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H Magdelenat

Publications and source records attributed to H Magdelenat.

At least 73 records · Page 4Linked to original sources

Human breast cancer cells share antigens with the myeloid monocyte lineage.

We have examined the expression of several myeloid cell associated antigens, some of which are involved in myelomonocyte adhesion, in seven well characterized human breast cancer cell lines, since common properties of adhesiveness and migration are found in haemopoietic cells and epithelial cancer cells. Five of these cell lines were of metastatic origin and two were derived from primary breast carcinoma. Antigenic expression was evaluated by immunofluorescence (IF), flow cytometry (FCM), radioimmunoassay on live cells (RIA) and immunoperoxidase staining. None of these cell lines expressed T or B lymphoid specific antigens. Myeloid antigens My4, MO1, and MOF11 (derived from the hybridization of mouse X63 - Ag8 cells with spleen cells from Balb/c mice immunized with purified human monocytes) were expressed in the 7 cell lines. Leu M1, Leu M3, My9, and MO2 antigens were expressed in some of the cell lines. Leu M2 and My7 antigens were not expressed or at very low levels. The expression of these myeloid antigens was also tested by immunoperoxidase staining, and found on frozen sections of normal mammary gland, fibroadenoma of the breast, primary breast cancer, and lymph node and skin metastases of breast tumours. This common expression in epithelial breast cells and in myeloid cells might be related to common biological functions such as interaction with extracellular matrix which precedes cell migration, a normal function of macrophages and an abnormal function expressed or amplified in human cancer epithelial cells.

Antibodies, Monoclonal↗

[Metastatic breast cancer. Modality of association of chemotherapy and hormonotherapy. Results of a controlled trial].

Two hundred forty-seven patients with metastatic breast cancer entered into the controlled trial. Its aim was to define the optimal modality of association between hormonotherapy and chemotherapy. Chemotherapy was given a monthly course of an association including: adriamycin: 45 mg/m2 on day 1; cyclophosphamide: 400 mg/m2 on days 1, 2, 3; 5 fluoro-uracil: 500 mg/m2 on days 1, 2, 3; methyl-prednisolone: 80 mg/m2 on days 1, 2, 3. Hormonotherapy was tamoxifen (TAM) at the daily dose of 30 mg. 82 patients in group I were given TAM alone for 4 months and then chemotherapy + TAM; 83 patients in group II were given simultaneously TAM + chemotherapy; 82 patients in group III were given chemotherapy alone for 8 months and then TAM + chemotherapy. The response rates in groups I, II and III were respectively of 59, 74 and 62%. The difference in favour of group II was marginally significant. The survival curves were significantly higher in group II and III than in group I (P = 0.04). This result appears as the consequence of the poor prognostic of the sub-group of 45% patients who did not respond to TAM. These results seem to emphasize that target cells of hormonotherapy are not target cells of chemotherapy and that this difference is persisting for long time under treatment, that others modalities of association between chemotherapy and hormonotherapy must be studied with the aim of reducing the kinetic's implication of chronic administration of TAM.

Adult↗

Steroid receptor status difference in recurrent intracranial meningioma and breast cancer in the same patient.

The authors report a case of multiple recurrent intracranial meningioma associated with breast cancer in a menopausal woman. High affinity estrogen (ER) and progestin receptors (PR) were assayed independently in the meningioma and the tumor. ER were found to be very low in the meningioma and high in the breast tumor. On the contrary PR were found to be high in the meningioma and could be not detected in the breast tumor. This unique case suggests that meningioma and breast cancer are not under the same type of hormonal influence.

Adenocarcinoma, Mucinous↗

Enzyme immunoassay of estrogen receptors in fine needle aspirates of breast tumors.

