The milieu surrounding neoplasms consisting of cells, vessels, soluble factors, and molecules, that can influence and be influenced by, the neoplasm's growth.
A condition of decreased oxygen content at the cellular level.
A cell line derived from cultured tumor cells.
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.
Relatively complete absence of oxygen in one or more tissues.
Local surroundings with which cells interact by processing various chemical and physical signals, and by contributing their own effects to this environment.
A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.
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.
The total amount (cell number, weight, size or volume) of tumor cells or tissue in the body.
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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
The ability of tumors to evade destruction by the IMMUNE SYSTEM. Theories concerning possible mechanisms by which this takes place involve both cellular immunity (IMMUNITY, CELLULAR) and humoral immunity (ANTIBODY FORMATION), and also costimulatory pathways related to CD28 antigens (ANTIGENS, CD28) and CD80 antigens (ANTIGENS, CD80).
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.
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.
The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.
Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.
Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS.
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.
Transplantation between animals of different species.
Experimentally induced tumor that produces MELANIN in animals to provide a model for studying human MELANOMA.
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.
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.
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.
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.
Experimental transplantation of neoplasms in laboratory animals for research purposes.
A reduction in brain oxygen supply due to ANOXEMIA (a reduced amount of oxygen being carried in the blood by HEMOGLOBIN), or to a restriction of the blood supply to the brain, or both. Severe hypoxia is referred to as anoxia, and is a relatively common cause of injury to the central nervous system. Prolonged brain anoxia may lead to BRAIN DEATH or a PERSISTENT VEGETATIVE STATE. Histologically, this condition is characterized by neuronal loss which is most prominent in the HIPPOCAMPUS; GLOBUS PALLIDUS; CEREBELLUM; and inferior olives.
Tumors or cancer of the human BREAST.
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.
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.
Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.
The classes of BONE MARROW-derived blood cells in the monocytic series (MONOCYTES and their precursors) and granulocytic series (GRANULOCYTES and their precursors).
An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
A 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.
Ability of neoplasms to infiltrate and actively destroy surrounding tissue.
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.
A basic helix-loop-helix transcription factor that plays a role in APOPTOSIS. It is composed of two subunits: ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR and HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT.
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.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Tumors or cancer of the MAMMARY GLAND in animals (MAMMARY GLANDS, ANIMAL).
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.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
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.
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.
Deficient oxygenation of FETAL BLOOD.
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.
Cellular signaling in which a factor secreted by a cell affects other cells in the local environment. This term is often used to denote the action of INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS on surrounding cells.
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.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
Agents and endogenous substances that antagonize or inhibit the development of new blood vessels.
Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS.
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.
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.
A malignant epithelial tumor with a glandular organization.
A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.
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.)
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.
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.
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.
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).
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.
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.
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.
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)
Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.
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.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A 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.
Tumors or cancer of the COLON.
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.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.
Elements of limited time intervals, contributing to particular results or situations.
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.
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)
Treatments with drugs which interact with or block synthesis of specific cellular components characteristic of the individual's disease in order to stop or interrupt the specific biochemical dysfunction involved in progression of the disease.
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)
CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.
Tumors or cancer of the SKIN.
Processes required for CELL ENLARGEMENT and CELL PROLIFERATION.
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.
Culture media containing biologically active components obtained from previously cultured cells or tissues that have released into the media substances affecting certain cell functions (e.g., growth, lysis).
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)
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).
Established cell cultures that have the potential to propagate indefinitely.
Tumors or cancer of the LIVER.
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.
Tumors or cancer of the LUNG.
Antibodies produced by a single clone of cells.
A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
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)
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Tumors or cancer located in bone tissue or specific BONES.
A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)
A nitroimidazole that sensitizes normally radio-resistant hypoxic cells to radiation. It may also be directly cytotoxic to hypoxic cells and has been proposed as an antineoplastic.
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
A particular zone of tissue composed of a specialized microenvironment where stem cells are retained in a undifferentiated, self-renewable state.
Phenotypic changes of EPITHELIAL CELLS to MESENCHYME type, which increase cell mobility critical in many developmental processes such as NEURAL TUBE development. NEOPLASM METASTASIS and DISEASE PROGRESSION may also induce this transition.
Adherence of cells to surfaces or to other cells.
A type of extracellular vesicle, containing RNA and proteins, that is secreted into the extracellular space by EXOCYTOSIS when MULTIVESICULAR BODIES fuse with the PLASMA MEMBRANE.
A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
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.
Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.
Tumors or cancers of the KIDNEY.
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.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.
A tyrosine phosphoprotein that plays an essential role in CAVEOLAE formation. It binds CHOLESTEROL and is involved in LIPIDS transport, membrane traffic, and SIGNAL TRANSDUCTION.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A metabolic process that converts GLUCOSE into two molecules of PYRUVIC ACID through a series of enzymatic reactions. Energy generated by this process is conserved in two molecules of ATP. Glycolysis is the universal catabolic pathway for glucose, free glucose, or glucose derived from complex CARBOHYDRATES, such as GLYCOGEN and STARCH.
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)
Injections introduced directly into localized lesions.
The field of medicine concerned with understanding the biochemical basis of health and disease and involved in developing diagnostic and therapeutic methods that utilize MOLECULAR BIOLOGY techniques.
Tumors or cancer of the PROSTATE.
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.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.
Compounds that inhibit or prevent the proliferation of CELLS.
Methods which attempt to express in replicable terms the extent of the neoplasm in the patient.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
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.
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.
Cell adhesion molecules present on virtually all monocytes, platelets, and granulocytes. CD31 is highly expressed on endothelial cells and concentrated at the junctions between them.
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.
Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C; (CHEMOKINES, C); CC; (CHEMOKINES, CC); and CXC; (CHEMOKINES, CXC); according to variations in a shared cysteine motif.
A CD antigen that contains a conserved I domain which is involved in ligand binding. When combined with CD18 the two subunits form MACROPHAGE-1 ANTIGEN.
Methods for maintaining or growing CELLS in vitro.
A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.
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.
The finer blood vessels of the vasculature that are generally less than 100 microns in internal diameter.
Carcinoma that arises from the PANCREATIC DUCTS. It accounts for the majority of cancers derived from the PANCREAS.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
Tissues, cells or organs transplanted between animals of different species.
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.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
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.
Methods used for detecting the amplified DNA products from the polymerase chain reaction as they accumulate instead of at the end of the reaction.
The fluid of the body that is outside of CELLS. It is the external environment for the cells.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
All tumors in the GASTROINTESTINAL TRACT arising from mesenchymal cells (MESODERM) except those of smooth muscle cells (LEIOMYOMA) or Schwann cells (SCHWANNOMA).
Cell surface receptors that are specific for INTERLEUKIN-8. Two specific receptor subtypes (type A and B) have been found and bind IL-8 with high affinity.
Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells.
Bone-marrow-derived, non-hematopoietic cells that support HEMATOPOETIC STEM CELLS. They have also been isolated from other organs and tissues such as UMBILICAL CORD BLOOD, umbilical vein subendothelium, and WHARTON JELLY. These cells are considered to be a source of multipotent stem cells because they include subpopulations of mesenchymal stem cells.
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.
Use of attenuated VIRUSES as ANTINEOPLASTIC AGENTS to selectively kill CANCER cells.
The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.
Spindle-shaped cells with characteristic CONTRACTILE PROTEINS and structures that contribute to the WOUND HEALING process. They occur in GRANULATION TISSUE and also in pathological processes such as FIBROSIS.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
A 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.
Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
The pathological mechanisms and forms taken by tissue during degeneration into a neoplasm and its subsequent activity.
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.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
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.
A CXC chemokine that is chemotactic for T-LYMPHOCYTES and MONOCYTES. It has specificity for CXCR4 RECEPTORS. Two isoforms of CXCL12 are produced by alternative mRNA splicing.
CXCR receptors with specificity for CXCL12 CHEMOKINE. The receptors may play a role in HEMATOPOIESIS regulation and can also function as coreceptors for the HUMAN IMMUNODEFICIENCY VIRUS.
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.
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.
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.
Unique slender cells with multiple processes extending along the capillary vessel axis and encircling the vascular wall, also called mural cells. Pericytes are imbedded in the BASEMENT MEMBRANE shared with the ENDOTHELIAL CELLS of the vessel. Pericytes are important in maintaining vessel integrity, angiogenesis, and vascular remodeling.
An inhibitory B7 antigen that has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 PROTEIN. CD274 antigen provides negative signals that control and inhibit T-cell responses and is found at higher than normal levels on tumor cells, suggesting its potential role in TUMOR IMMUNE EVASION.
A family of zinc-dependent metalloendopeptidases that is involved in the degradation of EXTRACELLULAR MATRIX components.
Transfer of a neoplasm from its primary site to lymph nodes or to distant parts of the body by way of the lymphatic system.
The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.
The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.
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.
The origin, production or development of cancer through genotypic and phenotypic changes which upset the normal balance between cell proliferation and cell death. Carcinogenesis generally requires a constellation of steps, which may occur quickly or over a period of many years.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Accumulation or retention of free fluid within the peritoneal cavity.
A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for "cancer." (From Dorland, 27th ed)
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila.
A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.
Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.
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)
RNA present in neoplastic tissue.
A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.
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.
An endopeptidase that is structurally similar to MATRIX METALLOPROTEINASE 2. It degrades GELATIN types I and V; COLLAGEN TYPE IV; and COLLAGEN TYPE V.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
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.
Jain is regarded as a pioneer in the area of tumor microenvironment and widely recognized for his seminal discoveries in tumor ... from starving tumors to alleviating hypoxia. Cancer Cell, 26: 605-22, 2014 Jain, RK. Normalizing tumor vasculature with anti- ... Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers. J Clin Oncol, 31: 2205-18, 2013 Video of ... Normalizing Tumor Microenvironment to Treat Cancer: Bench to Bedside to Biomarkers; 2012 ASCO Annual Meeting Jain, RK. ...
The stromal reaction surrounding a tumor, as well as prostaglandins and hypoxia may play a role in this transition. Epithelial- ... Moreover, macrophages infiltrating the tumor microenvironment can transition towards a regulatory phenotype. Regulatory ... Tumor-associated macrophages may be any of these types, and they have been found to be important players in the tumor ... microenvironment. Analysis of the macrophage population and signaling in a tumor may provide useful clinical data. Macrophages ...
Hypoxia promotes apoptosis in both normal and tumor cells. However, hypoxic conditions in tumor microenvironment especially, ... likely through hypoxia-induced VEGF expression pathways. HIF1A overexpression in tumors may also occur in a hypoxia-independent ... During hypoxia, tumor suppressor p53 overexpression may be associated with HIF1A-dependent pathway to initiate apoptosis. ... While research efforts to develop therapeutic drugs to target hypoxia-associated tumor cells have been ongoing for many years, ...
The other way is to allow bacteria to sense the tumor microenvironment, for example hypoxia, by building an AND logic gate into ... To target the tumor cells, peptides that can specifically recognize a tumor were expressed on the surfaces of bacteria. ... Zu C, Wang J (August 2014). "Tumor-colonizing bacteria: a potential tumor targeting therapy". Critical Reviews in Microbiology ... Most often bacteria are used to deliver a therapeutic molecule directly to the tumor to minimize off-target effects. ...
... may also target the tumor microenvironment by suppressing the tumor hypoxic response, in which genes involved in ... the adaptation and survival of cells during hypoxia are induced. Tasquinimod reduces tumor angiogenesis; but its anti- ... Tasquinimod targets the tumor microenvironment and counteracts cancer development by inhibiting angiogenesis and metastasis and ... Tasquinimod is a novel small-molecule inhibitor that targets the tumor microenvironment by controlling the accumulation and ...
The breast tumour microenvironment is particularly hypoxic which allows it to modulate the expression of numerous 'pro-tumour' ... This increased ET-2 expression provides the tumour with autocrine protection from hypoxia-associated apoptosis allowing growth ... This hypoxic environment can be replicated in vitro, resulting in increased expression of ET-2 by breast tumour cells. ... Grimshaw MJ (May 2005). "Endothelins in breast tumour cell invasion". Cancer Letters. 222 (2): 129-38. doi:10.1016/j.canlet. ...
Tumor microenvironments like hypoxia activate transcription factors like the hypoxia-inducible factor to promote the ... Various types of hnRNPs such as hnRNPA1 and hnRNPA2 enter the nucleus during hypoxia conditions and modulate expression such ... Dombrauckas JD, Santarsiero BD, Mesecar AD (July 2005). "Structural basis for tumor pyruvate kinase M2 allosteric regulation ... leading to potential tumor formation. This inhibitory mechanism is important because it may suggest that the regulatory ...
"Epigenetic regulation of gene expression in cervical cancer cells by the tumor microenvironment". Clin Cancer Res. 6 (21): 480- ... "Hypoxia-inducible protein 2 is a novel lipid droplet protein and a specific target gene of hypoxia-inducible factor-1". FASEB J ... Hypoxia inducible lipid droplet-associated (Hilpda, also known as C7orf68 and HIG-2) is a protein that in humans is encoded by ... Low oxygen pressure (hypoxia), fatty acids, and beta-adrenergic agonists stimulate HILPDA expression. Nearly all cells have the ...
It targets tumor hypoxia, a common event in tumorigenesis where the tumor microenvironment is depleted of oxygen and becomes ... Tumors more than 2 cm in diameter and tumors with necrosis and vascular invasion have been correlated with a worse outcome. The ... Several studies have observed increased efficacy of TH-302 when the hypoxic tumor microenvironment has been exasperated. ... proximal location, smaller tumor size, and negative margins upon tumor resection. Epithelioid sarcoma is a slow-growing and ...
Hypoxia Response[edit]. As is common with tumor cells and other pathogens, the invasive hyphae of A. fumigatus encounters ... and ultimately localized hypoxic micro-environments.[16] The exact implications of hypoxia on fungal pathogenesis is currently ... SrbA functionality in hypoxia is dependent upon an upstream cleavage process carried out by the proteins RbdB, SppA, and Dsc A- ... The transcription factor SrbA is the master regulator in the fungal response to hypoxia in vivo and is essential in many ...
Hypoxia also causes the upregulation of hypoxia-inducible factor 1 alpha (HIF1-α), which induces angiogenesis and is associated ... The tumor microenvironment is often hypoxic. As the tumor mass increases, the interior of the tumor becomes farther away from ... The tumor microenvironment (TME) is the environment around a tumor, including the surrounding blood vessels, immune cells, ... Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing ...
Spill F, Reynolds DS, Kamm RD, Zaman MH (August 2016). "Impact of the physical microenvironment on tumor progression and ... Tumor hypoxia is the situation where tumor cells have been deprived of oxygen. As a tumor grows, it rapidly outgrows its blood ... The study of tumors in such conditions was pioneered by Dr L. H. Gray. An association between tumor hypoxia and metastatic ... Hypoxia Gilkes DM, Semenza GL, Wirtz D (June 2014). "Hypoxia and the extracellular matrix: drivers of tumour metastasis". ...
Huang Y, Lin D, Taniguchi CM (October 2017). "Hypoxia inducible factor (HIF) in the tumor microenvironment: friend or foe?". ... Acker T, Plate KH (2004). "Hypoxia and hypoxia inducible factors (HIF) as important regulators of tumor physiology". Cancer ... May 1999). "The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis". Nature. 399 ... Hypoxia often keeps cells from differentiating. However, hypoxia promotes the formation of blood vessels, and is important for ...
Chiche J, Brahimi-Horn MC, Pouysségur J (April 2010). "Tumour hypoxia induces a metabolic shift causing acidosis: a common ... Its overexpression in cancerous tissues compared to normal ones is due to hypoxic conditions in the tumor microenvironment ... a novel surrogate marker of tumor hypoxia, is associated with a poor prognosis in non-small-cell lung cancer". Journal of ... breast and lung where it promotes tumor growth by enhancing tumor acidosis. Carbonic anhydrases (CAs) are a large family of ...
Tumor growth is accompanied by increasing pressure on extracellular matrix structures, whereas the tissue microenvironment ... limited oxygen supply to tumor cells and the formation of active oxygen forms, hypoxia conditions, and permanent exposure to ... Tumor cells within a single tumor can simultaneously move both collectively and individually. In this case, the transition from ... This transformation in malignant tumors can be induced by transfection of various oncogenes. During transformation, tumor cells ...
... able to detach from the primary breast tumor and migrate to a secondary site from initiating division in the microenvironment ... This is by upregulation of VEGF mediated through the epidermal growth factor receptor (EGFR)-MAP/ERK Kinase (MEK)- hypoxia ... It maps to 8p22-p21.3, a region frequently deleted in solid tumors. It is suggested that this gene is a candidate tumor ... In tumor cells which are not expressing DLC1, Bcl-2 levels remain high and the ratio of Bax/Bcl-2 low, so apoptosis is ...
