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Biomedical subjects

J S Ro

Publications and source records attributed to J S Ro.

At least 19 recordsLinked to original sources
PubMed1990

Pirarubicin in combination chemotherapy for metastatic breast cancer.

Pirarubicin is an anthracycline with broad antitumor activity, and without significant cardiotoxicity in preclinical and early clinical trials. We treated 40 evaluable patients with metastatic breast cancer and no prior exposure to chemotherapy with 5-fluorouracil, pirarubicin, and cyclophosphamide at 21-day intervals until reaching cumulative doses of 800 mg/m2 of pirarubicin, or the development of progressive disease. The median age was 56 years and the median performance status, 1. Seventeen patients had prior hormone therapy and 12 had prior radiotherapy. The median number of metastatic sites was three, with 11 patients having less than three sites. Twelve patients were premenopausal. The median disease-free interval was 6 months. Four patients achieved a complete remission and 21 a partial remission, for an overall response rate of 63%. The median response duration was 8 months and the median time to progression for all patients was 9 months. The median survival has not been reached, but will exceed 13 months. Gastrointestinal toxicity was minimal to moderate, whereas myelosuppression was severe. Complete hair loss was observed by only 58% of patients. There were two episodes of mild congestive heart failure at high cumulative doses of pirarubicin; both were controlled with medical treatment. This three-drug combination containing pirarubicin is effective in treating metastatic breast cancer, with less severe toxicity than other anthracycline-containing combinations.

Adult↗
PubMed1990

Elliptinium acetate in metastatic breast cancer--a phase II study.

Thirty-five patients with metastatic breast cancer who had received one or two prior chemotherapeutic regimens were treated with elliptinium acetate at a dose of 80 mg/m2 for 3 days every 3 weeks. Of the 33 patients evaluable for response, 1 patient achieved complete remission, 4 achieved partial responses (15% overall objective response with 95% confidence interval of 5-32%), and 6 achieved minor response. Toxicity of the treatment was xerostomia, diarrhea, and nausea and vomiting. The drug was not myelosuppressive. Three patients showed evidence of elliptinium antibody, and treatment was discontinued. No episodes of hemolysis were observed. Elliptinium acetate showed modest antitumor activity in previously treated patients with metastatic breast cancer.

Adult↗
PubMed1989

c-erbB-2 amplification in node-negative human breast cancer.

c-erbB-2 gene analysis by Southern and DNA dot blot methods was done in 66 tumor samples from patients with histologically node-negative breast cancer. The c-erbB-2 gene was amplified 2- to greater than 8-fold in 13 tumors (20%). None of 59 tumors that were examined by the Southern method showed c-erbB-2 gene rearrangement. c-erbB-2 amplification was analyzed in relation to other prognostic factors. The c-erbB-2 gene was amplified in five of 36 (14%) diploid and eight of 30 (27%) aneuploid tumors. Thirteen of 54 (24%) tumors with nuclear Grade 1 or 2 displayed c-erbB-2 amplification, whereas none of 12 tumors with nuclear Grade 3 did. No correlation was observed with estrogen receptor content, tumor size, histological type, or age of patients. The median follow-up date for these patients was 85+ mo. Of 13 patients whose tumors showed c-erbB-2 amplification, six patients (46%) developed recurrence, and five patients (38%) died of metastatic disease. In contrast, of 53 patients whose tumors did not show c-erbB-2 amplification, 15 patients (28%) developed recurrence, and seven patients (13%) died of disease. In conclusion, our results show that c-erbB-2 gene amplification was more frequent in aneuploid tumors and tumors with poor nuclear grade. c-erbB-2 amplification may be considered a possible prognostic factor in node-negative breast cancer.

Adult↗
PubMed1989

A monoclonal antibody cocktail for detection of micrometastatic tumor cells in the bone marrow of breast cancer patients.