Enzyme immunoassay of estrogen receptors (ER-EIA) was compared to radioligand assay (ER-RLA) in fine needle aspirates of breast tumors. Fine needle aspiration is a relatively atraumatic means of harvesting malignant cells from breast tumors. Fine needle aspiration provides a homogeneous suspension (about 90% malignant cells) with a sufficient amount of cellular material (10 to 50 micrograms DNA per sample) for single point radioligand assays of extractable estrogen (ER) and/or progesterone receptor (PR) in about 85% of primary adenocarcinomas at the time of diagnosis. Sixty-one different samples of malignant mammary cells were obtained by fine needle aspiration from 43 adenocarcinomas, 11 metastatic axillary nodes or 7 cutaneous nodules. Thirteen patients were under antiestrogen therapy (tamoxifen). ER-EIA was performed with Abbott's reagents, following the manufacturer's protocol. ER-RLA was a single saturation (5 nM) dextran-charcoal assay with [3H]R2858 as the labeled estrogen. The sensitivity of ER-EIA allowed dilution of the sample up to 10 times (according to sample cellularity and ER level) with less than 20% deviation from undiluted samples. Three levels of dilution of the samples (1/1, 1/2, and 1/10) allowed them to fall at least once into the range of the ER-EIA standard curve. Quantitative correlation between ER-EIA and ER-RLA was high (r = 0.86), and highest (r = 0.97) when samples from patients undergoing tamoxifen treatment were excluded. Major discrepancies between ER-EIA and ER-RLA appeared in those patients undergoing tamoxifen therapy; much higher values were obtained by ER-EIA. Eight of 13 of these patients were ER negative by ER-RLA but ER positive by ER-EIA. This preliminary observation indicates that in vivo ER modulation by hormones and antihormones should be reevaluated.

Biopsy, Needle↗

[Breast cancer. Development of the concentration of hormonal receptors under cytotoxic chemotherapy].

38 patients with locally advanced breast cancer, were treated with a program of cytotoxic chemotherapy including Adriamycin, Cyclophosphamide, 5 Fluoro-uracile and Prednisone. The concentration of hormonal receptors (Estrogen ER and Progesterone receptor PR) in the tumor were studied before starting the chemotherapy and after one to 9 courses of chemotherapy. This therapeutic response rate was not related to the initial level of ER and PR. After chemotherapy, we observed an increase of ER level in 14 cases out of 29 (59%), of PR level in 17 out of 32 cases (53%); A therapeutic response is observed in 11 cases out of 17 when the PR concentration is increased and in 3 cases out of 15 when the PR concentration was either stable or decreased. These observations let us to suppose a selective initial activity of chemotherapy on lesser differentiated tumor cells.

Adult↗

Cytosol and nuclear estrogen receptors (occupied and unoccupied sites) and progesterone receptors in human breast cancer.

Estrogen and progesterone receptor concentrations in cytosol and nucleus were measured in 21 primary breast cancer tumors. Twelve out of the 21 tumor samples were cytosol estrogen receptor positive, 8 of which contained only unoccupied estrogen binding sites in the cytosol, but 2 of the 9 'estrogen receptor negative' samples did contain cytosol binding sites already occupied by endogenous hormone. Four other 'estrogen receptor negative' tumors only showed nuclear binding sites. Only 3 of the 12 'estrogen receptor positive' tumors also contained progesterone receptors. All of these tumors also had estrogen receptor in the nucleus. However, three of the 17 'progesterone receptor negative' samples had progesterone receptor only in the nucleus. The present data indicate that 3 possible classes of 'false negative' tumors can be encountered: estrogen receptors occupied by endogenous hormone, tumors containing only nuclear estrogen receptors, and tumors having only nuclear progesterone receptors. Measurement of nuclear estrogen receptor together with the progesterone receptor provides further information on whether the estrogen receptor system is not only present but also functional, and should be of value in the prediction of hormone dependent breast cancer.

Adult↗

Quantitative measurement of DNA strand breaks and repair in gamma-irradiated human leukocytes from normal and ataxia telangiectasia donors.

Fluorimetric analysis of DNA unwinding, which allows measurement of DNA strand breaks in human leukocytes, has been optimized by reducing the amount of cells required for the test and by modifying the DNA alkali unwinding conditions. This permitted measurement of DNA strand-break induction in cells irradiated with low (0.5-7 Gy) or high doses (5-20 Gy) of gamma rays. Linear dose-response curves were obtained for both dose ranges. Presence of cysteamine during irradiation caused a decrease in the extent of DNA strand breaks. The kinetics of the DNA strand-break rejoining process appeared to be biphasic over the dose range of 2-20 Gy when plotted on a linear vs linear axis (percentage of damage as a function of time). Since the rate of disappearance of damaged DNA was similar for any given dose and for all postirradiation incubation times tested, we have expressed the extent of repair after a given postirradiation incubation as the ratio of the slopes of the regression lines obtained from incubated and nonincubated cells. Leukocytes from 25 healthy donors were analyzed to determine an average value for controls. No difference in the level of DNA strand breaks and the rate of repair of these breaks was observed between leukocytes from three ataxia telangiectasia patients and those from normal donors.

