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Biomedical subjects

J Mattern

Publications and source records attributed to J Mattern.

At least 127 records · Page 7Linked to original sources
PubMed1979

[Chemotherapy in solid transplantation tumors following synchronization (author's transl)].

In order to examine whether the effects due to cytostatics might be improved by synchronization, cytosin-arabinoside, hydroxyurea or Vincristin were administered to rats bearing solid transplantation tumors, at different intervals following synchronization. The three substances, interfering with the S-phase of the cells, show significantly improved therapeutic results with quickly proliferating Walker-carcinosarcoma after a synchronization by hydroxyurea. Cyclophosphamide on the other hand, being effective through several phases of the cell cycle, furnishes no evidence of any essential therapeutic result. Analogous therapeutic experimentation using slowly growing neurosarcomas yielded no better results after synchronization. The concept of synchronization treatment may be approved, therefore, with certain limitations: firstly, synchronization with hydroxyurea can be maintained for a short time only, and the cancerous cells pass throught the first phases of the cell cycle following synchronization for the most part together with normal cells; secondly, only tumors with an important growth fraction and only cytostatics that do not affect several phases of the cell cycle are appropriate for synchronization therapy.

Animals↗
PubMed1978

[Resistance testing and chemotherapy results of bronchial tumours (author's transl)].

In a pilot study of 40 patients with inoperable bronchiogenic carcinomas the results of clinical therapy were compared with those of in vitro tests by measuring the effects of cytostatic agents on the incorporation of precursors into DNA and RNA in tumour cells incubated in vitro for short periods. Tumour cells that showed little inhibition by the cytostatic agents in vitro (less than 30% inhibition at a concentration of 10(-2) mg/ml adriamycin) came from patients who responded poorly to cytostatic therapy. On the other hand, tumour cells that were strongly inhibited in vitro (greater than 30% inhibition) came from tumours which proved to be sensitive to the chemotherapy given to the patient. A strong correlation existed between the inhibition of uridine incorporation by the tumour cells in vitro by adriamycin and the responses of the tumour to clinical therapy even when combination-therapy was given without adriamycin. There was also a significant correlation between the inhibiting effect of adriamycin in vitro and the survival time of the tumour patients.

Bronchial Neoplasms↗
PubMed1977

Detection of induced tumour-resistance to cyclophosphamide by the in vitro short term test.

Treatment of the solid Walker carcinosarcoma of the rat for a period of one year with cyclophosphamide (40 mg/kg at each passage; tumours were transplanted weekly) resulted in the formation of a cyclophosphamide-resistant tumour cell line. Without further treatment, animals injected with non-treated or cyclophosphamide pre-treated cells survived for 10 days on an average. After therapy with cyclophosphamide (2 x 38 mg/kg), rats with non-treated tumour cells survived 22 days whereas those with pre-treated tumours survived only for 17 days. Tumour cells which were shown to be sensitive in vivo also exhibited a larger reduction in 3H-thymidine and 3H-uridine incorporation in the in vitro short term test after incubation with urine from cyclophosphamide-treated rats or with 4-hydroperoxy-cyclophosphamide. The resistance to cyclophosphamide which was detected in animal experiments with Walker carcinosarcoma can therefore also be observed using the in vitro short term test.

Animals↗
PubMed1976

Clinical correlates of in vitro effect of adriamycin on advanced lung carcinoma.

The effect of 1.38 X 10(-5) M adriamycin on tritiated uridine incorporation was studied after 3 hours treatment of suspensions of 25 advanced human lung carcinomas in vitro. The results were correlated with the responses to clinical therapy. All tumours which showed an inhibition of uridine incorporation in vitro of more than 40% were also sensitive to clinical treatment with adriamycin.

Cells, Cultured↗
PubMed1975

[Incorporation of a 131-iodine-deoxycytidine monophosphate protamine complex into the DNA of tumor-bearing rats following partial synchronization with hydroxyurea].

The incorporation of 131-Iodo-deoxyuridine in rat tumours can be increased by partial synchronisation with hydroxyurea. The reported investigation was carried out to determine whether the incorporation could be further increased by using a basic 131-Iodo-deoxycytidine-monophosphate-protamine complex as a depot of Iodo-deoxyuridine. It was shown that the incorporation observed after synchronisation could be increased by using this complex (non-synchronized tumours 1,46% retention, synchronized tumours 2,28% retention; measured 4 hour after the final injection of hydroxyurea) whereas in a control group injected with 131-Iodo-deoxycytidine-monophosphate alone, only a small increase was observed. The large increase in activity in the liver and in the spleen (liver: non-synchronized 2,76%, synchronized 2,79% retention; spleen: non-synchronized 3,00, synchronized 3,80% retention; measured 4 hours after final injection of hydroxyurea) which is observed after injection of the 131-Iodo-deoxycytidine-monophosphate-protamine complex renders it unsuitable for use in the scintigraphic detection of tumours. 131-Iodo-deoxyuridine is shown to be more suitable for this purpose.

Animals↗
PubMed1975

[Possibilities and limits of pre-therapeutic neoplasm sensitivity cytostatics tests under short-term conditions].

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.

Animals↗
PubMed1975

Pharmacokinetics of guanazole in patients with acute myelocytic leukemia.

Levels of guanazole (GZ) in plasma and packed cells were determined after a single tracer dose of 14C-guanazole or during a 5-day continuous intravenous therapeutic infusion of unlabeled drug to 5 patients with acute myelocytic leukemia (AML). The levels of unlabeled drug were determined colorimetrically. GZ infected as a tracer dose was rapidly distributed in an apparent volume of 0.61 l/kg, which is somewhat less than that of total body water, and the drug appeared to be eliminated essentially unchanged by glomerular filtration. The mean apparent volume of distribution increased by about 15% during infusion. An increase of 60% was also noted in the half-life (t1/2) values, with a concimitant decrease in the mean value of renal clearance rate by 40%, except in 1 case. The study demonstrates that monitoring levels of guanazole is possible during infusion therapy and indicates that the data could be used to evaluate pharmacokinetic parameters predicting the time-course of such levels in patients.

Adult↗
PubMed1975

Sensitivity tests of tumors to cytostatic agents. II. Investigation on human tumors.

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.

Antineoplastic Agents↗