Biomedical subjects

M Görlich

Publications and source records attributed to M Görlich.

At least 19 recordsLinked to original sources

PubMed1999

Estradiol receptor and prognostic parameters of human breast cancer.

Estradiol receptors are regarded to predict a likely success of hormonal therapeutic efforts and the prognosis of breast cancer patients. But today its prognostic importance is controversial, discussed as either reflecting intrinsic property of the tumor tissue or better therapeutic accessibility of receptor positive tumors. Moreover, the most important clinical prognosticators--tumor size and axillary lymph node involvement do not seem to be related to the estradiol receptor status. In our investigation, the length of disease free interval is similar in estradiol receptor positive and negative patients and in all sites of distant metastases, but it is significantly reduced if more than 4 axillary lymph nodes are involved. Post recurrence survival is significantly longer in estradiol receptor positive than negative patients and also in patients treated by tamoxifen containing therapies. Its length is independent of the number of axillary lymph node metastases and the type of distant metastases, with a tendency to be longer in estradiol receptor positive than negative patients. In addition, the overall survival is longer for estradiol receptor positive than negative patients and becomes reduced with more than 4 axillary lymph node metastases. Frequency of deaths in estradiol receptor positive patients is half that of negative subjects. Furthermore, the length of overall survival is independent on the type of distant metastases, with tendency to be longer in estradiol receptor positive than negative patients. Longest overall survival could be observed for estradiol receptor positive patients who got therapy regimens containing tamoxifen. The weak prognostic advantages of estradiol receptor positive patients are interpreted by estradiol receptors as intrinsic parameters of breast cancer tissue characterizing more its biological behavior than therapeutic accessibility.

Adult↗

PubMed1997

Steroid hormone receptors and antineoplastic chemotherapy in human breast cancer.

Several clinical and experimental investigations suggest that the action of antineoplastic chemotherapy in premenopausal women influences the menopause. Such hormonal reactions are mediated via specific steroid hormone receptors. Therefore, connections between hormone receptors and antineoplastic chemotherapy can be assumed making possible to predict success of chemotherapy on the basis of receptor status. Nevertheless, clinical experiences and animal and cell culture experiments yielded controversial results. This was related to the predictive value of receptor status as well as to the benefits of combined hormone and chemotherapy treatments in concurrent or sequential form. It is undeniable that a displacing of steroidal ligand from its receptors by the usual antineoplastic drugs does not occur. Furthermore, the receptor levels remain unchanged after a treatment with antineoplastic drugs. Thus, the mechanism of action of chemotherapeutic drugs is not related directly to the presence or absence of steroid hormone receptors. Despite this fact the receptor status in chemotherapeutic regimes seems to be helpful to define low or high risk patients. Influences on the ER de-novo-synthesis, actions related to parameters representing reduced tumor growth rates, down-regulation of the receptor gene expression or via receptor mediated hormonal actions to other genes, like the apoptosis-related gene bcl-2, are thought to be possible mechanisms of action of antineoplastic drugs on steroid hormone receptors. Future investigations should monitor the ratios between exon lacking receptor variants and the wild-type receptor during chemotherapy or the control of a ligand uptake during chemotherapy by means of the positron emission tomography.

Antineoplastic Agents, Hormonal↗

PubMed1996

Cytokinetic investigations in human breast cancer by flow cytometrically recorded DNA/protein distributions.

This prospective study characterizes T1-T2 breast carcinomas (N = 114) and fibroadenomas (N = 16) by cell kinetic parameters derived from flow cytometrically recorded DNA/protein histograms. Ploidy level, cell cycle distribution and the number of cell subpopulations (SP) characterized by correlating DNA and protein values were assessed. The subpopulations were derived from the three-dimensional plot. The estrogen receptor (ER) status was determined biochemically (N = 61). Within the G1/0 cell peak 1-6 SP were evident in principle. Depending on the number of SP, two subsets were established: subset 1 with < or = 2 SP, subset 2 with > or = 3 SP. They differed significantly in proliferative activity expressed in the percentage of cells in the G2M phase. Subset 2 showed the higher activity. Analysis of subset distributions revealed that subset 1 prevails in favourable prognostic cases as ER positive cases (P < 0.03), lobular carcinomas (P < 0.01) and LN- cases (P < 0.03), whereas subset 2 prevails in the unfavourable counterparts. Analysis of variance showed that the main effect on proliferative activity indicated by G2M% is due to subpopulation composition rather than histologic type, nodal status or ER status (P < 0.01, P < 0.002, P < 0.05), not even due to ploidy level (P < 0.0001). The rationale for subset stratification may be cytogenetic variability connected with protein content heterogeneity accounting for kinetic SP.