In addition to cytokine-mediated mechanisms, PaSCs also produce a tumour supportive micro-environment through the production of ... Hypoxia also stimulates nuclear expression of HIF-1α followed by the production of vascular endothelial growth factor (VEGF) in ... The matricellular protein also facilitates a tumour supportive microenvironment through sustained fibrogenic stellate cell ... Pancreatic tumour cells stimulate the proliferation of PaSCs through the secretion of PDGF, and induce PaSC production of ECM ...
... "tumor bed effect". This enhanced aggressiveness is attributed to radiation-induced modifications of the tumor microenvironment ... However, tumor hypoxia that ensues activates a range of compensatory mechanisms that sustain vascularization, leading to ... Lewis, C. E.; De Palma, M.; Naldini, L. (2007). "Tie2-Expressing Monocytes and Tumor Angiogenesis: Regulation by Hypoxia and ... In mouse tumor models, anti-angiogenic therapy causes an elevation in tumor-promoting cytokines and growth factors that in turn ...
Additionally, in the microenvironment of cancer cells, there is an increase in hypoxia-inducible transcription factor 1-alpha ( ... Further studies in tumor biology have shown that the increased growth rate in cancer cells is due to an overdrive in glycolysis ... This micro-environment acidification can lead to cellular stress, which would lead to autophagy. Autophagy is activated in ... FUNDCI is also hypoxia sensitive, although it is constitutively present at the outer mitochondrial membrane during normal ...
believed that EMT is more likely to occur in BLBC and is stimulated by abnormal microenvironment such as hypoxia. EMT markers ... Although tumors are often larger and of later stage, basal-like subtypes are more sensitive to anthracycline-based neoadjuvant ... BLBC is easier to metastasize to brain and lung through blood vessels, but less to bone and liver, suggesting that tumors have ... It has been reported that EMT in tumors may be accompanied by an increase in neovascularization, which may accelerate the ...
Brown, J. M. (2007). "Tumor Hypoxia in Cancer Therapy". Oxygen Biology and Hypoxia. Methods in Enzymology. 435. pp. 297-321. ... The word 'niche' can be in reference to the in vivo or in vitro stem-cell microenvironment. During embryonic development, ... Effects of hypoxia on stem cell function, embryonic development, and tumor growth". Genes & Development. 20 (5): 557-70. doi: ... Hypoxia plays an important role in the regulation of cancer stem cell niches and EMT through the promotion of HIFs. These HIFs ...
Review Chiche J., et al., « Hypoxia-inducible carbonic anhydrase IX and XII promote tumor cell growth by counteracting acidosis ... denutrient tumor microenvironment leading to metastatic spread. Some of these targets (CA9, MCT, LAT1, ASCT2, xCT), with ... Hypoxia signalling in cancer and approaches to enforce tumour regression », Nature, (2006) 441, p. 437-43 Kroemer G., et al ... He has been the head of the Tumor Hypoxia and Metabolism Team and a visiting professor at Kyoto Medical University, Kyoto, ...
"Gold Nanoparticle Reprograms Pancreatic Tumor Microenvironment and Inhibits Tumor Growth". "Reprogramming Tumor ... leading to enhanced lipid biogenesis and utilization to survive and thrive under different environmental stress such as hypoxia ... Mukherjee's primary area of research revolves around tumor and tumor microenvironments. His research also deals with protein- ... Some of Mukherjee's research focuses on reprogramming tumor microenvironments. In this area, he has worked on disrupting CC-CAF ...
The hypoxia reduces the cytokine production for the anti-tumor response and progressively macrophages acquire pro-tumor M2 ... functions driven by the tumor microenvironment, including IL-4 and IL-10. Cancer immunotherapy covers the medical ways to ... In addition, a combination of hypoxia in the tumor and a cytokine produced by macrophages induces tumor cells to decrease ... so the immune system no longer attacks the tumor cells. Paradoxically, macrophages can promote tumor growth when tumor cells ...
Mechanical properties of the tumor microenvironment, such as hypoxia, can contribute to CSC survival and metastatic potential ... In different tumor subtypes, cells within the tumor population exhibit functional heterogeneity and tumors are formed from ... Spill F, Reynolds DS, Kamm RD, Zaman MH (August 2016). "Impact of the physical microenvironment on tumor progression and ... While former theory dictates the role of genetic, epigenetic and micro environment where tumour cell resides to acquire ...
Targeting hypoxia in the primary tumor and the suppression of the immune system could also stop the creation of pre-metastatic ... Tumor cells grown in different microenvironments yield different types of protein, indicating that varying types of oncological ... As the primary tumors release tumor cells into the bloodstream, myeloid cells that have been recruited by the tumor, can ... and extracellular matrix deposition and remodeling Hypoxia in the primary tumor and the movement of exosomes from the primary ...
... s (TAMs) are a class of immune cells present in high numbers in the microenvironment of solid tumors ... October 2010). "Macrophage expression of hypoxia-inducible factor-1 alpha suppresses T-cell function and promotes tumor ... Tumor microenvironment Komohara Y, Fujiwara Y, Ohnishi K, Takeya M (April 2016). "Tumor-associated macrophages: Potential ... TAMs affect most aspects of tumor cell biology and drive pathological phenomena including tumor cell proliferation, tumor ...
Tumor microenvironment Angiogenesis Endothelium Dudley, Andrew C. (2012-03-01). "Tumor Endothelial Cells". Cold Spring Harbor ... He identified tumor's response to hypoxia as a leading contributor to angiogenesis and cancer growth. Angiogenesis was ... Play media Tumor-associated endothelial cells or tumor endothelial cells (TECs) refers to cells lining the tumor-associated ... Immune therapies depend heavily on the abilities of effector lymphocytes to infiltrate tumors, and the tumor endothelium is a ...
Disorder involving pauses in breathing during sleep Time of useful consciousness Tumor hypoxia, the situation where tumor cells ... "Heavy metals and low-oxygen microenvironment - its impact on liver metabolism and dietary supplementation". In Dietary ... Response of fish to environmental hypoxia, responses of fish to hypoxia Hypoxia-inducible factors Hypoxic hypoxia, a result of ... anaemic hypoxia), low cardiac output (stagnant hypoxia) or low haemoglobin saturation (hypoxic hypoxia). The consequence of ...
May 2009). "DNA cross-links in human tumor cells exposed to the prodrug PR-104A: relationships to hypoxia, bioreductive ... Benito J, Zeng Z, Konopleva M, Wilson WR (August 2013). "Targeting hypoxia in the leukemia microenvironment". International ... 11 August 2011). "Pronounced hypoxia in models of murine and human leukemia: high efficacy of hypoxia-activated prodrug PR-104 ... a nitrogen mustard prodrug activated by both hypoxia and aldo-keto reductase 1C3, in patients with solid tumors". Cancer ...
"Interaction of tumor cells with the microenvironment". Cell Communication and Signaling. 9 (18): 18. doi:10.1186/1478-811X-9-18 ... "Hypoxia and defective apoptosis drive genomic instability and tumorigenesis". Genes & Development. 18 (17): 2095-107. doi ... The dispersed tumors are called metastatic tumors, while the original is called the primary tumor. Almost all cancers can ... All tumor cells show the six hallmarks of cancer. These characteristics are required to produce a malignant tumor. They include ...
By producing anti-adhesive HA, HAS can allow tumor cells to release from the primary tumor mass, and if HA associates with ... Gao F, Okunieff P, Han Z, Ding I, Wang L, Liu W, Zhang J, Yang S, Chen J, Underhill CB, Kim S, Zhang L (2005). Hypoxia-induced ... This may contribute to the hydrated microenvironment at sites of synthesis, and is essential for cell migration by facilitating ... Hyaluronic acid is, thus, often used as a tumor marker for prostate and breast cancer. It may also be used to monitor the ...
Interaction of tumor cells with the microenvironment»։ Cell Communication and Signaling 9 (18): 18։ September 2011։ PMC 3180438 ... Hypoxia and defective apoptosis drive genomic instability and tumorigenesis»։ Genes & Development 18 (17): 2095-107։ September ... Johnson G (28 December 2010)։ «Unearthing Prehistoric Tumors, and Debate»։ The New York Times։ Արխիվացված օրիգինալից 24 June ... Tobacco use and cancer causation: association by tumour type»։ Journal of Internal Medicine 252 (3): 206-24։ September 2002։ ...
This creates a tumor microenvironment that is short of blood vessels (hypovascular) and so of oxygen (tumor hypoxia).[2] It is ... Pancreatic Neuroendocrine Tumors *^ Tejani MA, Saif MW (2014). "Pancreatic neuroendocrine tumors: Does chemotherapy work?". ... Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment (PDQ®) Incidence and Mortality "Archived copy". Archived from ... Cross section of a human liver, at autopsy, showing many large pale tumor deposits, that are secondary tumors derived from ...
Oxygen is an important biochemical factor to consider in differentiation via hypoxia-induced transcription factors (HIFs) and ... Microfluidics have been applied in these technologies to better mimic the in vivo microenvironment with patterned topographic ... circulating tumor cells. The reaction involves thermal cycling of the DNA sequence and DNA polymerase through three different ... Biological micropatterning can be used for high-throughput single cell analysis, precise control of cellular microenvironment, ...
Anaplastic astrocytoma is classified as grade III and are malignant tumors. They grow more rapidly than lower grade tumors and ... Kimelberg HK, Jalonen T, Walz W (1993). "Regulation of the brain microenvironment:transmitters and ions.". In Murphy S. ... application to cerebral hypoxia". Theoretical Biology and Medical Modelling. 4 (1): 48. doi:10.1186/1742-4682-4-48. PMC 2246127 ... Pilocytic astrocytoma are Grade I tumors. They are considered benign and slow growing tumors. Pilocytic astrocytomas frequently ...
"The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment". Cancer Microenvironment. 8 (3): 125-58. doi:10.1007/ ... is a transcription factor activated by many cellular stressors including hypoxia and ultraviolet radiation damage. ... Tumor suppressor genes[edit]. Many tumor suppressor genes effect signal transduction pathways that regulate apoptosis, also ... The tumor types are typical for each type of tumor suppressor gene mutation, with some mutations causing particular cancers, ...
... has led to the development of other antagomirs that can pair with specific microRNAs present in the tumor microenvironment or ... Several signaling pathways (TGF-β, FGF, EGF, HGF, Wnt/beta-catenin and Notch) and hypoxia may induce EMT.[15][16] In particular ... the growth rate of tumors, and the tumor forming potential in triple negative breast cancer cell lines using mouse xenografts.[ ... "Hypoxia induces epithelial-mesenchymal transition via activation of SNAI1 by hypoxia-inducible factor -1α in hepatocellular ...
SDH mutations have also been identified in gastrointestinal stromal tumors, renal tumors, thyroid tumors, testicular seminomas ... Succinate inhibition of prolyl hydroxylases (PHDs) stabilizes the transcription factor hypoxia inducible factor (HIF)1α.[6][26] ... leads to ROS production and creates a pro-oxidant microenvironment.[29] ... Mutations in SDH, hypoxia or energetic misbalance are all linked to an alteration of flux through the TCA cycle and succinate ...
After the breast-cancer cells have left the primary tumor, they interact with the bone microenvironment and secrete osteolytic ... hypoxia and low pH) and biological (immune surveillance, inhibitory cytokines and regulatory extra-cellular matrix (ECM) ... Apart from the breast tumor cells, the resident stromal cells also contribute to tumor survival. Growth factors such as ... It is highly expressed in tumor stroma and stimulates tumor-cell proliferation. It is hypothesised that TNC stimulates invasion ...
Hypoxia-inducible factors also influence adenosine signalling. In the central nervous system (CNS), ATP is released from ... The P2RX7 receptor is overexpressed in most malignant tumors. The expression of the adenosine A2A receptor on endothelial cells ... depending on the inflammatory microenvironment, the expression of adenosine receptors on the neutrophil, and the affinity of ... Colgan, Sean P.; Eltzschig, Holger K. (17 March 2012). "Adenosine and Hypoxia-Inducible Factor Signaling in Intestinal Injury ...
Ungefroren H, Sebens S, Seidl D, Lehnert H, Hass R (September 2011). "Interaction of tumor cells with the microenvironment". ... Nelson DA, Tan TT, Rabson AB, Anderson D, Degenhardt K, White E (September 2004). "Hypoxia and defective apoptosis drive ... The dispersed tumors are called metastatic tumors, while the original is called the primary tumor. Almost all cancers can ... The dispersed tumors are called metastatic tumors, while the original is called the primary tumor. Almost all cancers can ...
There is evidence that emphasizes the role of autophagy as both a tumor suppressor and a factor in tumor cell survival. Recent ... These metabolic stresses include hypoxia, nutrient deprivation, and an increase in proliferation. These stresses activate ... to recycle vital molecules and generate a pool of building blocks to help the cell respond to a changing microenvironment. ... By inhibiting autophagy genes in these tumors cells, regression of the tumor and extended survival of the organs affected by ...
Yu L, Quinn DA, Garg HG, Hales CA (June 2008). "Deficiency of the NHE1 gene prevents hypoxia-induced pulmonary hypertension and ... Microenvironment acidification assessed with fluorescence lifetime imaging". The Journal of Biological Chemistry. 277 (49): ... tumor promoters, and others. Sodium-hydrogen antiporter 1 has been shown to interact with carbonic anhydrase II and CHP. It is ... Rios EJ, Fallon M, Wang J, Shimoda LA (November 2005). "Chronic hypoxia elevates intracellular pH and activates Na+/H+ exchange ...
Lennon SV, Martin SJ, Cotter TG (1991). "Dose-dependent induction of apoptosis in human tumour cell lines by widely diverging ... Oxidative stress also plays a role in the ischemic cascade due to oxygen reperfusion injury following hypoxia. This cascade ... The rise of oxygen levels due to cyanobacterial photosynthesis in ancient microenvironments was probably highly toxic to the ... hydrogen peroxide and tumor promoters are repaired slowly compared to breaks induced by ionizing radiation". Carcinogenesis. 7 ...
... the Bad and the Unknown of CD38 in the Metabolic Microenvironment and Immune Cell Functionality of Solid Tumors". Cells. 9 (1 ... hypoxia, and/or chronic liver disease or chronic kidney disease, and in elderly patients. Dipyridamole potentiates the action ... the function of adenosine is primarily that of cytoprotection preventing tissue damage during instances of hypoxia, ischemia, ...
MMPs also degrade ECM to provide space for vasculature to grow to the tumor, for the tumor cells to migrate, and for the tumor ... Liu, H; Ma, Q; Xu, Q; Lei, J; Li, X; Wang, Z; Wu, E (2012). "Therapeutic potential of perineural invasion, hypoxia and ... Cancer develops and progresses as the microenvironment undergoes dynamic changes. The stromal reaction in cancer is similar to ... The tumor-induced stromal change hypothesis claims that tumor cells can dedifferentiate into fibroblasts and, themselves, ...
"Targeting the tumor and its microenvironment by a dual-function decoy Met receptor". Cancer Cell. 6 (1): 61-73. doi:10.1016/j. ... HIF1 can bind to one of the several hypoxia response elements (HREs) in the MET promoter. Hypoxia also activates transcription ... which in turn leads to formation of pores in tumor cells. In ADCC, the Fab domain of a mAb binds to a tumor antigen, and Fc ... DN30 inhibits tumour growth and prevents metastasis in animal models. OA-5D5 is one-armed monoclonal anti-MET antibody that was ...
... these molecules can act as tumor-targeting drug delivery systems. Once within the tumor microenvironment, these complexes ... This active stage leads to a state of cellular hypoxia, which causes an increased regulation of pro-angiogenesis proteins such ... Tumor progression occurs as a result of the transition from a tumor in the dormant proliferation stage to the active stage as a ... At most, this type of targeting would only have a minor effect on killing the tumor. Tumors are constantly changing and thus ...
SDH mutations have also been identified in gastrointestinal stromal tumors, renal tumors, thyroid tumors, testicular seminomas ... Mutations in SDH, hypoxia or energetic misbalance are all linked to an alteration of flux through the TCA cycle and succinate ... leads to ROS production and creates a pro-oxidant microenvironment. In addition to its metabolic roles, succinate serves as an ... Since PDHs have an absolute requirement for molecular oxygen, this process is suppressed in hypoxia allowing HIF1α to escape ...
... such as in growing tumors. Metabolic alterations in response to hypoxia can be triggered in a direct manner, such as the switch ... such as in growing tumors. Metabolic alterations in response to hypoxia can be triggered in a direct manner, such as the switch ... how they are affected in the tumor cells and in the cells of the microenvironment, most prominently in immune cells. ... how they are affected in the tumor cells and in the cells of the microenvironment, most prominently in immune cells. ...
