By Luana Schito, Gregg L. Semenza (auth.), Giovanni Melillo (eds.)
The imbalance among swiftly proliferating tumor cells and insufficient and inefficient tumor vasculature results in a lessen in oxygen degrees (hypoxia and/or anoxia) in tumor tissues. Intra-tumor hypoxia profoundly impacts the organic habit of melanoma cells, which turn into proof against traditional cures and obtain a extra invasive and metastatic phenotype. Hypoxia is a trademark of the malignant phenotype and a key characteristic of the tumor microenvironment. Hypoxia Inducible issue 1 (HIF-1) is a grasp regulator of the transcriptional reaction to oxygen deprivation. HIF triggers the expression of genes whose items set off angiogenesis, lessen oxygen intake, change metabolism to glycolysis, hold a stem mobile phenotype and choose for extra invasive and metastatic cells. healing ways focusing on HIF, at once or downstream mediators of its transcriptional job, are being built. Intra-tumor hypoxia is a subject has been gaining medical curiosity during the last few years for its large involvement in lots of physiological and pathological strategies.
This quantity will hide the newest learn and translational facets linked to intra-tumor hypoxia, besides possibilities for drug improvement provided through this targeted function of the tumor microenvironment. the continued efforts to translate our realizing of the biology underlying intra-tumor hypoxia in potential healing recommendations face many demanding situations, yet this publication will provide a chance for an in-depth research of the elemental mechanisms implicated within the adaption to low oxygen degrees and may scrutinize the opportunity of possibilities which are being pursued in either learn and the drug improvement industry.
Read Online or Download Hypoxia and Cancer: Biological Implications and Therapeutic Opportunities PDF
Similar nonfiction_11 books
The consecutive-k method used to be first studied round 1980, and it quickly grew to become a truly well known topic. the explanations have been many-folded, includ ing: 1. The process is easy and common. So most folk can are aware of it and plenty of can perform a little research. but it may possibly develop in lots of instructions and there's no loss of new issues.
In an period that has introduced new and unforeseen demanding situations for nearly each corporation, one will be hard-pressed to discover any dependable supervisor who's now not brooding about what the long run will deliver. within the wake of those demanding situations, strategic making plans has moved from being the reserve of enormous businesses to turning into a vital desire for even small and medium-sized agencies.
Extra resources for Hypoxia and Cancer: Biological Implications and Therapeutic Opportunities
Nature 458:1127–1130. 1038/nature07986 Groth A et al (2003) Human Tousled like kinases are targeted by an ATM- and Chk1-dependent DNA damage checkpoint. Embo J 22:1676–1687 Halazonetis TD, Gorgoulis VG, Bartek J (2008) An oncogene-induced DNA damage model for cancer development. Science 319:1352–1355. 1140735 Hammond EM, Giaccia AJ (2004) The role of ATM and ATR in the cellular response to hypoxia and re-oxygenation. DNA Repair (Amst) 3:1117–1122. 035 Hammond EM, Giaccia AJ (2005) The role of p53 in hypoxia-induced apoptosis.
Hypoxia is not the only non-DNA damaging stress, which has been shown to induce ATM activity. For example, heat, high salt, and agents which modify chromatin have all been associated with an increase in ATM activity in the absence of DNA damage (Bakkenist and Kastan 2003). The induction of ATM by chromatin-modifying agents suggests the possibility that ATM responds directly to the stalled replication forks in hypoxia, as they would presumably present altered chromatin modifications. In addition, hypoxia is a strong modulator of the chromatin context, with many different chromatin modifications being induced in response to hypoxia (Johnson et al.
M. Olcina and E. M. Hammond knockdown sensitizes cells to hypoxia/reoxygenation as assayed by colony formation assay (Hammond et al. 2004). The increased sensitivity to hypoxia/reoxygenation observed upon CHK1 loss is thought to be predominantly dependent upon inhibition of CHK1 during reoxygenation since loss of CHK1 activity during both reoxygenation and hypoxia does not lead to additional sensitization. Once active, CHK1 will phosphorylate downstream targets including TLK1 in hypoxia (Pires et al.