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R Kiss

Publications and source records attributed to R Kiss.

At least 235 records · Page 13Linked to original sources

Characterization of the morphonuclear features and DNA ploidy of typical and atypical carcinoids and small cell carcinomas of the lung.

The authors analyzed several cytomorphonuclear parameters related to chromatin distribution and DNA ploidy in typical and atypical carcinoids and in small cell lung cancers. Nuclear measurements and analysis were performed with a SAMBA 200 (TITN, Grenoble, France) cell image processor with software allowing the discrimination of parameters computed on cytospin preparations of Feulgen-stained nuclei extracted from deparaffinized tumor tissues. The authors' results indicate a significant increase in DNA content--assessed by integrated optical density (IOD)--from typical carcinoids to small cell lung carcinomas, with atypical carcinoids showing an intermediate value. Parameters related to hyperchromatism (short and long run length and variance of optical density) also characterize the atypical carcinoids as being intermediate between typical carcinoids and small cell lung cancers. The systematic measurement of these cytomorphonuclear parameters seems to define an objective, reproducible "scale" of differentiation that helps to define the atypical carcinoid and may be of value in establishing cytologic criteria for differential diagnosis.

Carcinoid Tumor↗

An antioxidant drug, silibinin, modulates steroid secretion in human pathological adrenocortical cells.

Because human adrenocortical cells from different adrenal disorders exhibit pathologically altered corticosteroid synthesis, and free radical mechanisms may induce pathological changes in the activities of corticosteroid biosynthetic enzymes (cytochrome P-450), we examined the effect of an antioxidant, silibinin, on basal and ACTH-stimulated secretion of several corticosteroids in isolated adrenal cells from an aldosterone-producing adenoma, atrophied adrenal tissues surrounding the adenoma, and hyperplastic adrenals from Cushing's syndrome. In the presence of a high concentration (100 mumol/l) of silibinin, variably diminished secretion of basal aldosterone, corticosterone, cortisol, 18-OH-corticosterone and 11-deoxycorticosterone was found. In contrast, the addition of 0.01 mumol silibinin/l, which failed to produce a clear effect on basal corticosteroid secretion, resulted in a potentiation of ACTH-stimulated secretion of several corticosteroids in the adenomatous and hyperplastic adrenocortical cells. These results suggest that the dose-dependent dual effect of silibinin on corticosteroid secretion may be attributed to corresponding changes in the activities of cytochrome P-450 enzymes, and that stimulation of ACTH-induced corticosteroidogenesis by silibinin is presumably due to the antioxidant property of the drug.

18-Hydroxycorticosterone↗

Correlation between nuclear cytomorphometric parameters and estrogen receptor levels in breast cancer.

The authors studied the relationships existing between various cytomorphonuclear parameters recorded on 25 primary breast cancers and their estrogen receptor (ER) content. Cell image analyses of Feulgen-stained imprint smears, allowing determination of morphologic, densitometric, as well as textural parameters, were assessed by using the SAMBA 200 system (TITN, France). The ER levels were measured by the conventional dextran-coated charcoal assay. The authors then divided the 25 cancers into three categories: (1) "ER-negative or poorly positive tumors," i.e., those having less than 50 fmol ER/mg protein; (2) "ER-positive tumors," i.e., those containing between 50 and 150 fmol ER/mg protein; and (3) "ER highly positive tumors," i.e., those having more than 150 fmol ER/mg protein. The authors' results show that ER-negative or poorly positive breast cancers possess cells with bigger nuclei and higher DNA content, related to higher proliferation index than ER-rich tumors. Furthermore, the chromatin pattern of cells from ER-negative or poorly positive breast cancers is significantly more condensed than the thinly textured chromatin of ER highly positive tumors. Cell image analysis of Feulgen-stained imprints is proposed as an additional tool for grading malignancy.

Breast Neoplasms↗

Influence of pituitary grafts or prolactin administrations on the hormone sensitivity of ovarian hormone-independent mouse mammary MXT tumors.