Ataxia Telangiectasia↗

A simple spectrophotometric assay of plasminogen activator: comparison with the fibrinolytic method.

We describe a simple assay of plasminogen activator in which the enzyme reacts with a mixture of plasminogen and H-D-valyl-L-leucyl-L-lysine-p-nitroanilide for 1 h at 37 degrees C after which the absorbance is measured at 405 nm. The method detects as little as 2 CTA milliunits of activator and is linear over a 100-fold range of enzyme concentration. The new procedure has been used successfully for the assay of activator in breast tumor cytosols, cell culture supernatants, and pleural or ascitic fluids. Thirty-two biological samples have been assayed for plasminogen activator activity with both the spectrophotometric method and a classical fibrinolytic technique using radiolabeled fibrin. Although the two series of results are significantly correlated, the activities measured with the former assay are significantly different from those determined with the latter. It is shown that the spectrophotometric method is, in many respects, superior to the fibrinolytic procedure.

Ascitic Fluid↗

Biochemical characterization of 17 beta-hydroxysteroid dehydrogenase in human meningioma.

17 beta-Hydroxysteroid dehydrogenase (E2-DH) activity was characterized on a semipurified microsomal preparation of human meningioma tissue (mean Km of 2 microM and Vmax of 500 pmol/mg protein/10 min) and then assayed in 49 meningioma specimens with high progesterone receptor and low estrogen receptor levels. Of these 49 tumors, 36% contained an E2-DH activity greater than 1,000 pmol/mg protein/10 min and similar to that of uterine myometrium. In this limited series of tumors, no correlation between E2-DH activity and progesterone receptor levels was noted.

17-Hydroxysteroid Dehydrogenases↗

[Metastatic breast cancer: a comparative study of the efficacy of tamoxifen and the sequential administration of tamoxifen and medroxyprogesterone acetate].

Seventy-nine patients with an histologically proven disseminated breast cancer, never treated before with additive hormonal therapy, entered into a randomized trial between june 1981 and december 1982. In the first group 44 patients were given continually a daily dose of tamoxifen (TAM) of 20 mg/m2. In the 2nd group 35 patients were given a daily dose of TAM of 20 mg/m2 for 15 days and then an oral daily dose of medroxyprogesterone acetate of 350 mg/m2 for the next 15 days. In both groups I and II, the treatment was stopped at the first manifestation of progression of the disease. The hormonal receptor status was determined in 30 patients of the group I and 23 patients of the group II. An objective response to treatment was observed in 48 per cent of the patients of the group I and 60 per cent of the group II. This difference is not significant (X2 = 1,05). However, the mean duration of therapeutic response is significantly higher in the group II (p = 0,01).

Adenocarcinoma↗

[Steroid receptors in the central nervous system. Implications in neurology].

This review deals with steroid hormones and receptors in relation to the physiology and the pathology of the central nervous system (CNS) and meninges. In recent years experiments performed in animals showed that: 1) endogenous steroid hormones cross the blood brain barrier: 2) radiolabelled steroid hormones bind in specific areas of the CNS; 3) all five classes of steroid receptors, i.e. oestrogen, progesterone, androgen, glucocorticoid and mineralocorticoid receptors (OR, PR, AR, GR, MR), are present in brain tissues, especially in the hypothalamus and the limbic system; 4) the interaction of steroid hormones and specific receptors induces the synthesis of proteins in the CNS; 5) finally, in situ metabolism of steroid hormones has been evidenced by the presence of specific enzymes. A few studies in human brain tissues have shown the presence of GR and OR as well as enzymes involved in the metabolism of sex steroid hormones. In neurology, some epidemiological and clinical data suggest the implication of steroid hormones and receptors in human CNS: 1) the influence of oestrogens in tardive dyskinesia; 2) the relevance of hormonal changes in benign intracranial hypertension; 3) the usefulness of glucocorticoid therapy in many patients with intracranial tumors and/or edema. Due to feasibility, most researches have concerned tumors: meningioma, neurinoma and glioma. Firstly, a reappraisal of biochemical and histochemical technics used to detect and characterize the receptors in tumors is presented. Then results from the recent literature are reviewed. In meningioma, PR was found in 89 p. 100 (152/177) of the cases, usually at moderate to high levels (up to 33 000 fmol/gT). In addition, PR has been fully characterized from a biochemical point of view. Furthermore, it has been hypothesized that PR may be a marker of leptomeningeal cells since it was detected at high levels in well differentiated tumors provided they had no or few psammoma. This was further supported by the discovery of PR in normal leptomeninges in human adults. OR was detected in 48 p. 100 (87/177) of the meningioma, at low levels. This is in contrast with PR but the percentage of cases with OR raises to 70 p. 100 (42/60) if one considers only tumors assayed for both cytosolic and nuclear receptors. Therefore it has been suggested that OR had translocated into the nucleus, at least in some cases, and subsequently the hypothesis of functional OR in meningioma was raised. AR was also detected in meningioma. Furthermore AR levels were found to correlate well with PR levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex Hormones↗

[Metastatic breast cancer: controlled trial of chemotherapy with and without hormones].

