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Biomedical subjects

S Seeber

Publications and source records attributed to S Seeber.

At least 289 records · Page 16Linked to original sources

[Combined doxorubicin and bleomycin treatment of metastasising thyroid carcinoma: results in 21 patients (author's transl)].

The effectiveness of combined cytostatic treatment with doxorubicin and bleomycin was analysed in 21 patients with metastasising thyroid carcinoma which had progressed despite both surgical and radiotherapy. Tumour histology (anaplastic carcinoma in 50%), age and general condition of all patients pointed to a poor prognosis. Significant success (full or partial remission) occurred in eight patients. It is possible that these results can be improved if chemotherapy is started earlier and other cytostatic drugs are used in case of failure of treatment.

Adult↗

Cystostatic efficacy of DNA-complexes of adriamycin, daunomycin, and actinomycin D. II. Comparative in vivo studies in an Ehrlich-ascites tumor.

The cytostatic efficacy of the antibiotics adriamycin, daunomycin and actinomycin D and of DNA-complexes of these compounds was compared in an Ehrlich ascites tumor in vivo. Various doses of the individual drugs and their DNA-complexes were injected intraperitoneally into female NMRI mice following 8 days after inoculation of 10(6) Ehrlich ascites cells. Survival analyses of animals demonstrated that by addition of DNA therapeutic indices were improved for adriamycin, daunomycin and actinomycin D, DNA alone had no effect on this tumor. Since earlier biochemical data (Seeber et al., 1977) had shown decreased in vitro cytotoxicity of DNA-bound antibiotics, this increase in therapeutic efficacy is probably due to an altered pharmacological behaviour after complex formation with a prolongation of effective intraperitoneal drug levels and decreased systemic toxicity.

Animals↗

[On the problem of praetherapeutic sensitivity testing of human tumours based on incorporation studies of nucleic acid precursors in vitro (author's transl)].

Praetherapeutic sensitivity tests of human solid tumours based on incorporation studies of nucleic acid precursors have been described by various authors. This review intends to show that such tests may only be of rather limited value for the design of individual chemotherapeutic regimens. In many drugs, a correlation between biochemical and clinical effects has not yet been established. The reliability of praetherapeutic sensitivity tests is further impaired by general methodological difficulties of short-term cultures, individual pharmacology and toxicology of cytostatic agents as well as pharmacological and biochemical drug interactions in combination chemotherapy. Praetherapeutic testing with individual cytostatic drugs is discussed.

Alkylating Agents↗

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↗

[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↗

[Macromolecular biochemistry of normal and pathological white blood cells in man].

Leucocytes from normal donors and leukemia patients were isolated and lebelled in vitro with 32P-orthophosphate in order to compare labelling characteristics of nuclear high-molecular weight RNA, labelling characteristics, nucleotide compositions and oligonucleotide frequencies of ribosomal 28 S RNA. These studies revealed 1. structural microheterogeneity of 28 S RNA between the various leukemia cells studies without presenting a leukemia-specific structural marker, 2. an impaired production of ribosomal 28 S RNA from its nuclear precursor 45 S RNA in acute myeloblastic leukemia compared to PHA-stimulated normal lymphocytes. In the second part of this work, the influence of RNA from immunocompetent lymphocytes on the PHA-stimulation of M. Hodgkin lymphocytes was analyzed; the third part deals with studies on macromolecular carriers forcytostatic anthracyclines in human leukemia cells.

Hodgkin Disease↗

The effects of various kinds of sparsely-ionizing radiation on total cell RNA and preribosomal nuclear RNA of Novikoff hepatoma ascites cells after in vivo labelling.

The effects of 300 kV X-rays, 60Co gamma-rays, 43 MV X-rays and 43 MeV electrons on total cell RNA and 45 S pre-r RNA were investigated in Novikoff Hepatoma ascites cells. Six hours after local irradiation of the animals with 600 rad, the tumour cells were labelled in vivo for 30 and 60 min. The specific activities of high-molecular-weight RNA were influenced differently. This may be due to divergent effects of the applied radiation qualities at the level of transcription and transformation (processing). In addition, these radiation effects are mediated by the adrenal glands in a rather complex manner. Therefore, the results presented in this study support the suggestion that an in vivo labelling system is unsuitable for the evaluation of quantitative radiation effects on RNA.