However, most studies consider hypoxia as a single entity, yet we now know that it is multifactorial. Furthermore, hypoxia is ... However, most studies consider hypoxia as a single entity, yet we now know that it is multifactorial. Furthermore, hypoxia is ... clinically applicable approaches to identify those tumors that contain hypoxia and realistic methods to target this hypoxia. ... and these can also influence the effects of hypoxia. Here, we review the various aspects of hypoxia, but also discuss the role ...
... but likely relies on the endometriotic microenvironment. The unique tumor microenvironment of endometriosis is composed of ... Understanding the unique molecular features of the endometriotic tumor microenvironment may lead to impactful precision ... the endometriotic tumor microenvironment, and available model systems for endometriosis-associated ovarian cancers. Continued ... develop from the molecular transformation of endometriosis or develop because of the endometriotic tumor microenvironment ...
D, tumor hypoxia was assessed with α-pimidizole mAbFITC/α-FITC-HRP secondary antibodies and quantitated in tumor sections (n ≥ ... and constitute the vascularized tumor microenvironment (TME), is critical for primary tumor growth, invasion, and metastasis (3 ... Targeting EphA3 Inhibits Cancer Growth by Disrupting the Tumor Stromal Microenvironment. Mary E. Vail, Carmel Murone, April Tan ... Targeting EphA3 Inhibits Cancer Growth by Disrupting the Tumor Stromal Microenvironment. Mary E. Vail, Carmel Murone, April Tan ...
Hypoxia is one of the major characteristics of the tumor microenvironment. Therefore, we tested the effect of hypoxia on MDSC. ... One of the major factors that distinguish the tumor microenvironment from lymphoid organs is hypoxia. It appears that hypoxia ... S3 shows ROS in MDSC from tumor and spleens of EL-4 tumor-bearing mice. Fig. S4 shows the effect of the tumor microenvironment ... Hypoxia-inducible factor (HIF) 1α was found to be primarily responsible for the observed effects of the tumor microenvironment ...
Hypoxia. Acidosis. Acidosis, Lactic. Signs and Symptoms, Respiratory. Signs and Symptoms. Acid-Base Imbalance. Metabolic ... The Gene Expression Studies of the Role of Tumor Microenvironments in Tumor Progression. The safety and scientific validity of ... The Gene Expression Studies of Tumor Microenvironments and Their Roles in Tumor Progression. ... We will also obtain the information on the tumor physiological parameters information measured in these tumors. ...
Combination Strategies Targeting Hypoxia Inducible Factor 1 (HIF-1) for Cancer Therapy ... The first edition of The Tumor Microenvironment is intended to give a current perspective on the role of the tumor ... The Tumor Microenvironment: New Insights into Regulation of Tumor pH by Carbonic Anhydrases ... The Tumor Microenvironment is the definitive text detailing cutting edge research by experts in the field and will be a valued ...
The tumour microenvironment : causes and consequences of hypoxia and acidity. Title The tumour microenvironment. Title ... The tumour microenvironment : causes and consequences of hypoxia and acidity, [editors, Jamie A. Goode and Derek J. Chadwick] ... The tumour microenvironment : causes and consequences of hypoxia and acidity, [editors, Jamie A. Goode and Derek J. Chadwick]. ... The tumour microenvironment : causes and consequences of hypoxia and acidity, [editors, Jamie A. Goode and Derek J. Chadwick]. ...
The current review focuses on the role of intra-tumor hypoxia as a mechanism of resistance to anti-angiogenic agents and ... Role of the hypoxic tumor microenvironment in the resistance to anti-angiogenic therapies Drug Resist Updat. 2009 Jun;12(3):74- ... 1 Tumor Hypoxia Laboratory - SAIC Frederick, Inc., NCI at Frederick, Frederick, MD 21702-1201, USA. ...
Hypoxia in the tumor microenvironment is likely to contribute to suppressing the antitumor activity of TAMs as it stimulates ... TAMs respond to tumor hypoxia by up-regulating the hypoxia-inducible transcription factors HIF-1 and HIF-2. Although both ... This ensures the revascularization of each hypoxic tumor area and protects tumor cells in these from hypoxia-induced cell death ... 2, angiogenesis: In areas of transient (avascular) and chronic (perinecrotic) tumor hypoxia, macrophages cooperate with tumor ...
Hypoxia and ROS affect immune cells in the tumor micro-environment, thereby affecting the … ... This makes the tumor hypoxic, resulting in the Warburg effect and an increased generation of reactive oxygen species (ROS). ... Solid tumors grow at a high speed leading to insufficient blood supply to tumor cells. ... Solid tumors grow at a high speed leading to insufficient blood supply to tumor cells. This makes the tumor hypoxic, resulting ...
The present study aimed to summarize the role of hypoxia in cancer therapy by regulating the tumor microenvironment (TME) and ... Hypoxia targeting might be relevant to overcome hypoxia-associated resistance in cancer treatment. ... Recent studies have shown that hypoxia is associated with poor prognosis in patients by regulating the TME. It confers ... Relevant published studies were retrieved from PubMed, Web of Science, and Embase using keywords such as hypoxia, cancer ...
... is one of key reasons that lead to the limited tumor perfusion as well as hypoxic and immunosuppressive tumor microenvironment ... Tumor Hypoxia. Hypoxic conditions in tumor cells due to the tumor outgrowing its blood supply. It is associated with increased ... Analysis of Tumor Mutations and Tumor Microenvironment Using Archival Paraffin-embedded Tumor Specimens ... breast tumors, colorectal tumors, and squamous cell carcinoma tumors, could be remarkably enhanced. As the results, the tumor ...
10 Tumor Microenvironment. *11 Assessing Hypoxia. *12 BBB Penetration. *13 Beyond Small Molecules ... He is an experienced protein biochemist and glycobiologist, with particular expertise in tumor biology and biomarker discovery ...
Each chapter presents a different mathematical model designed to investigate the interactions between tumor cells and the ... This edited volume discusses the complexity of tumor microenvironments during cancer development, progression and treatment. ... Hypoxia in Gliomas: Opening Therapeutical Opportunities Using a Mathematical-Based Approach. Pages 11-29 ... intravenous transport of the circulating tumor cells, the role of the tumor microenvironment in chemotherapeutic interventions ...
The conference brings together scientists to discuss different cellular and animal models of tumor microenvironment study and ... This volume covers the topics presented at the 3rd International Conference on Tumor Microenvironment and Cellular Stress by an ... Methods: Using Three-Dimensional Culture (Spheroids) as an In Vitro Model of Tumour Hypoxia ... Tumor Microenvironment. Study Protocols. Editors: Koumenis, C., Coussens, L.M., Giaccia, A., Hammond, E. (Eds.) ...
... as well as by hypoxia within glucose gradients. It is possible that the activation of AMPK in hypoxic tumor microenvironments ... and exposed tumor-bearing mice to the hypoxia probe pimonidazole (3, 10, 44, 45). Immunohistochemical analysis of these tumors ... by hypoxia and hypoxia combined with glucose deprivation suggested that oxygen and glucose gradients in solid tumors would be ... We observed that the WT tumors had more intense P-ACC1/2 staining than the HIF-1α-null tumors (average score, 150 for WT tumors ...
Expression-based analyses indicate a central role for hypoxia in driving tumor plasticity through microenvironment remodeling ...
To further explore the effect of hypoxia on the prognosis of patients with PAC as well as the tumor immune microenvironment, we ... However, the method to identify the degree of hypoxia in the tumor microenvironment (TME) is incompletely understood. The mRNA ... and low-risk groups in line with the hypoxia risk score. We established a hypoxia risk model according to four hypoxia-related ... Moreover, the hypoxia risk score can act as an independent prognostic factor in PAC, and a higher hypoxia risk score was ...
Targeting hypoxia in the tumor microenvironment: a potential strategy to improve cancer im ... Targeting hypoxia in the tumor microenvironment: a potential strategy to improve cancer immunotherapy. ... which is an intrinsic property of all solid tumors. In addition to its impact on shaping tumor invasion and metastasis, the ... Therefore, targeting hypoxia may provide a means to enhance the efficacy of immunotherapy. In this review, the potential impact ...
A tumor can change its microenvironment and the microenvironment can affect the way the tumor grows and spreads. Hypoxia, ... Hypoxia, glucose deprivation and acidosis are the hallmarks of tumor microenvironment. This study investigated the upregulation ... which collectively comprise the tumor microenvironment. Recent advances have indicated that the tumor microenvironment is ... Among the various conditions within the tumor microenvironment, hypoxia has been demonstrated to upregulate ABCG2 in a mouse ...
Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. Cancer Res. 2003;63(5):1138-1143.. View this article ... The tumor microenvironment plays an important role in tumor growth and metastasis. However, the mechanism by which tumor cells ... Ubiquitination of tumor suppressor PML regulates prometastatic and immunosuppressive tumor microenvironment. Ya-Ting Wang,1,2 ... Recent studies have revealed a 2-way interaction between tumor cells and immune cells in the tumor microenvironment. On one ...
This tumour microenvironment has a major impact on the biology of cancer cells and their response to chemotherapeutic agents. ... Here, a microfluidic device is presented that is easy to use and enables modelling and study of the tumour microenvironment in ... into the microenvironment and could be used to study cancer cells for which it is difficult to generate tumour spheroids. ... Another major application of the device is the study of effects of the microenvironment on cellular drug responses. Some data ...
Researchers found that hypoxia was associated with elevated genomic instability in 10 tumor types and saw widespread hypoxia- ... Characterization of the Tumor Microenvironment By Discovery Life Sciences Human Papillomavirus Positive Oropharyngeal Squamous ... Tumor Hypoxia Associated With Cancer Driver Mutation Signatures in 19 Tumor Types. Jan 14, 2019 ... Home » Disease Areas » Cancer » Tumor Hypoxia Associated With Cancer Driver Mutation Signatures in 19 Tumor Types ...
Additional Keywords : Tumor Microenvironment. Anti Therapeutic Actions : Hypoxia. Adverse Pharmacological Actions : Cancer ... Hypoxia enhances tumor stemness by increasing the invasive and tumorigenic side population fraction.Jun 30, 2008. ...
Additional Keywords : Tumor Microenvironment. Anti Therapeutic Actions : Hypoxia. [+] Resveratrol may be useful for CSC- ... The hypoxic microenvironment upgrades stem-like properties of ovarian cancer cells.Dec 31, 2011. ...
... acidification of tumour microenvironment and promotes several cancer processes leading to cell survival, tumour growth and ... Hypoxia, through hypoxia-inducible factors (HIFs), in addition to oncogenes activation and loss of tumour suppressors ... Model of tumour microenvironment and lactate shuttles in cancer. Cells located far from the perfused blood vessels become ... by stabilising hypoxia-inducible factor 1 α (HIF-1α), induces tumour angiogenesis. Normoxic cancer cells, that highly express ...
Talk Between Hypoxia and the Tumour via Exosomes , IntechOpen, Published on: 2017-02-01. Authors: Shayna Sharma, Mona Alharbi, ... 4. Exosomes, the tumour microenvironment and hypoxia. An evaluation of cancer cells and their microenvironment plays a critical ... 3. The tumour microenvironment and hypoxia. Under normal conditions, the cellular microenvironment inhibits the development of ... Tumour cells under hypoxia secrete molecules that modulate their microenvironment and facilitate tumour angiogenesis and ...
1α is an essential regulator of cell adaptation to hypoxia and is often upregulated in tumors due to intratumoral hypoxia or ... A RNA antagonist of hypoxia-inducible factor-1alpha, EZN-2968, inhibits tumor cell growth. Mol Cancer Ther 2008;7(11):3598-3608 ... HIF-1α regulates the interaction of chronic lymphocytic leukemia cells with the tumor microenvironment. Roberta Valsecchi, ... HIF-1α regulates the interaction of chronic lymphocytic leukemia cells with the tumor microenvironment. Blood, 127(16), 1987- ...
An agent-based model for drug-radiation interactions in the tumour microenvironment: Hypoxia-activated prodrug SN30000 in ... Molecular characterization of breast and lung tumors by integration of multiple data types with functional sparse-factor ... multicellular tumour spheroids Xinjian Mao, Sarah McManaway, Jagdish K. Jaiswal, Priyanka B. Patel, William R. Wilson, Kevin O ...