Two hundred and twenty-three patients with disseminated breast cancer entered in a randomized trial: Group I: 130 patients were given a monthly 5 day- course of a cytotoxic chemotherapy protocol including Adriamycine, Vincristine, Cyclophosphamide, 5 Fluoro-uracile (A.V.L.F.); Group II: 93 patients were given alternatively the same program and a non cross resistant program including: VM 26, Mitomycine C, Methotrexate (V.M.M.). The patients of these groups were randomized into three subgroups: Subgroup O: chemotherapy alone; Subgroup N: chemotherapy + Tamoxifen (20 mg/m2/day); Subgroup NN: chemotherapy + Tamoxifen + Norethisterone (40 mg/m2/day). Objective response rates to cytotoxic chemotherapy were respectively of 65 per cent and 68 per cent in groups I and II of chemotherapy. Further more mean-duration of response and survival were not different. Objective response rates were comparable in the three subgroups of chemo-hormonotherapy. However, the survival was significantly better in the subgroup N (with Tamoxifen) when compared with the subgroup O (without hormonotherapy), and marginally better (p = 0,09) when compared with the NN subgroup (with Tamoxifen + Norethisterone).

Adult↗

The value of a radioimmunological monitoring in cancer patients treated with interferon alpha.

Using a radioimmunoassay for human leukocyte interferon (IFN alpha), pharmacokinetic studies were carried out in twelve cancer patients given sequential intramuscular injections of Hu IFN alpha 2. Even though individual monitoring of serum IFN titers emphasized, for a given dose, marked quantitative variations of the observed maximum concentrations, their mean values were found to be dose-dependent (358 +/- 167 U/ml at 30.10(6) U and 1044 +/- 599 U/ml at 100.10(6) U doses). Comparison with bioassay results showed that IFN activities measured in sera were of the same order of magnitude as those calculated from radioimmunoassay standard curves. Data obtained from this series on observed peak time, half-life value and serum concentrations were consistent with those reported by the other groups using recombinant leukocyte interferon in clinical trial. Therefore, radioimmunoassay is an useful method for routinely assaying IFN alpha used either as antitumour or antivirus agent because of its high sensitivity (4 U/ml) and its simplicity.

Adult↗

Relationship between multiple forms of plasminogen activator in human breast tumors and plasma and the presence of metastases in lymph nodes.

Plasminogen activators (PAs), a family of proteases active in blood coagulation, may play an important role in cancer. Indeed, blood coagulation disorders, such as altered fibrinogen and fibrin metabolism and increased incidence of vascular thrombosis, are common in patients with advanced malignant disease. Different types of human tumors are known to contain high levels of PA. The isoelectric focusing patterns of the PAs present in tumors and plasma from patients with breast cancer were compared with those of purified human urokinase and melanoma tissue PA. The pattern of isoelectric molecular forms of PA active at pH 8 showed two groups of several bands: in plasma from tumor-bearing patients and controls, these groups were in the pl ranges of 6.6 to 6.8 and 8.0 to 8.5; in mammary adenocarcinoma tissue, the ranges were 6.8 to 7.9 and 9.0 to 9.4. These patterns were different from those obtained with purified markers; the latter were 5.8 to 9.4 and 5.9 to 7.6 for purified human urokinase and melanoma plasminogen tissue activator, respectively. PA activity in tumor-bearing patients was very high in malignant tissue and, on the contrary, very decreased in plasma; this latter decrease was correlated with the presence of metastases in the axillary lymph nodes. These results suggest that the high PA activity in the tumor tissue might participate in the destruction of the peritumoral tissue, thus allowing its invasion by tumor cells, whereas the low activity of PA in the plasma might increase plasma fibrin, reflecting thus an early disorder in blood coagulation which would enhance the formation of metastases.

Adenocarcinoma↗