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G Leclercq

Publications and source records attributed to G Leclercq.

At least 199 records · Page 11Linked to original sources
PubMed1977

Significance of quantitative assessment of estrogen receptors for endocrine therapy in advanced breast cancer.

The predictive significance of quantitative assessment of estrogen receptors in tumor tissue was analyzed in women with advanced breast carcinoma. Receptor concentration was measured by the 3H-estradiol binding capacity of the cytosol fraction of biopsies taken before initiation of the treatment. The E. O. R. T. C. criteria for the assessment of the patients' response were used. In a total of 34 assessments, 25 biopsies contained receptors; the remaining ones were negative. Objective remission to various endocrine therapies was recorded in only eight of the receptor-positive patients. Responses occurred along the whole scale of receptor concentrations with an apparent crowding in the region of the higher values. Linear logistic regression analysis revealed that among 12 variables of known prognostic value, receptor concentration was the most significant in relation to therapeutic response. Other significant variables were bone involvement and age. Computations yielded formulas that are presented in graph form and provide an estimate of the probability of a given patient to respond to endocrine treatments. On the other hand, the results suggest that all patients are possibly hormone dependent, although to variable degrees. The latter concept has very definite therapeutic implications.

Adrenalectomy↗
PubMed1976

Affinity of estradiol mustard for estrogen receptors and its enzymatic degradation in uterine and breast cancer cytosols.

Estradiol mustard (EM) is the 3,17beta-diester of estradiol-17beta (E2) with the nitrogen mustard derivative chlorphenacyl. The ability of EM to bind to cytoplasmic estrogen receptors was tested by inhibition of the binding of 3H-E2 to rat uterine cytosol at 18 degrees C and 30 degrees C. At both temperatures an inhibition curve was observed in the presence of a large excess of drug, suggesting that the latter has a very weak binding affinity (100,000 times lower than E2). Incubation of uterine cytosol with increasing amounts of 3H-E2 in the presence and absence of an excess of EM indicated that the drug interacted with the receptors at the same sites as E2 (competitive inhibition). Preincubation of uterine cytosol at 18 degrees C with EM induced a progressive reduction of 3H-E2 binding capacity. This reduction also occurred, although to a lesser extent, when long-term incubation of the cytosol with EM was performed in the presence of labelled E2 from the start. The process was faster at 18 degrees C than at 4 degrees C and did not occur with EM preincubated in homogenization buffer. Exchange assays by 3H-E2 of uterine receptors preincubated with labelled E2 and excess EM indicated that the drug-induced inhibition of binding capacity was reversible and produced no apparent alteration of the receptors. Furthermore, the rate of exchange was similar to that observed with receptors previously filled with unlabelled E2. In 9 "receptor-positive" cytosols from human breast cancers, time-course study of the binding of 3H-E2 in the presence of excess of EM yielded similar results as those obtained with rat uterine cytosol. These results show that EM has a very low binding affinity for the extrogen receptors and that it is metabolized into one or several compounds of higher binding affinity. They suggest that EM is probably not significantly concentrated by the estrogen target tissues such as mammary cancers. Therefore, the drug is unlikely to be very valuable in the treatment of breast cancer through a specific mechanism involving concentration by the estrogen receptors.

Animals↗
PubMed1976

Oestrogen receptors in male breast cancer.

Eleven samples from 7 primary and 4 metastatic male breast cancers were analysed for cytoplasmic oestrogen receptors. Two samples of metastatic cancers were obtained from a same patient 6 months apart. Receptors were assayed by measuring the binding affinity of cytosol fractions for 3H-oestradiol- 17beta. Saturable binding sites were obtained in 6 primary and 1 metastatic cancers. The dissociation constant of the binding reactions were within the range reported for the specific oestrogen receptors from female breast cancers. When present, receptor concentrations varied from 59 to 532 fmoles/mg tissue protein. Competition studies of the binding of 3H-oestradiol- 17beta by excess amounts of unlabelled steroid hormones or antihormones revealed that the receptors were specific for oestrogens and antioestrogens. By all these criteria, receptors from male mammary cancer were identical to those from female breast cancer. Chromosome analysis was performed in 6 patients. All had normal 46 XY male pattern indicating that no conspicuous genetic abnormalities such as those of the Klinefelter syndrome seemed responsible for the presence of the receptors.

Aged↗
PubMed1975

Oestrogen receptors in breast cancer: a changing concept.

