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R Paridaens

Publications and source records attributed to R Paridaens.

At least 91 records · Page 5Linked to original sources
PubMed1989

Influence of fetal calf serum in combination with pharmacological doses of progesterone or estradiol on proliferation and cell cycle kinetics of cultured mammary cancer cells.

We describe an original method to monitor clonal cell density (hyperplasia) and the cell cycle kinetics of neoplastic cells simultaneously. We thus characterize the in vitro influence of two different types of fetal calf serum (FCS), defined as FCS-S and FCS-I, on the progesterone- or estradiol-induced effect on proliferation and cell cycle kinetic parameters of the MXT mouse and MCF-7 human mammary cancer cell lines. The two sera were treated with dextran-coated charcoal. The FCS-S serum showed a stimulatory influence on MXT and MCF-7 growth, whereas FCS-I was devoid of any clear-cut influence. The cells were cultured on glass coverslips, placed in Petri dishes containing either a control or a hormone-added medium, fixed for histology and submitted to the Feulgen reaction, which allows selective and quantitative (stoichiometric) staining of DNA. Proliferation and cell cycle kinetics were analyzed on the same sample of cells by means of the SAMBA 200 cell image processor. Our results show that steroid-mediated effects were dramatically modulated according to the type of serum used. Furthermore, they also show that pharmacological doses of progesterone or estradiol decrease MXT cell growth by at least two different mechanisms: the first is related to cell cycle kinetics, i.e. an inhibition of the cells into the S phase, while the second remains unknown but seems to be cell cycle independent. High dose estradiol, but not progesterone, induced the same inhibitory influence on the MCF-7 cells.

Animals↗
PubMed1989

Detection of human papillomaviruses 16-18 in cervical cells by molecular hybridization: relationship with morphonuclear cell image analyses.

Forty-one Feulgen-stained cervical imprint smears were analyzed by means of the SAMBA 200 cell image processor in order to quantitatively score human papillomavirus (HPV) 16-18-induced morphonuclear modifications as assessed by morphometric, densitometric, and textural parameters. Molecular hybridization technology using 16 and 18 type specific genetic probes made it possible to divide our series into three groups: Group 1, containing noninfected smears; Group 2, containing "suspicious", i.e., borderline positive, smears; and Group 3, those related to infected patients. Our results show that nuclei from infected smears are much more hyperchromatic and bigger than those arising from noninfected smears. This quantitative description of HPV 16-18-induced chromatin modifications enabled us to create preliminary data banks which could lead to an objective and reproducible grading of unknown cases. This approach is now being prospectively assessed on a large series of cases because the value of the current study is limited until the data bank is tested against unknown specimens with a broader spectrum of HPV infection.

Adult↗
PubMed1989

Relationship between computerized morphonuclear image analysis and histopathologic grading of breast cancer.

A pilot study analyzed the relationship between several morphonuclear parameters and the Bloom-Richardson score for 37 invasive, not-otherwise-specified (NOS) ductal breast carcinomas. The SAM-BA 200 cell image processor and its software were used to measure the nuclear features on Feulgen-stained imprint smears. Two parameters representing the numbers of large and dense chromatin clots and two parameters describing the heterogeneity of the chromatin among nuclei in a specimen evolved in a continuous manner parallel with the Bloom-Richardson score from stages NOS-4 to NOS-8. The systematic measurement of these four parameters on a large series of breast cancers may be able to define an objective and reproducible "scale" of differentiation that could be a helpful tool for pathologists and clinicians.

Adult↗
PubMed1988

Six-year results of a multimodality treatment strategy for locally advanced breast cancer.