  • Although in this context their metabolism has received less attention, they signify a rich cell population in many solid tumors. (frontiersin.org)
  • Solid tumors are characterized by rapid cell growth that is not equally compensated with a functionally effective and efficient vasculature. (frontiersin.org)
  • Poor microenvironmental conditions are a characteristic feature of solid tumors. (frontiersin.org)
  • Most solid tumors are just like normal tissues in that they need a regular supply of oxygen and nutrients to be able to exist, as well as processes for the elimination of the waste products of cellular metabolism. (frontiersin.org)
  • Solid tumors grow at a high speed leading to insufficient blood supply to tumor cells. (nih.gov)
  • Hypoxia is an inherent feature in the microenvironment of solid tumors, which can promote tumor survival and also lead to tumor proliferation and metabolism [ 3 ]. (biomedcentral.com)
  • Increasing evidence suggests that one of the major barriers limiting the efficacy of immunotherapy seems to coalesce with the hypoxic tumor microenvironment (TME), which is an intrinsic property of all solid tumors . (bvsalud.org)
  • Low oxygen gradients (hypoxia and anoxia) are important determinants of pathological conditions under which the tissue blood supply is deficient or defective, such as in solid tumors. (asm.org)
  • This observation suggested the hypothesis that AMPK is important for the adaptive responses of energetically stressed cells in the hypoxic and glucose-deprived microenvironments present in solid tumors (e.g., reviewed in references 35 and 59 ). (asm.org)
  • Cancer cells are often confronted with a remarkable reduction in oxygen supply inside solid tumors, leading to intratumoral hypoxia. (hindawi.com)
  • Glucose depletion is often observed in malignant tumors due to insufficient blood supply in the core of solid tumors [ 5 ] and increased rate of glycolysis [ 6 ]. (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)
  • Hypoxic microenvironements in solid tumors are a result of available oxygen being consumed within 70 to 150 μm of tumour vasculature by rapidly proliferating tumor cells thus limiting the amount of oxygen available to diffuse further into the tumor tissue. (wikipedia.org)
  • During cancer progression, tumor cells acquire comprehensive metabolic reprogramming, and tissue hypoxia is a prominent feature of solid tumors leading to cell metabolism adaptive changes. (wikipedia.org)
  • Solid tumors like glioblastoma create microenvironments within and around themselves. (scienceblog.com)
  • SLC-0111 has been tested in Phase I clinical safety trials sponsored by Welichem Biotech Inc. in Canada for patients with advanced solid tumors. (scienceblog.com)
  • Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. (springer.com)
  • The presence of hypoxia in solid tumors is associated with a more malignant phenotype and resistance to chemotherapy. (clinicaltrials.gov)
  • LDH-A is a heterotetramer of LDH-M and favors conversion of pyruvate to lactate and is up-regulated in many solid tumors that have high HIF expression ( 3 , 15 ). (aacrjournals.org)
  • Hypoxia and expression of HIF-1α and HIF-2α are characteristic features of all solid tumors. (jci.org)
  • In addition to cancer cells, solid tumors consist of a variety of cell types and tissues defining a complex microenvironment that influences disease progression and response to therapy. (mit.edu)
  • DEDIĆ PLAVETIĆ NDP, BARIĆ MB, BRADIĆ LB, KULIĆ A, PLEŠTINA S. Hypoxia in solid tumors: biological responses to hypoxia and implications on therapy and prognosis. (srce.hr)
  • N.D.P. DEDIĆ PLAVETIĆ, M.B. BARIĆ, L.B. BRADIĆ, A. KULIĆ i S. PLEŠTINA, "Hypoxia in solid tumors: biological responses to hypoxia and implications on therapy and prognosis", Periodicum biologorum , vol.116, br. (srce.hr)
  • Rapid growth accompanied by inadequate angiogenesis is the reason why most solid tumors contain hypoxic regions. (srce.hr)
  • Increased metabolism and poor perfusion in solid tumors creates a physical microenvironment that consists of either hypoxic and/or acidic regions. (agilent.com)
  • A primary area of research in Dr. Knox's laboratory is the study of novel therapies (targeted therapies, radiosensitizers, radioprotectors, and biological response modifiers) for the treatment of solid tumors, with a particular focus on prostate cancer, breast cancer and melanoma, using small animal tumor models. (stanford.edu)
  • Hypoxia is a prominent feature of solid tumors known to contribute to malignant progression and therapeutic resistance. (aacrjournals.org)
  • Hypoxic stress alters the metabolism of tumor cells but also of macrophages, as one dominating immune cell population in most solid tumors, with subsequent changes in the microenvironment. (ovid.com)
  • Regions of low oxygenation (hypoxia) is believed to be the most critical deficiency, since it has been well documented to play a significant role in influencing the response to conventional radiation and chemotherapy treatments, as well as influencing malignant progression in terms of aggressive growth and recurrence of the primary tumor and its metastatic spread. (frontiersin.org)
  • These cells also contribute to tumor progression via regulation of angiogenesis and tumor cell motility. (rupress.org)
  • The purpose of this study is to analyze the gene expression patterns associated with various microenvironmental stresses in tumors to understand their roles in tumor progression and treatment responses. (clinicaltrials.gov)
  • We will correlate the gene expression signatures of different microenvironmental stresses with the measured physiological parameters to understand their role in tumor progression, treatment response and clinical outcomes. (clinicaltrials.gov)
  • The first edition of The Tumor Microenvironment is intended to give a current perspective on the role of the tumor microenvironment in malignant progression and detail strategies for novel therapies directed towards the cellular matrix. (springer.com)
  • That these cells might help to drive tumor progression has been inferred over a number of years from studies looking at the link between TAM levels and prognosis. (aacrjournals.org)
  • These observations accord well with the results of animal studies using macrophage-depleted mice to investigate the role of macrophages in tumor progression in vivo . (aacrjournals.org)
  • This edited volume discusses the complexity of tumor microenvironments during cancer development, progression and treatment. (springer.com)
  • While the role of exosomes during tumour progression remains to be fully established, we postulate that tumour cells release exosomes loaded with specific molecules in response to the microenvironment to prepare for and promote metastasis to specific organs. (intechopen.com)
  • Tumor microenvironment represents an attractive new drug target because it allows complex interaction between a tumor and its surrounding normal cells, molecules, and blood vessels, which all participate in tumor progression. (hindawi.com)
  • Recent advances have indicated that the tumor microenvironment is critically important for cancer initiation, progression, metastasis, and drug resistance, thus providing opportunities for therapeutic intervention. (hindawi.com)
  • The last decades were characterized by substantial progress in the understanding of the role of the immune system in tumor progression. (springer.com)
  • Microvesicles as a Biomarker for Tumor Progression versus Treatment Effect in Radiation/Temozolomide-Treated Glioblastoma Patients. (upenn.edu)
  • Cancer pathogenesis may be described as a multistep process including transformation , growth promotion and, in clinically evident tumors, malignant progression [ 10 ]. (hindawi.com)
  • Hypoxia is a prominent characteristic of many acute or chronic inflammatory diseases, and exerts significant influence on their progression. (jci.org)
  • Here, we aimed to investigate the expression, function, and underlying mechanisms of aHIF in EOC progression under hypoxia. (dovepress.com)
  • In vitro and in vivo assays were conducted to explore the function and mechanism of aHIF in hypoxia-induced EOC progression. (dovepress.com)
  • Our findings help clarify the role of lncRNA in hypoxia-induced EOC progression. (dovepress.com)
  • Extracellularly, PGI is known as an autocrine motility factor (AMF) eliciting mitogenic, motogenic, differentiation functions as well as tumor progression and metastasis. (wikipedia.org)
  • Tumor progression was quantified by bioluminescence imaging (BLI), copper depletion status by Cp oxidase levels, lysyl oxidase (LOX) activity by ELISA, and collagen deposition. (aacrjournals.org)
  • The potential role of HIF on tumour progression and dissemination. (springer.com)
  • Tumor progression is driven by mutations that confer growth advantages to different subpopulations of cancer cells. (cshlpress.com)
  • They compare cancer evolution to organismal evolution and describe how ecological theories and mathematical models are being used to understand the complex dynamics between a tumor and its microenvironment during cancer progression. (cshlpress.com)
  • NIH-supported primary applications of Principal Investigators at the IMMR center are dedicated to multifunctional profiling of tumor tissue microenvironment (TME) during cancer progression and therapeutic intervention 1, 6-7 . (wvu.edu)
  • Tissue hypoxia, acidosis, and highly-reducing redox status are well-established hallmarks of cancer while interstitial inorganic phosphate (Pi) has been recently recognized as a new potential marker of tumor progression and aggressiveness 7 . (wvu.edu)
  • However, very little is known about spatio-temporal changes in p02 and pH during tumor progression and therapy. (mit.edu)
  • Hypoxia and acidosis are known to drive changes in tumor cell metabolism and promote progression. (agilent.com)
  • ATF4 couples MYC-dependent translational activity to bioenergetic demands during tumour progression. (stanford.edu)
  • Acute deletion of ATF4 significantly delays MYC-driven tumour progression and increases survival in mouse models. (stanford.edu)
  • Our results establish ATF4 as a cellular rheostat of MYC activity, which ensures that enhanced translation rates are compatible with survival and tumour progression. (stanford.edu)
  • We are examining the effect of exposure to intermittent hypoxia in modifying the expression of genes likely to be associated with metastasis and tumour progression in xenograft models of human cervix carcinoma and pancreatic cancer. (utoronto.ca)
  • Analysis of the effects of exposure to acute hypoxia on oxidative lesions and tumour progression in a transgenic mouse breast cancer model. (utoronto.ca)
  • Together, our results show a critical role of miR-191 in hypoxia-induced cancer progression and suggest that miR-191 inhibition may offer a novel therapy for hypoxic breast tumors. (sigmaaldrich.com)
  • Cancer cells are the driving force of tumor development and progression. (spandidos-publications.com)
  • The tumor microenvironment is also considered to play an active role rather than simply acting as a by-stander in tumor progression. (spandidos-publications.com)
  • Through different pathways, tumor cells efficiently recruit stromal cells, which in turn, provide tumor cell growth signals, intermediate metabolites, and provide a suitable environment for tumor progression as well as metastasis. (spandidos-publications.com)
  • Understanding the role of the tumor microenvironment in tumor progression provides us with novel approaches through which to target the tumor microenvironment for efficient anticancer treatment. (spandidos-publications.com)
  • In this review, we summarize the mechanisms involved in the recruitment of stromal cells by tumor cells to the primary tumor site and highlight the role of the tumor microenvironment in the regulation of tumor progression. (spandidos-publications.com)
  • The tumor microenvironment, which consists of resident fibroblasts, endothelial cells, pericytes, leukocytes and extracellular matrix, also contributes to the progression of cancer ( 3 ). (spandidos-publications.com)
  • As the tumor microenvironment actively participates in tumor progression and metastasis rather than acting as a by-stander, therapeutic strategies targeting the tumor microenvironment hold great potential. (spandidos-publications.com)
  • Moreover, we will highlight the role of the tumor microenvironment in the regulation of tumor progression and discuss the potential value for cancer therapy. (spandidos-publications.com)
  • Accumulating evidence has confirmed that tumor cells must recruit and reprogram the surrounding normal cells to serve as contributors to tumor progression. (spandidos-publications.com)
  • Studies from my laboratory demonstrate that MLLs are critical players in Hox gene expression, cell cycle progression, hypoxia signaling, angiogenesis, and in tumor growth. (uta.edu)
  • Mixed lineage leukemia-4 regulates cell cycle progression and cell viability and its depletion suppresses growth of xenografted tumor in vivo, British Journal of Cancer 2012 , 107, 315-24. (uta.edu)
  • This so-called intra-tumoral hypoxia is associated with increased risk of local spread, metastasis, and patient mortality ( 5 ). (frontiersin.org)
  • The intimate communication between cancer cells and host-derived stromal and myeloid cells ( 1 ), which are recruited from the bone marrow ( 2 ) and constitute the vascularized tumor microenvironment (TME), is critical for primary tumor growth, invasion, and metastasis ( 3 ). (aacrjournals.org)
  • Soluble factors secreted by tumor or stromal cells are rich in the TME and contribute to abnormal proliferation, angiogenesis, metastasis, and drug resistance [ 6 ]. (biomedcentral.com)
  • This book explores the many biological and physiological aspects of the tumor as a tissue and includes chapters on the variety of cells that influence tumor growth and spread as well as the cell-associated and soluble proteins that can promote invasion and metastasis. (springer.com)
  • These highly versatile cells respond to the presence of stimuli in different parts of tumors with the release of a distinct repertoire of growth factors, cytokines, chemokines, and enzymes that regulate tumor growth, angiogenesis, invasion, and/or metastasis. (aacrjournals.org)
  • The distinct microenvironments where tumor-associated macrophages (TAM) act include areas of invasion where TAMs promote cancer cell motility, stromal and perivascular areas where TAMs promote metastasis, and avascular and perinecrotic areas where hypoxic TAMs stimulate angiogenesis. (aacrjournals.org)
  • Compelling evidence has emerged in recent years for macrophages playing an important role in tumor cell invasion into surrounding normal tissues, proliferation and survival, and metastasis to local and distant sites. (aacrjournals.org)
  • In addition to its impact on shaping tumor invasion and metastasis , the hypoxic TME plays an essential role in inducing immune suppression and resistance though fostering diverse changes in stromal cell biology . (bvsalud.org)
  • We demonstrated that VEGF-targeted drugs, as well as gene deletion of Vegf , inhibit primary tumor growth but promote tumor invasiveness and metastasis in the RIP1-Tag2 model 2 . (nature.com)
  • Several reports have established that low oxygen tension (i.e. hypoxia) is a common feature of the tumour microenvironment often enhancing the process of epithelial‐to‐mesenchymal transition (EMT) in cancer cells, thus promoting tumourigenesis and metastasis. (intechopen.com)
  • Pluripotency factors, such as NANOG, play a critical role in the maintenance and specification of cancer stem cells, which are required for primary tumor formation and metastasis. (pnas.org)
  • Even senior scientists can be surprised by new data - something Dr. Sean Egan experienced when he found out that breast cancer metastasis can be very different from their original primary tumour. (tfri.ca)
  • Having an increased level of GLUT1, in the case of hypoxic tumors, increases the flux of glucose into the cells allowing for a higher rate of glycolysis and thus greater risks of metastasis (as elaborated upon below). (wikipedia.org)
  • Many tumors, including breast cancer, are maintained by a subpopulation of cells that display stem cell properties, mediate metastasis, and contribute to treatment resistance. (pubmedcentralcanada.ca)
  • In fact, decades of research have led to the view that tumors are in effect organ-like structures composed of numerous cell types whose interaction is required to drive and promote growth and metastasis. (pubmedcentralcanada.ca)
  • Subsequent studies have provided evidence that these CSCs mediate tumor metastasis and, by virtue of their relative resistance to radiation and chemotherapy, contribute to relapse following therapy ( 5 , 6 ). (pubmedcentralcanada.ca)
  • Metastasis of cancer cells from primary tumor site to secondary locations is considered a late event in multistep tumorigenesis, and causes most cancer-related mortality. (intechopen.com)
  • Understanding the differences in the characteristics of the microenvironment surrounding the primary tumor and their respective metastasis might help improve strategies to comprehend cancer. (biomedcentral.com)
  • The tumor and the microenvironment (ME) that surrounds it are necessary to initiate a series of steps to invade, colonize, and grow in a distant tissue for induce metastasis [ 1 ]. (biomedcentral.com)
  • Metastasis is a complex and multifaceted process that has an influence on the tumor cells (mutations, epigenetic changes, and characteristics) as well as on the availability of growth factors, interaction with other tumor cells, and new surrounding ME [ 1 ]. (biomedcentral.com)
  • The formation of metastasis by tumour cells is thought to be dependent on the expression of specific phenotypes by individual tumour cells. (utoronto.ca)
  • Cancer stem cells, hypoxia and metastasis. (utoronto.ca)
  • This stands as a first report of identification of a microRNA mediator that links hypoxia and the TGFβ signaling pathways, both of which are involved in regulation of breast cancer metastasis. (sigmaaldrich.com)
  • Delineating the mechanisms by which hypoxia affects tumor physiology at the cellular and molecular levels is crucial for a better understanding of the process of tumor development and metastasis and for the design of better antitumor modalities. (asm.org)
  • It is known that non-tumor cells are presumably and genetically more stable than tumor cells, thus, therapies targeting the tumor microenvironment are less likely to cause adaptive mutations and rapid metastasis. (spandidos-publications.com)
  • These studies have revealed that specific miRNAs exhibit an aberrant expression profile in tumor tissue, and are involved in various aspects of tumorigenesis, including growth, apoptosis, metastasis and particularly angiogenesis ( 10 - 14 ). (spandidos-publications.com)
  • Such conditions occur because the tumor vascular supply, which develops from the normal host vasculature by the process of angiogenesis, is generally inadequate in meeting the oxygen and nutrient demands of the growing tumor mass. (frontiersin.org)