Adult↗

PubMed1996

Estradiol receptors and metastasis in human breast cancer.

The localization and extent of metastasis determined the prognosis of breast cancer in a decisive manner. Thereby axillary lymph node involvement represents one of the most important prognostic indicators. The estradiol receptor status is also attributed some prognostic importance. There might therefore be relations between these prognostic factors. However, the majority of investigators could not find a correlation between the extent and timing of regional lymph node involvement and estradiol receptor status. In contrast, there are numerous findings which confirm correlations between estradiol receptors and the localization, extent, and timing of distant metastasis. The findings obtained in more recent years have been collected and discussed in relation to events included in the process of metastasis such as release of proteases and existence of receptor variants.

Breast Neoplasms↗

PubMed1995

Increased expression of Candida albicans secretory proteinase, a putative virulence factor, in isolates from human immunodeficiency virus-positive patients.

The increased prevalence and the severity of oropharyngeal candidiasis in human immunodeficiency virus (HIV)-positive patients are attributed exclusively to the virus-induced immune deficiency of the host. The present study was aimed at answering the question of whether Candida albicans secretory proteinase, a putative virulence factor of the opportunistic C. albicans yeast, has any potential influence on the clinical manifestation of oropharyngeal candidiasis in HIV-positive patients. We measured the secretory proteinase activities of clinical C. albicans isolates from the oropharynges of either HIV-positive individuals (n = 100) or a control group (n = 122). The mean secretory proteinase activity of C. albicans isolates from the HIV-positive group (4,255 +/- 2,372 U/liter) was significantly higher compared with that of isolates from the control group (2,324 +/- 1,487 U/liter) (P < 0.05). The higher level of secretory proteinase activity in the culture supernatants of individual C. albicans isolates correlated with the increased level of proteinase expression on the cell surface, as revealed by cytofluorometry, and with higher levels of secretion of the immunodetectable protein, as shown by Western blotting (immunoblotting). Proteinase activity within the population of C. albicans isolates from HIV-positive individuals was independent of the patient's clinical disease stage and the CD4+/CD8+ cell numbers. Furthermore, no correlation of the proteinase activities with the C. albicans serotype was found, although C. albicans serotype B was significantly more frequent in the HIV-positive group (40%) compared with that in the control group (12%). However, a positive correlation of proteinase activity to antifungal susceptibility was evident. The C. albicans isolates from the HIV-positive group that were characterized by higher levels of proteinase activity were also less susceptible to the widely used azole antifungal ketoconazole and fluconazole. Collectively, the present data are consistent with a concept of early preferential selection of a subpopulation of C. albicans in HIV-infected patients.

Adult↗

PubMed1994

[Tamoxifen flare].

Tamoxifen flare is a relatively seldom occurring phenomenon but it can force to therapeutical consequences. In every case a careful control of patients has to perform. As yet do not exist clear definitions as well as precise explanations of mechanism of action of flare and tamoxifen withdrawal response. These are related to normal metabolism of tamoxifen and can not explain satisfying flare occurrence in a small number of patients only. By reason of clinical experiences in most cases flare can be regard a sign for hormone sensitivity of the tumor and its following regression. But again do not exist clear explanations for this fact.

Breast Neoplasms↗

PubMed1993

Chromatographic investigations of estradiol receptor from breast cancer tissue.

DEAE-cellulose chromatography of non-activated and activated estradiol receptors yields a different, characteristic elution pattern. This chromatography should therefore be able to demonstrate the presence of intact receptors. For clinical receptor investigations, it is usual to select arbitrary cut-off values for receptor quantity and Kd to classify into receptor positive and negative cases. DEAE-cellulose chromatography confirmed the results obtained by such classification in most cases, except those which had been classified as negative on the basis of Kd values higher than 2 nM. In these cases, DEAE-cellulose chromatography indicated the presence of estradiol receptors and therefore a misclassification of the measured results. Thus DEAE-cellulose chromatography can contribute to a clarification of the equivocal results. On the other hand, we did not get any indications of damages to the receptor molecule which in our previous investigations were found to be the result of violent homogenization procedures.

Animals↗

PubMed1993

Enrichment of estradiol receptor from calf uterus.

