Biomedical subjects
Publications and source records attributed to M Kaufmann.
Various human tumours have been investigated using, as previously described an in vitro method for sensitivity testing. This test provides information both on the rates of proliferation of tumours and on their resistance to cytostatic agents.
The following cytostatic agents were tested for activity in vivo and in vitro inWalker carcinosarcoma 256 of the rat: cyclophosphamide, triaziquon, 5-fluorouracil, methotrexate, adriamycin, dactinomycin, daunorubicin, hydroxyurea, procarbazin and vincritine. With the exception of vincristine, the results of therapy in vivo could be predicted by using a rapid in vitro test system. This involved, for cyclosphosphamide, triaziquon, adriamycin, and daunorubicin, the measurement of 3H-uridine or 3H-thymidine incorporation. The activities of methotrexate and 5-fluorouracil could be determined from 3H-deoxyuridine incorporation and that of dactinomycin from 3H-uridine incorporation. The results of short-term tests (uring adriamycin, daunorubicin, and dactinomycin) in roughly 100 human tumors were compared with data in the literature on therapy with the same cytostatic agents. Good agreement was found between the results of in vitro tests and the literature data on clinical therapy.
Certain substances which influenced nucleic acid metabolism were found to have about the same cytostatic activity on human cells when measured in tissue culture experiments (cell numbers) or in short-term cultures (3-H-uridine incorporation in cell suspensions). By treatment with a dose of cytostatics corresponding to 10 times therapeutic dose, chemosensitive tumors can be distinguished from non-responsive tumors. By using this in vitro test system to investigate the sensitivities of 100 human tumors, it is shown that 28 of these tumors were responsive to adriamycin, daunomycin and Actinomycin D. Good agreement was observed between these in vitro results and the literature data on clinical therapy using these particular substances.
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The sensitivity of tumors to cyclophosphamide was tested in vitro. For this purpose, the urine of cyclophosphamide-treated rats (90 min., 500 mg/kg) was used. This method of activating cyclophosphamid proved more advantageous than other methods; all cytostatically effective metabolites can be used in the test and the production of metabolites can easily be standardized. Consequently results with good reproducibility can be obtained. In various long-term and short-term test models with animal transplantation-tumors in vitro, the effects of the cyclophosphamide metabolites depended on the dose used. This test results in the various test models are comparable. In the tissue-culture of tumors (long-term test) sensitivity was evaluated by using morphological criteria as well as by counting cell numbers. In the short-term test the sensitivity of tumors was found out by influencing the nucleic acid syntheses (3-H-thymidine-, 3-H-uridine-incorporation). As the tissue-culture meets with difficulties as a routine clinical examination, the use of the short-term test is recommended. Using as model the fast proliferating WALKER-256-carcinosarcoma and a slowly proliferating rat adenocarcinoma, the results of the sensitivity-test in vitro were compared with the effects of therapy in animal tests. Tumor remissions corresponding with the results reached in vitro, which depended on dosis, could also be achieved in both transplantation-tumors. Human tumors, tested in in vitro studies (short-term-test), show a different sensitivity to cyclophosphamide.
This is a case report of a newborn infant with an isolated complet paresis of the peroneal nerve, diagnosed shortly after birth. The etiology of this quite rare observation in a newborn is discussed and the literature reviewed.
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The effects of ten different substances on the mouse sarcoma 180 have been compared using in vivo and in vitro test systems. The size of the tumours was taken as a measure of the success of the therapy in animal experiments. The in vitro effects were estimated by measuring the incorporation of radioactively labelled uridine in tumour cell suspensions from solid tumours, in ascites tumours and in tissue culture. Similar results were obtained using all three in vitro test systems. Four substances (daunomycin, fluoruracil, actinomycin D, adriamycin) exhibited activity both in vivo and in vitro, whereas five substances (cytosinarabinoside, methotrexate, ibenzmethyzin, triaziquone, bleomycin) showed no activity in any of the test systems used. With podophyllic acid ethyl hydrazide, however, no correlation between in vivo and in vitro effects was observed. Studies on the influence of the cytostatic agents on the rate of transport of uridine into the cells showed that podophyllic acid ethyl hydrazide strongly reduced the permeability of the cells to radioactive uridine.
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