  • Although the rapid proliferation of tumors can stimulate the growth of new vasculature and the tumor-induced angiogenesis leads to the unorganized growth of vasculature, the precisely distributed vasculature in normal tissues contributes to the delivery of oxygenated blood. (biomedcentral.com)
  • The onset and maintenance of tumor angiogenesis also seems to be driven, in part, by these cells. (aacrjournals.org)
  • Similarly, a recent study using small interfering RNA to inhibit CSF-1 expression by MCF-7 xenografts confirmed these findings, showing that lower numbers of TAMs are accompanied by a marked reduction in tumor growth and angiogenesis ( 5 ). (aacrjournals.org)
  • Mechanical Forces in Tumor Angiogenesis. (bioportfolio.com)
  • Thus, the invasive phenotype observed under angiogenesis inhibition requires Hif-1α , but is not directly caused by acute hypoxia. (nature.com)
  • Many of these changes involve HIF-1α 7 , thus we speculated that HIF-1α might play an important role in the microenvironment where angiogenesis is disturbed. (nature.com)
  • However, only few nanoparticles are capable of spreading throughout the entire tumor because of several biological barriers in the tumor microenvironment, such as the dense tumor stroma, abnormal angiogenesis, and elevated tumor interstitial fluid pressure (IFP). (thno.org)
  • Hypoxia inducible factor-1α (HIF-1α) is a key oxygen-regulated transcriptional activator, playing a fundamental role in the adaptation of tumor cells to hypoxia by upregulating the transcription of target genes related to multiple biological processes, including cell survival, proliferation, angiogenesis and anti-apoptosis.Significant HIF1A expression has been noted in most solid tumors studied, which include cancers of the gastric and colon. (wikipedia.org)
  • Hypoxia-inducible transcription factors (HIFs) 1 are central mediators of cellular adaptation to hypoxia that control the expression of genes involved in anaerobic metabolism, intracellular pH, angiogenesis, and cell growth and survival ( 1 ). (mcponline.org)
  • HIFs represent a critical signaling node in the switch to protumorigenic inflammatory responses through recruitment of protumor immune cells and altered immune cell effector functions to suppress antitumor immune responses and promote tumor growth through direct growth-promoting cytokine production, angiogenesis, and ROS production. (jci.org)
  • It has become clear that hypoxia shapes and induces specific macrophage phenotypes that serve tumor malignancy, as hypoxia promotes immune evasion, angiogenesis, tumor cell survival, and metastatic dissemination. (jci.org)
  • Hypoxia is a common condition encountered within the tumour microenvironment that drives proliferation, angiogenesis, and resistance to therapy. (europa.eu)
  • Using OFDI-based techniques, measurements of tumor angiogenesis, lymphangiogenesis, tissue viability and both vascular and cellular responses to therapy were demonstrated, thereby highlighting the potential of OFDI to facilitate the exploration of pathophysiological processes and the evaluation of treatment strategies. (mit.edu)
  • In this work, we show that the expression of the angiogenesis-related, immediate early gene CCN1 (formerly known as CYR61 ), considered to be involved in tumor growth and invasiveness, is enhanced upon hypoxia stress primarily in a protein kinase A and cyclic AMP-responsive element binding protein (CREB) and CRE-dependent manner in various cell lines. (aacrjournals.org)
  • Identifying and characterizing the molecular mechanisms that govern the response of tumors to hypoxia may be instrumental to identify the tumors that will respond favorably to inhibition of angiogenesis and thus lead to the development of treatments that could complement hypoxia-inducing treatment modalities. (aacrjournals.org)
  • We have also shown that CREB plays a pivotal role in tumor growth and angiogenesis in hepatocellular carcinoma (HCC) in vivo ( 10 ). (aacrjournals.org)
  • The secretion of angiogenesis factors such as the fibroblast growth factor, VEGF, platelet-derived growth factor, interleukin-8, angiogenin, and CCN1, is enhanced in response to hypoxia ( 10 , 14 - 22 ). (aacrjournals.org)
  • We are investigatting the tumor microenvironment especially the hypoxia signaling, angiogenesis and their impacts on tumor growth, chemosensivity and therapy. (uta.edu)
  • For example, in the study by Cha et al , miR-519c was demonstrated to be a hypoxia-independent regulator of HIF-1α, functioning through the direct binding to the 3′-UTR of the HIF-1α gene and leading to reduced tumor angiogenesis ( 21 ). (spandidos-publications.com)
  • Metabolic alterations in response to hypoxia can be triggered in a direct manner, such as the switch from oxidative phosphorylation to glycolysis or inhibition of fatty acid desaturation. (frontiersin.org)
  • Indeed, a complex pathway exists that regulates the adaptive response to hypoxia. (frontiersin.org)
  • The master regulators of the cellular response to hypoxia constitute a heterodimeric complex formed by a constitutively expressed nuclear HIFβ, and a cytoplasmic oxygen-dependent HIFα (HIF-1α, HIF-2α, and HIF-3α) subunit. (frontiersin.org)
  • We have been investigating the relationship between the activation of hypoxia-inducible factor 1 (HIF-1), the primary transcriptional regulator of the mammalian response to hypoxia, and 5′-AMP-activated protein kinase (AMPK), another regulatory system important for controlling cellular energy metabolism. (asm.org)
  • Together, these findings suggest that enhanced glucose absorption and/or glycolytic activity mediated by HIF-1 in response to hypoxia activates c-Jun/AP-1, as well as other targets of c-Jun N-terminal kinases. (asm.org)
  • Consequently, the cellular response to hypoxia has important implications for both health and for diseases including (but not limited to) cancer, ischemia and chronic inflammation. (keystonesymposia.org)
  • Macrophages and neutrophils are major cellular components of innate immunity and contribute not only to O 2 deprivation at the site of inflammation, but also alter many of their functions in response to hypoxia to either facilitate or suppress inflammation. (jci.org)
  • A key physiological response to hypoxia is the rise in levels of the hormone erythropoietin (EPO), generating an increase in red blood cells. (elsevier.com)
  • Specific DNA segments located next to the EPO gene were shown to manage the response to hypoxia and how this was available across all types of tissues in the body, including the kidneys - where EPO is typically produced. (elsevier.com)
  • However, the transcriptional response to hypoxia is not limited to regulation by HIF-1 and other transcription factors such as the cyclic AMP (cAMP) responsive element-binding protein (CREB) may be involved in a tissue-specific manner, either independently or in cooperation with HIF-1 ( 8 - 11 ). (aacrjournals.org)
  • Moreover, we have shown that in response to hypoxia, wild-type CREB (wtCREB) increases the expression of CREB-mediated genes, whereas the CREB-mutated in cysteines at positions 300 and 310 (CREB300/310) already mimics at normoxia the increased activity of wtCREB at hypoxia ( 13 ). (aacrjournals.org)
  • Cells stably expressing a dominant-negative PERK allele and mouse embryonic fibroblasts with a homozygous deletion of PERK exhibited attenuated phosphorylation of eIF2α and reduced inhibition of protein synthesis in response to hypoxia. (asm.org)
  • A number of studies have indicated that alterations in microRNA (miRNA) expression may be involved in the regulation of the cellular response to hypoxia. (spandidos-publications.com)
  • Furthermore, a number of studies have indicated that alterations in miRNA expression may be involved in the regulation of the cellular response to hypoxia ( 15 - 18 ). (spandidos-publications.com)
  • Among the proteins considered instrumental in establishing the TME ( 1 ), Ephs and their cell-associated ephrin ligands are implicated in neoangiogenesis and invasive tumor growth, and are increasingly being recognized as therapeutic targets entering clinical trials ( 4 ). (aacrjournals.org)
  • Effective eradication of malignant disease requires therapeutic strategies that factor in targeting the tumor microenvironment. (springer.com)
  • The current review focuses on the role of intra-tumor hypoxia as a mechanism of resistance to anti-angiogenic agents and speculates on therapeutic approaches that might circumvent resistance and thereby improve clinical outcome. (nih.gov)
  • This review will discuss the evidence for differential regulation of TAMs in these microenvironments and provide an overview of current attempts to target or use TAMs for therapeutic purposes. (aacrjournals.org)
  • We aimed at analyzing the tumor microenvironment and the recent trends for the therapeutic applications and effectiveness for several k. (bioportfolio.com)
  • Pancreatic cancer (PAC) is one of the most devastating cancer types with an extremely poor prognosis, characterized by a hypoxic microenvironment and resistance to most therapeutic drugs. (biomedcentral.com)
  • In addition, we outline how hypoxia can be manipulated to tailor the immune response and provide a promising combinational therapeutic strategy to improve immunotherapy . (bvsalud.org)
  • Join this webinar to learn how spatial resolution of gene expression in tumor tissue reveals new insights in biomarker discovery and therapeutic response. (genomeweb.com)
  • and critically evaluate novel targets for imaging or therapeutic intervention that would be of use to the tumor microenvironment community and pharmaceutical industry. (springer.com)
  • Hypoxia, cancer metabolism and the therapeutic benefit of targeting lactate/H(+) symporters. (nih.gov)
  • Tumor-Induced Immune Suppression - Prospects and Progress in Mechanisms and Therapeutic Reversal presents a comprehensive overview of large number of different mechanisms of immune dysfunction in cancer and therapeutic approaches to their correction. (springer.com)
  • Recently, the discovery and elucidation of specific hypoxia-inducible pathways has raised the possibility of developing new strategies for therapeutic benefit based on targeting hypoxia-sensitive pathways. (keystonesymposia.org)
  • Based on these mechanisms, Ms-DDS could deliver maximum quantity of drugs to the therapeutic targets including tumor tissues, cells, and subcellular organelles and eventually exhibit the highest therapeutic efficacy. (thno.org)
  • To maximize the therapeutic efficacy, nanoparticles should be able to penetrate into the deep tumor tissue, have high-affinity interaction with tumor cells and release the drugs outside or within the tumor cells. (thno.org)
  • The interaction between CSCs and their microenvironment provides new targets for therapeutic intervention. (pubmedcentralcanada.ca)
  • These effects are largely mediated by a family of hypoxia-inducible transcription factors (HIFs), which serve as the master regulators of cellular responses to inadequate oxygenation and HIFs and their regulatory factors are now emerging as therapeutic targets in a number of disease states. (jci.org)
  • The knowledge gained assisted us to design new radiotracer for diagnostic of hypoxic tumors (described in WP2) and peptides that can manipulate the copper metabolism, towards development of new therapeutic agents to neurological diseases (WP3). (europa.eu)
  • In this review article, we present recent updates on the hematologic tumor microenvironment following the 3rd Scientific Workshop on the Haematological Tumour Microenvironment and its Therapeutic Targeting organized by the European School of Hematology, which took place at the Francis Crick Institute in London in February 2019. (haematologica.org)
  • The content covers basic research and possible clinical applications with the major therapeutic angle of utilizing basic knowledge to devise new strategies to target the tumor microenvironment in hematologic cancers. (haematologica.org)
  • The microenvironment of these metastases is currently being studied owing to the discovery of new therapeutic targets. (biomedcentral.com)
  • The Moffitt Cancer Center has been investigating various approaches to target these microenvironmental phenotypes for improved therapy, including novel methods to neutralize tumor acidity via ingested buffer treatment, and modulation of mitochondrial respiration to increase therapeutic efficacy of hypoxia-activated pro-drugs. (agilent.com)
  • My professional interest is to investigate the causes and consequences of the abnormal metabolic phenotypes of cancer cells in response to microenvironmental stresses such as hypoxia and nutrient deprivation, with the prospect that therapeutic approaches might be developed to target these metabolic pathways to improve cancer treatment. (stanford.edu)
  • Therefore, further studies must provide new insight into the tumor microenvironment for better cancer therapeutic strategies. (spandidos-publications.com)
  • Low oxygen tension or hypoxia is a determining factor in the course of many different processes in animals, including when tissue expansion and cellular metabolism result in high oxygen demands that exceed its supply. (frontiersin.org)
  • However, as the modulated action of hypoxia-inducible factors or the oxygen sensors (prolyl hydroxylase domain-containing enzymes) can also lead to changes in enzyme expression, these metabolic changes can also be indirect. (frontiersin.org)
  • This poor vessel irrigation leads to a highly heterogeneous tumor mass with variable oxygen pressure and nutrient levels that cancer cells as well as TME cells need to overcome. (frontiersin.org)
  • The tumor microenvironment caused rapid and dramatic up-regulation of arginase I and inducible nitric oxide synthase in MDSC, which was accompanied by down-regulation of nicotinamide adenine dinucleotide phosphate-oxidase and reactive oxygen species in these cells. (rupress.org)
  • Diminished oxygen availability (hypoxia), as a hallmark of the TME, presents in the majority of tumors, arising from an imbalance between increased oxygen consumption and inadequate oxygen supply. (biomedcentral.com)
  • The irregular distribution of tumor vasculature caused by persistent hypoxic conditions can result in an increase in the distance between the capillaries, exceeding the capacity of oxygen to diffuse [ 11 , 12 ]. (biomedcentral.com)
  • This makes the tumor hypoxic, resulting in the Warburg effect and an increased generation of reactive oxygen species (ROS). (nih.gov)
  • NEW YORK (GenomeWeb) - An international team of researchers has mapped the landscape of tumor hypoxia in 19 tumor types in order to determine what effect such low levels of molecular oxygen can have on the tumors' mutational signatures. (genomeweb.com)
  • The topics covered in this book include the quantitative image analysis of a tumor microenvironment, the microenvironmental barriers in oxygen and drug delivery to tumors, the development of tumor microenvironmental niches and sanctuaries, intravenous transport of the circulating tumor cells, the role of the tumor microenvironment in chemotherapeutic interventions, the interactions between tumor cells, the extracellular matrix, the interstitial fluid, and the immune and stromal cells. (springer.com)
  • These findings imply that HIF-1 and AMPK are components of a concerted cellular response to maintain energy homeostasis in low-oxygen or ischemic-tissue microenvironments. (asm.org)
  • We have been studying the relationship between the activity of hypoxia-inducible factor 1 (HIF-1), the primary transcriptional regulator of the response of mammalian cells to oxygen deprivation (e.g., see references 21 , 43 , and 50 ) and the regulation of c-Jun/AP-1 transcription factors ( 31 , 32 ). (asm.org)
  • Reduced oxygen tension due to imbalanced oxygen supply and consumption is termed hypoxia and is one of the most commonly observed features in solid tumours. (intechopen.com)
  • A leading team of scientists at Toronto's Princess Margaret Cancer Centre is set to expand its groundbreaking research into the effects of low oxygen levels (hypoxia) on tumour aggressiveness th. (tfri.ca)
  • 2 , 5 , 6 A common feature of inflamed tissues is represented by hypoxia, a condition of low partial oxygen pressure (pO 2 , 0-20 mmHg), which arises as a result of dysfunctional vascular network and diminished O 2 supply and affects the phenotype and functions of every cell exposed to it. (bloodjournal.org)
  • Briefly, transcriptional activation is mediated primarily by the hypoxia-inducible factor-1 (HIF-1), a heterodimer of the constitutive HIF-1β subunit and an oxygen-sensitive α-subunit (HIF-1α/-2α). (bloodjournal.org)
  • One feature of inflammation sites is low oxygen (O 2 ) tension, termed "hypoxia. (jci.org)
  • Tumor hypoxia is the situation where tumor cells have been deprived of oxygen. (wikipedia.org)
  • As a tumor grows, it rapidly outgrows its blood supply, leaving portions of the tumor with regions where the oxygen concentration is significantly lower than in healthy tissues. (wikipedia.org)
  • A common condition is hypoxia, a shortage of oxygen as the tumor outgrows its blood supply. (scienceblog.com)
  • Tumor cells shift to making their energy through glycolysis, a method of metabolism that does not require oxygen. (scienceblog.com)
  • Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment, or hypoxia. (wikipedia.org)
  • The HIF signaling cascade mediates the effects of hypoxia, the state of low oxygen concentration, on the cell. (wikipedia.org)
  • Hypoxia in cancers has evoked significant interest since 1955 when Thomlinson and Gray postulated the presence of hypoxia in human lung cancers, based on the observation of necrosis occurring at the diffusion limit of oxygen from the nearest blood vessel, and identified the implication of these observations for radiation therapy. (springer.com)
  • Here, we report that hereditary leiomyomatosis and renal cell cancer tumors indeed overexpress LDH-A, that LDH-A inhibition results in increased apoptosis in a cell with FH deficiency and that this effect is reactive oxygen species mediated, and that LDH-A knockdown in the background of FH knockdown results in significant reduction in tumor growth in a xenograft mouse model. (aacrjournals.org)
  • Low oxygen levels, or hypoxia, is a key feature of inflamed tissue and is due to damage to the local vasculature and increased oxygen consumption by pathogens and infiltrating immune cells. (jci.org)
  • Maintaining energy homeostasis under hypoxia, or low oxygen conditions, has important implications for several research areas, including cancer biology, cardiovascular function, stroke, and stem cell biology. (agilent.com)
  • The rapid growth of tumour cells and their inability to form normal blood vessels reduce the blood supply and oxygen tension. (ecancer.org)
  • Cancer cells adapt to hypoxia using various pathways, allowing tumors to thrive in a low oxygen state. (aacrjournals.org)
  • Inadequate oxygen (hypoxia) triggers a multifaceted cellular response that plays a significant role in both normal physiology and pathology. (aacrjournals.org)
  • The term hypoxia is used to describe oxygen deficiency occurring in tissues due to various reasons. (termedia.pl)
  • cytotoxic hypoxia where the quantity of oxygen delivered to tissues is sufficient but toxic damage of tissue has occurred. (termedia.pl)
  • Thus, hypoxemic hypoxia is the easiest to manage of all forms of oxygen deficiency. (termedia.pl)
