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Concept
Tumor hypoxia
Summary
Tumor hypoxia is the situation where tumor cells have been deprived of oxygen. 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. 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. In order to support continuous growth and proliferation in challenging hypoxic environments, cancer cells are found to alter their metabolism. Furthermore, hypoxia is known to change cell behavior and is associated with extracellular matrix remodeling and increased migratory and metastatic behavior.
A particular change in metabolism, historically known as the Warburg effect results in high rates of glycolysis in both normoxic and hypoxic cancer cells. Expression of genes responsible for glycolytic enzymes and glucose transporters are enhanced by numerous oncogenes including RAS, SRC, and MYC.
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. 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.
These genes include: solute carrier family 2 (GLUT1), hexokinase (HK), phosphoglucose isomerase (PGI), phosphofructokinase (PFKL), fructose-bisphosphate aldolase (ALDO), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase (PGK), phosphoglycerate mutase (PGM), enolase 1 (ENOA), pyruvate kinase (PK), pyruvate dehydrogenase kinase, isozyme 1 (PDK1) and lactate dehydrogenase A (LDH-A).
Official source
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Neoplasm
A neoplasm (ˈniː.oʊˌplæzəm,_ˈniː.ə-) is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, when it may be called a tumour or tumor. ICD-10 classifies neoplasms into four main groups: benign neoplasms, in situ neoplasms, malignant neoplasms, and neoplasms of uncertain or unknown behavior.