Between 1976 and 1982, 59 patients with locally advanced breast cancer were treated with preoperative supervoltage radiotherapy, adjuvant preoperative and postoperative hormonochemotherapy, and modified radical mastectomy. Systemic treatment, which was started simultaneously with radiotherapy, consisted of a combination of daily oral tamoxifen and a monthly alternation of Doxorubicin + vincristine and cyclophosphamide + methotrexate + 5-fluorouracil (CMF). One of each cycle was given preoperatively at half dosage and five of each were repeated postoperatively at full dosage. All patients became operable. Results of pathologic examination of the operative specimen, available in 51 patients, showed complete disappearance of tumor tissue in breast areas in eight patients, of which three still had positive axillary nodes. After a median follow-up time of 6 years locoregional failure was observed in 12 patients (20%) but in only three (5%) did it occur before distant failure. The actuarial median survival of the entire patient population is close to 4 years. Seven patients are alive without recurrence at greater than 9 years. This aggressive multidisciplinary treatment approach is associated with a projected 30% long-term survival (10 years), excellent local control, but substantial toxicity.

Adult↗
PubMed1988

Prevention of ovarian damage induced by cyclophosphamide in adult female mice by hormonal manipulations.

Doses of 10 or 20 mg cyclophosphamide/kg body weight were administered daily to mice for up to 20 days. This caused significant reductions in the incidence of prenatal (developing) follicles and significant increases in atretic (degenerating) follicles within the ovaries. Attempts to prevent cyclophosphamide-induced damage by simultaneous treatment with oestrogen alone, oestrogen plus progesterone, or danazol (a synthetic androgen) demonstrated that danazol effectively prevented the ovarian damage. The efficacy of danazol was considered to be due to its ability to inhibit LH/FSH secretion and, indirectly, the development of new ovarian follicles.

Animals↗
PubMed1987

Estrogen conjugates and serum factors mediating the estrogenic trophic effect on MCF-7 cell growth.

Estrogens stimulate growth of MCF-7 breast cancer cells in monolayer culture. Possible interference of serum factors leading to an estrogen-insensitive cell growth was analyzed in various experiments carried out on serum batches producing no estradiol stimulation. Out of five estrogen conjugates, only 3-glucurono-estradiol partly suppressed the inhibition of hydroxytamoxifen; the conjugate also reduced the estrogen receptor content of the cells, probably by a down regulation process ("processing"). Moreover, prolonged subcultures in dextran-coated charcoal-treated serum attempting to remove possible intracellular estrogens produced no growth stimulation. Interference by hormone carriers of the serum was ruled out by the fact that two strong synthetic estrogens, moxestrol and diethylstilbestrol with weak binding affinity for these carriers, were unstimulatory. Reduction of the carrier concentration also failed to confer any estrogen sensitivity. This lack of effect of most estrogen conjugates and serum carriers seems to contradict the hypothesis of their interference leading to an estrogen-insensitive growth. Presence in the serum of potential inhibitors towards estrogen action was also examined. Dilution of sera inducing an estrogenic stimulated growth failed to show any growth increase, either in the absence or presence of estradiol, thus excluding the possibility of a major influence of an antagonism on growth control. Moreover, clonogenic assays in soft agar eliminated the hypothesis that a difference between "active" (stimulatory with estradiol) and "inactive" serum batches may result from distinct adherence properties rather than from real growth stimulation. All of these data are consistent with the concept that serum factors which are not of estrogenic nature mediate the trophic effect of estradiol; their absence in some serum batches may lead to an estrogen-insensitive cell growth.

Animals↗
PubMed1987

Effect of ovariectomy, hypophysectomy and/or GnRH analog (HRF) administration on the cell proliferation of the MXT mouse hormone-dependent mammary tumor.