  • For most cells, hypoxia is defined as molecular oxygen levels reduced to less than 2%, with the level of 1.2% defining moderate hypoxia and the level below 0.2% defining deep hypoxia and anoxia. (termedia.pl)
  • Tumor cells are particularly prone to hypoxia due to their high density and poor vascularization limiting their oxygen supply. (termedia.pl)
  • In the tumor microenvironment cells often face a certain degree of oxygen and nutrient deprivation. (ovid.com)
  • In these three types of tumors, treatment is more effective in the primary tumor than in BM due to several factors, including BBB. (biomedcentral.com)
  • We will review how tumor cells recruit stromal cells to the primary tumor site and build the microenvironment. (spandidos-publications.com)
  • In 1960, Klein and colleagues found that when mice developed primary methylcholanthrene-induced sarcomas, they also developed an antitumor immune response mediated by lymph node cells to a secondary challenge comprising cancer cells derived from the primary tumor ( 4 ). (sciencemag.org)
  • The paradoxical and critical finding of the study was that this anticancer immune response did not control the growth of the primary tumor, despite its ability to prevent the establishment of a secondary tumor comprising cancer cells derived from the primary tumor. (sciencemag.org)
  • In traditional immunological terminology, the primary tumor evaded immune control by establishing an immune-privileged microenvironment that is functionally analogous to that of certain normal tissues, such as the eye ( 5 ). (sciencemag.org)
  • Unfortunately, the tumor neo-vasculature that is formed is not only primitive and chaotic when compared to the normal tissue vascular supply from which it develops, but it also suffers from numerous structural and functional abnormalities. (frontiersin.org)
  • Eph receptor tyrosine kinases are critical for cell-cell communication during normal and oncogenic tissue patterning and tumor growth. (aacrjournals.org)
  • 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)
  • Tumor tissue or cells are studied either using immunohistochemistry or flow cytometry. (upenn.edu)
  • We have shown that hypoxia, as measured by EF5 binding correlates to the level of tumor aggression in glial brain tumors, soft tissue sarcomas and head/neck squamous cell cancers. (upenn.edu)
  • Tissue hypoxia occurs in a range of physiologic and pathophysiologic states. (keystonesymposia.org)
  • We reported that monocyte differentiation into iDCs under chronic hypoxia promotes the onset of a unique migratory phenotype by differentially modulating the expression profile of chemokines/receptors and genes involved in cell adhesion and tissue remodeling. (bloodjournal.org)
  • In the setting of obesity, hypoxia develops as adipose tissue mass expands, initiating inflammatory responses. (jci.org)
  • With regard to PEGylated passively targeted nanoparticles, many can successfully extravasate into the tumor tissue following intravenous injection. (thno.org)
  • Also, a balance needs to be found between the stability of the nanoparticles during the transport in blood circulation and the ideal tumor cellular uptake after extravasation into tumor tissue. (thno.org)
  • Doxorubicin has poor tissue penetration and targets the regions of tumors that are located in proximity to the tumor vessels. (clinicaltrials.gov)
  • Soft tissue sarcomas have evidence supporting the presence of hypoxia based on pO2 histography, F-MISO and gene expression profiling. (clinicaltrials.gov)
  • Noninvasive spatially- and temporally-resolved in vivo monitoring of critical parameters of tissue microenvironment provides unique insights into the role of TME in cancer aggression, metastatic activity, and treatment efficacy and creates novel opportunity for designing TME-targeted anticancer therapies. (wvu.edu)
  • Tissue hypoxia is not only associated with a variety of pathological conditions such as pulmonary, cardiovascular and neoplastic diseases, but also occurs during normal embryonic development and plays an important role in stem cell maintenance. (keystonesymposia.org)
  • Using entirely intrinsic mechanisms of contrast within murine tumor models, OFDI is able to simultaneously, rapidly, and repeatedly probe the microvasculature, lymphatic vessels, and tissue microstructure and composition over large volumes. (mit.edu)
  • These factors, which can be specific to the individual tumour or normal tissue and to their environment, can vary from patient to patient. (utoronto.ca)
  • One part of the research in our laboratory focuses on understanding how these factors influence tumour and normal tissue response to radiation treatment in individual patients. (utoronto.ca)
  • The combination of tissue-/tumour-specific promoters with HRE core sequences has been found to enhance the specificity and efficacy of this system. (ecancer.org)
  • Moreover, it also emphasises on several tissue and tumour-specific promoters, along with their application in cancer gene therapy. (ecancer.org)
  • Eventually, it describes the dual-targeting transcriptional regulation systems with an emphasis on hypoxia-inducible tumour-specific promoters for hypoxia and tissue-specific gene therapy. (ecancer.org)
  • In turn, these recruited cells release growth-promoting signals and intermediate metabolites as well as remodel tissue structure to build the microenvironment. (spandidos-publications.com)
  • A tumor is a highly complex tissue composed of neoplastic and stromal cells. (spandidos-publications.com)
  • In the injured mouse tissue, renal-infiltrating CD4 + and CD8 + T cells express hypoxia-inducible factor-1 (HIF-1), which alters their cellular metabolism and prevents their apoptosis in hypoxia. (sciencemag.org)
  • Perturbation of these environmental adaptations by selective HIF-1 blockade inhibited infiltrating T cells and reversed tissue hypoxia and injury in murine models of lupus. (sciencemag.org)
  • It explores the changes that cancer cells can induce in nearby normal tissue, the new relationship established between them and the stroma, and the interaction between the immune system and tumour growth. (oup.com)
  • The coexistence in some patients of cancer cells and T cells that recognize them indicates that tumors may exhibit the phenomenon of immune privilege, in which immunogenic tissue is protected from immune attack. (sciencemag.org)
  • The importance of a stromal microenvironment, especially one that has characteristics of a "wound" or regenerating tissue, has been recognized for at least a century ( 3 ), but its possible role in blunting an immune attack of cancer cells awaited the discovery of adaptive cellular immunity. (sciencemag.org)
  • The complex biology of tumors presents challenges in designing treatments that will eliminate the malignant cells as well as the supporting network of vasculature and stroma that allows for the comparison of tumors to developing organs in embryos. (springer.com)
  • Several chapters describe endothelial cells and pericytes that form tumor vasculature. (springer.com)
  • Tumor vasculature normalization by orally fed erlotinib to modulate the tumor microenvironment for enhanced cancer nanomedicine and immunotherapy. (bioportfolio.com)
  • The abnormal tumor vasculature is one of key reasons that lead to the limited tumor perfusion as well as hypoxic and immunosuppressive tumor microenvironment (TME). (bioportfolio.com)
  • The tumor vasculature is poor and heterogeneous which may result in inadequate oxygenation and changed energy status. (dissertations.se)
  • Hypoxia, through hypoxia-inducible factors (HIFs), in addition to oncogenes activation and loss of tumour suppressors constitute major regulators of not only the "Warburg effect" but also many other metabolic pathways such as glutaminolysis. (nih.gov)
  • 7 , 8 , 10 HIF-1 expression and activity are tightly regulated by various cofactors and transcription factors, and HIF-independent pathways mediating gene induction by hypoxia have also been described. (bloodjournal.org)
  • Bone marrow-derived progenitor cells, including VEGFR2 + endothelial progenitor cells (EPCs) and copper-dependent pathways, model the tumor microenvironment. (aacrjournals.org)
  • How metabolic pathways are regulated to meet the unique needs of tumor cells is not well understood, but mounting evidence suggests that metabolic regulation in cancer cells is intimately linked with the signal transduction pathways that control cell growth and proliferation. (keystonesymposia.org)
  • Reviews in this series discuss the roles of hypoxia and HIFs in the regulation of inflammatory pathways, immune cell metabolism, mucosal inflammation, the tumor microenvironment, intestinal inflammation and colorectal cancer, and recovery from radiation-induced gastrointestinal toxicity. (jci.org)
  • Activation of hypoxia signaling pathways stimulates neoangiogenesis, alters tumor metabolism, promotes a more aggressive tumor behavior and significantly affects its responsiveness to therapy. (srce.hr)
  • In order to consolidate the relationships between OSA, insulin resistance and diabetes, it is necessary to identify pathogenic pathways connecting the two key elements of OSA - intermittent hypoxia (IH) and sleep fragmentation - with loss of sensitivity to insulin in its target tissues and pancreatic islet β-cell dysfunction. (ersjournals.com)
  • Somatic mutation profiles of several cancer genomes suggest EphA3 as a tumor suppressor, but its oncogenic expression pattern and role in tumorigenesis remain largely undefined. (aacrjournals.org)
  • In particular, up-regulation of hypoxia-inducible factor (HIF), which occurs as a consequence of hypoxia as well as from alterations in certain oncogenes or mutations in tumor suppressor genes, results in the increased transcription of genes involved in glucose transport, glucose metabolism, lactate formation, and lactate export from cells ( 2 - 6 ). (aacrjournals.org)
  • Role of oncoproteins and tumor suppressor proteins in transcription regulation and DNA repair. (uthscsa.edu)
  • Cancer genetic, epidemiolog, tumor suppressor genes. (uthscsa.edu)
  • This hypoxia-induced G 1 /S arrest is independent of functional p53 tumor suppressor protein, since cells with mutant p53 and p53 knockout cells also arrest at the G 1 /S interface under hypoxic conditions ( 22 ). (asm.org)
  • Oncogene activation and tumor-suppressor gene inactivation are considered as the main causes driving the transformation of normal somatic cells into malignant tumor cells. (spandidos-publications.com)
  • Tumorigenesis is a complicated and multistep process, in which successive mutations in oncogenes and tumor-suppressor genes virtually result in enhanced proliferation and resistance to cell death. (spandidos-publications.com)
  • Furthermore, hypoxia is often associated with other microenvironmental parameters, such as elevated interstitial fluid pressure, glycolysis, low pH, and reduced bioenergetic status, and these can also influence the effects of hypoxia. (frontiersin.org)
  • Here, we review the known effects of hypoxia and ROS on the function and physiology of dendritic cells (DCs). (nih.gov)
  • Since hypoxia is a major cause of extracellular acidosis in tumors, here, we have focused on the applications of imaging to understand the effects of hypoxia in tumors and to target hypoxia in theranostic strategies. (springer.com)
  • To investigate the effects of hypoxia in cultured cells, XF technology has been adapted to function in reduced O2 environments (i.e. a hypoxia chamber). (agilent.com)
  • The poor tumor microenvironment also causes these cells to upregulate the expression of various genes and biosynthesis of proteins, an effect that not only increases their survival potential but can also increase tumor aggressiveness and metastatic spread. (frontiersin.org)
  • Monocytes enter tumors through blood vessels throughout the life span of tumors, from early-stage tumor nodules that are beginning to vascularize to late-stage tumors that are invasive and metastatic. (aacrjournals.org)
  • What role does obesity play in metastatic breast cancer and how does it affect the tumour microenvironment? (tfri.ca)
  • Furthermore, hypoxia is known to change cell behavior and is associated with extracellular matrix remodeling and increased migratory and metastatic behavior. (wikipedia.org)
  • Cancer research provides information on the fate of metastatic cancer cells in each sequential movement or heterogeneous tumor microenvironment. (intechopen.com)
  • Growing amount of evidence suggest that hypoxia induces transcription of tumor promoting genes leading to increased tumor cell proliferation and metastatic potential. (srce.hr)
  • The most frequent malignant brain tumors are metastatic in origin and primarily originate from lung cancer, breast cancer, and melanoma. (biomedcentral.com)
  • Our research is examining metastatic phenotypes that are expressed only transiently and that may be induced by exposure of tumour cells to conditions, such as hypoxia, which occur in the tumour microenvironment. (utoronto.ca)
  • We have found in animal model systems that exposure to hypoxia, both in vitro and in vivo, can cause transient increases in the metastatic potential of tumour cells and that exposure to transient hypoxic episodes may be particularly important for this increased metastatic potential. (utoronto.ca)
  • The tumor microenvironment and metastatic disease. (utoronto.ca)
  • Hypoxic tumors are more metastatic, are more resistant to radiotherapy and chemotherapy, and have a poorer prognosis than better-oxygenated ones, irrespective of therapy ( 28 , 29 , 72 ). (asm.org)
  • Through reciprocal communication, cancer cells and the microenvironment act in collusion leading to high proliferation and metastatic capability. (spandidos-publications.com)
  • The reciprocal communication between cancer cells and the microenvironment eventually leads to enhanced proliferation and metastatic capability, and finally death. (spandidos-publications.com)
  • With this review, we want to summarize our current knowledge of the hypoxia-induced changes in metabolism during cancer development, how they are affected in the tumor cells and in the cells of the microenvironment, most prominently in immune cells. (frontiersin.org)
  • However, the oncogenic transformation process not only involves cancer cells, but it also alters their tumor microenvironment (TME), which includes stromal and infiltrating immune cells ( 3 ). (frontiersin.org)
  • The unique tumor microenvironment of endometriosis is composed of epithelial, stromal, and immune cells, which adapt to survive in hypoxic conditions with high levels of iron, estrogen, and inflammatory cytokines and chemokines. (mdpi.com)
  • Although an important role of MDSC in tumor-associated immune suppression is well established in recent years, its nature remains unclear. (rupress.org)
  • In addition to blood vessels and malignant cells, tumors consist of fibroblasts, immune and inflammatory cells, and a myriad of proteins that comprise the extracellular matrix. (springer.com)
  • Additional chapters describe the influence of infiltrating cells of the immune system on tumor growth. (springer.com)
  • Hypoxia and ROS affect immune cells in the tumor micro-environment, thereby affecting their immune function. (nih.gov)
  • Understanding their precise roles and interplay is important given that an adaptive immune response is required to clear tumor cells. (nih.gov)
  • To further explore the effect of hypoxia on the prognosis of patients with PAC as well as the tumor immune microenvironment, we established a hypoxia risk model and divided it into high- and low-risk groups in line with the hypoxia risk score. (biomedcentral.com)
  • We established a hypoxia risk model according to four hypoxia-related genes, which could be used to demonstrate the immune microenvironment in PAC and predict prognosis. (biomedcentral.com)
  • In summary, we established and validated a hypoxia risk model that can be considered as an independent prognostic indicator and reflected the immune microenvironment of PAC, suggesting the feasibility of hypoxia-targeted therapy for PAC patients. (biomedcentral.com)
  • It has been found that hypoxia was served as a primary factor in the formation of tumor immunosuppressive microenvironment, which enhances tumor immune evasion by suppressing the anti-tumor immune responses [ 8 ]. (biomedcentral.com)
  • In this review , the potential impact of hypoxia within the TME, in terms of key immune cell populations , and the contribution to immune suppression are discussed. (bvsalud.org)
  • Researchers have learned how to manipulate the immune system to generate tumor specific immune response, which raises high expectations for immunotherapy to provide breakthroughs in cancer treatment. (springer.com)
  • It is increasingly clear that tumor-induced abnormalities in the immune system not only hampers natural tumor immune surveillance, but also limits the effect of cancer immunotherapy. (springer.com)
  • Therefore, it is critically important to understand the mechanisms of tumor-induced immune suppression to make any progress in the field and this monograph provides these important insights. (springer.com)
  • In this study, we identified by gene expression profiling a significant cluster of genes coding for immune-related cell surface receptors strongly up-regulated by hypoxia in monocyte-derived mDCs and characterized one of such receptors, TREM-1, as a new hypoxia-inducible gene in mDCs. (bloodjournal.org)
  • On the other hand, innate immune cells, such as neutrophils and macrophages, have been frequently shown to infiltrate tumors and promote an immunosuppressive environment. (pnas.org)
  • Our results show that, when nutrients are low, tumor cells secrete factors related to wound healing that stimulate endothelial cells and attract innate immune cells. (pnas.org)
  • This suggests that targeting signals elicited by metabolic stress may help the immune system target malignant cells and that metabolites regulate the communication between immune and tumor cells also through modulation of peptidic signals. (pnas.org)
  • These cancer stem cells (CSCs) are regulated by complex interactions with the components of the tumor microenvironment - including mesenchymal stem cells, adipocytes, tumor associated fibroblasts, endothelial cells, and immune cells - through networks of cytokines and growth factors. (pubmedcentralcanada.ca)
  • The tumor immune response is in a dynamic balance between antitumor mechanisms, which serve to decrease cancer growth, and the protumor inflammatory response, which increases immune tolerance, cell survival, and proliferation. (jci.org)
  • In addition to being a feature of inflammation, hypoxia also induces and regulates the inflammatory response by inducing the release of inflammatory cytokines, directing immune cell infiltration, and tuning the responses of the immune cells themselves. (jci.org)
  • The contributors review efforts to characterize the subclonal architecture and dynamics of tumors, understand the roles of chromosomal instability, driver mutations, and mutation order, and determine how cancer cells respond to selective pressures imposed by anticancer agents, immune cells, and other components of the tumor microenvironment. (cshlpress.com)
