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Biomedical subjects

C G Schmidt

Publications and source records attributed to C G Schmidt.

At least 217 records · Page 12Linked to original sources
PubMed1977

The combined modality approach in the treatment of inoperable small-cell anaplastic carcinoma of the lung.

The combined modality approach with combination chemotherapy ("Comb" or "BACO") and radiotherapy was used in a pilot study comprising 35 evaluable patients with inoperable small-cell anaplastic carcinoma of the lung. Treatment strategy was based on prior assessment of prognostic factors such as histology, performance status and extent of disease. Median survival time was 39.8 weeks for "COMB" treated patients and 21.2 weeks for "BACO" treated patients. Although the combined modality approach has been very helpful against a variety of human cancers it should be used with caution since not all combination chemotherapy regimens are compatible with radiotherapy. Mechanisms of interactions between cytostatic agents and X-rays are discussed with regard to enhanced tumor cell kill and possible toxic side effects.

Alopecia↗
PubMed1977

Cytostatic efficacy of DNA-complexes of adriamycin, daunomycin and actinomycin D. I. Comparative studies in Novikoff hepatoma, human mammary carcinoma cells and human leukemic leukocytes.

Inhibitory effects of adriamycin, daunomycin, actinomycin D and of the related DNA-complexes on DNA and RNA synthesis were compared by precursor uptake studies in Novikoff hepatoma cells, human mammary carcinoma cells and human leukemia cells. In addition, nuclear RNA labelling profiles were analyzed in human acute leukemia blast cells and nucleolar RNA synthesis was studied in Novikoff hepatoma cells in vitro after incubations of the tumor cells with adriamycin and DNA-adriamycin. The studies revealed that compared to the free drugs a) the DNA complexes were generally less active with respect to inhibition of overall DNA and RNA synthesis in these divergent tumor cell types, b) characteristic differences between adriamycin and daunomycin which are related to a more rapid cellular uptake of daunomycin were still present after complexing of both drugs to calf thymus DNA, and c) the intracellular mode of action of the free antibiotics was not changed by complex formation with DNA. These results indicate that a preferential incorporation of the macromolecular complexes into the tumor cells by pinocytosis--as originally postulated by Trouet et al. (1972)--is not likely for Novikoff hepatoma cells, human mammary carcinoma cells and human acute leukemia blast cells. In contrast, it may be concluded from this study that the DNA complexes dissociate already at the outer cell membrane resulting in a generally decreased but kinetically drug-specific cellular uptake. In a second communication it will be demonstrated that these in-vitro effects do not correlate with the therapeutic efficacy efficacy of the complexed drugs in vivo.

Acute Disease↗
PubMed1977

[Integrated chemotherapy and radiotherapy of inoperable bronchial carcinoma: preliminary results in 50 cases (author's transl)].

Fifty patients with inoperable bronchial carcinoma were treated with a combined schedule of adriamycin, cyclophosphamide and vincristine. In those cases with locally/regionally confined tumour spread this was followed - after three chemotherapy cycles - by radiotherapy to mediastinum, hilar region and tumour of 3000 rad focal dose. Remission was achieved in 25 of 27 patients with small-cell carcinoma: full clinical remission in 12, part remission in 13. Mean duration of the (in most instances still continuing) remission has so far been 4 + months. Mean survival time is, of course, not yet calculable. Only a few patients had to be admitted to hospital for short periods because of toxic reactions. Four full and 11 part remission (some still continuing) have so far been achieved in the group of larger-cell carcinoma (squamous cell, 4; large cells, 5; anaplastic, medium-large, undifferentiated or polymorph, 14).

Bronchial Neoplasms↗
PubMed1977

Oral anticoagulation in the treatment of a spontaneously metastasising murine tumour (3LL).

The effects of long-term anticoagulation with phenprocoumon on growth of the Lewis lung carcinoma (3LL) were studied. Oral anticoagulation initiated at the day of i.m. transplantation of the 3LL into C57BL mice significantly inhibited primary tumour growth and reduced the number of spontaneous metastases to the lungs. Intermittent anticoagulation was without effect on metastasis formation but still retarded primary growth. There was no influence of anticoagulation on the mean survival time (MST) of tumour-bearing animals. Phenprocoumon appears to improve the results of cyclophosphamide of 5-fluorouracil treatment, but there were no statisticially significant differences. In contrast, bleomycin treatment in combination with adjuvant anticoagulation suggested a possible drug synergy. No significant influence of anticoagulation on the response of the primary tumour to irradiattion was found, though the MST of irradiated and anticoagulated animals was greater than in the solely irradiated controls. The present investigations suggest that coumarin derivatives have some direct tumour-inhibiting capacities, but exert their antimetastatic action via deceleration of the blood clotting mechanism.

4-Hydroxycoumarins↗
PubMed1977

[Chemotherapy of malignant bone tumors].

In several primary malignant tumors significant improvement of formely bad prognosis has been achieved by the introduction of new cytostatic compounds and the study of new cytostatic combination regimens. Adjuvant chemotherapy in osteosarcoma and Ewing's sarcoma led to remarkable increase in survival rates. Leaning on natural history and on remission rates reached by cytostatic treatment in metastasizing stages of disease, proposals for adjuvant chemotherapy are made and chemotherapy regimen appliable on out-patient basis is described.

Antineoplastic Agents↗
PubMed1977

[Chemotherapy in non-Hodgkin's lymphomas (author's transl)].

