[Drug therapy of malignant melanoma based on a cell culture test].
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Biomedical subjects
Publications and source records attributed to S Vaage.
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Murine hybridoma antibodies to a human B-cell lymphoma were developed. After screening against normal T cells, monocytes, and granulocytes 11 antibodies that reacted with cells from other B-cell lymphomas remained, of which 10 showed individually distinct staining patterns, as tested by indirect fluorescence. When tested against lymphomas or cell lines, none of these antibodies revealed staining patterns suggesting reactivity with conventional B-cell surface markers, such as immunoglobulin, complement factor 3 receptors, or HLA-DR antigens. Only one of the antibodies (GB1) reacted with human serum, as determined by a blocking assay. The antibodies were found to belong to different immunoglobulin isotypes. Two antibodies (GB13 and GB14) reacted with greater than 5% of normal peripheral blood mononuclear cells. These reactions were mainly due to reactivity with B cells. The antibodies reacted only in a few cases with acute leukaemias, B-cell lines, and follicular lymphomas. On the other hand, distinct patterns of reactivity in different histological groups of diffuse lymphomas were obtained, suggesting that the antibodies may be useful in delineating phenotypic subsets among human B-cell lymphomas.
In 18 biopsy specimens from human breast carcinoma a comparison was made between DNA measurements obtained by microspectrophotometry (MSP) of Feulgen-stained nuclei in imprints and flow cytometry (FCM) of nuclei stained with ethidium bromide. For each specimen FCM was performed both with ethanol-fixed cells and unfixed cells. In addition, single cell suspensions were made from other 11 fresh mammary cancer biopsies. Parts of these suspensions were analysed both by MSP (Feulgen-stained smears) and FCM (ethanol-fixed, mitramycin-stained cells). The MSP histograms show selected tumour cells and tumour-like cells. This explains the higher proportion of cells with DNA content above the 2 c level. A good agreement was found between the results obtained by MSP and FCM with regard to the ploidy of the DNA stemline(s). FCM of fixed cells (multiple-step procedure) yielded a slightly lower proportion of diploid cells than FCM of the unfixed cells (one-step procedure), probably owing to loss of small cells during the different preparation steps. It is concluded that the results from DNA-histograms obtained from MSP and FCM can be compared as to DNA-stemline ploidy of the cell population but not as to the proportion of cells with non-diploid DNA-content.
To study the usefulness of an in vitro colony-forming assay in predicting individual clinical responses to chemotherapy, tumor cells obtained from 150 melanoma metastases (119 patients) were grown in soft agar according to the method of Courtenay and Mills (1978), and tested for sensitivity to DTIC, CCNU, vinblastine, procarbazine, abrin and ricin. In 83% of the cases colony formation was observed (plating efficiency, PE, greater than 0.01%). Twenty-seven per cent of the tumors gave PEs greater than 1%, 45% gave PEs in the range 0.1-0.9%, whereas 11% of the tumors gave 0.01-0.09%. The PEs were not correlated with the degree of pigmentation or with the clinical course. Evaluable chemosensitivity data were obtained on 104 metastases from 83 patients. Large differences in sensitivity were seen. In cases which were evaluable both in vivo and in vitro a clear correlation was found between the in vitro chemosensitivity, expressed as the expected growth delay, and the clinical response to chemotherapy. Tumors from patients with partial response, mixed response or stable disease after prior progression, all had rather high in vitro sensitivity to the drug used (expected growth delay greater than 2.0), whereas patients with progression had lower sensitivity. The results confirm that the soft agar method used here provides good culture conditions for human melanoma cells and show that chemosensitivity data can be obtained in a high percentage of melanoma patients. The approach used seems promising in aiding clinicians to adjust chemotherapy to individual patients.
Biopsy specimens from 29 patients with operable breast carcinomas were examined by Feulgen-DNA microspectrophotometry. A diploid DNA stemline was found in ten tumors, seven of which were stage I carcinomas. In 19 tumors, ten of which were stage II cancers, a non-diploid DNA stemline was observed. The diploid tumors were most often estrogen receptor-positive (nine of nine examined carcinomas), whereas 13 of 19 non-diploid tumors studied did not contain estrogen receptors. The mean nuclear size of the non-diploid tumor cells was increased compared with that of the diploid malignant cells. Three grade I carcinomas were diploid, whereas three grade III tumors were non-diploid. Of the 23 grade II carcinomas, seven were diploid and 16 non-diploid. Hum Pathol 13:626-630, 1982.
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The influence of cardiopulmonary bypass on the adhesiveness of blood platelets, using both bubble (Bentley and Rygg-Kyvsgaard) and membrane (Landé-Edwards) oxygenators, was investigated. With both types of oxygenators, there was a considerable fall in platelet adhesiveness during cardiopulmonary bypass, particularly with the Rygg-Kyvsgaard apparatus. The adhesiveness increased 30 minutes after bypass, but it was still not restored to the initial value.
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Three cases of sarcoma developing after irradiation for breast cancer are reported. A malignant mesenchymoma in the sternum--a combination of osteogenic sarcoma and rhabdomyosarcoma--is the first documented case of its kind occurring after radiation therapy. Of the other two tumors one was an extraskeletal osteogenic sarcoma in the soft tissues of the thoracic wall and one a rhabdomyosarcoma in the axilla.