Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bleomycin either alone or in combination with radiotherapy was used in the treatment of 24 patients with non-resectable cancer of the oesophagus. Improvement in performance (swallowing) status was observed in 75% of patients, although only 19% were known to be alive after 1 year of follow-up. Patients with liver cancer were treated with adriamycin. The response rate was dose dependent and was 40% at best. Combination of adriamycin with other drugs did not improve the response rate. Intra-arterial adriamycin appears more efficacious and gave a response rate of 60%.
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PMID:African trials in chemotherapy of gastrointestinal cancer. 7 58

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.
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PMID:[Experimental studies on the antitumor activity of monoclonal antibody--bleomycin A6 conjugate against human liver cancer]. 172 Feb 70

The combined antitumor effects of local hyperthermia and a simultaneous injection of bleomycin suspended in sesame oil (BLM-sesame oil) into the proper hepatic artery were studied in a model of liver cancer in rabbits. Fourteen days after inoculation of VX2 carcinoma into the left anterior lobe, 107 rabbits were used for the experiments. Local hyperthermia of 43-47 degrees C for 20 minutes was administered directly to the liver tumor via a 915 MHz microwave. In a preliminary study, administration of sesame oil alone into the proper hepatic artery led to a peripheral hepatic artery embolization, as evidenced by microangiography, and to the inhibition of tumor growth. The tumor-bearing rabbits were placed into groups of six. The first group was treated with hyperthermia, the second with a saline solution of bleomycin given intra-arterially, the third with a combination of hyperthermia and a saline solution of bleomycin given intra-arterially, the fourth with BLM-sesame oil given intra-arterially, the fifth with a combination of hyperthermia and sesame oil given intra-arterially, and the sixth with a combination of hyperthermia and BLM-sesame oil given intra-arterially. Consequently, the concomitant application of hyperthermia and intra-arterial injection of sesame oil led to a prominent inhibition of tumor growth, as compared with each modality alone (P less than 0.001). The most significant effect was obtained in the case of a combination of hyperthermia and BLM-sesame oil, as compared with a combination of hyperthermia and sesame oil (P less than 0.001). Local hyperthermia concurrent with the blockage of blood flow supplying the tumor led to a prominent inhibition of tumor growth, and addition of bleomycin to this regimen had an even greater antitumor effect. Thus, a combination of hyperthermia and chemoembolization with BLM-sesame oil is an effective treatment for liver cancer, at least in rabbits.
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PMID:Destruction of VX2 tumor in rabbits by hyperthermia plus bleomycin suspended in sesame oil. 242 62

Bleomycin is a membrane impermeable chemotherapeutic agent that is relatively innocuous extracellularly but highly cytotoxic when delivered directly to the cytoplasm. We report on the development of a liposome delivery system that targets Her-2 overexpressing breast cancer cells and breaches the endosomal barrier, delivering bleomycin to the cytoplasm. The liposomes are conjugated to the antibody trastuzumab, which results in specific binding and internalization of liposomes into Her-2 overexpressing cells. In addition, the liposomes are disulfide bonded to a pore-forming protein listeriolysin O (LLO) which forms pores in the endosome and allows the liposomal cargo to pass into the cytoplasm. We demonstrate specific delivery to Her-2 positive MCF-7/Her18 cells relative to Her-2 negative MCF-7 cells using a fluorescent probe calcein within the immunoliposomes. When calcein is replaced by bleomycin, the liposomes effectively reduce viability of five different Her-2 overexpressing cell lines (BT-474, SKBR-3, MCF-7/Her18, HCC-1954 and MDA-453) while harming to a much lesser extent Her-2 negative breast cell lines (MCF-7, MCF-12a and MCF-10a). The liposomes also affect trastuzumab-resistant cells, reducing MDA-453 cell number by 97% compared to untreated cells. Importantly, the concentration of drug needed to reduce tumor cell growth and viability using this liposome therapy is approximately 57,000-fold less than the concentration needed if drug is delivered extracellularly, raising the possibility of increased therapeutic specificity with decreased side effects.
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PMID:Targeting Her-2+ breast cancer cells with bleomycin immunoliposomes linked to LLO. 2262 4

The roles and model of action of the chromatin assembly complex factor-1B (CHAF1B) gene in liver cancer have not been fully elucidated. The CHAF1B gene in human hepatocellular carcinoma cell line HUH-7 was knocked down using a lentivirus and the transfected cells were assayed for migration and invasion abilities and cell cycle arrest using the scratch wound healingand Transwell assays as well as flow cytometry, respectively. Cells transfected with an empty vector were used as the control. The expression of genes was profiled. Models were constructed using CHAF1B-knockdown cells and investigated for tumor growth and pathological changes. Our experiments revealed that the knockdown of the CHAF1 gene reduced the invasion and migration ability of HUH-7 cells. Gene expression profiling revealed that after knockdown, PSMB6, SLC30A7, SMC3, TWF2 and BLM genes had the most marked changes as compared with the control. Western blot and RT-PCR analyses revealed that following the knockdown of the CHAF1B gene, protein and mRNA levels of the PSMB6, SLC30A7 and SMC3 genes were significantly upregulated, while those of the BLM and TWF2 genes were significantly downregulated. In the HUH-7-knockdown cells, there were significantly fewer G0/G1 cells and more S1 cells as compared with the control (36.10 vs. 54.10% and 59.7 vs. 40.8%, respectively), while the number of G2/M cells was similar (4.20 vs. 5.10%). The volumes of the tumors were similar between those injected with the empty vector and control, but were significantly smaller in the knockdown models, suggesting that the knockdown of the CHAF1B gene inhibited tumor growth. H&E staining revealed that tumors were developed in mice in all groups.
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PMID:CHAF1B knockdown blocks migration in a hepatocellular carcinoma model. 2976 68