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Biomedical subjects

G Horvath

Publications and source records attributed to G Horvath.

At least 91 records · Page 5Linked to original sources
PubMed1983

Is there a direct correlation between the activities of various lysosomal enzymes and prolactin secretion in the rat anterior pituitary?

The degree of endocrine activity by rat pituitary lactotrophs was manipulated and the lysosomal involvement in the release and intracellular degradation of PRL was monitored by concomitant assays of acid phosphatase, beta-glucuronidase, dipeptidyl peptidases I and II, and nonspecific esterases in the anterior lobe. The in vitro release of PRL by cell cultures was inhibited by 0.5 or 1.5 microM bromocriptine during 24 or 72 h of incubation and by 0.75 microM for 4 h. Long term treatment caused a 40% reduction in the total PRL content of cells and media; however, after 4 h of bromocriptine treatment, no reduction in PRL content was found. TRH (10 ng/ml) in medium for 4 h increased PRL release, whereas it produced intracellular hormone depletion. In vitro treatment of anterior lobes of diestrous rats with 1 microM dopamine decreased PRL release by 50%. No changes in lysosomal enzyme activities were observed after the inhibition of release or stimulation of the in vitro secretion of PRL. Haloperidol (2.5 mg/kg BW) caused a 90% increase in serum PRL concentrations in diestrous rats 1 h after sc injection. alpha-Methyl-p-tyrosine (200 mg/kg BW, ip) stimulated in vivo PRL secretion, monitored 1, 4, and 24 h after drug administration. The administration of 100 micrograms/rat bromocriptine for 3 consecutive days, a single dose of 100 micrograms/rat polyestradiol phosphate, and their combination resulted in the expected changes in PRL production in female rats. These in vivo treatments failed to alter lysosomal enzyme activities in the anterior pituitary. These findings suggest that the release, intracellular accumulation, or depletion of PRL occurred without concomitant changes in lysosomal enzyme activity in the anterior pituitary. We suggest that the system of lysosome-dependent hormone degradation may involve more specific enzymes than those monitored to date.

Acid Phosphatase↗
PubMed1975

Light-dependent absorption and selective scattering changes at 518 nm in chloroplast thylakoid membranes.

The light-induced absorbance change at 518 nm of isolated chloroplasts consists of a rapid phase, and a slow phase which is complete in about 20 sec. The slow component of the 518 nm absorbance change correlates with the light-induced change in 90 degrees light scattering at 518 nm. Both show a similar time course, similar pH dependence with a maximum at pH 6.0, and similar sensitivity to inhibitors and to treatment of the chloroplasts with a low concentration of glutaraldehyde. Their light minus dark difference spectra are similar with maxima at about 520 nm. It is concluded that they are manifestations of the same phenomenon, and the slow absorbance increase at 518 nm is due to enhanced scattering. It is proposed that the light-induced changes in scattering at 518 nm reflect alterations in selective dispersion, due to proton uptake and conformational changes in the chloroplast thylakoid membrane.

Carbonyl Cyanide m-Chlorophenyl Hydrazone↗
PubMedDate not supplied

Matrix metalloproteinases-2 and -9 in cervical cancer: different roles in tumor progression.

The incidence of uterine cervical cancer has increased slightly in Western countries, with an increase in relatively young women. Overexpression of matrix metalloproteinases (MMPs)-2 and -9 has turned out as a prognostic factor in many cancers. We compared the expression of the proteins MMP-2 and MMP-9 in cervical primary tumors with clinical outcome and risk factors of cervical cancer. One hundred sixty-one patients with cervical cancer treated in Umeå University Hospital or Sahlgrenska University Hospital, Sweden, between 1991 and 1995 were included in the study. Paraffin-embedded tissue samples obtained prior to treatment were examined immunohistochemically by specific antibodies for MMP-2 and MMP-9. Forty-two percent of the tumors were intensively positive for MMP-2 and 31% for MMP-9. Nineteen percent of the samples were intensively positive for both proteinases and 47% negative or weak for both. Overexpression of MMP-2 seemed to predict unfavorable survival under Kaplan-Meier analysis and in the multivariate analysis. Early sexual activity and low parity seemed to correlate to overexpression of MMP-2. MMP-9 was not associated with survival or sexual behavior. Intensive MMP-9 was noted in grade 1 tumors. We conclude that MMP-2 and MMP-9 have different roles in uterine cervical cancer. MMP-2 could be associated with aggressive behavior, but MMP-9 expression diminishes in high-grade tumors.

Adult↗
PubMedDate not supplied

Radioimmunotherapy of nude mice with intraperitoneally growing ovarian cancer xenograft utilizing 211At-labelled monoclonal antibody MOv18.

