Biomedical subjects

R Paridaens

Publications and source records attributed to R Paridaens.

114 records · Page 7Linked to original sources

PubMedDate not supplied

Comparison of biochemical and immunoenzymatic macromethods and a new immunocytochemical micromethod for assaying estrogen receptors in human breast carcinomas.

Estrogen receptors (ERs) were assayed in 23 breast carcinomas by: (1) the conventional biochemical assay with dextran-coated charcoal (DCC); (2) the immunoenzymatic assay using a monoclonal antibody (MAb), ER-EIA (Abbott); and (3) an original cytochemical method using another MAb, ER-ICA (Abbott). The first two techniques were performed on biopsy samples, whereas the last was carried out on fine needle aspiration (FNA) samples. The ER contents in aspirates were evaluated by: (1) scaled proportions of colored neoplastic cells; (2) scaled coloration intensity; (3) total grading (= proportion plus intensity); (4) product grading (= proportion times intensity); and (5) a new index (NI) described in this paper. The ER-EIA assay correlated best, with a high statistical significance, with the NI (P less than .001); NI was also the only index that significantly correlated (P less than .05) with the DCC results. The results show that the ER-ICA assay offers the great advantages of being applicable to FNA specimens and of producing rapidly available results. This new technique enriches the panel of MAbs for the diagnosis of adenocarcinomas and offers a new tool for the therapeutic follow-up of breast cancer patients. Our preliminary results suggest that the anti-ER MAbs might be helpful for measuring the hormone dependence of small lesions not assayable by DCC, even under endocrine therapy, thus avoiding false-negative assays.

Antibodies, Monoclonal↗

PubMedDate not supplied

In vitro influence of estradiol or progesterone on the thymidine labeling indices of human benign breast tumors.

Using an in vitro tritiated thymidine (3H-dThd) nuclear labeling followed by autoradiography, the effects of 17-beta-estradiol (E2) or progesterone (Pg) on cell proliferation were studied in 22 human benign breast tumors, i.e. 7 fibroadenomas 8 fibrocystic dysplasias 4 gynecomastias and 3 phyllodas. Small tumor fragments were incubated in a chemically-defined medium without serum and were hormonally stimulated in vitro. The procedure used allowed discrimination between weak labeling, suggestive of DNA repair mechanism, and strong labelling, suggesting a true DNA synthesis (S phase). Taking this into account, our results have shown that both estradiol and progesterone can induce in vitro cell replication of both ER+PgR+ and ER-PgR- human breast fibroadenoma, without affecting those of fibrocystic dysplasia, gynecomastia and phylloda. Progesterone, but not estradiol, might significantly decrease DNA repair mechanism in fibrocystic dysplasia, according to the Pg-induced decrease of nuclear incorporation of small amounts of 3H-dThd. We have thus characterized a dynamic test of hormone dependence which permits in vitro study of the hormonal sensitivity of human benign breast tumors, as well as that of any other human neoplasm. This test could be of great value to help clinicians to diagnose and treat hormone-dependent neoplasms properly. Its clinical relevance is now under study.

Autoradiography↗

PubMedDate not supplied

Oral versus intramuscular high-dose medroxyprogesterone acetate (HD-MPA) in advanced breast cancer. A randomized study of the Belgian Society of Medical Oncology.

Ninety postmenopausal women with advanced breast cancer were randomly assigned to be treated with HD-MPA administered either by oral route (daily dose 900 mg) or by intramuscular injections (1 g IM daily X 5 q w during 4 consecutive weeks followed by maintenance with 1 g twice weekly). Among 78 evaluable cases, most heavily pretreated, remissions, lasting for a median duration of 11 months, were more frequent on oral (8/37 = 22%) than on IM therapy (5/41 = 12%). In both arms, high estrogen receptor levels and various clinical factors were associated with higher response rates i.e., age greater than 60, Karnofsky greater than 70, light prior systemic treatment. Side-effects, consisting mainly of weight gain, hypertension and tremor occurred with equal frequency on oral or IM treatment. Five patients complained of pain at the sites of IM injections. Thus, we recommended that, whenever possible, the oral route should be preferred. During the same study, in 20 patients (11 on oral and 9 on IM therapy), blood was drawn at 0, 30, and 60 days of treatment for the assessment of MPA and hormone levels. In both arms, at 60 days, comparable levels of circulating MPA were obtained, with a very significant drop of cortisol, androstenedione, and estrone. These endocrine results, together with our clinical data, indicate that HD-MPA therapy is active on estrogen-dependent tumors with the same specificity as that of other modalities aiming to suppress the adrenal function. Its antineoplastic action in humans could be ascribed at least in part to its suppressive action on the adrenals, resulting in a severe estrogenic deprivation in postmenopausal women.

