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This Week in the British Journal of Cancer: May 22, 2012

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In the British Journal of Cancer, researchers from South Korea present a dose-escalation study of the drug irinotecan for patients with advanced gastric cancer, and determine the drug's effect on the UGT1A1 genotype. The team administered increasing doses of irinotecan to 43 patients and sequenced DNA isolate from their peripheral blood to determine their UGT1A1 genotypes. The overall response rate was 9.3 percent, and the disease control rate was 62.8 percent. The team also found that patients with the UGT1A1 genotype had a lower incidence of toxic side effects during treatment. "Individualized irinotecan dose escalation based on patient tolerance was not associated with increased toxicity and shows modest activity as salvage chemotherapy for advanced gastric cancer," the authors write. "The role of UGT1A1 genotype in clinical toxicity requires further evaluation."

Also in the British Journal of Cancer, researchers in the UK report that HIF-pathway inhibitor NSC-134754 induces metabolic changes and anti-tumor activity without impeding vascular function. The team treated human prostate cancer cells and prostate tumor-bearing mice with NSC-134754. In vitro, the compound reduced lactate production and glucose uptake while significantly increasing intracellular glucose and glutamine uptake, the researchers found. Furthermore, they found that the compound led to significantly higher tumor necrosis 48 hours after treatment in vivo. However vessel perfusion and VEGF levels were unchanged after treatment. "Our data support the further evaluation of NSC-134754 as an anti-cancer agent," the team adds.

Finally in the British Journal of Cancer, investigators in Japan report that expression of the FoxP3 transcription factor in tumor cells causes immunoregulatory function of signet ring cell carcinoma of the stomach. The team analyzed FoxP3 levels in 194 gastric cancer patients and in gastric cancer cell lines,and found FoxP3-positive tumor cells in 79.3 percent of signet ring cell carcinoma patients. They also found that FoxP3 expression was significantly correlated with lymph node metastasis. "Our findings suggested that FoxP3 expression by tumour cells might have important roles in immune escape of gastric carcinoma, and be associated with the malignant potential of scirrhous gastric carcinoma," the team adds.

The Scan

Study Finds Sorghum Genetic Loci Influencing Composition, Function of Human Gut Microbes

Focusing on microbes found in the human gut microbiome, researchers in Nature Communications identified 10 sorghum loci that appear to influence the microbial taxa or microbial metabolite features.

Treatment Costs May Not Coincide With R&D Investment, Study Suggests

Researchers in JAMA Network Open did not find an association between ultimate treatment costs and investments in a drug when they analyzed available data on 60 approved drugs.

Sleep-Related Variants Show Low Penetrance in Large Population Analysis

A limited number of variants had documented sleep effects in an investigation in PLOS Genetics of 10 genes with reported sleep ties in nearly 192,000 participants in four population studies.

Researchers Develop Polygenic Risk Scores for Dozens of Disease-Related Exposures

With genetic data from two large population cohorts and summary statistics from prior genome-wide association studies, researchers came up with 27 exposure polygenic risk scores in the American Journal of Human Genetics.