[Current status of diagnosis and treatment of gastric cancer peritoneal metastasis].

Peritoneal metastasis is the most common distant metastasis of gastric cancer. As an end-stage event of gastric cancer, patients with peritoneal metastasis often have lost the chance of radical resection, and even after palliative surgical resection, the long-term outcomes are still not satisfactory. In recent years, with the application and promotion of laparoscopic technology, neoadjuvant intraperitoneal and systemic chemotherapy, hyperthermic intraperitoneal chemotherapy and cytoreductive surgery, through perioperative comprehensive treatment strategies by multidisciplinary team, the quality of life and survival of patients with peritoneal metastasis have been significantly improved. Some patients with gastric cancer peritoneal metastasis diagnosed by laparoscopy even get the opportunity to have radical cytoreductive surgery and hyperthermic intraperitoneal chemotherapy after neoadjuvant intraperitoneal and systemic chemotherapy. Taking into account the progress in the treatment of gastric cancer peritoneal metastasis in recent years, this article intends to combine current clinical evidence and to discuss the key issues in the course of clinical diagnosis and treatment of gastric cancer peritoneal implantation and metastasis, including the imaging diagnosis of peritoneal metastasis, laparoscopic examination, evaluation of peritoneal metastasis and comprehensive treatment plan.

Assessment of the antimalarial potential of tetraoxane WR 148999.

The antimalarial peroxide, dispiro-1,2,4,5-tetraoxane WR 148999, was synergistic with chloroquine, quinine, mefloquine, and artemisinin against both D6 and W2 clones of Plasmodium falciparum. In consideration of the contrasting antagonism between artemisinin and chloroquine, these drug combination data imply that WR 148999 and artemisinin may not share a common mechanism of action. For Plasmodium berghei-infected mice given oral, subcutaneous, and intraperitoneal doses of WR 148999 ranging from 2 to 1024 mg/kg in the Thompson test, median survival times were 8.8, 11.8, and 27.5 days, respectively, compared to 8 days for control animals. Using subcutaneous administration, WR 148999 had a considerably longer duration of action than did artemisinin against P. berghei. WR 148999 did not significantly inhibit cytochrome P450 isozymes CYP 2C9, 2C19, 2D6, 2E1, or 3A4 (IC50 >500 microM) but did inhibit CYP 1A2 with an IC50 value of 36 microM, suggesting that WR 148999 may be metabolized by the latter CYP isozyme. These results combined with previous observations that formulation strategies and incorporation of polar functional groups in a series of WR 148999 analogs both failed to enhance tetraoxane oral antimalarial activity suggest that oral bioavailability of tetraoxane WR 148999 is more likely a function of extensive first-pass metabolism rather than solubility-limited dissolution.