bleomycin-a6 and Liver-Neoplasms

Boanmycin hydrochloride, a new antitumor agent, has a short half-life and fast clearance speed in vivo. The aim of this research was to investigate the effectiveness of peritumor injection of boanmycin hydrochloride within temperature-sensitive gel in situ using Hep-G2 hepatoma nude mice model.. Nude mice with human Hep-G2 tumor in right flank were randomly divided into four groups: normal saline group, in situ gel only group, boanmycin hydrochloride in situ saline group, and boanmycin hydrochloride in situ gel group, and were treated with injection of corresponding agents into peripheral tissue of the tumor. The volume of the tumor and the body weight of the mice were regularly measured, and tumor growth curve was generated. The size, internal echo, and blood flow of the tumors were observed by color Doppler ultrasonography. Histopathologic changes of the tumor after treatment were observed under both optical and transmission electron microscopy.. The tumor growth was significantly inhibited by peritumoral therapy in boanmycin hydrochloride in situ gel group with the tumor inhibitory rate of 86.76%. The blood flow of the tumor was still seen in both normal saline group and in situ gel only group on color Doppler ultrasound. Punctate calcification and dotted blood flow were seen in boanmycin hydrochloride group; however, there was massive calcification and no blood flow in the tumor in the boanmycin hydrochloride in situ gel group. Large areas of necrosis and apoptotic cells were shown by microscopic observation in boanmycin hydrochloride in situ gel group.. Temperature-sensitive boanmycin hydrochloride in situ gel can effectively delay the release of boanmycin hydrochloride and increase its anticancer effects for liver cancer in animal model.

Topics: Animals; Bleomycin; Hep G2 Cells; Humans; Liver Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Temperature; Ultrasonography; Xenograft Model Antitumor Assays

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

Boanmycin (bleomycin A6, BM), an antitumor antibiotic, was conjugated to monoclonal antibodies including R19, H111 and CCT2. The immunoconjugates exhibited selective cytotoxicity to related target cells including cecum cancer Hce-8693 cells, liver cancer BEL-7402 cells and leukemia CEM cells. They were highly effective against related human tumor xenografts in nude mice, and the inhibition rates by the conjugates were much higher than those by free BM. The inhibition rate by R19-BM conjugate against human cecum cancer xenografts reached 90%. BY immunoelectron microscopy, CCT2-BM conjugate showed specific binding and internalization in leukemia CEM cells. The results indicate that boanmycin-monoclonal antibody immunoconjugates are highly active both in vitro and in vivo.

Topics: Adenocarcinoma; Animals; Antibiotics, Antineoplastic; Antibodies, Monoclonal; Bleomycin; Carcinoma, Hepatocellular; Cecal Neoplasms; Humans; Immunotoxins; Liver Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Tumor Cells, Cultured

Bleomycin A6 (A6), a single component of bleomycin complex, is highly active against human liver cancer cells in vitro and xenografts in nude mice. A6 was conjugated to monoclonal antibody H111 directed against human hepatoma BEL - 7402 cells, using Dextran T40 as an intermediate. The conjugate consisted of a coupling molar ratio of 1:264 for H111 and A6, and retained 6.3% of A6 activity. As determined by clonogenic assay with hepatoma BEL - 7402 cells exposed to the agents for 1 h, the IC90 values for H111 - A6 conjugate, free A6 and M3 - A6 conjugate (an irrelevant conjugate) were 0.17 mu mol/L, 17 mu mol/L and 7 mu mol/L respectively. The cytotoxicity of Hill - A6 conjugate to target cells was markedly blocked by unconjugated H111 but not by irrelevant monoclonal antibody M3. The H111 - A6 conjugate exhibited 78% inhibition on the growth of hepatoma BEL - 7402 xenografts in nude mice, whereas the equivalent doses of free A6, M3 - A6 conjugate and H111 plus A6 mixture showed approximately 30% inhibition. Histopathological examination showed no toxic changes in the liver, lung, kidney and bone marrow in the H111 - A6 conjugate--treated animals. These results suggest that the conjugate of monoclonal antibody and bleomycin A6 exhibits specific cytotoxicity to target liver cancer cells and the conjugate is highly effective against liver cancer xenografts in nude mice with more marked tumor inhibition than free A6 at comparable dose levels.

Topics: Animals; Antibodies, Monoclonal; Bleomycin; Carcinoma, Hepatocellular; Humans; Immunotoxins; Liver Neoplasms; Male; Mice; Mice, Nude; Neoplasm Transplantation; Pharyngeal Neoplasms; Tumor Cells, Cultured; Tumor Stem Cell Assay

Topics: Animals; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Hepatocellular; Colony-Forming Units Assay; Humans; Interphase; Liver Neoplasms; Mice; Mice, Nude; Neoplasm Transplantation; Tumor Cells, Cultured; Tumor Stem Cell Assay