The type of therapy in non-Hodgkin's lymphomas (NHL) depends on the state of the disease and on histological classification. As in Hodgkin's lymphoma radiotherapy is indicated with localized disease, whereas chemotherapy is given in disseminated cases. In contrast to Hodgkin's lymphoma chemotherapy is indicated earlier (already in most stage II cases), since dissemination may occur outside the typical lymph node areas. Division of NHLs according to higher or lower degree of malignancy is possible histologically on the basis of the Kiel classification as well as of the Rappaport classification. Low-grade malignant lymphomas are treated best with conventional doses of an alkylating agent. An intensive combined chemotherapy is not indicated. Because of the tendency to early and frequent relapses a cyclic maintenance therapy with an alkylating agent is incidated. High-grade malignant lymphomas have to be treated with agressive combination chemotherapy in order to get the patient into complete remission with the possibility for a long relapse-free interval. Up to now there is no indication that any of the published chemotherapy combinations is definitely superior to the others. It is most important to apply the therapy consequently for at least six months. The value of a maintenance therapy is not yet proven.

Antineoplastic Agents↗
PubMed1977

[Integrated treatment of the inoperable bronchial carcinoma (author's transl)].

The inoperable bronchial carcinoma tends to early formation of metastases. If the tumor responds well to different cytostatic drugs, chemotherapy is absolutely necessary. In this case, combined therapy has better results than monotherapy. We use chemotherapy prior to radiotherapy in order to prevent hematogenic extension of the disease and to ameliorate the receptiveness of the primary tumor. In order to avoid local recurrence it is necessary to submit the primary tumor and the mediastinum to radiotherapy. A focal dose of 3000 rd within three weeks is considered to be sufficient. This dose generally does not cause severe myelosuppression, so that the chemotherapy can be continued. A report is given on the provisional results of different chemotherapeutic combinations. Further studies, however, are absolutely necessary in order to be in a position to give recommendations of common validity.

Bronchial Neoplasms↗
PubMed1976

The effect of hyperthermia on DNA repair.

In the past there were many individual observations on the value of hyperthermia in the treatment of human neoplasia but most of the information about the value of hyperthermia as a single agent or in the combined modality approach has come from laboratory investigations. Dose response curves for cell survival after exposure to heat are similar in shape to cell survival curves obtained after irradiation or treatment with some cytostatic agents. The shoulder in such curves suggests that repair of sublethal or potentially lethal damage takes place after hyperthermic treatment. On the level of molecular biology the process of cellular repair should correspond to repair of damage inflicted on deoxyribonucleic acid (DNA). We have shown by means of the BUdR assay that such DNA-repair synthesis does take place upon exposure to heat. Many investigations have provided evidence of a synergism between hyperthermia and ionizing irradiation or some cytostatic agents. It was suggested that such synergism might be caused by the inhibition of repair of sublethal damage by heat. After inflicting DNA damage by a strong alkylating agent (NA-AAF) we could demonstrate DNA-repair synthesis by means of the BUdR-assay during exposure to heat. At the present time results obtained by assaying DNA repair on the basis of cell survival and by means of the BUdR-assay are difficult to reconcile.

Acetoxyacetylaminofluorene↗
PubMed1976

The effect of bleomycin on mitochondrial DNA.

Covalently closed circular mitochondrial DNA (mt-DNA) from mouse fibroblasts (L-cells) forms a separate band from nicked circular or linear DNA molecules in ethidium bromide-cesium chloride byoyant density gradient analysis. The conversion of covalently closed circular mt-DNA to nicked circular or linear DNA may serve as a sensitive method of detecting DNA strand breaks induced by bleomycin (BLM). At a very high concentration BLM induces the conversion of closed circular mt-DNA to nicked circular or linear DNA, however even after 24 h of exposure to BLM at a high concentration a considerable amount of closed circular mt-DNA molecules remains intact.

Animals↗
PubMed1976

[Chemotherapy of malignant melanoma (author's transl)].

Chemotherapy of malignant melanoma is indicated in advanced disease when local treatment is no longer possible. The results of single-agent chemotherapy, including alkylating agents, antimetabolites and several antibiotics as well as vinca alkaloids and recently the nitrosoureas, are critically reviewed. The overall response rates do not reach levels about 15 percent. The imidazole carboxamide compound (DTIC) has been most extensively studied, And increases the response rate to about 25 percent. The influence of pretreatment and the preponderance of certain localizations, and also the survival rates of responders, partial responders and nonresponders are discussed. Combination chemotherapy seems not to be superior to single-agent therapy. Various factors, including biochemical, pharmacological, cytokinetic and immunologic parameters that differentiate responders from nonresponders, still require examination.

Alkylating Agents↗
PubMed1976

Human chorionic gonadotropin (HCG) in monitoring the course of testicular tumours.

In 29 patients with metastasising testicular tumours serial determination of HCG was performed for monitoring cytostatic chemotherapy. Clinical remissions and stable disease were accompanied by normalisation of elevated HCG values in 85% and 80% of all cases, respectively. Despite the normalisation of HCG levels, no complete disappearance of clinically detectable tumour lesions could be seen in the herein presented cases. Seventeen percent of the patients showed normal HCG levels, although they had progressive disease. Recurrent disease was associated with preceeding increase of HCG in only 33% of the cases. Because of the frequency of mixed tumour tissues in teratomas, additional methods for monitoring therapy should be used.

Chorionic Gonadotropin↗