma cells, sarcomas, prostate carcinoma cells, breast carcinoma cells, colon carcinoma cells and cervical carcinoma cells. (freepatentsonline.com)
  • When established 3D melanoma cultures were inoculated with HSV-1 by placing virus on the surface of cultures, virus infection caused extensive death of melanoma cells growing on the surface of the 3D matrix and significantly decreased the number of tumor cell spheroids within the matrix. (asm.org)
  • We demonstrate that down regulation of c-FLIP L enhances the PD-1 blockade efficacy in B16 melanoma tumor model. (frontiersin.org)
  • Similar results were observed in a melanoma-derived cell line. (aacrjournals.org)
  • The research forms part of the 'CARPETS' phase 1 clinical trial initiated by Professor Michael Brown, Director of the Cancer Clinical Trials Unit at the RAH to treat advanced melanoma patients, now extended to include patients with other advanced solid tumors including, small cell lung cancer, sarcomas and triple negative breast cancer. (news-medical.net)
  • The main effector cells responsible for tumor eradication were identified as CD8 + cytotoxic T cells that were found to recognize a recently described immunodominant viral gag-encoded cytotoxic T lymphocyte (CTL) epitope, which is unrelated to the viral env-encoded T helper peptide sequence. (rupress.org)
  • Here, we show that let-7 functionally inhibits non-small cell tumor development. (pnas.org)
  • Cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (c-FLIP) is a key anti-apoptotic regulator that inhibits cell death mediated by the death receptors Fas, DR4, DR5, and TNF-R1 ( 9 ). (frontiersin.org)
  • Here, we report that indeed TA potently and specifically inhibits the chymotrypsin-like activity of purified 20S proteasome (IC 50 = 0.06 μg/ml), 26S proteasome of Jurkat T-cell extracts, and 26S proteasome of living Jurkat cells. (aacrjournals.org)
  • Our present study suggests that TA targets and inhibits the proteasome in tumor cells, which may contribute to the previously observed anticarcinogenic activity of TA. (aacrjournals.org)
  • Here, we report that ester-bond containing TA potently and selectively inhibits the chymotrypsin-like activity in purified 20S proteasome, 26S proteasome of Jurkat T-cell extracts, and 26S proteasome in intact Jurkat cells. (aacrjournals.org)
  • Cotransfection of SP1 cells with green fluorescent protein (GFP)-tagged Tiam1 fragment cDNA and Tiam1 cDNA effectively blocks Tiam1-ankyrin colocalization in the cell membrane, and inhibits GDP/GTP exchange on Rac1 by ankyrin-associated Tiam1 and tumor-specific phenotypes. (rupress.org)
  • 0.01) in the presence of stromal cells with predominant cytoplasmic expression. (nih.gov)
  • To address this question definitively, we developed techniques for purification and characterization of major stromal cell types. (jci.org)
  • We are using state-of-the-art molecular and cell biology techniques like RNA immunoprecipitation (Figure 1) and next-generation sequencing as well as diverse cell based assays including life-cell imaging (Figure 2/Movie). (dsmz.de)
  • He has over 25 years experience in cell biology with specific interests in cell culture technology, neuroscience and stem cell research. (smi-online.co.uk)
  • This is the first description of an antitumor function for NKT cells in the absence of exogenously administered potent stimulators such as IL-12 or α-galactosylceramide. (rupress.org)
  • More recently, NKT cells have been isolated and characterized ( 5 )( 6 )( 7 )( 8 ), and their role in IL-12-mediated antitumor activity has been defined ( 9 ). (rupress.org)
  • V. M. D. C. Weisse and C. M. V. K. Sorenmo, "Recurrence Rates and Sites for Grade II Canine Cutaneous Mast Cell Tumors Following Complete Surgical Excision," Journal of the American Animal Hospital Association, Vol. 38, No. 1, 2002, pp. 71-73. (scirp.org)
  • In advanced stage we observed a hypothesis-generating trend that high Robo 4 and Slit 2 expression is associated with delayed development of tumor recurrence compared to patients with low Robo 4 and Slit 2 expression, respectively. (medsci.org)