A three-step procedure to enrich estradiol receptor protein from calf uterus nearly 30,000-fold has been described. Over-all yield is 12%. Control of the single steps has been performed by sodium dodecyl sulfate-electrophoresis, sucrose density gradient centrifugation, gel filtration and determination of receptor quantity. Immunological properties of the preparation obtained have not been controlled.

Ammonium Sulfate↗

PubMed1993

Estradiol receptor and prognosis in human breast cancer and its metastases.

Follow-up of 86 patients for at least 40 months confirmed age dependency of receptor binding capacity in primary breast tumors but not in lymph node metastases. In most cases receptor binding capacity was higher in lymph node metastases than in primary tumors. Prognosis of the disease expressed as percentage of patients who survived and had a disease-free interval is related to receptor binding capacity of the primary tumors investigated. In our investigation, a value of 60 fmol/mg protein seems to be a suitable cut-off value to distinguish between breast cancer patients with good and bad prognosis. Receptor levels of lymph node metastases showed a similar behaviour as those of primary tumors related to percentage of patients who survived, but not to disease-free interval.

Adult↗

PubMed1992

Investigations of droloxifene and other hormone manipulations on N-nitrosomethylurea-induced rat mammary tumours. 1. Influence on tumour growth.

The effect of droloxifene, a new anti-oestrogenic drug, on N-nitrosomethylurea-induced mammary tumours of Sprague-Dawley rats was investigated and compared with that of tamoxifen. The response of tumour growth to ovariectomy or to treatment with aminoglutethimide or high doses of oestradiol was also studied. Ovariectomy was by far the most effective treatment for mammary-tumour-bearing animals. More than 75% of the tumours in ovariectomized rats did not grow progressively but remained in remission for up to 12 weeks after castration when the experiment was terminated. The inhibitory effects of droloxifene and tamoxifen on mammary tumour growth were similar, but body weight loss of animals treated with tamoxifen was more marked than that of animals treated with droloxifene at the same dose and schedule.

Animals↗

PubMed1992

Investigations of droloxifene and other hormonal manipulations on N-nitrosomethylurea-induced rat mammary tumours. 2. Influence on oestrogen receptor.

In N-nitrosomethylurea-induced rat mammary tumours, tamoxifen is found to compete at the binding sites of the oestradiol receptor if a receptor determination is performed 1 day following the last drug application to animals. Despite a higher binding affinity of droloxifene (3-OH-tamoxifen) to oestradiol receptor, compared to tamoxifen, its influence on the measurable receptor quantity is only very weak or not demonstrable. Therefore, binding affinity is not a valid explanation for the different influences of the two anti-oestrogens on the receptor. These only can be attributed to different behaviour patterns of both substances in relation to their half-lives and metabolism and accumulation in the organism. Owing to the short half-life of droloxifene, even 1 day after the last application too little drug is available to compete for oestradiol binding sites. In the case of both anti-oestrogenic substances, cessation of drug application for 8 weeks abolished any influence on the oestradiol receptor. Furthermore, failure of aminoglutethimide to influence the oestradiol receptor could be observed because this substance does not act via this receptor. The experiments performed confirm literature data regarding the effect of aminoglutethimide therapy on oestradiol receptors in breast tumour tissue of human beings. In summary: receptor investigations of N-nitrosomethylurea-induced rat mammary tumours, used as a model to test therapy regimens with droloxifene or other drugs with a short half-life, may be of limited value only.

Aminoglutethimide↗

PubMed1992

Characterization of two human mammary carcinomas, MT-1 and MT-3, suitable for in vivo testing of ether lipids and their derivatives.

The human mammary carcinomas MT-1 and MT-3 originate from surgical material and were transplanted in nude mice. Both tumors have been classified as estradiol- and progesterone receptor-negative. Therapeutic doses of hormones and anti-hormones remained without growth inhibitory effect. MT-1 and MT-3 proved to be sensitive to conventional cytostatic drugs used for treatment of mammary carcinomas; striking is their sensitivity to ether lipids. Therefore, they are considered suitable tumor models for this class of substances.

Animals↗

PubMed1989

[Multicenter pilot studies on the determination of steroid hormone receptors].

Corresponding the international tendency two trials have been performed in GDR to compare results of hormone receptor determinations with prepared probes by several laboratories. As probes we used lyophilized calf uterus. Methods applied for receptor determinations based on dextran charcoal technique, but allowed modalities developed in the various laboratories. In consequence of extensive scattering of results got during the first trial an additional investigation basing on a standard procedure was performed in the second trial. Using this standard procedure better corresponding results could be found in comparison to investigations following the laboratory modalities. Consequently application of a standardized technique in all laboratories should be demanded. Final aim of these efforts is to obtain a reliable semiquantitative classification of low, medium and high receptor contents in the tissue probes investigated.

