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Worcester, MA, United States

Mitchell D.C.,Acceleron Pharmaceuticals | Bryan B.A.,Ghosh Science and Technology Center
Journal of Cellular Biochemistry | Year: 2010

Healthy cells, as well as benign and malignant tumors, depend upon the body['s blood supply to bring in oxygen and nutrients and carry away waste products. Using this property against tumors, anti-angiogenic therapy targets the tumor vasculature with the aim of starving the tumor, and has demonstrated exceptional clinical efficacy against a number of tumors. This review discusses the current state of knowledge regarding anti-angiogenic therapies presently available to patients, and garners from both preclinical and clinical literature the benefits and side effects associated with anti-angiogenic therapies, the unfortunate mechanisms of acquired resistance to these novel therapeutics, and highlights\ promising next generation anti-angiogenics that may overcome the limitations encountered with first generation therapies. © 2010 Wiley-Liss, Inc. Source


Street C.A.,Ghosh Science and Technology Center | Routhier A.A.,Ghosh Science and Technology Center | Spencer C.,Ghosh Science and Technology Center | Perkins A.L.,Ghosh Science and Technology Center | And 5 more authors.
International Journal of Oncology | Year: 2010

The role of the RhoA/Rho kinase (ROCK) signaling pathway in cell survival remains a very controversial issue, with its activation being pro-apoptotic in many cell types and anti-apoptotic in others. To test if ROCK inhibition contributes to tumor cell survival or death following chemotherapy, we treated cisplatin damaged neuroblastoma cells with a pharmacological ROCK inhibitor (Y27632) or sham, and monitored cell survival, accumulation of a chemoresistant phenotype, and in vivo tumor formation. Additionally, we assayed if ROCK inhibition altered the expression of genes known to be involved in cisplatin resistance. Our studies indicate that ROCK inhibition results in increased cell survival, acquired chemoresistance, and enhanced tumor survival following cisplatin cytotoxicity, due in part to altered expression of cisplatin resistance genes. These findings suggest that ROCK inhibition in combination with cisplatin chemotherapy may lead to enhanced tumor chemoresistance in neuroblastoma. Source


Routhier A.,Ghosh Science and Technology Center | Astuccio M.,Ghosh Science and Technology Center | Lahey D.,Ghosh Science and Technology Center | Monfredo N.,Ghosh Science and Technology Center | And 16 more authors.
Oncology Reports | Year: 2010

Primarily through in vitro studies, the Rho-family of small GTPases and their effector proteins have been implicated in mediating oncogenic properties of cancer cells. We sought to determine if pharmacological inhibition of the RhoA effector proteins known as Rho-kinases (ROCK) with the small molecule inhibitor Y-27632 could inhibit melanoma in vitro and in vivo. We demonstrate that Y-27632 treatment of a panel of melanoma cells alters cellular morphology leading to spindly cells with decreased lamellipodia and increased filopodia formation. Y-27632 treatment decreases invasion and alters cell survival of cultured melanoma cells. IP injection of Y-27632 in tumor-bearing mice resulted in a reduction in melanoma tumor volume compared to control treated mice. These findings suggest that ROCK inhibition can reduce melanoma tumorigenicity. Source

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