peplomycin and Carcinoma

The Japanese Society of Thyroid Surgery undertook a pilot study of treatment for anaplastic thyroid carcinoma in a cooperative setting. The treatment consisted of cisplatin 40 mg/m2 drip intravenous infusion (div), day 1, adriamycin 60 mg/m2 iv, day 1, etoposide 100 mg/m2/day div, days 1-3, peplomycin 5 mg/body/day sc, days 1-5 and granulocyte colony-stimulating factor (G-CSF) 2 micrograms/kg/day sc, days 6-14. This was scheduled to be repeated every 3 weeks. Local radiation therapy was added for patients in whom it was indicated. A total of 17 patients (mean age, 66 yr) were enrolled. Ten patients had advanced disease with measurable lesions and 2 patients experienced partial remission lasting 2 and 3 months, respectively. Six of 7 patients were treated with the same modality of treatment as an adjuvant. Three died of progressive disease after 3-7 months and three others have survived for 3-11 months. The toxicities of the chemotherapy were mainly bone marrow suppression, despite G-CSF support. Transient liver dysfunction was also noticed. These results indicate that this combined a treatment can be given to patients with acceptable toxicity. The degree of leukopenia was greater than expected, partly due to the advanced age of the patients and the low dose of G-CSF. In addition, 8 available thyroid specimens were examined for the mdr 1 gene and P-glycoprotein, but all were negative. Further study of anaplastic thyroid carcinoma by this cooperative group will be carried out.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Doxorubicin; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hematologic Diseases; Humans; Male; Middle Aged; Peplomycin; Pilot Projects; Survival Rate; Thyroid Neoplasms; Thyroidectomy

Chemosensitivity to anticancer drugs was compared between two human esophageal carcinoma cell lines, T.Tn and YES-6 cells. T.Tn cells were more resistant than YES-6 cells to peplomycin (PEP) but not to the other anticancer drugs such as camptothecin, mitomycin C and cytosine arabinoside. Western blot analysis showed higher expression levels of m-calpain and activated mu-calpain in T.Tn cells than in YES-6 cells. On the other hand, YES-6 cells showed a high expression level of calpastatin, which is a calpain-specific endogenous inhibitor. To investigate whether calpain activity was involved in the chemosensitivity, T.Tn cells were transfected with calpastatin cDNA in an inducible expression vector. The induction of calpastatin was accompanied by increased chemosensitivity to PEP. The increases in calpastatin levels were followed by serial increases in the expression levels of NF-kappaB p65 and Fas. Since purified m- or mu-calpain degraded NF-kappaB p65 in vitro, it is possible that calpastatin suppressed calpain-mediated degradation of NF-kappaB p65. Fas ligand (Fas-L) protein levels increased after treatment of the parental T.Tn and calpastatin-transfected cells with PEP, suggesting the synergism between calpastatin-induced Fas and PEP-induced Fas-L. These results suggest that calpain/calpastatin expression levels are effective markers for predicting the sensitivity of human esophageal carcinoma cells to PEP.

Topics: Antibiotics, Antineoplastic; Calcium-Binding Proteins; Carcinoma; Cell Line, Tumor; Esophageal Neoplasms; Fas Ligand Protein; fas Receptor; Humans; Peplomycin; Transcription Factor RelA

