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Biomedical subjects

G Leclercq

Publications and source records attributed to G Leclercq.

At least 181 records · Page 10Linked to original sources
PubMed1983

[Relation between estrogen and progesterone receptors and response to hormone therapy].

In mammary cancers, and more especially at the stage of generalization, the detection of estrogen receptors plays a prominent role in the choice of treatment. Recent studies indicate that nearly half of cancers containing receptors are responsive to various hormone treatments while only a minority of cancers not containing receptors are responsive to the same treatments. The present review emphasizes the benefits of a quantitative dosage of these receptors compared to their simple detection. It also evaluates the predictive value of progesterone receptors as an additional test for hormonodependence. Finally, it analyses the part played by receptors dosage in the current therapeutic strategy as well as in the development of new clinical protocols.

Antineoplastic Agents↗
PubMed1983

Guide-lines in the design of new antiestrogens and cytotoxic-linked estrogens for the treatment of breast cancer.

Antiestrogens (Tamoxifen) are used for the treatment of breast cancer. However these compounds are also weak estrogens that may stimulate tumor growth. Cytotoxic-linked estrogens (Estradiol Mustard, Estracyt) are devoid of major therapeutic activity. This led to search for new antiestrogens devoid of estrogenicity and for active cytotoxic-estrogens. Hydroxylation of C-4 of triphenylethylene antiestrogens (tamoxifen, CI 628 and U 23,469) largely increases their binding affinity for the estrogen receptor (ER). Hydroxylation also increases the in vitro antitumor activity of the drugs as shown by their higher ability to inhibit the growth of the ER-positive cell line MCF-7. Triphenylethylene antiestrogens contain an aminoethoxy side chain which appears essential for their physiological activity. Removal of the chain of tamoxifen suppresses its antiestrogenicity and antitumor activity. The grafting of side chains on a weak estrogen of the gem-diphenylethylene category produces "symmetrical" antiestrogens devoid of estrogenic activity. This observation raises the question of the role played by the third phenyl ring of the triphenylethylenes since the trans-isomers of the latter display antiestrogenicity and the cis-isomers estrogenicity. Comparison of the binding affinity for ER and antitumor activity of di- and triphenylethylene antiestrogens suggests that this third phenyl ring increases the interaction with ER of the 4-phenolic group of the drugs and/or their aminoethoxy side chain. An analogue of this chain is without any biological activity suggesting that the di-(tri)pheny-lalkene structure is required for promoting the interaction of the chain with ER. New chemical structures yielding antiestrogens with antitumor activity are also reviewed. New cytotoxic estrogens designed for producing lethal damage of DNA show a low binding affinity for ER. Moreover, there is no evidence suggesting specific antitumor activity. Such activity may be more easily obtained with estrogens bearing reagents for proteins rather than DNA. The biological properties of a 2-mesylate derivative of estrone irreversibly interacting with ER supports the concept. On MCF-7 cells, the drug displays a strong antitumor activity which can only be suppressed by high, equimolar, concentrations of estradiol. It is devoid of cytotoxic activity on the ER-negative cell line Evsa-T suggesting that ER is involved in its action.

Antineoplastic Agents↗
PubMed1981

Cytotoxic estrogens in hormone receptive tumors.

A high proportion of human mammary cancers contain a measurable amount of estrogen receptors. The presence of estrogen receptors correlates well with the response of patients to endocrine therapy, but not with their response to chemotherapy. However, receptor-mediated chemotherapy should result in more selective and efficient treatment of receptor-positive tumors. Several agents containing an estrogenic and a cytotoxic moiety have been synthesized in the past. It is not surprising that the affinity of these compounds for the estradiol receptor is very low, since most of them were synthesized before our knowledge of hormone receptor mechanisms. An international workshop on cytotoxic estrogens was held on September 27-28, 1979, in Diepenbeek, Belgium, to celebrate the opening of the Dr. L. Willems-Instituut. The purpose of the workshop was to determine the structural requirements for binding to the estrogen receptor and to obtain a consensus on screening techniques for selecting potential drugs of this type.

Animals↗
PubMed1981

[Histofluorescence localization of cellular sites binding steroid hormones in human breast cancers].

Cytochemical steroids binding activity of human mammary cancer cells is demonstrated in cryostat frozen sections using hydrophilic fluorescent steroid hormone ligands. The cytochemical results indicate that mammary carcinomas are composed of heterogeneous populations of positive and negative cancer cells in varying proportions. A comparison with biochemical data was made. There exists no correlation between the results obtained with the histochemical and the biochemical techniques. The specificity of this new tool of investigation is discussed.

Adenocarcinoma↗
PubMed1981

New aspects in the development of cytotoxic-linked estrogens for the control of breast neoplasia.

The interest of cytotoxic-linked estrogens as therapeutical drugs for controlling the growth of breast cancers relies on their potential binding to estrogen receptors (ER) in these cancers. 14, 15-alpha and beta epoxide derivatives of estradiol-17 alpha and 17 beta were investigated for their ER binding affinity and their cytotoxic activities on the MCF-7 and Evsa-T cell lines. 14, 15 alpha and beta-epoxides of estradiol 17 alpha as well as the 14, 15 alpha epoxide of estradiol 17 beta bound to ER. No compound revealed any cytotoxicity on the cell lines. A 11 beta-aziridine derivative of estrone showed significant binding activity to ER. Concentrations of 10(-7) and 10(-8) M of this compound act stimulating on the growth of MCF-7 cell line. 10(-6) M is slightly inhibitory. There is no effect on Evsa-T cells. Binitrogen mustard derivatives of hexestrol and diethylstilbestrol displayed a very low binding activity whereas mononitrogen mustards of estrone showed a significant binding activity. At concentrations of 10(-6) M all mustard compounds inhibited the growth of MCF-7 cell line. The inhibitory influence of the mononitrogen mustards were higher than those of the binitrogen mustards. With regard to the Evsa-T cells only mononitrogen mustard displayed a growth inhibiting effect.

Breast Neoplasms↗
PubMed1980

Clinical significance of the quantitative assessment of estrogen receptors in advanced breast cancer.

The predictive value of the estrogen receptor (ER) assay with regard to the response to hormonal treatment was analyzed in women with advanced breast carcinoma. The significance of ten clinical variables of putative prognostic value was also investigated. A total of 49 courses of endocrine therapy were available for study. The respective merits of using the receptor information as a qualitative or a quantitative variable were compared. Linear logistic regression analysis showed that the quantitative information was significantly related to the therapeutic response (P < 0.0001) and proved to be superior to the qualitative information. Compared with the clinical variables tested with the logistic model, receptor concentration was by far the most important single predictor of response. Nevertheless, introduction of two of these clinical variables (i.e., age and menopausal status) into the model in addition to receptor concentration improved its predictive value. Presented in graphic form, the improved model provides a simple means to estimate the probability that a given patient will respond to endocrine therapy. Successive ER assays were available in a series of patients who had received no systemic treatment. In ER+ cases, there was a significant correlation between receptor concentrations in the consecutive assays. There was no influence of the time interval between tissue samplings. Data were also consistent in ER- patients. These results give support to the practice of routine receptor determination in the primary tumor at the time of mastectomy. It is concluded that the distinction between hormone-responsive and hormone-resistant tumors appears artificial. The therapeutic implications of a continuous gradient of hormone-dependency among breast cancers are discussed.

Adrenalectomy↗