The MXT tumor is an experimental mammary neoplasm which is maintained by serial transplantation using B6D2F1 mice, and which contains significant amounts of estrogen and progesterone receptors. The aim of the present study is to examine the effects of ovariectomy (OVX) or ovariectomy plus hypophysectomy (OVX-HX) on both the macroscopic growth and the cell proliferation of this tumor. This cell proliferation was evaluated by means of in vivo tritiated thymidine autoradiography. In addition, we investigated the effects of a GnRH analog (Gonadorelin: HRF, 5-oxo-Pro-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-hydrochloride) on MTX tumor cell proliferation on 7 day-OVX and 5 day-HX (OVX-HX) mice. The uterine luminal epithelium was chosen to monitor the methodology. Our data clearly demonstrate that there is a delay in the growth of MXT tumors grafted into hypophysectomized animals and, to a lesser degree, ovariectomized animals. With respect to proliferation, castration induced a dramatic decrease of the thymidine labelling index (TLI) in the tissue used to monitor the methodology (the uterine luminal epithemium); in contrast, no cell proliferation was induced by hypophysectomy or HRF administration. In 4-week-old MXT tumors, ovariectomy also markedly decreased the TLI within a few days of its taking place. However hypophysectomy, performed on castrated animals, induced a significant and transient increase of cell proliferation in this neoplasm, an increase which lasted from the 2nd to the 5th day following the operation. The high basal level of MXT cell proliferation recorded in OVX-HX animals decreased dramatically after the administration of HRF between 12 and 48 h prior to the sacrifice of the animals. It is concluded that the HRF exerts a direct effect on the MXT tumor cells, and this HRF might be essential for their growth.

Animals↗
PubMed1987

Endocrine effects of Trilostane: in vitro and in vivo studies.

Trilostane (4-alpha-5-epoxy-17 beta-hydroxy-3-oxo-5-alpha-androstan-2-carbonitrile) is a modified steroidal molecule. In vitro and in vivo studies in rats have shown that it inhibits adrenal, ovarian and placental steroid synthesis. It seems to act by exerting a selective blockade on 3 beta-hydroxysteroid dehydrogenase. In this study, we investigated whether this molecule interacts with hormone receptors for estrogen, androgen or progesterone. We also tried to demonstrate the effect which Trilostane may have on cellular cultures of human mammary carcinoma (MCF-7 Evsa-T). We also studied hormonal modifications in a series of 12 patients treated with different doses of Trilostane, since this drug is supposed to inhibit the production by the adrenal glands of mineralocorticoids, of glucocorticoids and of the precursors of estrogens. Our results indicate that Trilostane does not react with any of the main hormonal sex steroid receptors, nor does it interfere with cultures of human mammary cancer cells either containing estrogen receptors and therefore allegedly hormone-dependent (MCF-7 line), or estrogen receptor-negative cells, presumably independent of hormonal manipulations (Evsa-T cell line). Finally, endocrine studies on postmenopausal women with advanced breast cancer show that Trilostane significantly reduces the plasma levels of estrone and of its major androgen precursor (androstenedione). However, the latter inhibition is no different from that exerted by hydrocortisone acetate administered alone at a dose of 40 mg/day. The results of clinical trials comparing hydrocortisone alone with hydrocortisone plus Trilostane are awaited.

Antineoplastic Agents↗
PubMed1987

In vitro studies of canine mammary tumors: influence of 17-beta-estradiol and progesterone on cell kinetics parameters.

Using an in vitro tritiated thymidine nuclear labeling followed by autoradiography, the effects of 17-beta-estradiol (E2) or progesterone (Pg) were studied in 30 canine mammary tumors that were incubated and hormonally stimulated in vitro. In 10 of these tumors, the synthetic (S) phase duration was also measured in absence or in presence of E2, by using a double labeling with tritiated thymidine. Our results demonstrate that E2, and, to a lesser degree, Pg can induce cell replication in both estrogen receptor-positive (ER+ PgR+) and estrogen receptor-negative (ER- PgR-) canine mammary tumors. The mitogenic effect of E2 may involve a shortening of the DNA S cell cycle phase. We have also found a significantly positive relationship between the estrogen and the progesterone receptor concentrations and the basal proliferation rate in these tumors, whereas no correlation was found between steroid receptor contents and the maximal level of stimulation achieved after E2 or Pg exposure.

Animals↗
PubMed1986

Steroid dynamics in the normal and carcinomatous mammary gland.