The resistance of malignant tumors to chemotherapy with anticancer drugs has been considered to be due partly to overexpression of the multidrug resistance gene (mdr1) and its gene product, P-glycoprotein (P-GP), which acts as a drug efflux pump for several chemotherapeutic agents. In order to elucidate the mechanism of anticancer drug resistance in anaplastic thyroid carcinoma with very poor prognosis, we examined the expression of mdr1 mRNA and P-GP, and analyzed their relationships to chemotherapy response. Twenty surgical samples from 16 patients with anaplastic thyroid carcinoma were used. The mdr1 mRNA expression was examined by reverse transcription and polymerase chain reaction, and P-GP expression was evaluated by an immunohistochemical method using JSB-1 monoclonal antibody. Of the 20 clinical samples, expression of mdr1 mRNA and P-GP was observed in three and four samples, respectively. Three of the patients from whom the samples were obtained had been given anticancer drugs before biopsy. Of 12 patients who received chemotherapy for clinically evaluable diseases, 2 responded well, but 10 showed no response. All except one patient died of cancer progression. There was no relationship between the response to chemotherapy and the expression of mdr1 and P-GP. The expression of mdr1 mRNA and/or P-GP was observed in 5 of 16 patients with anaplastic thyroid carcinoma. However, the appearance of anticancer drug resistance in anaplastic thyroid carcinoma may not be explained solely by the expression of mdr1 and P-GP.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; ATP Binding Cassette Transporter, Subfamily B, Member 1; Carcinoma; Carmustine; Cyclophosphamide; Doxorubicin; Drug Resistance, Multiple; Etoposide; Female; Gene Expression; Humans; Immunoenzyme Techniques; Male; Middle Aged; Peplomycin; Polymerase Chain Reaction; RNA, Messenger; Thyroid Neoplasms

Topics: 4-Nitroquinoline-1-oxide; Animals; Bleomycin; Carcinoma; Peplomycin; Rats; Rats, Inbred Strains; Tongue Neoplasms

A phase II study of peplomycin, an analogue of bleomycin, was carried out in 42 patients with advanced or recurrent breast cancer by a cooperative group consisting of 15 institutes throughout Japan, and the following results were obtained. Among the 42 patients, 38 were evaluable, in whom the overall response rate was 7.9% (3/38). For the various histologic types, the response rate was 33.3% (2/6) for papillotubular carcinoma and 9.1% (1/11) for medullary tubular carcinoma. The response rate was 33.3% (2/6) in patients without prior treatment and 3.1% (1/32) in those with prior treatment. Side effects of nausea, anorexia, malaise, alopecia and pyrexia occurred frequently, and a decrease in WBC and an increase in GOT were observed temporally. Pulmonary toxicity was observed in 7 patients.

Topics: Adult; Aged; Anorexia; Bleomycin; Breast Neoplasms; Carcinoma; Carcinoma, Papillary; Drug Evaluation; Female; Humans; Middle Aged; Nausea; Neoplasm Recurrence, Local; Peplomycin

Topics: Animals; Bleomycin; Carcinoma; Cricetinae; Floxuridine; Kinetics; Male; Mesocricetus; Peplomycin; Tissue Distribution; Tongue Neoplasms

In the period between November 1972 and December 1982, 27 patients with nasopharyngeal carcinoma were treated. The male to female ratio was 20:7. and ages ranged from 17 to 71 years with a median of 46. Most of the cases were classified as stage 4. Histological findings according to the WHO classification revealed undifferentiated carcinoma in two-thirds of all cases. The cumulative survival rate was 41.9% over a three-year-period and 17.1% over a five-year-period. Both primacy lesion and regional lymph node metastases were well controlled by radiation therapy. In patients with cranial nerve palsy and/or destruction of the skull base, distant metastasis developed severely later. Most of the distant metastases were found in bone and/or in the lung. In 14 of the 27 cases, systemic chemotherapy using various drugs, either alone or in combination, was performed. No complete response was obtained. Partial response was observed when adriamycin and vincristine were used in combination. Minor response was observed when pepleomycin or adriamycin was used alone. The sequential combination of bleomycin and mitomycin-c also produced minor response. Pre-radiation chemotherapy is recommended to obtain more effective results. The combined use of cis-diamminedichloroplatinum (cisplatin) and pepleomycin (peplomycin) was reported to be effective in nasopharyngeal carcinoma. The testing of pre-radiation chemotherapy using this combination is encouraged for in the treatment of nasopharyngeal carcinoma.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Female; Humans; Male; Middle Aged; Mitomycin; Mitomycins; Nasopharyngeal Neoplasms; Peplomycin

Topics: Adenocarcinoma; Aged; Antibiotics, Antineoplastic; Bleomycin; Carcinoma; Carcinoma, Squamous Cell; Drug Therapy, Combination; Female; Humans; Lung; Lung Neoplasms; Male; Middle Aged; Peplomycin