Administration, Oral↗

PubMedDate not supplied

Effect of estradiol -17- beta (E2) on cell proliferation in the uterus and the MXT mammary tumor borne by intact, ovariectomized and/or hypophysectomized mice.

The aim of the present work was to study the effects of estradiol (E2) on cell proliferation in well-differentiated mammary MXT tumors borne either by intact (INT), or by castrated (OVX), or by hypophysectomized (HX), or by castrated and hypophysectomized mice) OV-X-HX). Ovariectomy and hypophysectomy were performed, respectively, 6 days and 5 days before the sacrifice of animals bearing tumors during a 28 day period. Cell proliferation was measured by using an in vivo nuclear labeling with tritiated thymidine (3H-TdR) followed by autoradiography. Uteri were used as controls for the methodology. Our data demonstrate that E2 exerts a significant and transient stimulatory effect on cell proliferation in the uterine luminal and glandular epithelia of OVX or OVX-HX adult mice. This mitogenic enhancement is significantly higher in OVX-HX mice than in the other experimental groups. In MXT tumors, a significant increase of cell proliferation is induced by E2 in INT or OVX mice; however, no enhancement occurs after HX performed either in intact or in castrated mice. In the latter situation (HX), a dramatic increase of basal cell proliferation rates is consistently observed in tumors, as compared to those levels observed in INT or in OVX animals. The paradoxical increase in basal proliferation rates of MXT mammary tumors in HX animals was not suppressed by administration of ovine prolactin. This suggests that other hypothalamo-hypophysial factors might be endowed with direct inhibitory influence on growth of the MXT tumors.

Animals↗

PubMedDate not supplied

Effect of estradiol on proliferation and on cell loss in the MXT mouse mammary tumor.

The MXT tumor is an experimental mammary tumor, maintained by transplantation in B6D2F1 mice, which contains significant amounts of estrogen and progesterone receptors. The aim of the present work was to study the effect of estradiol (E2) administration on the cell kinetic parameters (thymidine labeling index: TLI, S phase duration: TS, cell cycle duration: Tc, growth fraction: GF, potential doubling time: T, cell loss factor: luminal diameter) of an MXT anaplastic carcinoma strain. These parameters were analyzed using single-, double- or repetitive-tritiated thymidine (3H-TdR) labeling techniques. Uteri were used as controls for the methodology. Our data clearly demonstrate that E2 exerted a marked stimulatory effect on the tumor cell proliferation. This effect is the net result of a shortening of the mean cell cycle duration (Tc) and of a 3-fold increase of the number of cells produced per time unit in 89% of the total cancer cell population. Beside this stimulatory effect, E2 produces a marked increase of the tumoral cell loss. This loss seems to affect a cell fraction which has reached the quiescent state (Q) for a short time.

Animals↗

PubMedDate not supplied

Influence of inoculation sites and tumor cell culture techniques on the phenotype of a mixed cartilage- and bone-producing mouse mammary tumor.

We have previously reported the characterization of an intraperitoneally (IP) transplantable bone-forming MXT tumor. However, the question was unresolved as whether the bone-forming cells originated from either the host animal or from the neoplasm itself. The present work attempts to answer this question by studying the influences of inoculation sites (subcutaneously, SC; intraperitoneally, IP; in the brain, IB; intracranially, ICR) on both the cartilage- and bone-forming tumor phenotypes. Furthermore the influence of cell culture procedures (two- and three- dimensional cultures) on these phenotypes was investigated. SC administered MXT cancer cells never produce bone-forming tumors, suggesting the existence in the dermis of substance(s) inhibitory to the formation of cartilage or bone. On the contrary, our data clearly demonstrate that bone-forming tumors can be obtained by either IP route, in a way which mimics endochondral ossification, or in the brain (IB), a region usually devoid of connective tissue. This observation substantiates the hypothesis according to which the tumor itself is able to produce osseous tissue. Another main finding is the increasing occurrence of skeletal tissues produced by cells proceeding from three-dimensional culture. Finally, ICR and IB tumors exerted a bone-lytic action against the host skull suggesting that tumor cells either produce osteolytic substances (prostaglandins, enzymes) and/or that they contain various cell types exhibiting different properties toward osteogenesis. This model offers new perspectives for studying the mechanisms of both normal and pathologic osteogenesis.

Animals↗