Inhibition of lymphatic metastasis in a syngeneic rat fibrosarcoma model by an angiogenesis inhibitor, AGM-1470.

We examined whether lymphatic metastasis was inhibited by the potent angiogenesis inhibitor AGM-1470 [O-(chloroacetyl-carbamoyl)fumagillol, TNP-470] using a rat lymphatic metastasis model. Clone A of the rat fibrosarcoma AS653HM, when inoculated into the footpads of syngeneic rats, highly and preferentially metastasized to lymph nodes. In contrast, when AGM-1470 was administered subcutaneously to rats bearing the tumor cells, the tumor growth and incidence of metastasis in the lymph nodes were reduced in a dose- and schedule-dependent manner. Similar inhibition of lymphatic metastasis was also observed in the rats in which treatment with AGM-1470 was initiated following resection of the primary tumor in the foot, indicating that the treatment with AGM-1470 inhibited the progression of lymphatic metastasis at the metastatic sites of the lymph nodes. These results suggest that AGM-1470 can be a potential agent to prevent lymphatic metastasis.

Effects of lansoprazole with or without amoxicillin on ulcer healing: relation to eradication of Helicobacter pylori.

We studied the effects of lansoprazole with or without amoxicillin on the quality of ulcer healing in relation to eradication of Helicobacter pylori. Ulcer healing rates for lansoprazole 30 mg q.d. alone (group A) were 100% for duodenal ulcers (DU; n = 20) and 92% for gastric ulcers (GU; n = 15). The healing rates for lansoprazole 30 mg plus amoxicillin 1-2 g q.d. (group B) were 100% for both DU (n = 20) and GU (n = 12). Endoscopic findings after treatment showed that the red scar/white scar ratio in group A was 16/4 for DU and 12/1 for GU. The red scar/white scar ratio in group B was 4/16 for DU and 6/6 for GU. The numbers of H. pylori in gastric mucus did not change throughout the course of treatment in group A but decreased significantly, without H. pylori relapse, in group B. Changes in ammonia concentration in gastric juice, as well as serum gastrin and pepsinogen I and II levels, differed between group A and group B. Concomitant treatment with lansoprazole and high-dose amoxicillin eradicated H. pylori and modified gastric secretory function, resulting in high-quality ulcer healing.

[Fundamental study and clinical testing of human tumor clonogenic assay (HTCA)].

Through our retrospective analysis of HTCA and clinical effects as well as fundamental studies, the following results were obtained: In this retrospective study, HTCA for lung cancer showed a predictive accuracy of 71%, a true positive rate of 50% and a true negative rate of 77%. To obtain good predictive accuracy, HTCA should be modified to provide conditions comparable to those in vivo with regard to drug concentration and drug exposure time. More precise analysis of the pharmacokinetics of anticancer agents might yield methodological improvement. A decrease in the chemosensitivity spectrum in vitro was observed after chemotherapy. This might be related to evidence that patients with prior chemotherapy exhibited a poor response rate to chemotherapy. There were no active anticancer agents against specimens with aplating efficiency of more than 0.04%. More extensive prospective trials will be necessary to determine the clinical value of HTCA. HTCA could be a superior assay for detecting the anti-tumor activity of new agents and a useful method for in vitro phase II study.