didimethylsulfoxide-dichloroplatinum(ii) and Liver-Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Evaluation; Floxuridine; Fluorouracil; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Middle Aged; Organoplatinum Compounds; Survival Rate

In hepatocellular carcinoma cell lines, the intensity of staining with the monoclonal antibody C-219 to the multidrug-resistant gene (mdr1) product P-glycoprotein and the intensity of the band at a molecular weight of 170 KDa on Western blot were associated closely with resistance to Adriamycin but not with the resistance to cis-dichlorodiamine platinum (CDDP). In clinical specimens, noncancerous liver tissue was regularly stained with this antibody on the biliary canalicular front of the hepatocyte cell membrane. In liver cancer tissue, however, regular staining as in the noncancerous regions of the liver was observed in only 16% of the patients, irregular staining was seen in only 24%, and no staining was seen at all in 60%. Staining of P-glycoprotein with the C-219 antibody is technically simple and is useful for studying the role of P-glycoprotein in drug-resistant hepatocellular carcinoma.

Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Blotting, Western; Carcinoma, Hepatocellular; Doxorubicin; Drug Resistance; Drug Screening Assays, Antitumor; Gene Expression Regulation, Neoplastic; Humans; In Vitro Techniques; Liver; Liver Neoplasms; Membrane Glycoproteins; Neoplasm Proteins; Organoplatinum Compounds; Tumor Cells, Cultured

The effect of immunotargeting chemotherapy for hepatoblastoma (HB) and hepatocellular carcinoma (HCC) following the application of adriamycin (ADM) or cis-platinum conjugated with anti-alpha-fetoprotein (AFP) antibody was evaluated experimentally and clinically. The conjugate was made from mouse monoclonal antihuman AFP antibody linked to ADM or CDDP, with a weight ratio of 2.5:1 via a dextran bridge. Experimentally, AFP-producing human HCC transplanted subsequently on nude mice was used. A mixture of the antibody and ADM or CDDP was prepared with the same ratio. Each drug was injected intraperitoneally, three times at the total dose of 14.4 mg/kg as ADM and one time at the dose of 8 mg/kg as CDDP. Tumor growth was inhibited significantly in the conjugate group compared with the other mixture group, the ADM or CDDP group, and the control group. Clinically, the conjugates were administered intraarterially in 4 cases (2 HBs and 2 HCCs) and intravenously in one case (1 HB). ADM and CDDP conjugated with anti-AFP antibody were used in 2 cases and 3 cases, respectively. Antitumor effects from the viewpoint of volume suppression rate showed partial response in 2 cases and no change in 3 cases. The immunotargeting chemotherapy using anti-AFP monoclonal antibodies may be a promising method for treatment of malignant epithelial liver cancer in children.

Topics: Adolescent; alpha-Fetoproteins; Animals; Antibodies, Monoclonal; Antineoplastic Agents; Doxorubicin; Female; Humans; Infant; Liver Neoplasms; Liver Neoplasms, Experimental; Male; Mice; Mice, Inbred BALB C; Organoplatinum Compounds; Prognosis