UNLABELLED: As an approach to the study of the origin of estrogens in breast cancer tissue, the concentration of estrogens and their androgen precursors, as well as aromatase and 17 beta-dehydrogenase activities in normal glandular (GL) and cancerous (CA) breast tissue were determined and correlations with plasma levels and/or receptor status were studied. In both normal GL and CA breast tissue, steroid concentrations were significantly higher than plasma conc., except for dehydroepiandrosterone sulphate (DHEAS), estrone sulphate (E1S) and testosterone (T). Androgen conc. were lower, but estrogen conc. were higher in CA than in GL breast tissue. Estradiol (E2) conc. was positively correlated with the E2R conc., mean E2 conc. corresponding to an estimated E2R occupancy of about 25%. Aromatase and 17 beta-hydroxysteroid dehydrogenase (E2DH) (E2----E1) activities were observed in all breast CA and GL tissues, aromatase accounting probably only for a small fraction of tissue estrogens. E2DH, but not aromatase activity, was significantly higher in E2R+ than in E2R- tissues and was negatively correlated with tissue dehydroepiandrosterone (DHEA) and DHEAS conc.; the latter two steroids are non competitive inhibitors of E2DH which inactivates E2 to E1. CONCLUSION: in both normal and carcinomatous breast tissue, conc. of E1 and E2 are significantly higher than in plasma, suggesting either uptake or local synthesis. As to the latter, aromatase activity accounts probably only for a minor fraction of the tissue estrogens. Breast CA tissue has higher aromatase and E2DH activity than normal glandular tissue, E2 conc. and E2DH activity being higher in E2R+ hormone sensitive, tumors than in E2R-tumors. Tissue conc. of DHEA(S) which inhibits oxidative inactivation of E2, is negatively correlated with E2DH activity and may have an important modulating role in intratissular estrogen metabolism.

17-Hydroxysteroid Dehydrogenases↗
PubMed1986

Carminomycin versus doxorubicin in advanced breast cancer, a randomized phase II study of the E.O.R.T.C. Breast Cancer Cooperative Group.

Sixty-four patients with advanced progressive breast cancer resistant to conventional treatments were entered into the present study. They were randomized to receive either Carminomycin (CMM) 20 mg/m2 or Doxorubicin (DOX) 75 mg/m2, both drugs being administered by i.v. bolus every 3 weeks until progression of the disease. Five patients were not eligible and response could not be evaluated in another eight patients. Three patients had only one course due to disease-related early death. Among twenty-seven evaluable patients who received at least two courses of DOX one complete response and seven partial responses were observed for an overall response rate of 30%. CMM showed significantly lower (P = 0.04) antitumor activity with only one partial response (4%) among the 24 patients who received at least two courses of therapy. Median duration of response dating from the start of chemotherapy was 46 weeks on DOX (range 18-102+) and 30 weeks for the single partial response on CMM. Although the median time to progression for all patients receiving CMM (9 weeks) was significantly shorter (P = 0.04) than for those receiving DOX (30 weeks), patients on DOX had only a marginally longer duration of survival (P = .28) than those initially treated with CMM. Myelotoxicity was more severe in the CMM treated group than in the DOX group. Other toxicities such as alopecia, nausea and vomiting were slightly more severe in the DOX treated group. On the basis of this and other similar randomized studies, CMM cannot be recommended for further application in the treatment of advanced breast cancer.

Adult↗
PubMed1986

Aromatase, 17 beta-hydroxysteroid dehydrogenase and intratissular sex hormone concentrations in cancerous and normal glandular breast tissue in postmenopausal women.