The aim of this study was to investigate the therapeutic efficacy of 211At-labelled monoclonal antibody given intraperitoneally to nude mice with intraperitoneal growth of a human ovarian cancer cell line. Female nude mice were inoculated intraperitoneally with 1 x 10(7) cells of the human ovarian cancer cell line NIH:OVCAR 3. After about two weeks they were injected with the 211At-labelled specific monoclonal antibody MOv18 intraperitoneally. For comparison, other groups of mice were given the same labelled antibody intravenously, 211At-labelled unspecific antibody C242 intraperitoneally or unalbelled MOv18 intraperitoneally. Six weeks later the animals were sacrificed and the occurrence of tumour and ascites was determined. When the mice were treated with 211At-labelled MOv18 intraperitoneally 9 out of 10 were apparently free of both ascites and tumour compared to none of the mice given unlabelled antibody. 211At-labelled MOv18 given intravenously or 211At-labelled unspecific antibody given intraperitoneally were less effective. Regional radioimmunotherapy with the alpa-emitter 211Astatine seems to be an effective treatment of nude mice with intraperitoneally growing human ovarian cancer. Hopefully this treatment can be given in an adjuvant setting to women with minimal residual ovarian cancer in the future.

Animals↗
PubMedDate not supplied

Comparison of the therapeutic efficacy of 211At- and 131I-labelled monoclonal antibody MOv18 in nude mice with intraperitoneal growth of human ovarian cancer.

The purpose of the present study was to compare the therapeutic efficacy of the alpha-emitter Astatine-211 with the beta-emitter Iodine-131 bound to the specific monoclonal antibody MOv18. The measurements were performed in an ovarian cancer cell line (NIH:OVCAR 3) growing intraperitoneally in nude mice. Two weeks after the intraperitoneal inoculation of 1 x 10(7) cells of the human ovarian cancer cell line NIH:OVCAR-3 twenty mice were treated intraperitoneally with the specific monoclonal antibody MOv-18 labelled with either 211At (310-400 kBq) or 131I (5100-6200 kBq). The pharmacokinetics and biodistribution of labelled antibody in tumour-free animals were studied and the resulting bone marrow dose was estimated. When the mice were treated with 211At-labelled antibody 9 out of 10 mice were free of macro- and microscopic tumour compared to 3 out of 10 when Iodine-131 was used. The equivalent dose to the bone marrow was 2.4-3.1 Sv from 211At- and 3.4-4.1 Sv from 131I-irradiation. The therapeutic efficacy of 211At-labelled specific antibody is very good and, at approximately equivalent bone marrow doses, better than that of 131I.

Alpha Particles↗
PubMedDate not supplied

Progression of human endometrial adenocarcinoma heterotransplanted into nude mice from hormone-sensitive to hormone resistant growth.

We have used a human tumor nude mouse model involving heterotransplantation and serial passage of an estrogen receptor (ER) positive, progesterone receptor (PgR) negative human endometrial adenocarcinoma. The effects of estradiol treatment on tumor growth, ER activation and PgR induction were investigated two and four years after heterotransplantation. In Experiment I, two years after initial heterotransplantation, tumor growth and proliferative rate showed a dose-related decrease, ER was activated by estradiol treatment (measured through an increased amount of ER bound with high affinity to nuclear element(s) (ERhs) and PgR was induced. Two years later (Experiment II), the amount of ER1s (ER measured in cytosolic fraction) as well as of ERhs was lower than at the beginning of Experiment I. ER could again be activated by estradiol treatment and PgR was also induced. However, in this experiment no effect either of tumor growth or of proliferative rate was observed during the estradiol treatment. Our study therefore indicates that an estrogen non-sensitive growth can develop during serial passages in intact, non-treated female nude mice, although the capacity for ER activation and PgR induction is maintained.

Adenocarcinoma↗
PubMedDate not supplied

Estradiol induced changes in tumor growth and steroid receptor content in a heterotransplanted human endometrial adenocarcinoma.

To study the importance of estrogen availability to growth pattern and other tumor characteristic such as estrogen receptor (ER) and progesterone receptor (PgR) content and histopathology, we have used a human tumor-nude mouse model, in which an ER- and PgR-positive and estradiol-sensitive (stimulated) human endometrial adenocarcinoma was heterotransplanted and serially passed in female (non-oophorectomized) nude mice over a period of one year. Pieces from this tumor were transplanted into oophorectomized nude mice, randomly divided into two groups, one with and one without estradiol treatment (preparation phase). After four weeks, pieces from both these groups were again transplanted into oophorectomized nude mice, each group being randomly allocated to two subgroups, one with and one without estradiol treatment (experimental phase). Tumor growth was measured during the experimental phase, whereas both ER and PgR content and histopathology were analyzed after the experimental phase. Our findings indicate that even short-term growth under estradiol-poor conditions can trigger such progressive changes as reduced steroid receptor content, development of a less differentiated tumor and tendency to enhanced tumor growth. On the other hand, estradiol-rich conditions enhanced ER activation, PgR induction and tumor differentiation in the same tumor line. The estrogenic conditions under which a tumor grows may thus be crucial determinants of tumor progression.

