zhengguangmycin and Nasopharyngeal-Neoplasms

Combined therapy has been advocated for modern tumor treatment; the combined target therapy is a valuable research direction. Based on the previous research of nasopharyngeal carcinoma (NPC) radioimmunotherapy, this experiment was designed to develop two immunoconjugates of the monoclonal antibody BAC(5):PYM-BAC(5) and (131)I-BAC(5), and to assess the inhibition effects of their combined treatment on the NPC CNE-2 cells cultured in vitro.. Dextran T40 was used as media to link PYM and BAC(5). The conjugate PYM-BAC(5) was identified by testing its immunoactivity and the inhibition to mycobacterium. BAC(5) was labeled with (131)I by Chloramin-T method. Five experimental groups were set up:(1)PYM-BAC(5) group, (2)free PYM group, (3)(131)I-BAC(5) group, (4)(131)I-mIgG group, (5)the combined target treatment group ( (131)I-BAC(5)+PYM-BAC(5)). The antitumor effects of the five groups were assessed with MTT method.. The 50% inhibition doses(IC(50)) of PYM-BAC(5) group and PYM group were 46.57 microg/ml and 316.7 microg/ml, respectively. The IC(50) of (131)I-BAC(5) group and (131)I-mIgG group to CNE2 were 4.42 x 10(5) Bq/ml and >11.1 x 10(5) Bq/ml,respectively. In the combined target treatment group(PYM-BAC(5)+(131)I-BAC(5)),the IC(50) of PYM-BAC(5) was 7.01 microg/ml and of (131)I-BAC(5) was 0.54 x 10(5) Bq/ml, which much less than other separate treatment groups.. The inhibition effects of the target treatment ((131)I-BAC(5) and PYM-BAC(5)) on the NPC CNE-2 cells are stronger than non-target treatment (free PYM and (131)I-BAC(5)). The combined target treatment of the two immune ((131)I-BAC(5)+PYM-BAC(5)) conjugates gets stronger inhibition effects than their separate treatment.

Topics: Antibiotics, Antineoplastic; Antibodies, Monoclonal; Bleomycin; Cell Line, Tumor; Combined Modality Therapy; Humans; Immunoconjugates; Iodine Radioisotopes; Nasopharyngeal Neoplasms; Radioimmunotherapy

Pingyangmycin (PYM), produced by Streptomyces pingyangensis n. sp., was found to be identical to bleomycin A5. In the present study, a comparative observation was carried out in 10 human cancer cell lines. As determined by a colony-forming assay, the dose-response curves obtained from cells exposed to PYM for 1 h were of one type only: biphasic exponential. The sensitivities of these cells derived from different types of tumors, however, varied with a broad range of ID50 values (0.03-0.82 microgram/ml). A hepatoma cell line (BEL-7402) and three lines derived from squamous carcinomas of the esophagus (Eca109 and CaEs17) or the nasopharynx (CNE) were relatively sensitive (ID50 less than 0.20 microgram/ml) to PYM which is known to have clinical activity against these diseases. Two gastric adenocarcinoma cell lines (MGc80-3 and BGC-823) and a pulmonary adenocarcinoma cell line (SPC-A-1) appeared to be less sensitive to the drug, with ID50 values of 0.21-0.47 microgram/ml. PYM was 7-fold more effective against LTEP-78 cells derived from pulmonary squamous carcinoma as opposed to SPC-A-1 cells, resulting in a low ID50 value of 0.04 microgram/ml. However, PYM as a single agent has not yet received full evaluation in relation to this type of lung cancer. In contrast with other cell lines of squamous cancer origin, HeLa and CC-801 cells derived from uterine cervix carcinomas which have been evaluated as highly responsive to PYM had the highest ID50 values (greater than 0.70 microgram/ml).

Topics: Adenocarcinoma; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Hepatocellular; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Liver Neoplasms; Lung Neoplasms; Nasopharyngeal Neoplasms; Tumor Cells, Cultured; Tumor Stem Cell Assay; Uterine Cervical Neoplasms

Established human cancer cell lines derived from liver cancer (BEL-7402), nasopharyngeal cancer (CNE-2) and stomach cancer (MGC-803) were used in this study. These human cancer cells have been serially transplanted in nude mice. As determined by clonogenic assay, pingyangmycin (bleomycin A5) was highly cytotoxic to these three cell lines, of which the liver cancer cell line was more sensitive than the other two. At a tolerated dose level, pingyangmycin exhibited a remarkable growth inhibition on the growth of the liver cancer and stomach cancer xenografts, the inhibition rates being 70% and 85%, respectively. No pathologic changes were found in the organs of treated animals.

Topics: Adenocarcinoma, Mucinous; Animals; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Hepatocellular; Carcinoma, Squamous Cell; Cell Line; Female; Liver Neoplasms; Male; Mice; Mice, Nude; Nasopharyngeal Neoplasms; Neoplasm Transplantation; Stomach Neoplasms; Tumor Cells, Cultured