Animals↗

[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↗

[Post-MOPP chemotherapy of Hodgkin's disease (author's transl)].

In 18 patients with advanced Hodgkin's disease, refractory to previous 'C-MOPP' treatment, a new therapeutic protocol of adriamycin, DTIC, CCNU and bleomycin was introduced. Three patients who had previously failed to respond to any other chemotherapy failed also to respond to the new one. But two complete and 11 partial remissions were obtained in the other 15 patients who had previously responded to C-MOPP before becoming refractory to it. Two patients had further progression of the disease during the new treatment.

Adult↗

[Adriamycin, cyclophosphamide, and 5-fluorouracil in the treatment of metastasizing breast cancer (author's transl)].

In a prospective study eleven patients with metastasizing breast cancer were treated with 5-fluorouracil, adriamycin, and cyclophosphamide )FAC). Complete remission occurred in three patients, with two of them still in remission four and thirteen months later. Partial remission (50% decrease in tumour size for more than four weeks) was achieved in five cases, with three of them still in remission. Time for remission induction was one to three months. The mean duration of complete remissions is not yet reached after thirteen months- that of partial remissions was 6.5 months. Two patients showed stable disease for four and more than eleven months, respectively. Only in one case progressive disease was noticed. Mean survival time from the start of therapy was 7.5 months for all patients. For complete and partial responders mean survival is not yet reached after eighteen months. With one exception therapy was given on an outpatient basis. Experimental and clinical data on therapeutic synergism of adriamycin, cyclophosphamide, and 5-fluorouracil show no advantage of the three-drug combination over the combination of adriamycin and cylophosphamide alone.

Breast Neoplasms↗

[cis-Diamino-dichloro-platinum (II) in the treatment of otherwise treatment-resistant malignant testicular teratoma (author's transl)].

cis-Diamino-dichloro-platinum (II) (DDP, NSC-119875) is an inorganic compound with cytostatic properties which have only recently been appreciated. DDP has an action which may tentatively be described as alkylating through some, as yet unknown, metabolic product. In a phase I study the effectiveness against testicular neoplasma had been established. A prospective trial was, therefore, conducted to test the drug's efficiency in patients with disseminated non-seminomatous testicular cancer refractory to all previously used combinations of chemotherapy. In a group of 22 patients the results were: 1 CR, 14 PR, 2 NC, and 5 PD. Because of these results, DDP was made part of an induction regime for disseminated and non-seminomatous testicular tumors.

Adolescent↗

[Actinomycin-D therapy in testicular cancer (author's transl)].

In early stages of the disease the prognosis of testicular cancer has been improved mainly by the introduction of radical surgical procedures. Cytostatic treatment of metastasising testicular cancers has only been of limited value. Actinomycin D has been shown to be one of the most potent agents in malignant teratomas. Own results are presented for 21 eligible patients who received actinomycin D alone. One complete remission and 4-partial remissions were achieved giving an overall response rate of 19%. This precentage seems to be low compared to similar data in the current literature. The result may be explained by the selection of the patients with a high percentage showing far advanced disease before therapy was initiated. However, comparing the data presented with those from our own study on combination chemotherapy and with the more recent results in the literature, single agent chemotherapy does not seem to be the method of choice in metastasising testicular cancer. Improvement of the results by the integration of combination chemotherapy, hormonal therapy and irradiation will have to be based on prospective, controlled studies.

Adult↗

[Results of combined chemotherapy in treatment-resistant leukaemia of adults (author's transl)].

In 21 patients with acute leukaemia not or no longer responsive to conventional chemotherapy, and in four patients with chronic myeloid leukaemia in the blast phase, intensive combination treatment was started with thioguanine, daunomycine, cytarabine, methotrexate, prednisone, cyclophosphamide, and vincristine. Six patients with acute leukaemia went into complete remission, three into partial remission. The mean duration of remission was relatively short at 11 weeks. Of the four patients in the blast phase of chronic myeloid leukaemia two had objective and subjective remission. The toxicity of the combined treatment was not marked and subjective tolerance good. Such combined treatment is a realistic means of managing treatment-resistant acute leukaemia and chronic myeloid leukaemia in the blast phase.

Acute Disease↗