Changes in thymidylate synthase and its inhibition rate and changes in dihydropyrimidine dehydrogenase after the administration of 5-fluorouracil with cisplatin to nude mice with gastric cancer xenograft SC-1-NU

Abstract

Combined administration of cisplatin with 5-FU did not further increase thymidylate synthase inhibition over that occurring with 5-FU alone, which does not support the hypothesis that cisplatin combined with 5-FU modulates thymidylate synthase inhibition in enhancing the anticancer effect of 5-FU. Changes in DPD after the administration of 5-FU may provide an insight into tumor sensitivity and resistance to 5-FU.

Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expression after administration of 5‐fluorouracil to patients with colorectal cancer

“…34 Moreover, nude mice studies with human gastric cancer xenografts also demonstrated a dramatic decrease in DPD activity after short-term exposure to 5FU. 35 In line with the latter reports, our data show that DPD mRNA expression in primary tumors is down regulated by 5FU. Further investigations have to bring more light on the mechanism behind this 5FU-induced down regulation of DPD.…”

HOXA13 contributes to gastric carcinogenesis through DHRS2 interacting with MDM2 and confers 5‐FU resistance by a p53‐dependent pathway

“…GC cells (5 × 10 6 ) with HOXA13 knockdown or DHRS2 overexpression were suspended in 100 µL of PBS and subcutaneously injected into flanks of the mice. Seven days after subcutaneous inoculation, the mice were randomly divided into two groups (3 mice/group) and injected with either PBS or 5‐FU (20 mg/kg/day) by intraperitoneal injection every other day for 11 days (i.e., 6 injections) . Tumor volume (mm 3 ) was estimated weekly by using the following formula: tumor volume (mm 3 ) = length × width 2 × 0.5 .…”

Extracellular Vesicles from Cancer-Associated Fibroblasts Containing Annexin A6 Induces FAK-YAP Activation by Stabilizing β1 Integrin, Enhancing Drug Resistance

“…The mice were euthanized 2 days after the final injection, and the intraperitoneal tumors were then removed and weighed. The doses of these inhibitors were based on previous reports (18)(19)(20). All animal studies were conducted using protocols approved by Kumamoto University Institutional Animal Care and Use Committee.…”