Oestrogen receptors were found in 156 (73%) out of 214 primary breast cancers and in 98 (58%) out of 168 metastatic deposits. These proportions reached 82% and 70% respectively in the second half of the study. Receptors were not found in samples of normal breast tissue but small amounts were present in tissue from some hyperplastic lesions and in male gynaecomastia. Receptor concentrations in the malignant samples were evenly distributed over a wide range of values, suggesting that even "negative" tumours might contain trace amounts undetectable by the method used. Each tumour was characterized by a given level of receptor concentration. In most cases the amounts found in the invaded axillary nodes and their corresponding primary tumours were the same. We suggest that quantitative rather than qualitative assessment should provide an appropriate criterion for studies of biochemical and clinical correlations.

Binding Sites↗
PubMed1975

Estradiol-dependent collagenolytic enzyme activity in long-term organ culture of human breast cancer.

An organ culture method suitable for the maintenance of viable human breast cancer for at least 14 days has been described. This method was applied to a total of 94 breast cancer specimens. It allowed good survival of "soft" tumors of various histological types, with loose connective stroma even in hormone-free medium. In contrast, "scirrhous" cancers showed poor survival in hormone-free medium; viable cells were maintained only at the very periphery of the explants. Supplementation of the medium with insulin (10 mug/ml), ovine prolactin (5 mug/ml), and hydrocortisone (1 mug/ml) in various combinations seemed to induce enlargement of viable cancer cells and moderate loosening of the stroma in some cases. However, it did not improve the survival of central tumor cords in scirrhous explants. Further supplementation of the medium with 17 beta-estradiol (minimum effective dose, 0.1 to 10 ng/ml), although it did not affect soft tumors, markedly improved survival of the cancer cells of scirrhous tumors throughout the whole explants, with evidence of collagen digestion around the neoplastic cells. This was observed in 18 of 20 scirrhous cancers subjected to this treatment. Estradiol need not be present during the whole culture period; the results at 14 days were identical in explants treated with estradiol for the first 7 days only or for the entire period. Addition of purified collagenase during the first 24 or 48 hr of culture resulted in complete dissolution of the collage. After such treatment, culture under the usual conditions resulted in excellent survival of the explants without improvement from hormone supplementation; thus, while estradiol was necessary when collagen was present, it was not longer required after collagen digestion. It can be concluded that breast cancer cells in organ culture are only slightly, or not at all, hormone dependent for survival, provided that they are not restrained by a dense collagen barrier. The estrogen-induced changes allowing survival inside the scirrhous explants strongly suggest the presence of an estrogen-dependent collagenolytic enzyme system in the collagen-rich breast cancers. This system could represent an important component of the hormone dependency of human breast cancer growth.

Adenocarcinoma, Mucinous↗
PubMed1975

[Hormonal receptors of malignant breast tumors].

Tissue samples from 166 primary and 136 metastatic breast cancers were analysed for the presence of estrogen receptors. It was found by measuring the affinity of the cytoplasmic fraction of these samples for 3H-estradiol-17 beta that receptors were present in 72 p. 100 and 54 p. 100 of primary and metastatic cancers respectively. Receptor concentration varied among sample in an apparently continuous distribution from zero to 2,080 femtomoles per mg tissue protein. This suggests that mammary tumors are different from one another more in a quantitative than in a qualitative way. Detectable amounts of receptors were found in samples from mammary dysplasia, fibroadenomas as well as from one papilloma; none was detected in samples from non-tumorous mammary gland, nipple areola or skin. At mastectomy, no correlation was found between presence or absence of receptors in the primary tumors, and presence or absence of metastatic axillary nodes. On the other hand both the primary and its axillary metastases almost always displayed the same characteristic as far as presence or absence of receptors was concerned. Analysis of clinical studies reported seems to indicate that women with advanced breast cancer respond in a fair proportion of cases to various endocrine treatments when tumor tissue biopsies contain estrogen receptors whereas the probability of a response is very low in their absence.

Adenofibroma↗
PubMed1975

Significance of tissue estrogen receptors in the strategy of breast cancer treatment.

Using evidences of estrogen receptors in mammary tumor tissues it was tried 1. to find substances which inhibit the tumor growth by their binding to the estrogen receptors; 2. to predict responsiveness to endocrine therapy; and 3. to find a definition of an improved therapeutic strategy in breast cancer. There is a continuously increasing rate of receptor positive tumors, caused by an improved technique of determination and tissue handling. Estrogen receptors were detected in 73 per cent of all primary mammary tumors and 58 per cent of metastatic tumors respectively. As new therapeutic substances nafoxidine and Estracyt were tested in controlled clinical trials. To get exact data about hormonal sensitivity further quantitative investigations of receptor activities of mammary tumors and their therapeutical responsiveness have to be done. As a new step in the strategy of breast cancer therapy based on receptor determinations a combined therapy with hormones and cytotoxic chemotherapeutics has to be checked in clinical trials in uture.

Antibiotics, Antineoplastic↗