  • Actually, tumor cells can efficiently recruit stromal cells ( 4 ), immune cells ( 5 ) and vascular cells ( 6 ) by secreting stimulatory growth factors, chemokines and cytokines. (spandidos-publications.com)
  • Immunoediting, or the elimination of immunogenic cancer cells ( 7 ), could be excluded, which left the possibility of immune suppression by the tumor microenvironment (TME). (sciencemag.org)
  • We will, therefore, summarize the most essential and relevant studies in the field of cancer-related metabolism, highlighting the regulating properties of hypoxia pathway proteins. (frontiersin.org)
  • The researchers found that the combined treatment with temozolomide and SLC-0111 in cell culture experiments: 1) reduced glioblastoma cell growth, 2) induced arrest of the cell-division cell cycle by creating breaks in DNA, 3) shifted the tumor metabolism and intracellular acid-base balance by decreasing metabolic intermediates, and 4) inhibited enrichment of brain tumor initiating cells. (scienceblog.com)
  • As such, hypoxia and HIF signaling predominates normal intestinal metabolism and barrier regulation during both homeostasis and active inflammation. (jci.org)
  • This alters the phenotype and metabolism of macrophages, to induce a tumor-promoting reprogramming. (ovid.com)
  • We show that inhibiting the expression of AlkB homolog 5 (ALKBH5), which demethylates m 6 A, or the hypoxia-inducible factors (HIFs) HIF-1α and HIF-2α, which activate ALKBH5 gene transcription in hypoxic breast cancer cells, is an effective strategy to decrease NANOG expression and target BCSCs in vivo. (pnas.org)
  • Hypoxia-inducible factors (HIFs) are heterodimeric transcription factors that play a key role in cellular adaptation to hypoxia. (mcponline.org)
  • Activation of HIFs by hypoxia and inflammation. (jci.org)
  • Hypoxia-inducible factors (HIFs), HIF-1 and HIF-2, chiefly mediate the hypoxic response. (ecancer.org)
  • VEGF-A , Epo ) containing regulatory elements in their promoter regions, known as hypoxia-response elements (HREs) that serve as the binding site of HIFs, have been identified [ 1 , 2 ]. (ecancer.org)
  • In mammals, the hypoxia-dependent changes, on a gene expression level, are primarily mediated by the α-subunits of hypoxia-inducible transcription factors (HIFs). (spandidos-publications.com)
  • Clinical resistance is a complex phenomenon in major human cancers involving multifactorial mechanisms, and hypoxia is one of the key components that affect the cellular expression program and lead to therapy resistance. (biomedcentral.com)
  • The precise mechanisms of drug resistance in tumors are complex and multifactorial, but they can be grouped into three categories: insufficiency of pharmacokinetic properties, intrinsic factors of tumor cells, and external conditions of tumor cells in the tumor microenvironment (TME) [ 3 ]. (biomedcentral.com)
  • While exploring cellular mechanisms of ATP regulation, we observed that 5′-AMP-activated protein kinase (AMPK) activity was induced in both cell types, particularly under conditions of hypoxia and glucose deprivation. (asm.org)
  • 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)
  • ABCG2 also plays a critical role in hypoxic defense mechanisms within the tumor microenvironment [ 3 ]. (hindawi.com)
  • The PI3K-Akt-mTOR signaling pathway is one of the primary mechanisms for controlling tumor cell growth, survival, and motility in response to oncogenic signaling and extracellular cues. (keystonesymposia.org)
  • The molecular mechanisms of hypoxia induced breast cell migration remain incompletely understood. (sigmaaldrich.com)
  • This review discusses hypoxia and mechanisms for hypoxia-inducible gene expression, as well as gene therapy strategies targeting tumour hypoxia. (ecancer.org)
  • Hypoxia: A key feature of the tumor microenvironment triggers several mechanisms of evasion from natural killer and cytotoxic T lymphocytes surveillance. (crp-sante.lu)
  • Hypoxia due to causes other than hypoxemia appears to be most dangerous for the system, as only the molecular adaptation mechanisms which require more time for full activation compared to the systemic mechanisms are available in such cases [1]. (termedia.pl)
  • The effect of hypoxia on post-transcriptional and post-translational mechanisms determining the efficiency of gene expression was also described. (termedia.pl)
  • Double KO mice of Vegf and hypoxia inducible factor-1α ( Hif-1α ) showed increased life span and suppressed tumor growth due to increased apoptosis. (nature.com)
  • A transformed cell is identified by the loss of control of proliferation and deregulation of apoptosis producing an excess of cell number and forming a mass (tumor). (hindawi.com)
  • Hypoxia is a key stress that triggers apoptosis in various tumors, including epithelial ovarian cancer (EOC). (dovepress.com)
  • Functional data revealed that aHIF knockdown accelerated cell apoptosis under hypoxia and inhibited EOC tumorigenesis and tumor growth in vivo. (dovepress.com)
  • Additionally, aHIF overexpression inhibited cell apoptosis and enhanced cell proliferation under hypoxia in EOC. (dovepress.com)
  • Mechanistically, the dysregulation of certain key mitochondrial apoptosis pathway-related genes, including Bcl-2, Bax, Caspase-7, and Caspase-9, may partially explain aHIF-regulated EOC apoptosis and growth under hypoxia. (dovepress.com)
  • These data provide the first convincing evidence that aHIF may inhibit EOC apoptosis and thereby promote tumor growth through activation of the mitochondrial apoptosis pathway under hypoxia. (dovepress.com)
  • Antisense oligonucleotide mediated knockdown of HOXC13 affects cell growth and induces apoptosis in tumor cells and over expression of HOXC13 induces 3D-colony formation" RSC Advances, 2013 , 3(10): 3260-3269. (uta.edu)
  • Astorvastatin reduced the HIF-1α protein expression in hypoxia-induced PC3 cells, and induced apoptosis of both control and hypoxia-induced cells with and without irradiation. (portlandpress.com)
  • Radioresistance of prostate cancer may be mainly due to hypoxia in the center of tumors, which could induce a G 2 /M cell cycle arrest, inhibit apoptosis, and reduce the number of senescent cells [ 6 ]. (portlandpress.com)
  • Such an effect together with the increased tumor retention of anti-PDL1 antibody, a clinically approved checkpoint blockade agent, finally contributes to the greatly improved tumor inhibition effect in cancer immunotherapy. (bioportfolio.com)
  • Therefore, our work presents a general yet effective strategy using a clinical drug to enhance the efficacies of cancer nanomedicine and immunotherapy by normalizing tumor vasculatures and modulating TME. (bioportfolio.com)
  • In recent years, many clinical trials have been performed on immunotherapy for tumors, but the efficacy of clinical treatment achieved on PAC are limited [ 10 ]. (biomedcentral.com)
  • Although the specific mechanism of PAC immunotherapy resistance is still unclear, we believe that it is inseparable from the "barren soil" caused by hypoxia. (biomedcentral.com)
  • Targeting hypoxia in the tumor microenvironment: a potential strategy to improve cancer immunotherapy. (bvsalud.org)
  • Therefore, targeting hypoxia may provide a means to enhance the efficacy of immunotherapy . (bvsalud.org)
  • We demonstrate that although MDSCs from peripheral lymphoid organs and the tumor site share similar phenotype and morphology, these cells display profound functional differences. (rupress.org)
  • Macrophages also form a major component of the inflammatory infiltrate seen in both primary and secondary tumors ( 2 ), where, as will be seen below, they also exhibit a distinct phenotype and are termed tumor-associated macrophages (TAM). (aacrjournals.org)
  • Hypoxia leads to a more migratory and inflammatory DC phenotype. (nih.gov)
  • Lastly, hypoxia alters DCs to shift the T- cell response towards a tumor suppressive T h 17 phenotype. (nih.gov)
  • Here, using a genetic targeting strategy, we investigated the contribution of Hif-1α to the changes of tumor phenotype in the Vegf -deleted islet tumors in RIP1-Tag2 mice. (nature.com)
  • 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 this study, we report that exposure of breast cancer cells to hypoxia (i.e., reduced O 2 availability), which is a critical feature of the tumor microenvironment, induces N 6 -methyladenosine (m 6 A) demethylation and stabilization of NANOG mRNA, thereby promoting the breast cancer stem cell (BCSC) phenotype. (pnas.org)
  • Increased NANOG mRNA and protein expression, and the breast cancer stem cell (BCSC) phenotype, were induced by hypoxia in an HIF- and ALKBH5-dependent manner. (pnas.org)
  • A common feature at pathologic sites is represented by hypoxia, a condition of low pO 2 , which creates a unique microenvironment affecting cell phenotype and behavior. (bloodjournal.org)
  • We are also initiating studies to examine the role of hypoxia in modifying or maintaining the aggressive phenotype of tumour stem cells. (utoronto.ca)
  • Death of tumor cells turned out as a communicative system attracting macrophages and directing their phenotype. (ovid.com)
  • In addition the balance between cell proliferation and the rate of cell death is disturbed, which results in tumor growth. (dissertations.se)
  • miR-191 enhances breast cancer aggressiveness by promoting cell proliferation, migration and survival under hypoxia. (sigmaaldrich.com)
  • At the cellular level, exposure of cells to hypoxia has an immediate and reversible effect on proliferation. (asm.org)
  • In contrast to MDSC from the spleen, MDSC from the tumor site rapidly differentiated into macrophages. (rupress.org)
  • Exposure of spleen MDSC to hypoxia resulted in the conversion of these cells to nonspecific suppressors and their preferential differentiation to macrophages. (rupress.org)
  • Thus, hypoxia via HIF-1α dramatically alters the function of MDSC in the tumor microenvironment and redirects their differentiation toward tumor-associated macrophages, hence providing a mechanistic link between different myeloid suppressive cells in the tumor microenvironment. (rupress.org)
  • Hypoxia stabilizes HIF-αs in macrophages and neutrophils, and these O 2 -sensitive transcription factors are key regulators of inflammatory responses in myeloid cells. (jci.org)
  • The role of tumor-associated macrophages (TAMs) in cancer is often correlated with poor prognosis, even though this statement should be interpreted with care, as the effects of macrophages primarily depend on their localization within the tumor. (jci.org)
  • Here we discuss how hypoxia and cell death adds the cross-talk between cancer cells and macrophages. (ovid.com)
  • A better understanding of ABCG2 regulation by the tumor microenvironment may help design novel strategies to improve treatment outcome. (hindawi.com)
  • This study aims to evaluate the regulation of ABCG2 in response to a few characteristic growth conditions within the tumor microenvironment, including hypoxia, glucose deprivation, and low pH. (hindawi.com)
  • The local microenvironment contributes to the regulation of DC development and functions. (bloodjournal.org)
  • With the discovery of the hypoxia-inducible factor (HIF), the intervening years have also seen significant progress in understanding the transcriptional regulation of hypoxia-induced genes. (springer.com)
  • Analogous to the regulation of normal stem cells by their "niche," CSCs are regulated by, and in turn regulate, cells within the tumor microenvironment. (pubmedcentralcanada.ca)
  • HIF-inducible miR-191 promotes migration in breast cancer through complex regulation of TGFβ-signaling in hypoxic microenvironment. (sigmaaldrich.com)
  • Hypoxia-inducible tumour-specific promoters as a dual-targeting transcriptional regulation system for cancer gene therapy. (ecancer.org)
  • This review will also focus on hypoxia-inducible tumour-specific promoters as a dual-targeting transcriptional regulation systems developed for cancer-specific gene therapy. (ecancer.org)
  • Hypoxia promotes breast cancer cell invasion through HIF-1α-mediated up-regulation of the invadopodial actin bundling protein CSRP2. (crp-sante.lu)
  • However, unlike normal tissues, tumors continually expand in size and a point is reached where the host vascular supply becomes inadequate in supplying these needs. (frontiersin.org)
  • One of the major unresolved questions is the role of MDSCs in peripheral lymphoid organs and tumor tissues as well as their relationship with MΦ and DCs. (rupress.org)
  • aHIF levels were increased in EOC tissues and were upregulated by hypoxia in EOC cells. (dovepress.com)
  • To effectively deliver drugs to tumor tissues, nanoparticles need to remain stable during blood circulation and exhibit enhanced accumulation in the tumor. (thno.org)
  • Beyond anatomical resolution provided by MRI, these approaches report on multiple functional parameters of the microenvironment in living tissues when combined with specially designed paramagnetic probes 5-6 . (wvu.edu)
  • α-Subunits are post-translationally stabilized under hypoxia and translocate to the nucleus where they dimerize with HIF-1β transactivating the hypoxia responsive element (HRE) present in the promoter of many O 2 -sensitive genes. (bloodjournal.org)
  • Depletion of mAKAP or disruption of its targeting to the perinuclear (in cardiomyocytes) region altered the stability of HIF-1 and transcriptional activation of genes associated with hypoxia. (wikipedia.org)
  • Using bioinformatic analysis, hypoxia‑inducible factor (HIF)‑1α was identified as one of the target genes of miR‑18a, and based on the function of HIF‑1α in hypoxia, miR‑18a was predicted to regulate HIF‑1α expression. (spandidos-publications.com)
  • ROS might enter DCs via aquaporins in the plasma membrane, diffusion across the plasma membrane or via extracellular vesicles (EVs) released by tumor cells. (nih.gov)
  • called hypoxia hereafter) in an HIF-1-dependent manner ( 31 ) and showed that this HIF-1-dependent c-Jun phosphorylation absolutely requires extracellular glucose utilization ( 32 ). (asm.org)
  • Furthermore, hypoxia increases the number of extracellular vesicles released from cancer cells and also modifies their bioactivity and function. (intechopen.com)
  • The aim of this chapter is to review the association between the tumour microenvironment and extracellular vesicles (EVs), focusing on a specific subpopulation of EVs of endocytic origin, termed exosomes. (intechopen.com)
  • Glycolysis, in turn, changes the acid-base balance at the tumor - the extracellular space becomes more acidic and the tumor cell interiors become more alkaline, adapting to this change. (scienceblog.com)
  • I adapted novel fluorescence resonance energy transfer (FRET) -based nanocrystal (NC) biosensors for use with MPM to qualitatively measure in vivo extracellular pH in tumors at high-resolution. (mit.edu)
  • The microenvironment of tumors contains numerous cell types in addition to cancer cells, which include bone marrow-derived inflammatory cells, lymphocytes, blood vessels, fibroblastic cells, and the extracellular matrix composed of collagen and proteoglycans ( 1 , 2 ). (sciencemag.org)
  • In the first part of the proposal, we will determine the cellular responses to various microenvironmental factors (such as lactosis, acidosis, hypoxia, glucose deprivation) in cultured epithelial cells (commercially obtained) making use of DNA microarray analysis. (clinicaltrials.gov)
  • Hypoxia, glucose deprivation and acidosis are the hallmarks of tumor microenvironment. (hindawi.com)
  • Hypoxia-induced acidosis potentiates accumulation of free metal ions such as Fe 3+ and Cu 2+ . (wvu.edu)
  • While progress has been made in identifying individual gene products whose synthesis is altered under hypoxia, little is known about the mechanism by which hypoxia induces a global downregulation of protein synthesis. (asm.org)
  • This nanovaccine, comprising a simple physical mixture of an antigen and a synthetic polymeric nanoparticle enhances antigen delivery and cross-presentation, generates a strong cytotoxic T-cell response with low systemic cytokine expression, and leads to potent tumor growth inhibition in melanoma, colon cancer and HPV tumor models. (utsouthwestern.edu)
  • Inhibition of MLL suppresses tumor growth in vivo (mice model). (uta.edu)
  • Atorvastatin could enhance radiosensitivity in hypoxia-induced prostate cancer cells, which may be related with inhibition of HIF-1α protein. (portlandpress.com)
  • This is mainly happening when cells actively proliferate and the proliferating mass becomes distant from the blood vessels, such as in growing tumors. (frontiersin.org)
  • Such chronic hypoxia or diffusion-restricted hypoxia causes the necrosis of tumor cells within the 180-μm periphery of blood vessels. (biomedcentral.com)
  • They can be thought of as inhabiting within a complex milieu of normal cells, blood vessels, endogenous small molecules, and secreted factors, which collectively comprise the tumor microenvironment. (hindawi.com)
  • However, hypoxia promotes the formation of blood vessels, and is important for the formation of a vascular system in embryos and tumors. (wikipedia.org)
  • The process from the spreading of cancer cells to the seeding of newly formed tumor colonizations is governed by sequential events, including local invasion, intravasation into stroma and blood vessels, survival in circulation, e. (intechopen.com)
  • These types of events trigger an adaptive process called the "hypoxia response," Prof. Johnson explained, and can influence the creation of new blood vessels or an increase in red blood cells. (elsevier.com)
  • The interdependence between inflammation and hypoxia has been evident for many years. (jci.org)
  • Together, these reviews identify a number of hypoxia-regulated processes that could potentially be targeted to modulate inflammation. (jci.org)
  • If acute inflammation remains unresolved for any reason and progresses to chronic inflammation, which is the major driver of the pathogeneses of many diseases including cancer, the inflammatory cells are broken down and various inflammation inducers such as tumor necrosis factor (TNF)-α, interleukin-1 (IL)-1, and IL-6 are secreted, leading to DNA damage or mutations to form tumors [ 8 - 10 ]. (medsci.org)
  • Whether endometriosis-associated ovarian cancers develop from the molecular transformation of endometriosis or develop because of the endometriotic tumor microenvironment remain unknown. (mdpi.com)
  • In this review, we will describe the unique molecular features of endometriosis-associated ovarian cancers, the endometriotic tumor microenvironment, and available model systems for endometriosis-associated ovarian cancers. (mdpi.com)
  • Here, we report unexpected EphA3 overexpression within the microenvironment of a range of human cancers and mouse tumor xenografts where its activation inhibits tumor growth. (aacrjournals.org)
  • We have performed studies using EF5 in animal models of cancer and, since 1998 have been performing clinical trials to evaluate the presence and level of hypoxia in various human cancers. (upenn.edu)
  • We are currently funded by the NIH to perform studies in human brain tumors, head and neck cancers, sarcomas, cervix, and intraperitoneal cancers. (upenn.edu)
  • Dr. Evans is investigating factors that cause the resistance of tumors to therapy, in particular hypoxia in human cancers. (upenn.edu)
