Stimulation in rat DMBA-mammary tumours of the synthesis of a protein similar to the oestrogen-induced protein of the rat uterus [proceedings].

The induction by estradiol-17beta (E2) in DMBA-induced mammary tumors of a protein similar to that found in the uterus of estrogen-treated rats is reported. It is called an indirect protein (IP) and was demonstrated by an increased incorporation of labeled amino acids in a specific band of polyacrylamide gel electrophoresis. All the tumors contained the receptor for estrogen. A definite IP peak was shown by using a cytosol mixture that was enriched in the IP fraction by precipitation with 80% ammonium sulphate before electrophoresis. Data indicate that IP may represent a basic feature of target tissue response to estrogen stimulation. Measurement of IP synthesis might offer a method for investigating estradiol dependence.     

Physiological and pharmacological effects of estrogens in breast cancer.

Focus here is on the mechanism of action of both estrogens and antiestrogens at the tumor cell levels in breast cancer. The interactions of estrogens and their antagonists are emphasized and analyzed in terms of current and potential clinical applications to breast cancer treatment. This review deals with these interrelationships at the molecular levels, not just with general aspects of endocrine interrelationships. The article is divided into 8 main parts: 1) an introduction, which reviews historical understanding of receptor technology and significances; 2) main properties of estrogens and estrogen receptors; 3) the influence of estrogens and antiestrogens on growth of experimental mammary tumor systems; 4) the suppression of or administration of estrogens for treatment of advanced human breast cancer; 5) estrogen receptivity of mammary tumors; 6) progress in treatment of advanced breast cancer derived from studies on the mode of action of estrogens; 7) the prognostic significance of estrogens and estrogenic receptivity (the estriol theory); and 8) concluding remarks on the future paths of receptor research.     

Controlled clinical trial of L-dopa and nafoxidine in advanced breast cancer: an E.O.R.T.C. study.

L-Dopa lowers plasma prolactin levels, and there have been reports that patients with advanced breast cancer have been successfully treated with L-dopa. To test the potential value of L-dopa in this disease a randomized clinical trial of L-dopa and nafoxidine (as the reference compound) was conducted in postmenopausal women with advanced breast cancer. Objective remissions were obtained in sever out of 36 patients (19%) treated with nafoxidine but in none out of 40 patients treated with L-dopa. L-Dopa in the dose schedule used seems to be ineffective in advanced breast cancer.     

Assessment of estrogenic recruitment before chemotherapy in advanced breast cancer: Preliminary results of a double-blind randomized study of the eortic breast cancer cooperative group

We investigated whether estrogenic recruitment could enhance the antitumor effect of chemotherapy in 165 patients with advanced breast cancer, presumably sensitive to hormonal treatments (ER + and/or PgR + lesions). The therapeutic regimen consisted of: (a) estrogenic suppression by aminoglutethimide 1 g/day + hydrocortisone 40 mg/day; surgical castration in premenopausal patients only; (b) FAC (5FU 500 mg/m²; ADM 50 mg/m²; CPA 500 mg/m²) for 3 weeks; (c) following randomization, exactly 24h prior to chemotherapy, patients had to take 1 tablet of either placebo (PL) or 50 μg ethinylestradiol (EE2). Tolerance, responses, time to progression and median survival were identical in both groups. Thus, EE2 before chemotherapy did not contribute to the efficacy of this particular therapeutic regimen, which yielded an overall response rate of 64%. We conclude that the validity of the hormonal recruitment concept has not yet been established in clinical practice, so that this approach remains experimental.     

Induction of progesterone receptor in an estrogen, progesterone receptor-negative breast cancer cell line

In MCF-7 cell culture, some sera endow estradiol-17 beta with strong growth promoting properties ("active" sera) while other fail to display this property ("inactive" sera). Passage from "inactive" to "active" sera are shown here to induce the appearance of a progestin binding capacity in the receptor negative line Evsa-T. Competition with various unlabeled steroids established the specificity of this binding reaction. The induction of progesterone receptor required neither estrogens, nor ER and failed to confer major growth sensitivity to hormonal steroids: only medroxyprogesterone acetate was slightly inhibitory at high concentration. These observations disclose the influence of seric factors independent of estrogens and of ER-related mechanisms on PgR induction.     

Comparative trial of nafoxidine and ethinyloestradiol in advanced breast cancer: an E.O.R.T.C. study.

A randomized clinical trial of nafoxidine, a non-steroidal oestrogen antagonist, and ethinyloestradiol in postmenopausal patients with advanced breast cancer produced objective remissions in 31% of 49 women receiving nafoxidine and in 14% of 49 receiving ethinyloestradiol. The differences in remission rates was almost significant (0.05 less than P less than 0.10). Life-threatening complications were more frequent with ethinyloestradiol than with nafoxidine but the latter produced specific toxic reactions on skin and hair that may limit its practical usefulness. Synthetic oestrogen antagonists may occupy a privileged place in the treatment of breast cancer, and other representatives of this new class of compounds should be accurately assessed in randomized clinical trials.     

Innovative microscale workflow from fungi cultures to Cell Wall-Degrading Enzyme screening

This study aimed at developing a complete miniaturized high-throughput screening workflow for the evaluation of the Cell Wall-Degrading Enzyme (CWDE) activities produced by any fungal strain directly cultivated on raw feedstock in a submerged manner. In this study, wheat straw was selected as model substrate as it represents an important carbon source but yet poorly valorised to yield high added value products. Fungi were grown in a microbioreactor in a high-throughput (HT) way to replace the fastidious shaking flask cultivations. Both approaches were compared in order to validate our new methodology. The range of CWDE activities produced from the cultures was assayed using AZO-died and pNP-linked substrates in an SBS plate format using a Biomek FXp pipetting platform. As highlighted in this study, it was shown that the CWDE activities gathered from the microbioreactor cultivations were similar or higher to those obtained from shake flasks cultures, with a lower standard deviation on the measured values, making this new method much faster than the traditional one and suitable for HT CWDE production thanks to its pipetting platform compatibility. Also, the results showed that the enzymatic activities measured were the same when doing the assay manually or using the automated method.