In a study of the origin of estrogens in patients with breast cancer, the concentrations of estrogens and their androgen precursors, and aromatase and 17 beta-hydroxysteroid dehydrogenase (E2DH) activities were determined in normal glandular and cancerous breast tissue. The correlation between tissue estrogens, precursor concentrations, enzyme activities and plasma levels and/or receptor status were calculated. In both normal glandular and carcinomatous breast tissue, the concentrations of androstenedione (A), dehydroepiandrosterone (DHEA), 5 androstene-3 beta, 17 beta-diol (5-Adiol), estrone (E1), estradiol (E2) and progesterone (P) were significantly higher than plasma concentrations. While testosterone (T) concentrations were similar, dehydroepiandrosterone (DHCA) and estrone sulphate (E1S) concentrations were lower in tissue than in plasma. In carcinomatous tissue androgen concentrations were lower, but estrogen concentrations were higher than in glandular breast tissue. Estradiol (E2) concentration was positively correlated with the receptor concentration with the mean E2 concentration corresponding to an estimated receptor occupancy of about 25%, probably sufficient for a submaximal biological response. Aromatase and E2DH (E2----E1) activities were observed in all breast cancer and glandular breast tissues, activities being higher in carcinoma than in glandular breast tissues; nevertheless, aromatase activity accounts probably only for a small fraction of tissue estrogen concentration. E2DH, but not aromatase activity, was significantly higher in estrogen receptor positive than in estrogen receptor negative tissues and was negatively correlated with tissue dehydroepiandrosterone (DHEA) and its sulphate (DHEAS) concentration; the latter two steroids are non competitive inhibitors of E2DH which inactivates E2 to E1. This effect of DHEA(S) may constitute a mechanism by which these androgens stimulate cancer growth and a rationale (besides suppression of estrogen precursors) for medical or surgical adrenalectomy in hormone sensitive metastatic mammary cancer. E2DH activity might constitute an additional marker of hormone dependency of mammary cancer.

17-Hydroxysteroid Dehydrogenases↗
PubMed1986

Sensitivity of the hormone dependent MXT-mouse mammary carcinoma to estradiol during tumoral growth. An autoradiographic study.

The MXT transplantable mammary tumor is an ovarian sensitive carcinoma of the B6D2F1 mouse strain. The present work documents the mitogenic effect of a single near-physiological dose (pulse) of estradiol (E2) in castrated mice bearing MXT neoplasms 2-7 weeks after their inoculation. Histological sections of tumors and uteri (as control E2 target organs) were processed and nuclear thymidine labeling indices (TLI) were determined by autoradiography. Tumor estrogen receptors contents were evaluated in parallel. The results indicate that the MXT tumor keeps a constant sensitivity to E2 6 weeks after implantation.

Animals↗
PubMed1985

The effects of therapy on estrogen receptors in breast cancer.

The importance of estrogen receptors (ER) in predicting the results of therapy in advanced-stage breast carcinoma is now generally accepted. It is, therefore, important to know whether therapy itself, besides other factors, could affect ER status. The aim of the authors was to investigate this problem by reviewing the data from the literature. They have taken into account the effects of hormonal and/or chemotherapy and of radiotherapy, moreover, they have considered the importance of the time elapsed since the suspension of treatment. Hormonal therapy appears to be the kind of treatment more clearly correlated with a loss of ER: the authors have reported some hypotheses about the possible mechanisms of this action. The effect of chemotherapy is much less clear; the data about radiotherapy are few, unhomogeneous and, often, insufficient. Instead, it appears quite clear that ER tend to regain their original status after the suspension of therapy. More studies, are needed before any definitive conclusion can be drawn; it will be necessary to take into account also the possible effect of the different criteria for the preselection of patients. The actual data appear, anyway, to confirm the importance of routine receptor assay on breast tumors, especially after systemic treatment and independently of the kind of therapy itself.

Antineoplastic Agents↗
PubMed1985

Aminoglutethimide and estrogenic stimulation before chemotherapy for treatment of advanced breast cancer. Preliminary results of a phase II study conducted by the E.O.R.T.C. Breast Cancer Cooperative Group.

While both endocrine therapy and chemotherapy are of proven value in the treatment of advanced breast cancer, the effects of combining these two methods or applying them consecutively have been relatively disappointing. This may be due to endocrine therapy suppressing cell division, in hormone-dependent tumors, whereas chemotherapy acts mainly on active-dividing cells. A trial protocol has therefore been devised which seeks to exploit the properties of both types of therapy. Oestrogen suppression is first obtained by aminoglutethimide (Orimeten) plus hydrocortisone; after 2 weeks, ethinyloestradiol is given to induce cell division and followed 24 h later by a combination of 3 cytotoxic agents given intravenously. This pattern of therapy, repeated at regular intervals, appears to be producing favorable clinical results. A phase-III study is being started among patients with hormone-dependent advanced breast cancer.

Adult↗