The glutathione S-transferase (GST) family of enzymes help detoxify compounds, including chemotherapy drugs. Genetic variations, or polymorphisms, in these enzymes have been associated with changes in enzyme activity, sensitivity to chemotherapy, and patient survival.
Jan Stoehlmacher, M.D., and Heinz-Josef Lenz, M.D., of the University of Southern California/Norris Comprehensive Cancer Center, and their colleagues examined the association between three different GST polymorphisms (GSTP1, GSTM1, and GSTT1) and survival of patients with advanced colorectal cancer who received platinum-based chemotherapy.
The authors found that the GSTP1 polymorphism was associated with increased survival in these patients, but that the GSTM1 and GSTT1 polymorphisms had no effect on patient survival. These findings appear in the June 19 issue of the Journal of the National Cancer Institute.
Gene in Human Herpesvirus May Play a Role in Malignant Transformation:
New research suggests that the K1 gene of human herpesvirus-8 (HHV-8) may be involved in malignant transformation. Om Prakash, Ph.D., of the Ochsner Clinic Foundation in New Orleans, and his colleagues generated transgenic mice that expressed the HHV-8 K1 gene. The gene expression resulted in constitutive activation of transcription factors and increased activity of certain protein kinases, which led to enhanced signal transduction and increased cell proliferation. Tumors in the K1 transgenic mice showed characteristics of a spindle-cell sarcomatoid tumor and a malignant plasmablastic lymphoma. These findings appear in the June 19 issue of the Journal of the National Cancer Institute.
Researchers Examine Methods to Evaluate Antiangiogenic Therapies:
Antiangiogenic therapies that target blood vessel growth are being tested in clinical trials. However, it is difficult to measure the effect of these therapies on the angiogenic activity of a tumor. Several studies have established that the measurement of tumor microvessel density, an often-quantified aspect of tumor vasculature, is a useful prognostic indicator for many different cancers. This finding has led some investigators to assume that microvessel density can also be used to evaluate the efficacy of antiangiogenic treatment.
In a review article in the June 19 issue of the Journal of the National Cancer Institute, Lynn Hlatky, Ph.D., and Philip Hahnfeldt, Ph.D., of Harvard Medical School, and Judah Folkman, M.D., of Children's Hospital, Boston, review the evidence that supports the use of microvessel density as a prognostic indicator and discuss the prevailing misconceptions concerning microvessel density as they relate to antiangiogenic therapy. The authors recommend that studies that focus on the fundamental biology of angiogenesis are likely to identify characteristics of tumor vasculature that could serve as more appropriate surrogate end points for treatment efficacy than microvessel density.
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