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Biomedical subjects

H Sauer

Publications and source records attributed to H Sauer.

At least 343 records · Page 19Linked to original sources

Biochemical control of high-dose methotrexate/Leucovorin rescue therapy.

High-dose methotrexate/Leucovorin rescue therapy is based on the assumption of differences in the transport system for folate compounds between normal and malignant proliferating cells. Thus, under normal conditions, methotrexate (MTX) and Leucovorin (citrovorum factor, CF) in low doses can enter the cells by an active transport system, whereas in some malignancies - such as osteosarcoma - these substances only penetrate through the cell membrane by passive diffusion if they are given in very high doses. Therefore, after high-dose MTX treatment, the cytotoxic effect of the folate antagonist is compensated for by rescue with Leucovorin in low doses only in the normal cell system. The consequence of this kind of treatment is a selective antitumor effect. To avoid cytotoxic side effects, this therapeutic regimen must be monitored carefully. The decrease of the ratio of 3H-deoxyuridine (dUR) beta H-thymidine (dTR) incorporation into the DNA of the cells is a good biochemical parameter for estimating the MTX effect on rapidly proliferating cell systems. Using this indicator, it was shown that the usually administered dose of Leucovorin is not sufficient for an effective rescue of the bone marrow cells as long as the MTX serum concentration is equal or higher than 10(-6) M. If in critical cases the MTX elimination is retarded, a rescue can only be achieved by Leucovorin at doses tenfold higher than the actual amount of MTX in the whole body system. The Leucovorin rescue does under such circumstances can be calculated according to the formula Leucovorin (mg) = 10 x MTX (mg/l) x 0.76 x body weight (kg).

Bone Marrow↗

[Radiational basis and practice of the citrovorum factor (Leucovorin) protection after high-dose methotrexate therapy. High-dose methotrexate/leucovorin].

The effects of methotrexate on the DNA metabolism of human lymphoblast cultures and bone marrow cells were estimated. The ratio of the 3H-deoxyuridine and 3H-thymidine incorporation rates ia a good parameter for the methotrexate effect. Citrovorum factor (5-formyltetrahydrofolic acid) reverses methotrexate toxicity only when its concentration exceeds that of methotrexate at least ten times. Guidelines for the practice of high-dose methotrexate therapy and the following citrovorum factor rescue, especially for patients with retarded methotrexate elimination are presented. A new simple formula enables the exact calculation of the citrovorum factor dose for individual patients according to their methotrexate serum levels. This formula, derived from the experimental data of the bone marrow and lymphoblast culture cells, gives a rational basis for the high-dose rescue with citrovorum factor in cases with expected or manifest toxicity, and means, moreover, a safety factor for the practice of high-dose methotrexate therapy.

Bone Marrow↗

[Studies on the E rosette test (author's transl)].

The number of T lymphocytes in the peripheral blood of normal subjects and patients with bronchial carcinoma was determined by using the E rosette test. In a comparative study we counted the "total" rosette forming cells and the "active" rosette forming cells using a lymphocytes-sheep red cells-ratio (Ly-SRBC-R) of 1:8 and 1:40. The numbers or rosettes in the two test systems are in correlation with the Ly-SRBC-R despite other differences in the techniques. -A significant difference was determined between normal subjects and patients with the "active" rosette test only with a L-SRBC-R of 1:40. By contrast the values with the L-SRBC-R of 1:8 were not very different between the two groups. -Also the number of "total" rosettes was significantly different between blood donors and carcinoma patients, using the L-SRBC-R. 1:40. -These results are not of direct clinical relevance, because the values of normal subjects and carcinoma patients are overlapping.

Bronchial Neoplasms↗

[Determination of TAA-binding cells in peripheral blood of breast cancer patients (author's transl)].