The sensitivity of MXT mouse mammary tumors to ovarian hormones was assessed by the following parameters: growth in vivo; presence or absence of estrogen receptors and progesterone receptors; and histological differentiation. A spontaneous evolution from hormone sensitivity (HS) to hormone independence (HI) was observed when the tumors underwent monthly transplantation onto intact recipient mice, with the tumors fulfilling the criteria of HI tumors after the 12th transplantation. In contrast, the tumors recovered most of the criteria of hormone sensitivity when pituitary isografts were placed under the kidney capsules of HI tumor-bearing animals or when these animals received daily administrations of prolactin over several months. Sensitivity to 17 beta-estradiol, progesterone, or prolactin was further assessed by actinomycin binding on the nucleus and thymidine labeling index, both measured by autoradiography. These technical approaches revealed that 17 beta-estradiol and prolactin stimulated the thymidine labeling index of both HI (despite the lack of detectable estrogen receptors) and HS MXT tumors whereas progesterone influenced only that of HS cancers. The three hormones significantly stimulated [3H]actinomycin D binding within HS tumors but not within HI ones. However, such "HI" tumors were characterized by increased actinomycin binding and thymidine labeling index in comparison with HS neoplasms. Thus, all the data presently reported strongly suggest that prolactin is able to restore the hormone-sensitive phenotype within so-called MXT hormone-independent tumors.

Adenocarcinoma↗

[Regression of a pituitary tumor, associated with primary hyperthyroidism, under the effect of 1-thyroxine].

The authors report on a successful medical treatment of a 36-year-old woman who had hypothyroidism and pituitary adenoma. Primary hypothyroidism was evidenced by decreased serum thyroxine (23 nmol/l; 1,77 micrograms/dl) and increased plasma thyroid-stimulating hormone (TSH) levels (108 mU/l). Pituitary mass with suprasellar expansion (1 cm in diameter) was proven by computed tomography (CT). The patient had been treated conventionally with 1-thyroxine and this medication was continued during a 1-year follow-up. Not only did she become symptom-free but control CT scanning revealed a large reduction of tumor size and the disappearance of suprasellar expansion.

Adult↗

In vivo influence of androgens on the cell kinetics and chromatin pattern of the MXT mouse mammary tumor treated or not by aminoglutethimide.

We characterized the influence of androstenedione, 5-alpha-dihydrotestosterone and 17-beta-estradiol on the chromatin organization and the cell kinetics (distribution of the cells into the G0-G1, S and G2+ M fractions) of MXT mouse mammary tumors grafted onto animals that were left intact or that were oophorectomized and/or treated with aminoglutethimide. The cell kinetics and chromatin pattern were monitored by analyzing Feulgen-stained MXT imprint smears through a cell image processor, the SAMBA 200 system. We have also assayed the estrogen and progesterone receptors of these MXT tumors, which appeared to possess both of these biological markers. Our results show that ovariectomy or aminoglutethimide treatment slowed down the MXT tumor growth without any additive effect between them. Androstenedione exerted a stimulating influence on the cell kinetics, which were very similar to those observed after estradiol administration; the treatment of castrated animals with aminoglutethimide completely abolished this androstenedione-induced stimulating influence, however. This androgen lacked any apparent efficiency to transform cell nuclei from a state of castration-induced chromatin condensation into a thinly textured and decondensed state, as did estradiol. Dihydrotestosterone was able to activate the cell kinetics of MXT tumor grafted onto castrated animals as well as those of MXT neoplasms grafted on oophorectomized mice treated with aminoglutethimide. Dihydrotestosterone also possesses the property to transform condensed chromatin into decondensed chromatin. It thus appeared that androstenedione and dihydrotestosterone could activate MXT cell proliferation, as did estradiol, although it appeared that their mechanisms of action were quite distinct from each other.

Aminoglutethimide↗

Influence of L-thyroxine, L-triiodothyronine, thyroid stimulating hormone, or estradiol on the cell kinetics of cultured mammary cancer cells.

We describe the in vitro influence of 3,5,3'-triiodo-L-thyronine (T3), L-thyroxine (T4), a thyroid-stimulating hormone (TSH), and/or estradiol (E2: chosen as the control of the methodology) on the cell kinetics (cell distribution in the S + G2 + M phases) of mouse MXT and human MCF-7 mammary cancer cells. Experiments were performed by means of a cell image processor, analyzing MCF-7 or MXT cells that had been grown on glass cover slips and whose nuclei had been stained by the Feulgen reaction, which is selective and quantitative (stoichiometric) with respect to DNA. We show that T3, T4, and TSH at 0.01 microM dramatically stimulate the cell kinetics of the MXT mouse and the MCF-7 human mammary cancer cell lines. Indeed, the three hormones bring about a significant transient increase in the S + G2 + M fraction as does E2. Furthermore, our data indicate that E2 and TSH are antagonistic with regards to MXT or MCF-7 cell kinetics.

Animals↗

Inhibitory action of androstenedione on the proliferation and cell cycle kinetics of aromatase-free MXT and MCF-7 mammary tumour cell lines.