  • Almost 65 years later, tumor heterogeneity of nearly every parameter measured including tumor oxygenation, and the dynamic landscape of cancers and their microenvironments are clearly evident, providing a strong rationale for cancer personalized medicine. (springer.com)
  • The authors also discuss improved methods to monitor tumor evolution (e.g., liquid biopsies) and the development of more effective strategies for managing and treating cancers (e.g., immunotherapies). (cshlpress.com)
  • Each chapter presents a different mathematical model designed to investigate the interactions between tumor cells and the surrounding stroma and stromal cells. (springer.com)
  • Yet, considering the complex interactions (stromal cells can both promote and inhibit tumor cell growth), therapies targeting the tumor microenvironment for cancer therapy should be highly selective. (spandidos-publications.com)
  • Here, we review the evidence that stromal cells of the tumor microenvironment mediate this restriction by excluding T cells from the vicinity of cancer cells. (sciencemag.org)
  • But, as a result of being in these adverse microenvironmental conditions, those same tumor cells can exhibit resistance to conventional cancer therapies, including radiation and certain types of chemotherapy. (frontiersin.org)
  • Numerous attempts have, and are being made, to identify the microenvironmental conditions within tumors so as to select appropriate therapies to target those cancer cells that thrive in the hostile microenvironment. (frontiersin.org)
  • Understanding the unique molecular features of the endometriotic tumor microenvironment may lead to impactful precision therapies and/or modalities for prevention. (mdpi.com)
  • Thus, there remains a critical need to understand the tumor microenvironment and to develop anti-cancer therapies that address this aspect of malignant disease. (springer.com)
  • RATIONALE: Biological therapies such as erlotinib may interfere with the growth of the tumor cells and slow the growth of the tumor. (bioportfolio.com)
  • and (v) the effects of therapies on the microenvironment and some opportunities to target the niche directly in order to improve current treatments. (haematologica.org)
  • Molecular and functional imaging have critically important roles to play in personalized medicine through the detection of hypoxia, both spatially and temporally, and by providing new understanding of the role of hypoxia in cancer aggressiveness. (springer.com)
  • These advances have provided the ability to silence HIF and understand the associated molecular and functional consequences to expand our understanding of hypoxia and its role in cancer aggressiveness. (springer.com)
  • Paradoxically, hypoxia in tumors is correlated with a worse prognosis, suggesting that the hypoxic response may provoke tumor aggressiveness ( 1 - 3 ). (aacrjournals.org)
  • While hypoxia is clearly critical for outcome of cancer patients, it is generally associated with the other crucial Ps and as such any discussion of the role of hypoxia in tumors must be made in connection with the other hostile microenvironmental parameters. (frontiersin.org)
  • The present study aimed to summarize the role of hypoxia in cancer therapy by regulating the tumor microenvironment (TME) and to highlight the potential of hypoxia-targeted therapy. (biomedcentral.com)
  • The role of hypoxia in development of the mammalian embryo. (springer.com)
  • The role of hypoxia-inducible factor in wound healing. (springer.com)
  • As a tumor grows, these subpopulations expand, accumulate new mutations, and are subjected to selective pressures from the environment, including anticancer interventions. (cshlpress.com)
  • Clinical trials in glioblastoma often initiate with patients that have a tumor recurrence, and we have demonstrated in vivo efficacy for SLC-0111 with temozolomide in a recurrent glioblastoma," the researchers wrote in their study, published in JCI Insight . (scienceblog.com)
  • Khramstov, V. V., In vivo molecular EPR-based spectroscopy and imaging of tumor microenvironment and redox using functional paramagnetic probes. (wvu.edu)
  • Clinical and in-vivo studies on various 64Cu(II)-PET radiotracers resulted in controversial reports on the specificity of the current tracers for hypoxia imaging due to non-selective bio-distribution & low S/B ratio. (europa.eu)
  • To probe functional changes in the metabolic microenvironment, I measured in vivo P02 during tumor growth and antiangiogenic (vascular targeted) treatment in preclinical tumor models. (mit.edu)
  • Moreover, we report for the first time that CREB-mediated CCN1 transcription is enhanced in hypoxic regions of tumors in vivo . (aacrjournals.org)
  • HIF signaling serves as a major adaptive mechanism in tumor growth in a hypoxic microenvironment. (jci.org)
  • These include the role of host cell PD-L1 expression, efficacy of dual innate and adaptive checkpoints, the role of IFNα targeting, tumor-reprogrammed resident T cells, targeting tertiary lymphoid structures, strategies to facilitate T cell infiltration in tumor microenvironment, and synergistic interactions between radiation and checkpoint blockade. (utsouthwestern.edu)
  • Induction of new blood vessel formation via the secretion of proangiogenic factors is one of the main adaptive responses engaged by tumor cells under hypoxic conditions. (aacrjournals.org)
  • Hypoxia targeting might be relevant to overcome hypoxia-associated resistance in cancer treatment. (biomedcentral.com)
  • Both pharmacological factors, including inadequate drug concentration at the tumor site, and cellular factors can contribute to clinical resistance [ 2 ]. (biomedcentral.com)
  • The treatment resistance factor that is emphasized is hypoxia. (upenn.edu)
  • Additionally, TAMs in the hypoxic niches within the tumor are known to mediate resistance to several anticancer treatments and to promote cancer relapse. (jci.org)
  • We find that hypoxia fosters relative resistance to T-DM1 in HER2 + cells (SKBR3 and BT474). (aacrjournals.org)
  • To further investigate this potential mechanism, we focused on determining the contribution of bioenergetics-ATP depletion-to hypoxia-inducible c-Jun phosphorylation in wild-type (WT) and HIF-1-null mouse embryo fibroblasts (MEFs). (asm.org)
  • Improved Methods to Generate Spheroid Cultures from Tumor Cells, Tumor Cells & Fibroblasts or Tumor-Fragments: Microenvironment, Microvesicles and miRNA. (upenn.edu)
  • Here we report that exposure of human diploid fibroblasts and transformed cells to hypoxia led to phosphorylation of eIF2α, a modification that was readily reversed upon reoxygenation. (asm.org)
  • PERK −/− mouse embryo fibroblasts failed to phosphorylate eIF2α and exhibited lower survival after prolonged exposure to hypoxia than did wild-type fibroblasts. (asm.org)
  • 1 Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. (nih.gov)
  • Work at all levels of biological organization is involved, from protein to lipoprotein biochemistry and molecular biology through cell and tumour biology, animal models for studies on pulmonary and cardiovascular pathophysiology and viral and bacterial infection processes, to clinical studies on human population and the AIDS epidemic. (ubc.ca)
  • Graded hypoxia modulates the invasive potential of HT1080 fibrosarcoma and MDA MB231 carcinoma cells. (utoronto.ca)
  • In sharp contrast, tumor MDSC suppressed both antigen-specific and nonspecific T cell activity. (rupress.org)
  • breast tumors, colorectal tumors, and squamous cell carcinoma tumors, could be remarkably enhanced. (bioportfolio.com)
  • Genomic alterations have long been recognized as an important factor in tumor formation and drive tumor cell growth. (bioportfolio.com)
  • Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blockin. (bioportfolio.com)
  • Glutaminolysis contributes also to synthesis of lipids, amino acids, nucleotides and generation of lactate that is transported out of the cell by the ubiquitous monocarboxylate transporter 1 (MCT1) and the hypoxia inducible MCT4. (nih.gov)
  • The RIP1-Tag2 transgenic mouse model overexpresses SV40 T antigen under the control of the insulin promoter, resulting in development of islet cell tumors 4 . (nature.com)
  • We noticed that the culture exposed to hypoxia showed overall increase of S phase-positive cells and hypothesized that SPCA2 upregulation under hypoxia can be linked to Mn 2+ -dependent cell cycle arrest. (biochemj.org)
  • The research team led by Hjelmeland and co-first authors Nathaniel Boyd, Ph.D., and Kiera Walker, both working in Hjelmeland's UAB lab, studied glioma cells in cell-culture that were derived from an aggressive pediatric primary glioblastoma and from an adult recurrent tumor. (scienceblog.com)
  • Consequently, maladapted tumor-associated vascular endothelial cells may confer stem cell-like activity to indolent tumor cells. (haematologica.org)
  • The ability of a cell to form a tumor is context dependent, where one environment may promote tumor growth but another will not [ 6 ]. (biomedcentral.com)
  • These steps in which tumor cells are established at another cell niche are not an intrinsic program. (biomedcentral.com)
  • Our results show that hypoxia through hypoxia-inducible factor (HIF) brings about a time-dependent increase in the level of an oncogenic microRNA, miR-191 in various breast cancer cell lines. (sigmaaldrich.com)
  • We further established that miR-191 is a critical regulator of transforming growth factor beta (TGFβ)-signaling and promotes cell migration by inducing TGFβ2 expression under hypoxia through direct binding and indirectly by regulating levels of a RNA binding protein, human antigen R (HuR). (sigmaaldrich.com)
  • During the past decades of cancer research, our focus on cancer research has shifted from the malignant cancer cell itself to the tumor microenvironment and the complex interactions. (spandidos-publications.com)
  • Reducing renal hypoxia by inhibiting the hypoxia-inducible factor-1 (HIF-1) reduced T cell infiltration and kidney injury in lupus-prone mice, suggesting that targeting HIF-1 might be effective for treating lupus nephritis. (sciencemag.org)
  • Depending on the mode of tumor cell death macrophage polarization ranges from the extremes of pro-inflammatory activation toward anti-inflammatory/immuno-suppressive activation. (ovid.com)
  • These gene signatures will be used to analyze and annotate the gene expression patterns in the tumor samples and whether hyperthermia will affect the physiological parameters and the corresponding gene signatures. (clinicaltrials.gov)
  • We will also obtain the information on the tumor physiological parameters information measured in these tumors. (clinicaltrials.gov)
  • B. The data of the tumor physiological parameters measured and the response to treatments and other clinical outcomes of these patients will also be acquired. (clinicaltrials.gov)
  • In response to the differences in the physiological blood circulation, tumor microenvironment, and intracellular environment, Ms-DDS can change their physicochemical properties (such as size, hydrophobicity, or zeta potential) to achieve deeper tumor penetration, enhanced cellular uptake, timely drug release, as well as effective endosomal escape. (thno.org)
  • To fully characterize and probe the tumor microenvironment, new tools are needed to quantitatively assess microanatomical and physiological changes during tumor growth and treatment. (mit.edu)
  • Treatment of mice with an agonistic α-EphA3 antibody inhibits tumor growth by severely disrupting the integrity and function of newly formed tumor stroma and microvasculature. (aacrjournals.org)
  • Of these poor microenvironmental conditions within tumors, low oxygenation (hypoxia) is the one that has been the focus of most studies and is often considered as the only factor of importance. (frontiersin.org)
  • Coupled with discoveries in 1953 by Gray and others that anoxic cells were resistant to radiation damage, these observations have led to an entire field of research focused on exploiting oxygenation and hypoxia to improve the outcome of radiation therapy. (springer.com)
  • The levels of many of these proteins in human tumors correlate positively with the numbers of TAMs present in those tumors ( 3 ). (aacrjournals.org)
  • Hypoxia, a hallmark of cancer, regulates the trafficking of several receptor proteins with potential implications for tumor targeting. (aacrjournals.org)
  • Hypoxia-inducible factor belongs to the Per-ARNT-Sim (PAS) family of proteins. (termedia.pl)
  • 2 Another example is the abnormal activation of the fibro blast growth factor receptor 1 (FGFR1)-ETS2 pathway in tumor-associated-vascular endothelial cells during chemotherapy. (haematologica.org)
  • The development of hypoxia has profound consequences on tumor growth characteristics and on tumor response to radiotherapy and chemotherapy. (asm.org)
  • Our data define EphA3 as a novel target for selective ablation of the tumor microenvironment and demonstrate the potential of EphA3 agonists for anticancer therapy. (aacrjournals.org)
  • Hypoxia inducible factor-1α (HIF-1α) is a transcription factor that regulates gene expression under hypoxic conditions 7 . (nature.com)
  • HIF-1α critically regulates the interaction of neoplastic CLL cells with the leukemic microenvironment. (bloodjournal.org)
  • To enable clinical translation, they developed a hypoxia-activated prodrug (SN38023) that targets DNA-PKc. (utsouthwestern.edu)
  • To achieve this goal, we will perform gene expression analysis of the tumor samples collected from an IRB-approved study (IRB #: 4516-05-2R2) International Phase III Study of Chemoradiotherapy versus Chemoradiotherapy Plus Hyperthermia for Locally Advanced Cervical Cancer directed by Dr. Mark Dewhirst. (clinicaltrials.gov)
  • A. The research materials will include the tumor biopsy obtained before and after HT treatments to be used for gene expression studies as well as for the IHC and ISH studies to the findings from our microarray analysis. (clinicaltrials.gov)
  • Therefore, targeting gene expression in hypoxic cells by placing transgene under the control of a hypoxia-responsive promoter can be a good strategy for cancer-specific gene therapy. (ecancer.org)
  • The hypoxia-inducible gene expression system has been investigated more in suicide gene therapy and it can also be of great help in knocking down cancer gene therapy with siRNAs. (ecancer.org)
  • In this review, hypoxia-inducible gene expression system as well as gene therapy strategies targeting tumour hypoxia will be discussed. (ecancer.org)
  • Hypoxia, indicating solid tumours, may prove to be an ideal target for tumour-specific gene therapy. (ecancer.org)
  • Several studies have used HRE sequences in combination with a minimal promoter to restrict the gene expression in the hypoxic tumour environment [ 3 - 7 ]. (ecancer.org)
  • A hypoxia-inducible gene expression system has been investigated majorly in the suicide gene therapy studies to propel drive selective prodrug activating enzyme expression under hypoxic conditions [ 8 , 9 ]. (ecancer.org)
  • Moreover, these studies have also considered hypoxia-mediated proapoptotic gene expression [ 10 , 11 ]. (ecancer.org)
  • In hypoxic tumors, hexokinase mRNA abundance is significantly increased as well as protein levels. (wikipedia.org)
  • and radiosensitizes hypoxic tumors. (utsouthwestern.edu)
  • While the active agent (IC87361) radiosensitizes in both hypoxia and normoxia, the prodrug (SN38023) has radiosensitizing effects only in hypoxic tumors. (utsouthwestern.edu)
  • Based on thorough examination of recent literature and experimental data accumulated in our laboratories, we published a new hypothesis of a Janus-faced tumor microenvironment (TME) and its role in tumorigenesis 8 . (wvu.edu)
  • In data released by the American Cancer Society in 2019, PAC has a 5-year overall survival rate of only 9% and is one of the tumors with the lowest survival rate [ 1 ]. (biomedcentral.com)
  • 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)
  • 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)
  • In experiments with mice, the combined treatment with temozolomide and SLC-0111: 1) delayed tumor growth of a patient-derived, recurrent glioblastoma xenograft implanted beneath the skin of immunocompromised mice, as compared to temozolomide alone, and 2) improved survival of the mice when the xenograft was implanted in the brain, a placement that more closely models glioblastoma in patients. (scienceblog.com)
  • The survival of developing tumors depends on the ability of the tumor cells to respond to the generation of hypoxic regions in the growing tumors. (aacrjournals.org)
  • Hypoxia-inducible factor (HIF) 1α was found to be primarily responsible for the observed effects of the tumor microenvironment on MDSC differentiation and function. (rupress.org)
  • A number of tumor-derived chemoattractants are thought to ensure this ongoing recruitment, including colony-stimulating factor-1 (CSF-1 also known as M-CSF), the CC chemokines, CCL2, CCL3, CCL4, CCL5, and CCL8, and vascular endothelial growth factor (VEGF). (aacrjournals.org)
  • Moreover, the hypoxia risk score can act as an independent prognostic factor in PAC, and a higher hypoxia risk score was correlated with poorer prognosis in patients as well as the immunosuppressive microenvironment of the tumor. (biomedcentral.com)
  • We report that exposure of breast cancer cells to hypoxia stimulated hypoxia-inducible factor (HIF)-1α- and HIF-2α-dependent expression of AlkB homolog 5 (ALKBH5), an m 6 A demethylase, which demethylated NANOG mRNA, which encodes a pluripotency factor, at an m 6 A residue in the 3′-UTR. (pnas.org)
  • Previous researches identified a hypoxia-upregulated lncRNA named "a natural antisense transcript of hypoxia-inducible factor 1 (aHIF)" in some tumors. (dovepress.com)
  • Moreover, FH deficiency is known to up-regulate expression of hypoxia-inducible factor (HIF)-1α by enhancing the stability of HIF transcript. (aacrjournals.org)
  • ETMI exerted its anti-inflammatory activity by modulating the main inflammatory indicators such as cyclooxygenase (COX)-2, interleukin (IL)-6, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, and nitric oxide (NO) in a dose-dependent manner. (medsci.org)
  • This study examines whether lipid A may directly modulate the radioresponse of tumor cells by activating inducible nitric oxide synthase (iNOS) or cyclooxygenase-2 (COX-2) through nuclear factor-kappaB (NF-kappaB) signaling. (jove.com)
  • Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that plays a pivotal role in mediating such responses. (aacrjournals.org)
  • The main transcription factor involved in cellular adaptation to hypoxic conditions is hypoxia-inducible factor 1 (HIF-1). (termedia.pl)
  • DCs can (cross-)present tumor antigen to activate naive T cells, which play a pivotal role in anti-tumor immunity. (nih.gov)
  • We have recently demonstrated that intratumoral CpG-B vaccination enhances anti-tumor immunity and tumor regression in mice. (bioportfolio.com)
  • As the results, the tumor uptake of drug-loaded nanoparticles as well as their interstitial penetration within the tumor would be greatly increased for mice pre-treated with erlotinib at the oral feeding dose of 50 mg/kg, leading to remarkably improved chemotherapeutic efficacy of nanomedicine. (bioportfolio.com)