Rüdiger Liersch, Wolfgang E. Berdel, Torsten Kessler's Angiogenesis Inhibition PDF

By Rüdiger Liersch, Wolfgang E. Berdel, Torsten Kessler

ISBN-10: 354078280X

ISBN-13: 9783540782803

Angiogenesis is attracting elevated clinical and scientific curiosity. The id of novel mediators and focusing on molecules has resulted in major development in our figuring out of tumor angiogenesis and tumor vessel focusing on. vital advances in melanoma therapy have already emerged, and sooner or later, blood vessel focusing on will play an important function inside of individualized healing concepts.

This quantity offers a normal evaluation of the most recent advancements in angiogenesis inhibition in melanoma. All facets from the bench to the bedside are thought of, with unique cognizance either to uncomplicated learn and to its translation into scientific perform. person chapters are dedicated to the jobs of angiopoietins, HIF-1a, chemokines, PDGF and VEGF, and vascular integrins. the most recent result of scientific trials on healing compounds are provided, and diverse complicated focusing on techniques are mentioned. This booklet can be worthy to all who desire to research of the latest advances in learn and therapy during this fascinating field.

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Koh et al. site-independent mechanism. J Biol Chem 283: 16309–16319 Zhang H, Gao P, Fukuda R, Kumar G, Krishnamachary B, Zeller KI, Dang CV, Semenza GL (2007) HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHLdeficient renal cell carcinoma by repression of C-MYC activity. Cancer Cell 11:407–420 Zhong H, Chiles K, Feldser D, Laughner E, Hanrahan C, Georgescu MM, Simons JW, Semenza GL (2000) Modulation of hypoxiainducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/ PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics.

Another study has shown that growth of AKT-dependent prostate intraepithelial neoplasia requires mTOR-dependent activation M. Y. Koh et al. of HIF-1a, and that clinical resistance to mTOR inhibitors may emerge through upregulation of HIF-1a activity (Majumder et al. 2004). Also, loss of the VHL gene has been found to sensitize kidney cancer cells to the mTOR inhibitor CCI779 and correlated with inhibition of HIF-1a translation (Thomas et al. 2006). Another example of mutation that promotes HIF-1a translation was demonstrated in breast cancer where overexpressed 4E-BP1 and eIF4G function as a hypoxiaactivated switch that facilitate cap-independent translation over cap-dependent translation of HIF-1a and other key proangiogenic and prosurvival mRNAs (Braunstein et al.

Thus, HIF-1a mRNA is able to compete more effectively for the limited number of translation factors present in hypoxia, possibly through its binding to PTB and HuR (Galban et al. 2008; Schepens et al. 2005). mTOR has been implicated as contributing to HIF-1a accumulation in both normoxia and hypoxia (Bernardi et al. 2006; Brugarolas et al. 2004; Hudson et al. 2002; Majumder et al. 2004). The mechanism that may allow translation of HIF-1a in cancer cells is through accumulation of mutations in pathways regulating mTOR activity that bypass the hypoxia-mediated mTOR inhibition.

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Angiogenesis Inhibition by Rüdiger Liersch, Wolfgang E. Berdel, Torsten Kessler


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