We investigated whether monoclonal antibodies (MoAbs) reactive against both acidic and basic cytokeratins alone were sufficient to detect minimal numbers of contaminating epithelial tumor cells in the bone marrow of breast cancer patients. Monoclonal anti-cytokeratin antibodies (AE1 and AE3) were used to stain 14 breast carcinomas by the avidin-biotin-peroxidase technique. Nine tumors (64.3%) showed high reactivity and five (35.7%) showed low or moderate reactivity. Nine MoAbs that proved to be unreactive to light density bone marrow cells by immunoalkaline phosphatase histochemistry were screened for reactivity to breast carcinomas having only low or moderate positivity to cytokeratin antibodies. Three of nine MoAbs showed high percentages of positivity and were selected to supplement the anti-cytokeratin antibodies for immunohistochemical detection of minimal marrow disease in breast cancer patients. A MoAb cocktail was prepared, further tested for reactivity to another five breast carcinomas, and compared with cytokeratin staining alone. The cocktail labeled 100% of carcinoma cells in all the examined specimens. To determine the sensitivity of this panel for detecting minimal numbers of contaminating tumor cells in bone marrow, in vitro mixing experiments were performed. T47D breast carcinoma cells were mixed with bone marrow mononuclear cells at ratios from one tumor cell per 10 bone marrow cells up to one tumor cell per 1 x 10(6) marrow cells, and cytospin preparations were subsequently stained with the MoAb cocktail by the immunoalkaline phosphatase method. Our approach could detect one tumor cell in 1 x 10(5) hematopoietic cells.

Antibodies, Monoclonal↗
PubMed1988

Reduction to homozygosity at the SIS/PDGF-2 locus in human mesenchymal tumors.

Enhanced expression of the human SIS/PDGF-2 gene has been reported in a number of human cell lines, sarcomas, and glioblastomas. We have analyzed the SIS/PDGF-2 gene for structural alterations in fresh human tumors. DNA samples from 79 patients with solid tumors (63 mesenchymal tumors, 12 lung carcinomas, 4 breast carcinomas) were examined and compared with DNA samples from 50 leukemia patients and 14 unrelated individuals without malignant neoplasms. When DNA samples were digested with a HindIII restriction endonuclease, Southern blot analysis demonstrated two distinct bands (21kb and 18kb) after hybridization to the SIS/PDGF-2 gene probe. A pedigree analysis of a 43-member family indicated that these allelic variants segregated in a Mendelian fashion. There was, however, tumor specific allele loss in 18% of the mesenchymal tumors analyzed, which may indicate a common etiology for this tumor type.

Cell Line↗
PubMed1988

Multiple restriction fragment length polymorphisms of the human epidermal growth factor receptor gene.

We have examined the epidermal growth factor (EGF) receptor gene for structural alterations in fresh human tumors. DNA samples from 92 patients with solid tumors (lung cancer, 37; breast cancer, 24; head and neck cancer, 17; other tumors, 14) were analyzed and compared with those from 22 leukemia patients and 14 individuals without malignant neoplasms. When DNA samples were digested with HindIII restriction endonuclease, Southern blot analysis demonstrated 3 distinct polymorphic bands (9.8, 11, and 12 kilobases) after hybridization to the HER-A64-1 probe and another 2 distinct polymorphic bands (4.9 and 5.2 kilobases) after hybridization to the HER-A64-3 probe. Pedigree analysis of 43 members of a single family and comparative analysis of tumor and normal DNA samples from the same patients demonstrated that the variations in fragment size observed were due to 2 independent restriction fragment length polymorphisms in the region of the EGF receptor gene. Amplification of the EGF receptor gene was detected in 3 cases of breast cancer, but not in other tumors studied. We conclude that the human EGF receptor gene has multiple restriction fragment length polymorphisms and that in fresh human tumor samples rearrangement and amplification of the gene occur infrequently, if ever, within the region encompassed by the 2 complementary DNA probes used.

Alleles↗
PubMed1986

Structure-activity relationship of cardiac steroids having a doubly linked sugar and related compounds for the inhibition of Na+,K+-adenosine triphosphatase.

Forty-three different cardiac steroids having a doubly linked sugar and related compounds were tested for inhibition of Na+,K+-adenosine triphosphatase from guinea pig heart, and the structure-activity relationship has been discussed. The doubly linked glycosides showed higher activities than the respective genins. The inhibitory activities of these compounds were also dependent upon the presence of ring C substituents. The bufadienolide rhamnosides exhibited greater than three times the inhibitory activity of the parent genin, while the glucosyl residue exerted no significant activity.

Animals↗
PubMed1985

Structure-activity relationship of bufotoxins and related compounds for the inhibition of Na+, K+ -adenosine triphosphatase.

Forty kinds of bufotoxins and related compounds were tested for inhibition of Na+, K+ -adenosine triphosphatase from guinea pig heart, and the structure-activity relationship has been discussed. The inhibitory activities of bufotoxins were dependent upon the dicarboxylic acid and amino acid components. The compounds having both the arginine and suberic acid moieties showed the higher inhibitory activities. The sulfates and glucuronides of cardiac steroids exhibited much less potency than the parent genins. The mode of inhibition was determined by means of the Dixon and Lineweaver-Burk plots.

Animals↗