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Biomedical subjects

H Magdelenat

Publications and source records attributed to H Magdelenat.

At least 91 records · Page 5Linked to original sources

[Progesterone receptors in normal human leptomeninges in adults].

Cytosolic and/or nuclear 3H-R 5020 binding sites were detected in 6/6 samples of normal leptomeninges obtained at the time of operation in human adults. The levels of binding sites were higher in leptomeninges samples (range of values: 140-1780 fmol/gT) than in the corresponding intracranial tumors (one meningioma, two neurinomas, one metastasis) in 3 out of the 4 cases that were simultaneously studied. The 3H-R 5020 binding systems were characterized in 2 groups, A and B, of pooled samples representing respectively 4 and 17 samples of normal leptomeninges. The study of A (cytosolic and nuclear binding sites) and B (cytosolic binding sites) groups showed that binding systems had a limited capacity and a high affinity (Kd were respectively 2 X 10(-9) and 5.3 10(-10) M) as previously noted for the progestin receptor in human meningioma. Biochemical data and ultrastructural pictures obtained in the present study as well as in previous works, allow to consider the presence of the progestin receptor in normal leptomeninges.

Adult↗

[Phase-1 study of the tolerance for increasing doses of recombinant human alpha 2 interferon in patients with advanced cancer].

Thirteen patients with malignant tumors were entered into a phase I trial with recombinant DNA human alpha 2 interferon (IFN alpha 2). The patients were given I.M. escalating doses of IFN alpha 2 ranging from 1-10(6) to 200-10(6) IU with a 72 hours washout between injections. In the majority of the patients, subjective symptoms were noted: fever, headache, chills, nausea, myalgias. Asthenia, anorexia, drowsiness appeared after the highest doses and disappeared without any sequellae. Leucopenia and thrombopenia were seen in 11 out of 13 patients. Hepatocellular toxicity was observed in 9 cases. Cardiac and vascular functions were not impaired by IFN alpha 2. The pharmacokinetic studies showed a maximum serum concentration between 4 and 6 hours after injection and the peak value was directly proportional to the dose. No neutralizing INF alpha 2 serum factor was detected during the treatment. The peak value for serum beta 2 microglobulin occurred 48 hours after and the N.K. activity was variably modified by IFN alpha 2 injections. A major clinical response was observed in 1 case, a minor response in 3 cases and a stabilisation of the disease in 4 cases.

Adult↗

Lack of reverse transformation after treatment of A 549 human alveolar carcinoma cells with thioproline.

Clonal growth in anchorage dependent (on plastic) and independent (in soft agar) conditions of A 549 cells from a human alveolar carcinoma by thiazolidine-4-carboxylic acid (thioproline) was determined in order to check whether this drug was able to induce reversion towards a normal phenotype of in vivo growth, as described by Gosalvez in HeLa cells. The colony formation on plastic, the ability to form three-dimensional clones in soft agar and cell division in mass culture, were inhibited at similar rates when the cells were grown in the presence of increasing concentrations of thioproline. The morphology of cell clones arising on plastic in the presence of thioproline did not differ from that of untreated cell clones. This indicated that thioproline was unable to provoke 'reverse' transformation of A 549 cells in vitro.

Adenocarcinoma, Bronchiolo-Alveolar↗

[Drill biopsy and puncture biopsy for the determination of hormone receptors].

The assays of estrogen (ER) and even more progesterone (PR) receptors are highly required to elaborate the therapeutic strategy adapted to every breast cancer. In order to get this information in the absence of surgery (conservative treatment), three types of tissue sampling are available: drill-biopsy, "thru-cut", and fine needle aspiration. Reliable estimates of ER or PR can be obtained on drill-biopsy or "thru-cut" samples in about 80% of breast tumors measuring more than 2 cm. Fine-needle aspiration allows, up to now, only ER assay, in about 80% of all breast tumors.

Biopsy↗

Progestin and oestrogen receptors in meningiomas. Biochemical characterization, clinical and pathological correlations in 42 cases.

Progestin receptors (PR) were evaluated in 40 intracranial and 2 spinal meningiomas. PR measured with radiolabelled R 5020 were found in 93% of cases (39/42). PR levels were significantly higher (p = 0.05) in females (mean: 5,720 fmol/gmT) than in males (mean: 3,120 fmol/gmT). Biochemical characterization of the R 5020 saturable binding sites showed that they were mainly cytosolic, had a high affinity constant (Kd approximately equal to 1 nM) and were progestin specific. Correlation with sex suggested some biological activity of PR in meningiomas. Oestrogen receptors (OR) were evaluated in 36 intracranial and 2 spinal meningiomas. OR measured with radiolabelled R 2858 were present in 79% of cases (30/38). OR mean levels were equal in females (mean: 285 fmol/gmT) and in males (mean: 330 fmol/gmT). The relevance of PR and possibly OR in the biology of meningiomas and of leptomeninges was suggested by the presence of receptors in a sample of normal leptomeninges.