  • A comparison of the steroids produced by freshly isolated cells and two of the clones revealed some changes in the steroidogenic pathway. (nih.gov)
  • We found that these agents inhibited the mTOR(Mechamistic\Mammilian Target of Rapamycin) pathway in tumor cells growing under glucose starvation, but not under normal conditions. (mdpi.com)
  • Natural killer (NK) cells are tightly regulated by the JAK-STAT signaling pathway and cannot survive in the absence of STAT5. (aacrjournals.org)
  • This raises the possibility that tumors might compensate for therapy directed against one pathway by upregulating a different one. (aacrjournals.org)
  • GBM cells are at least partially resistant to long-term MRK-003 treatment, despite ongoing Notch pathway suppression, and show concomitant upregulation of Wnt and Hedgehog activity. (aacrjournals.org)
  • HGF-induced anterograde lysosome trafficking depended upon the PI3K pathway, microtubules and RhoA, resulting in increased cathepsin B secretion and invasion by the cells. (biologists.org)
  • Here, we utilized alginate-based, oxygen-controlled 3D tumor models to study the interdependence of culture context and the hypoxia response. (sigmaaldrich.com)
  • The CTCs and parental MDA-MB-231 cells were incubated at 21 and 0.2% (hypoxia) oxygen, respectively. (nih.gov)
  • Parental MDA-MB-231 cells induced ATF3 in hypoxia, whereas CTCs expressed it constitutively. (nih.gov)
  • In chronic hypoxia, CTCs demonstrated greater colony formation than parental cells. (nih.gov)
  • Circulating tumour cells (CTCs), isolated and cultured from murine blood, demonstrate a distinct response to hypoxia compared with parental MDA-MB-231cells. (nih.gov)
  • To determine whether CTCs have an altered hypoxia response, they had to be isolated and grown in culture. (nih.gov)
  • Reporter activity in HCT-116 cells transiently transfected with the various ABCG2 promoter constructs was measured with or without 24-h pretreatment with 2-DG (20 mM) or hypoxia. (hindawi.com)
  • Importantly, glucose deprivation and hypoxia were also found to enhance the resistance level of ABCG2-overexpressing resistant cells with pre-existing genetic and epigenetic MDR mechanisms. (hindawi.com)
  • Hypoxia-inducible transcription factors (HIFs) regulate a wide array of adaptive responses to hypoxia and are often activated in solid tumors and hematologic malignancies due to intratumoral hypoxia and emerging new layers of regulation. (bloodjournal.org)
  • INTRODUCTION: Vascuologenesis is the de novo establishment of blood vessels and vascular networks from mesoderm-derived endothelial cell precursors (angioblasts). (biomedsearch.com)
  • It provides a feasible mechanism of early tumour vascular supply which can co-exist and incorporate with later angiogenic mechanisms. (biomedsearch.com)
  • Vascular smooth muscle cells (VSMC), in contrast, did not change appreciably and remained coordinately smooth muscle differentiated. (jci.org)
  • The magic roundabout receptor 4 (Robo 4) is a tumor endothelial marker expressed in the vascular network of various tumor entities. (medsci.org)
  • Insulin-stimulated [ 3 H]leucine incorporation into protein was measured in parallel with studies of receptor regulation to assess the effect of preexposure of cells to insulin on cell metabolism. (aacrjournals.org)
  • In let-7g expressing tumors, reductions in Ras family and HMGA2 protein levels were detected. (pnas.org)
  • 4. The isolated stem cell of claim 2, wherein said isolated stem cell exhibits a glial fibrillary acidic protein (GFAP) astrocytic precursor marker. (freepatentsonline.com)
  • 16. The method of claim 14, wherein said stem cell exhibits a glial fibrillary acidic protein (GFAP) astrocytic precursor marker. (freepatentsonline.com)
  • Antibiotics usually target cell wall synthesis, protein translation, or the DNA replication machinery in bacteria. (aacrjournals.org)
  • Aberrant expression of the oncogenic transcription factor forkhead box protein 1 (FOXP1) is a common feature of diffuse large B-cell lymphoma (DLBCL). (bloodjournal.org)
  • A protein that helps maintain mouse stem cell pluripotency has been identified by researchers at the RIKEN Omics Science Center. (phys.org)