[Evaluation of serum ceruloplasmin and haptoglobin levels in patients with non-Hodgkin lymphoma].
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Biomedical subjects
Publications and source records attributed to S Eckhardt.
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5-FU is an active antimetabolite widely used in the therapy of human solid tumors. Its antitumor action can be potentiated by alkylating agents and other cytostatic drugs as well. This potentiation is evident in the case of gastric cancer, less manifest in the case of pancreatic cancer, and missing in colorectal cancer. Although 5-FU is a very active drug against breast cancer, its antitumor effect was never really investigated in a rational way with regards to potentiation by other agents. A reevaluation of drug combinations with 5-FU seems to be mandatory in the future.
Seven human testicular tumors were transplanted into artificially immunosuppressed mice. Two of them grew progressively (TT2 and TT6) and a serially transplantable line was developed from TT2. The xenografts maintained only the embryonal carcinoma components of originally mixed (embryonal cell carcinoma and choriocarcinoma) donor tumor. Although the histology did not change remarkably with passages, the xenografts lost their capacity to express human choriogonadotropin and alpha-fetoprotein. The latency period shortened, the growth rate remained similar with subsequent transplantations. The tumor cells of the TT2 line presented the human character according to chromosome analysis and were built up of two subsets of cells with a different DNA index estimated by flow cytometry. The embryonal cell carcinoma line was highly sensitive to CY and cisDDP. PVB combination was also effective, although the tumor growth inhibition proved to be only temporary.
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Lycurim [1,4-di(2'-methanesulfonyloxyethylamino)-1,4-dideoxymesoerythri tol dimethane sulfonate] is rapidly hydrolyzed in aqueous media to inactive products according to a second-order reaction. The respective rate constants are: k1 = 9.82 X 10(-2) and k2 = 1.76 X 10(-2) mumol/ml/min. The concentrations of the parent compound and alkylating intermediate(s) were measured by chemical trapping with N,N-diethyldithiocarbamic acid (DDTC). The rate of this reaction is substantially higher: k1 = 2.61 X 10(-1) and K2 = 4.76 X 10(-2) mumol/ml/min. By using 35S-labeled DDTC, alkylating compounds in concentrations as low as 0.04 microgram/ml could be detected in spiked plasma samples. After intracavitary application of 60 mg Lycurim no alkylating activity could be demonstrated in the plasma of patients at any time point.
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21 human renal cell carcinomas (RCC) were xenotransplanted into artificially immunosuppressed mice. 4 tumors grew successfully retaining some characteristics of the primary tumors (according to morphology and karyotype analysis), but losing metastatic capacity. One of the serially transplantable tumors (HT 40) with hyperdiploid cellular DNA content and estrogen receptor positivity failed to respond to the single maximally tolerated dose of several cytotoxic agents.
The occurrence of placental type alkaline phosphatase (Regan enzyme) was studied in various pathological conditions of the human stomach using polyacrylamide gel electrophoresis and various inhibition techniques. Placental type alkaline phosphatase could be demonstrated in 16 out of 22 gastric carcinomas, in 3 out of 11 moderate and 6 out of 6 severe dysplasias, we failed however to demonstrate it in any other pathological conditions of the stomach, i.e. in intestinal metaplasia. There was no correlation between the occurrence of Regan enzyme and histological type of gastric carcinomas. The appearance of placental type alkaline phosphatase in gastric dysplasias may be suggestive of malignant transformation and its determination in repeated biopsy samples may be a help in the follow-up of patients with abnormal gastroscopic findings.
21 patients with 'subsequent' monoclonal gammopathies which developed after non-tumour or tumour states were studied. The cases were selected from 221 patients producing M protein, partly based on retrospective analysis and partly on data of case history, autopsy, histology, and immunochemistry obtained during continuous observation. Possible ways of development of immunoglobulin-producing monoclonal cell clones are also discussed.
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The uptake of [3H]-dibromodulcitol ( [3H]-DBD) into glioblastomas, white matter and cerebrospinal fluid was studied in 10 patients. Single-tissue samples were taken from different subjects at 4, 15 and 24 hr after [3H]-DBD administration. The level of 3H-compounds in the central nervous system was similar after a single (400 mg/m2), or 3 smaller daily oral doses of 150-180 mg/m2 of [3H]-DBD. The distribution of radioactivity was uniform in the tumour, white matter and muscle. Between 3 and 15 hr after administration of DBD the concentration of radioactivity did not change significantly and was between 5 and 13 micrograms of DBD/g tissue wet wt. At the same time the level in the cerebrospinal fluid (CSF) remained between 1 and 4 micrograms/ml. Meanwhile, the average concentration of radioactivity in the plasma fell from 11 to 3 micrograms/ml. The elimination half-life of the labelled compounds from the tissues was about 1 day as judged from the limited number of non-serial data obtained 4 and 24 hr after the last dose of repeated drug administration.
Within 4 weeks after definitive surgery, 91 patients with supratentorial glioblastomas and malignant astrocytomas were randomized to one of three treatment arms: Group 1 received radiotherapy alone; Group 2 received dibromodulcitol (DBD) during radiotherapy, and treatment was then continued with DBD; and Group 3 received DBD during radiotherapy, followed by combination chemotherapy of CCNU and DBD. No severe myelotoxicity occurred, but combined treatment with CCNU and DBD occasionally caused a transient myelosuppression. Statistical analysis of 84 evaluable patients showed a significantly longer survival period in those who received chemotherapy during and after irradiation. Median survival times in the three groups were 40, 57, and 60 weeks, respectively; the corresponding p value for Groups 2 and 3 was 0.025 and 0.0015. The ratio of patients surviving over 18 and 24 months was highest in Group 3. This study suggests that the administration of DBD during irradiation might have been the main factor in improving survival times.
Fifty-seven patients with testicular tumors have been treated with combined chemotherapy (vinblastine, bleomycin and cisplatinum). By evaluation of therapeutic activity and toxic effects it was shown that Platidiam, Lachema, effectivity was identical with the two other cisplatinum preparations used in this study.
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