Adult↗

Comparison of effects of leukocyte and fibroblast interferon on immunological parameters in cancer patients.

Patients with metastatic cancer were given single intramuscular injections of 10(7) units of partially purified preparations of either leukocyte or fibroblast IFN. Serum levels of inteferon, of beta 2-microglobulin and of carcino-embryonic antigen (CEA), as well as NK activity of circulating lymphocyte, were followed over a period of 96 hr post injection. In confirmation of previous studies, levels of circulating IFN were lower after injection of fibroblast IFN than after injection of leukocyte IFN. Despite this difference in pharmacokinetics, the natural killer activity of circulating lymphocytes was enhanced with both IFNs. Levels of DEA were not influenced by the IFN injections. Leukocyte but not fibroblast IFN caused an increase in serum levels of beta 2-microglobulin in the circulation. A similar difference between leukocyte and fibroblast IFN in their ability to influence the beta 2-microglubulin system was observed in experiments on cell cultures. Only leukocyte IFN was able to cause release of beta 2-microglobulin by either leukocytes or fibroblasts.

Adult↗

Administration of fibroblast interferon to patients with advanced breast cancer: possible effects on skin metastasis and on hormone receptors.

Eleven patients with metastasized breast cancer received 8 intramuscular injections of 6 x 10(6) units of human fibroblast interferon over a period of 40 days. The injections did not cause local irritation or inflammation. Fever occurred in only 1 of the 11 patients. Although several types of metastases were monitored, only skin nodules consistently (10 out of 11 patients) exhibited changes that were suggestive of a therapeutic effect of the treatment regimen: either a simple decrease in size of some nodules or central necrosis accompanied by an inflammatory reaction. NK-activity of peripheral blood leukocytes was significantly increased after administration of the first dose; the effect of subsequent injections was less clear. Receptors for estrogens and progestogens were increased in the tumor biopsies of 2 out of 2 and 5 out of 6 patients tested respectively.

Breast Neoplasms↗

[Fine-needle aspiration biopsy and analysis of estrogen receptors in breast cancer].

Estrogen receptor concentration was measured in fine needle aspirates from 98 human mammary carcinomas. We performed a biochemical radiolabeled assay by the Charcoal-Dextran procedure on cytosols obtained after homogenization in a saline hypertonic buffer (0,4 M KCl) and centrifugation at 105,000 g. DNA content of the pellets was measured by fluorimetry. A sample of about 10(6) cells, containing at least 10 micrograms of DNA, was needed to obtain a reliable result. In this report, 74 samples were over 10 micrograms of DNA each. The analysis of these samples showed that, in 39 cases (52,8%), the estrogen receptor level was over the limit of 500 fmol/mg of DNA. In 5 cases (6,7%), the range was between 500 to 600 fmol/mg DNA and, in 30 cases (40,5%), it was under 500 fmol/mg DNA and was considered as negative. For 15 patients, estrogen receptors were determined on the same tumor, as removed by fine needle aspiration and by a surgical procedure (6 cases) or drill-biopsy (9 cases). There was a good correlation between the receptor content in needle aspirates and in tissue specimens for 13 cases out of 15.

Biopsy, Needle↗

[Disseminated breast carcinoma. Study of activity of immunotherapy with BCG and duration of the phase of intensive chemotherapy. Results of a randomized trial (author's transl)].

144 patients with disseminated breast cancer entered into a 4 arm randomized trial. They received a chemotherapy protocol combining monthly administration of adriamycin (40 mg/m2 on day 1), vincristine (1,2 mg/m2 of day 2), cyclophosphamide (400 mg/m2 on days 3, 4, 5), 5 fluorouracil (500 mg/m2 on days 3, 4, 5). Patients in groups I and III were given 6 courses at monthly intervals and patients in groups II and IV were given 10 courses. Then they were given indefinitely a monthly course of cyclophosphamide (100 mg/m2/day for 7 days), melphalan (2,5 mg/m2/day for 7 days), methotrexate (25 mg/m2/week for 3 weeks). Patients in groups III and IV were given 3 applications of living BCG disposed on a scratched area between courses of chemotherapy. The overall response rate was 73 per cent (105/144) and was comparable in each treatment group. The mean duration of response and the mean survival times were comparable in each treatment group. The mean duration of response and the mean survival times were comparable in the 4 treatment arms. The initial tumor mass, serial levels of CEA and skin responses to recall antigens were of prognostic significance. Age, hormonal status, initial lymphocytes count had no prognostic significance.