Adenocarcinoma↗
PubMedDate not supplied

Antiestrogenic treatment of advanced and recurrent carcinoma corporis uteri--a phase II study of toremifene.

The antitumor efficacy and toxicity of a new anti-estrogenic substance--toremifene--were investigated in a phase II study. Twenty-six patients were eligible for final evaluation (6 primary and 20 recurrent disease). A daily dose of 200 mg toremifene was given orally. Treatment continued for at least 3 months, until progression or significant side-effects were encountered. The response rate was 35% (3 CR and 6 PR). Six patients had NC and 11 did not respond to the treatment. The median duration of responses for CR was 10+ months (range 3(+)-19) and for PR 4 months (range 3(+)-16). The treatment seems to be well tolerated and effective.

Aged↗
PubMedDate not supplied

Enzyme immunoassay of progesterone receptor in cancerous and normal endometrial tissue. A comparison with dextran coated charcoal method.

Enzyme immunoassay (EIA) was compared with the dextran-coated charcoal method and Scatchard analysis for the measurement of progesterone receptor (PgR) in cancerous and normal endometrial samples. A highly significant correlation was obtained between the two assays in both types of tissue (rs = 0.77 and 0.91, respectively; p less than 0.001). The measurable amount of PgR was usually higher with EIA (mean increase 90 and 100 per cent, respectively). EIA is suggested to be a suitable method for PgR measurement in endometrial tissue (normal and cancerous) and can also be used for analysis of PgR in the nuclear fraction.

Biomarkers, Tumor↗
PubMedDate not supplied

Changes in tumor morphology in one human endometrial carcinosarcoma heterotransplanted into nude mice.

Tissue material from one human endometrial carcinosarcoma was transplanted into nude mice. In the third passage two independent tumor lines developed, which continued to grow independently. After the fifth passage one line could be diagnosed histopathologically as a poorly differentiated adenocarcinoma without sarcoma components, while the other line was still a carcinosarcoma. It was assumed that the development of two histologically different tumor lines could be due to clonal selection induced by the new host.

Adenocarcinoma↗
PubMedDate not supplied

Estrogen receptor activation in relation to previous estrogen treatment in carcinoma corporis uteri heterotransplanted into nude mice.

The interaction between estradiol and its receptor in human endometrial adenocarcinoma was investigated in a human tumor-nude mice model. Estradiol treatment was found to activate estrogen receptor (ER), estimated through the measurement of ER in the nuclear fraction. The receptor activation in the tumors was significantly higher in tumors previously treated with estradiol than in previously non-treated tumors. The activation seems also to be dependent on the estrogen dose. We concluded, that previous influence of estradiol may change the sensitivity of estrogen receptor positive tumors for its hormone, and therefore the measurement of the receptor content alone does not seem to be a sufficient marker for the prediction of the receptor activation process.

Adenocarcinoma↗
PubMedDate not supplied

Staging in local endometrial carcinoma. Assessment of magnetic resonance and ultrasound examinations.

Possible deep (more than an inner third of the uterine wall) myometrial invasion and cervical extension of endometrial carcinoma were evaluated prospectively using magnetic resonance (MR) and transabdominal real-time sonography (US) in 20 and 10 patients, respectively. The data obtained from these examinations were compared with hysterosalpingography (HSG) and clinical modalities including hysteroscopy, sounding and histopathologic findings after surgery. The concordance of outlining cervical extension was between MR and hysteroscopy 85 per cent, and between US and hysteroscopy 50 per cent. Deep myometrial tumor invasion was suggested in 4/10 patients by US and in 6/20 by MR, and was confirmed in all but one in each group at histologic examination of the resected uterus. There were no false negative US or MR examinations. Transabdominal US did not prove accurate in defining local endometrial carcinoma (distinguishing between stages I and II), but it may be used as an additional tool in revealing myometrial invasion. MR, however, seems to refine the delineation of uterine tumor growth.

Adult↗
PubMedDate not supplied

Heterotransplantation of human malignant endometrial tumors into nude mice.

Seven of 13 human malignant endometrial tumors heterotransplanted into nude mice were accepted. The graft acceptance was significantly higher in papillary than in endometroid adenocarcinomas (p less than 0.01), whereas there was no observed relation between transplantability rate and other clinical prognostic factors. Of the carcinosarcomas and endometroid adenocarcinomas only PgR negative tumors were accepted.

Animals↗