picibanil and Intestinal-Neoplasms

Topics: Adult; Aged; Ascites; Biological Products; Clinical Trials as Topic; Female; Humans; Intestinal Neoplasms; Intestine, Large; Leukocyte Count; Male; Middle Aged; Palliative Care; Picibanil; Prognosis; Skin Tests; Stomach Neoplasms; T-Lymphocytes

To examine the carcinogenetic and growth inhibitory effects of OK-432, large-bowel carcinoma was induced experimentally in rats by intrarectal injection of N-methyl-N-nitrosourea (MNU), and OK-432 was administered intradermally. Rats were sacrificed after six months and the large intestine was cut into serial sections. Histopathologic examination and analysis of the infiltrating mononuclear cells, using monoclonal antibodies, were performed. The average rate of carcinogenesis per rat was 15.7 +/- 8.5 in the MNU alone group (n = 10) and 8.3 +/- 3.5 in the MNU and OK-432 group (n = 6). The invasion was deeper than the muscularis propria in 16 out of 157 lesions (10.2 percent) in the MNU alone group and in one out of 50 lesions in the MNU + OK-432 group (2.0 percent) (P less than 0.05). When time of appearance of atypical glands or carcinomas were compared in the MNU alone and MNU + OK-432 group, carcinogenesis was found to be delayed in the MNU + OK-432 group. In the investigation of infiltrating mononuclear cells using monoclonal antibodies, there were increases in helper T cells in both the MNU alone and MNU + OK-432 groups, but there was little difference between the two groups. The results of this study suggest that the suppression of experimental carcinogenesis in the large bowel by the concomitant administration of OK-432 with MNU, may be due to the enhanced activation or prolonged activated state of immunocompetent cells, which appear via antigen recognition, by OK-432.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Animals; Biological Products; Intestinal Neoplasms; Male; Methylnitrosourea; Picibanil; Rats; Rats, Inbred Strains; Time Factors

Twelve patients with malignant ascites caused by gastro-intestinal cancer were treated by intraperitoneal administration of OK-432. Tumor cells from these patients were separated from ascitic fluid and cultured in vitro before OK-432 therapy. OK-432 was given intraperitoneally one to two times a week at doses ranging from 5 to 20 KE suspended in saline. Mononuclear lymphocytes were collected from the fluid at various intervals throughout the therapy. The effect of ascites-derived lymphocytes on ascites-derived autologous tumor cell growth was studied in vitro using microplate assay. Nine (responders) of 12 patients showed complete disappearance or significant reduction of ascitic fluid. Ascites-derived lymphocytes slightly inhibited autologous tumor cell growth only in one case before OK-432 therapy. Lymphocytes collected from ascites after OK-432 injection significantly inhibited auto-tumor cell growth in all of 9 responders. In 3 non-responders, however, auto-tumor cell growth inhibition was found only in one case. Interestingly, lymphocytes from non-responders significantly inhibited the growth of tumor cells taken from responders. Conversely, lymphocytes from responders did not inhibit non-responder-derived tumor cell growth. These findings imply that auto-tumor killing by OK-432-induced lymphocytes may depend more on the condition of the tumor cells than on the condition of the lymphocytes, and that the measurement of auto-tumor killing activity by ascites-derived lymphocytes may be useful as an indicator in OK-432 therapy.

Topics: Abdominal Neoplasms; Ascites; Biological Products; Cytotoxicity, Immunologic; Drug Evaluation; Humans; Intestinal Neoplasms; Methods; Peritonitis; Picibanil; Stomach Neoplasms; T-Lymphocytes, Cytotoxic

Topics: Adult; Aged; Biological Products; Female; Humans; Intestinal Neoplasms; Leukocyte Count; Male; Middle Aged; Picibanil; Stomach Neoplasms

Topics: Animals; Biological Products; Intestinal Neoplasms; Male; Methylhydrazines; Neoplasms, Experimental; Picibanil; Rats

Topics: Aged; Biological Products; Drug Therapy, Combination; Female; Fluorouracil; Humans; Intestinal Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasms; Pancreatic Neoplasms; Picibanil; Stomach Neoplasms; Tegafur