Circulating human breast tumor-associated antigen (TAA) specific lymphocytes were detected in breast carcinoma patients by antigen specific rosette technique. About 60 percent of patients with breast cancer showed a positive reaction in our test system, the number of rosettes were considerably increased in comparison to the values of blood donors. Following operation normally the number of TAA specific rosettes decrease, contrary, in all cases with recidives, tested, we found positive test results. There is evidence, that our modification of the specific rosette-technique is suitable for detection of malignomas and can be important for the postoperative control of patients with breast carcinoma.

Antigens, Neoplasm↗

[Current status in the treatment of breast cancer. I. Endocrine management--change of concepts and outlook for the future (author's transl)].

A renewal of interest in endocrine therapy of breast cancer is resulting from the demonstration of steroid hormone receptors in tumor cells sensitive to antiestrogens and the possibility for predicting endocrine responsiveness. Therefore new therapeutical concepts have been developed and some of the established endocrine regimens have been reduced to historical interest. It is more than doubtful that the present schematization in selecting the proper kind of endocrine treatment has any future as methodical difficulties in demonstrating hormone receptors will be overcome and the understanding of their biological function will increase.

Adrenal Cortex Hormones↗

[Current status in the treatment of breast cancer. II. Adjuvant chemotherapy, palliative polychemotherapy, chemoimmunotherapy--rating and results (author's transl)].

There is no well defined group of patients with primary breast cancer which benefits from combination chemotherapy as an adjuvant treatment, since, at present, the effect of this therapy in respect to the duration of disease-free interval, survival, and possible long-term side effects remain unknown. Therefore, controlled studies need to be initiated. Similarly, there seems to be no beneficial effect from unspecific immunotherapy. As far as combination chemotherapy in advanced breast cancer is concerned, we review on four different protocols which proved to be quite successful in our hands: adriamycine/cyclophosphamide (AC), cyclophosphamide/methotrexate/5-fluorouracil (CMF), CMF/vincristine/prednisone (CMFVP), and adriamycine/vincristine plus CMF plus Tamoxifen.

Antineoplastic Agents↗

[Immunological studies after the cryosurgical treatment of urologic tumors].

It is stated that a general final evidence is not yet possible from the existing results of immunological investigations and it may be possible only when taking into consideration the extensive furthering controls mentioned. On the basis of the therefore further existing uncertainty in the evaluation of the immunological valency of the cryotherapy, which is expressed also in literature, the originally optimistic suggestions concerning an increased immune response to the cryotherapy must be judged critically. Even when the clininically favourable courses after cryotherapy, above all in the treatment of the penis carcinoma, may be impressible--a cryospecific immune reaction was not to be proved by the test systems at our disposal.

Cell Migration Inhibition↗

[High-dose methotrexate/leucovorin adjuvant chemotherapy of osteogenic sarcoma: biochemical effects in DNA-synthesis of bone marrow cells (author's transl)].

DNA metabolism in bone marrow cells was measured under high-dose Methotrexate/Leucovorin adjuvant chemotherapy of a patient with primary amputation of his right leg because of osteogenic sarcoma. The biochemical data showed that there was no rescue effect of Leucovorin after 200 mg/kg Methotrexate. Corresponding to this "biochemical failure" of the rescue effect the patient died from the complications of a long and very severe bone marrow suppression. To improve the safety of this therapeutic regimen the intravenous injection and in some cases a higher dose of Leucovorin is recommended.

Bone Marrow↗

[Manipulations of immune reactions by antigen-immunosuppressive agent-conjugates. VI. Antigen specific binding of 6-mercaptopurine-protein conjugates by lymphocytes].

The immunologic specificity of 6-mercaptopurin-protein conjugates has been determined by rosette inhibition test using antigen-stimulated lymphocytes and antigen-coated sheep erythrocytes. The specific binding of antigen-immunosuppressive agent-conjugated onto immunocompetent cells is as strong as the binding of the native antigen. The increasing aggregation of the conjugates in consequence of the higher coupling ratio and the thus increased multivalence of the antigen may compensate the effect of antigen determinant loss.

Animals↗