The effects of androstenedione (AD) on cell proliferation and kinetics have been measured in MXT mouse and MCF-7 human mammary cancer cell lines using SAMBA 200 cell image analysis of Feulgen-stained nuclei. At a concentration of 0.01 microM AD inhibited the proliferation of both cell lines whereas a higher dose (1 microM) was inhibitory on MCF-7 cell proliferation but stimulatory in MXT cells. It is unlikely that these effects are due to aromization of AD into oestrogen since (a) both cell lines were devoid of aromatase and (b) both cell lines were similarly affected by oestradiol (E2), being stimulated at low concentrations and inhibited at high doses. Furthermore, inhibition by AD seems to occur, at least in part, by blockade of the cell cycle whereas that by E2 appears to be cell cycle independent.

Androstenedione↗

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↗

[Application of nuclear image analysis to diagnosis in oncology].

Cell image analysis applied to Feulgen stained cells allows description of each nucleus according to 15 parameters which measure DNA content, shape and size of the nucleus, as well as chromatin texture and distribution. We have studied the effects of hormones or chemotherapy on human and murine mammary cancer cell lines and on an in vivo murine mammary tumor. The method was then applied to different kinds of human cancers and proved to bring consistent results with anatomopathological grading (breast, colon, bladder), with estrogen receptor content (breast) and with molecular tumor marker (hybridization to the 16 or 18 papilloma virus in uterine cervix dysplasia).

Animals↗

In vivo relationship between morphonuclear parameters and hormone sensitivity of the murine MXT mammary tumor.

The initially hormonosensitive (HS) MXT mouse mammary tumor spontaneously evolved to hormonoin-dependence (HI). Using a SAMBA 200 cell image processor, we compared the DNA content and the chromatin structure of HS and HI tumor cells squashed onto histologic slides; the nuclei were colored by the Feulgen reaction. We compared HI and HS nuclei by a discriminant analysis using the 15 parameters obtained on each nucleus. We show that the percentage of well-classified granulocytes (2n DNA content control) versus HS or HI nuclei exceeded 99. On the other hand, this percentage did not reach 70 when we compared HS and HI. The cell cycle analysis revealed that the percentage of cells in S and G2 + M phases were significantly higher in HI tumors than in the HS. Hence, HI and HS MXT tumor nuclei seem to be morphologically identical, but are significantly different if we refer to cell proliferation rates.

Animals↗

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↗

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↗

Influences of dihydrotestosterone, testosterone, estradiol, progesterone, or prolactin on the cell kinetics of human hyperplastic prostatic tissue in organ culture.

In an effort to characterize the hormone sensitivity of human benign prostatic hyperplasia (BPH) maintained in organ cultures for 12-72 h, the influence of 5-alpha-dihydrotestosterone (DHT), testosterone (T), 17-beta-estradiol (E2), progesterone (Pg), or prolactin (PRL) was assessed on the cell proliferation rate of 25 BPH specimens by the use of tritiated thymidine incorporation followed by autoradiography. Significant increases in the thymidine-labeling index (TLI: percentage of labeled nuclei) were observed in glandular tissue after a 36-h incubation period in presence of DHT, E2, Pg, or PRL in 52%, 44%, 28%, and 60% of BPH cases, respectively. Nonparametric statistics (Spearman and Kendall rank correlation tests) have shown that 1) the steroid-induced TLI increases are dependent on the basal rate of cell proliferation, while the PRL-induced effect is independent of it, and 2) all the steroid-mediated effects on BPH TLI are correlated together, whereas they seem to be independent of the PRL-induced TLI increase. When T was compared with DHT on nine BPH specimens, three were found to be sensitive to both hormones, and two responded to DHT only. We propose that our study methods are suitable as a means to assess the hormone sensitivity of individual cases of BPH and possibly prostatic tumors.

Aged↗

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↗

Atrial natriuretic peptide directly inhibits corticosteroid biosynthesis in human aldosterone-producing adenoma.

The effect of human atrial natriuretic peptide (hANP) on aldosterone, 18-OH-cortisterone, corticosterone, deoxycorticosterone, and cortisol secretion was examined in isolated human aldosteronoma cells from five patients with primary aldosteronism. hANP exerted a nearly identical inhibitory action on basal secretion of each of these steroids and antagonized also the stimulating effects of ACTH, serotonin, metoclopramide and vasoactive intestinal polypeptide. The results suggest that in human aldosteronoma cells hANP may be a non-selective inhibitor of corticosteroid biosynthesis and that the site of inhibition of steroidogenesis may be localized to the early pathway of steroid biosynthesis.

Adenoma↗