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Palo Alto, CA, United States

Saville B.R.,Vanderbilt University | Kim Y.S.,Telik | Koch G.G.,University of North Carolina at Chapel Hill
Pharmaceutical Statistics | Year: 2011

For time-to-event data, the power of the two sample logrank test for the comparison of two treatment groups can be greatly influenced by the ratio of the number of patients in each of the treatment groups. Despite the possible loss of power, unequal allocations may be of interest due to a need to collect more data on one of the groups or to considerations related to the acceptability of the treatments to patients. Investigators pursuing such designs may be interested in the cost of the unbalanced design relative to a balanced design with respect to the total number of patients required for the study. We present graphical displays to illustrate the sample size adjustment factor, or ratio of the sample size required by an unequal allocation compared to the sample size required by a balanced allocation, for various survival rates, treatment hazards ratios, and sample size allocation ratios. These graphical displays conveniently summarize information in the literature and provide a useful tool for planning sample sizes for the two sample logrank test. Copyright © 2010 John Wiley & Sons, Ltd.

Glutathione transferases (GSTs) are enzymes that catalyze the conjugation of glutathione (GSH) to a variety of electrophilic substances. Their best known role is as cell housekeepers engaged in the detoxification of xenobiotics. Recently, GSTs have also been shown to act as modulators of signal transduction pathways that control cell proliferation and cell death. Their involvement in cancer cell growth and differentiation, and in the development of resistance to anticancer agents, has made them attractive drug targets. This review is focused on the inhibition of GSTs, in particular GSTP1-1, as a potential therapeutic approach for the treatment of cancer and other diseases associated with aberrant cell proliferation. © 2010 Macmillan Publishers Limited. All rights reserved.

This invention generally relates to compositions and methods for treating myelodysplastic syndrome. In one embodiment, this invention relates to methods for treating myelodysplastic syndrome with ezatiostat or a salt thereof and lenalidomide.

Telik | Date: 2012-12-18

Disclosed herein are substituted thiazoles and their salts that are VEGFR2 kinase inhibitors, useful in the treatment of cancer.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 100.00K | Year: 2001

DESCRIPTION: (provided by applicant) In addition to the unlimited potential of cancer cells for proliferation, a second important contributor to tumor growth and metastasis is the ability of cancer cells to avoid apoptotic cell death. This characteristic may also underlie resistance to chemotherapy. The physiological role of apoptosis in killing abnormally functioning cells can be subverted in cancer cells through genetic lesions that affect key proteins in apoptotic pathways, such as Bcl-2 and p53. Recently, an important family of apoptosis inhibitors, the AIP family of proteins, has been discovered. These proteins may be over expressed, or upregulated, in tumor cells, contributing to resistance to apoptosis. The goal of the present proposal is to discover small molecule antagonists of IAP function that act by inhibiting the BIR domain of the IAP. Inhibition of the BIR domain may produce agents with broad anticancer activity but little effect on normal tissues. These compounds will be used to validate IAP antagonism by BIR inhibition as a target for treating cancer. In addition, they will serve as a starting point for the development of novel cancer therapeutics. Small molecule inhibitors will be rapidly discovered using a proprietary drug discovery technology (TRAP) and profiled in cell-free, cell-based, and in vivo systems to establish their pro-apoptotic and anti-tumor activities. PROPOSED COMMERCIAL APPLICATION: Compounds that can be used to validate BIR inhibition as a successful approach to cancer treatment. Lead compounds the the discovery of novel cancer chemotherapeutics.

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