Adult↗

[Estrogen and progestin receptors in meningiomas: a study in 22 cases (author's transl)].

The authors have searched for oestrogene (RE) and progesterone (RP) receptors in 22 cases of meningiomas. Hormone receptors were determined on the cytosol and nuclear fractions of tumor tissues, using synthetic oestrogen R 2858 and progestin R 5020 in conditions where exchange was nearly achieved. The receptors were considered as present for values equal or higher than 100 femtomoles per gram of tumour tissue (fmol/gT). For the 22 studied cases the RE were present in 13 cases (59 p. 100) with values between 100 and 500 fmol/gT in 9 cases and higher than 500 fmol/gT in 4 cases. The RP were present in all cases (100 p. 100), with values between 100 and 500 fmol/gT in one case, between 500 et 5 000 fmol/gT in 13 cases and higher than 5 000 fmol/gT in 8 cases. The results were compared with neuropathologic data obtained by light microscopy. The clinical and biological significance of results are discussed.

Adult↗

[Effectiveness of VM 26, mitomycine C and methotrexate in advanced breast cancer refractory to a four drug combination (author's transl)].

56 patients with advanced breast carcinoma, primarily or secondarily resistant to a four drug combination including Adriamycine, Vincristine, Cyclophosphamide and 5 Fluoro-Uracile, entered a phase II trial using association of VM 26, Mitomycine C and Methotrexate. The tolerance was generally good, but 17 clinical manifestations of toxicity were observed out of 216 cycles of treatment (7,8%). THese mucosal and haematologic disorders have incitated to secondarily reduce of 20 per cent the current doses of Methotrexate. 28 patients out of 53 (53%) have objectively responded to treatment and in 16 of them, major responses (C.R + P.R. > 50%) were observed (30%). The median of survival responders was 11 months. The critical analysis of responses by site showed 53 per cent of objective regression of lung metastasis which appears higher than the incidence of response observed after treatment with drug combination including Adriamycine.

Adult↗

[Serum beta2-microglobulin and carcino-embryonic antigen in cancerous patients. A preliminary study of 258 cases (author's transl)].

In this preliminary study dealing with beta2-microglobulin (beta2m) levels in the series of 258 patients, two group are considered:--a group of 208 patients with evolutive tumour;--a group of 50 patients with no evolutive tumour. This study shows a significantly higher incidence of cases with elevated levels of carcinoembryonic antigen (CEA) and/or beta2m in group with evolutive cancer than in group with no evolutive cases. These elevated levels of beta2m are not related to other clinical, topographical, evolutive, immunological parameters. But the increase of serum beta2m levels in patients treated with combination of chemo and immunotherapy, may indicate a possible relationship between beta2m levels and lymphocyte activation.

Beta-Globulins↗

[Demonstration of osteoclastic acid phosphatase in the serum of patients with giant cell tumors. Preliminary study].

Starting from the fact that an ultrastructural cytochemical study of the Giant-Cell Tumour demonstrated the presence of a large amount of lysosomic acid phosphatase in the tumour cells, an attempt was made to evidence the presence of this enzyme in the serum of patients bearing such a type of bone tumor. Acrylamide gel electrophoresis of the serum allowed one to separate a number of isoenzyme with acid phosphatase activity and to characterize at least two bands different from those secreted by prostate, blood platelets, liver or spleen. The comparison between zymograms of normal and pathological sera, more particularly in Paget disease, led to consider that these two bands had an osteoclastic origin. Besides, these bands vanish after tumor eradication. Acrylamide gel electrophoresis of serum provides therefore a means to support the preoperative diagnosis of Giant-Cell Tumor and, eventually, to detect an early recurrence of the disease.

Acid Phosphatase↗

Human blood granulocyte macrophage progenitors (GM-CFU) during extended field radiation therapy.

The rate of the clonogenicity of granulocyte macrophage forming cells (GM-CFU) in agar was analysed using mononuclear cells from the peripheral blood of cancer patients undergoing total body irradiation (TBI, 5 patients, 1.5 Gy in 15 days) or hemicorporal irradiation of the lower (LHBI, 5 patients, 15 Gy in 15 days) or upper (UHBI, 4 patients, 15 Gy in 15 days) part of the body. Although the GM-CFU level in the blood is low compared with that in the bone marrow, and shows considerable variability, the preliminary results demonstrated that in most cases the GM-CFU level was increased around the 10th day after the beginning of irradiation, followed by a return to base level within a few days, for LHBI and TBI but not for UHBI. The question of whether the observed peak for the clonogenicity was due to stem cells leaving a radiation-injured compartment of the bone marrow or to vicarious stem cells migrating from non-irradiated regions, or was the result of enhanced activity of colony-stimulating factors, remains to be investigated.

Breast Neoplasms↗