bleomycin-a6 and Colonic-Neoplasms

To investigate the therapeutic effect of boanmycin (BAM, bleomycin A6) on colon carcinoma 26 and its hepatic metastasis in mice.. A series of models including subcutaneous transplantation, orthotopic transplantation in cecum subserosa, intra-hepatic transplantation of tumor, and intrasplenic transplantation of tumor accompanied with hepatic metastases were employed. In addition, LEICA Q 500IW image analysis system was used to determine the area of metastatic lesions in the liver in histopathological sections.. BAM at 5 mg.kg-1 and 2.5 mg.kg-1 inhibited the growth of subcutaneous tumors by 78.7% and 61.9%, and the orthotopic tumors by 99.4% and 90.0%; and the intra-hepatic tumors by 86.9% and 75.7%, respectively. Determined by the numbers of metastatic nodules, BAM at 10 mg.kg-1 and 5 mg.kg-1 inhibited hepatic metastases from intra-splenic transplantation by 97.6% and 56.8%; and evaluated by image analysis of metastatic lesions, by 100% and 63.3%, respectively.. Boanmycin is highly effective in a panel of models including the subcutaneous, orthotopic, intra-hepatic transplanted tumors, and hepatic metastases of murine colon carcinoma 26.

Topics: Animals; Antibiotics, Antineoplastic; Bleomycin; Colonic Neoplasms; Liver; Liver Neoplasms; Male; Mice; Mice, Inbred BALB C; Neoplasm Transplantation

Bleomycin A6 (A6), a single component of bleomycin complex, is highly active against human colon and cecum cancer cells in vitro and xenografts in nude mice. R19, a rat monoclonal antibody against human cecum cancer Hce-8693 cells, was linked to A6. R19-A6 conjugate retained complete activity of McAb R19 and 10% activity of A6. As determined by clonogenic assay with human cecum cancer Hce-8693 cells for 1 hour exposure. The 50% inhibitory concentration (IC50) values for R19-A6, A6 and M3-A6 (conjugate of irrelevant Mc-A6) were 0.019, 1.05 and 1.00 mumol/L, respectively. The effect of the conjugate R19-A6 was 55-fold stronger than that of free A6 and 53-fold than irrelevant conjugate M3-A6. Clonogenic assay with human colon cancer HT-29 cells showed that the IC50 values were 0.078 mumol/L and 4.0 mumol/L for R19-A6 and free A6, respectively. The cytotoxicity to Hce-8693 and HT-29 cells was markedly blocked by unconjugated McAb R19 but not by irrelevant McAb MARK-3. The R19-A6 conjugate exerted 90% inhibition on the growth of cecum cancer Hce-8693 xenografts in nude mice, whereas equivalent doses of free A6, R19 plus A6 mixture and M3-A6 showed 52%, 34% and 48% inhibition, respectively. Histopathological examination showed no toxic changes in the heart, lung, liver, kidney and bone marrow in the R19-A6 conjugate treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antibodies, Monoclonal; Bleomycin; Cecal Neoplasms; Colonic Neoplasms; Female; Immunotoxins; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Rats; Tumor Cells, Cultured

As evaluated by clonogenic assay, bleomycin A6 was found to be highly active against established human cancer cell lines derived from colon cancer (HT-29) and cecum cancer (Hce-8693). These human cancer cells have been serially transplanted in nude mice. At a tolerable dosage level, bleomycin A6 exerted remarkable growth inhibition on human colon cancer HT-29 and cecum cancer Hce-8693 xenografts (approximately 90% inhibition). No histopathological changes were found in the organs of treated animals. Compared on the basis of equitoxic doses (1/9 LD50), bleomycin A6 exerted much stronger growth inhibition against colon cancer HT-29 xenografts in nude mice than 5-fluorouracil and mitomycin C, with inhibition rates of 82%, 12% and 53%, respectively. More extensive necrosis was found in tumors treated with bleomycin A6 than in those treated with mitomycin C or 5-fluorouracil. The ratio values of non-necrotic tumor tissue to whole tumor tissue for bleomycin A6, mitomycin C and 5-fluorouracil were 0.33, 0.65 and 0.57, respectively. These observations indicate that bleomycin A6 is a potent antitumor agent against colon cancer xenografts and may be useful in human colon cancer chemotherapy.

Topics: Animals; Antineoplastic Agents; Bleomycin; Cecal Neoplasms; Colonic Neoplasms; Female; Fluorouracil; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Mitomycin; Mitomycins; Neoplasm Transplantation; Tumor Cells, Cultured; Tumor Stem Cell Assay