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

By Rüdiger Liersch, Wolfgang E. Berdel, Torsten Kessler

ISBN-10: 354078280X

ISBN-13: 9783540782803

Angiogenesis is attracting elevated clinical and medical curiosity. The identity of novel mediators and concentrating on molecules has ended in major growth in our knowing of tumor angiogenesis and tumor vessel concentrating on. vital advances in melanoma therapy have already emerged, and sooner or later, blood vessel focusing on will play an important position inside individualized healing concepts.

This quantity presents a basic evaluate of the most recent advancements in angiogenesis inhibition in melanoma. All points from the bench to the bedside are thought of, with distinctive cognizance either to simple learn and to its translation into medical 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 offered, and diverse complicated concentrating on innovations are mentioned. This publication might be worthy to all who desire to study of the newest advances in study and remedy during this fascinating field.

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J Exp Med 199:113–124 Kim MS, Kwon HJ, Lee YM, Baek JH, Jang JE, Lee SW, Moon EJ, Kim HS, Lee SK, Chung HY, Kim CW, Kim KW (2001) Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes. Nat Med 7:437–443 Koh MY, Darnay BG, Powis G (2008a) Hypoxiaassociated factor, a novel E3-ubiquitin ligase, binds and ubiquitinates hypoxia-inducible factor 1alpha, leading to its oxygen-independent degradation. Mol Cell Biol 28:7081–7095 Koh MY, Spivak-Kroizman T, Venturini S, Welsh S, Williams RR, Kirkpatrick DL, Powis G (2008b) Molecular mechanisms for the activity of PX-478, an antitumor inhibitor of the hypoxia-inducible factor-1alpha.

Hypoxia alone may be insufficient to induce p53 (Wenger et al. 1998) but may induce p53 accumulation when accompanied by acidosis and nutrient deprivation (Pan et al. 2004). Hypoxiainduced p53 protein is stabilized by a direct interaction with the ODD of HIF-1a, whereby one p53 dimer interacts with a single HIF-1a ODD domain. However, by binding to HIF-1a, p53 may also promote the ubiquitin-mediated degradation of HIF-1a via recruitment of MDM2 (Ravi et al. 2000). Consequently, loss of p53 in tumor cells results in an increase in hypoxiainduced HIF-1a and augments HIF-1-dependent transactivation.

PX-478 showed antitumor activity against a variety of established tumors with marked tumor regression accompanied by massive apoptosis, and in some cases cures (Jordan et al. 2005; Welsh et al. 2004). The antitumor response to PX-478 positively correlated with tumor HIF-1a levels. PX-478 is currently in Phase I clinical trial as an antitumor agent and HIF-1 inhibitor. 8 Conclusions While a number of agents have been found to inhibit HIF-1a levels in cells, only a few agents have been demonstrated to inhibit HIF-1a or 28 3 HIF-1 activity in tumors in vivo.

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

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