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.