Germany, East↗

PubMed1988

Activation of the estrogen receptor from N-nitrosomethylurea-induced rat mammary tumors.

The activation of the estrogen receptor (ER) from N-nitrosomethylurea (NMU)-induced rat mammary tumors was studied in vitro. The activation of the receptor induced by heating of the cytosol containing occupied ER was measured by a 3-4-fold increase of receptor binding to nuclei in comparison with the nuclear binding of the nonactivated ER. The activation of the ER was further shown by alteration of the elution profile from DEAE-cellulose. A shift of the receptor peak from 234 mM (Peak II, nonactivated ER) to 70 mM (Peak I, activated ER) phosphate buffer could be obtained. The overall recoveries of activated ER following chromatography on DEAE-cellulose were significantly lower than the recoveries of the nonactivated ER, 71 and 85%, respectively. Binding of the activated ER to nuclei and chromatography of the supernatant which is not able to bind to nuclei on DEAE-cellulose resulted in a decrease of Peak I and in an increase of the overall recovery. These findings suggest that the nuclear bound ER consists of two parts. One is represented partially by Peak I of the elution profile and the other one by that part of the receptor which can not be eluted from the column under the conditions used. Furthermore, the dissociation of tritiated estradiol (E3H) from the nonactivated ER followed a two component exponential function whereas after activation a monophasic dissociation curve could be observed. The mean half times for the dissociation of E3H from the activated and nonactivated ER were 101 and 7.2 min, respectively. Finally, the nonactivated molybdate stabilized ER sedimented in 5-20% sucrose density gradients as two peaks, one at 9.5 S and the other at 4 S. After activation of the ER only the smaller 4 S peak was evident. Molybdate inhibited the activation of the ER measured by nuclear binding assays, sucrose density gradient analysis, dissociation kinetics or ion exchange chromatography but not completely in every case.

Animals↗

PubMed1988

[Hormonal aspects of benign diseases of the breast].

Basing on references from literature it has been looked for possibilities to characterize benign lesions of the breast by endocrine data and to find a discrimination between types connected with high or low risk for breast cancer. Conventional investigations of hormonal excretions and measurements of plasma contents only provide data for statistical evaluations which can not be used to assess the situation of an individual patient. Obviously one has to look for the processes of hormonal promotion on a cellular level. These processes are thought to realize a non-hormonal initial event to a benign or malignant disease. This requires finding of corresponding representative data. Some possibilities as receptor investigations or recording of hormone induced secretion proteins have been discussed.

Breast Diseases↗

PubMed1986

Binding of estrogen receptor from N-nitrosomethylurea-induced rat mammary tumors to nuclei.

The binding of the cytoplasmic estrogen receptor (ERc) from N-nitrosomethylurea (NMU)-induced rat mammary tumors to the nucleus using a cell-free system is described. All tumors studied were estrogen-receptor-positive and most of them were hormone-dependent. Sixty-two percent of all tumors investigated (n = 134) decreased in size more than 30% 4-5 days after ovariectomy. Brief heating of the cytosol loaded with tritiated estradiol induced activation of the ERc measured by an increase of nuclear binding activity. Temperature-dependent activation was evident in every case. The optimal time and temperature of activation were 15-60 min at 30 degrees C. After denaturation of the ERc by heating for 20 min at 56 degrees C only small parts of free estradiol could be bound to nuclei. Mg2+ ions and EDTA inhibited the nuclear binding of the receptor. The nuclear binding assay was performed for 1 hr at 0-4 degrees C. After this time the activated ERc was bound nearly maximally to nuclei. Under optimized conditions 50-60% of the ERc could be bound to nuclei maximally. Using the same medium for the preparation of crude and purified nuclei the binding of the receptor to both kinds of nuclei was similar. Na2MoO4 prevented the activation of the ERc from NMU-tumors completely but did not influence the binding of the previously activated receptor to nuclei.

Animals↗

PubMed1985

Some aspects referring the methodology of estradiol receptor investigations for clinical purposes.

During the last years it had been tried to standardize the dextran-coated charcoal method for estradiol receptor determinations in the field of investigations of mammary tumor tissue probes intensively. But disintegration and homogenization of the tissue had not rendered enough attention in this connection. We could show that intensive homogenization procedures result in worse saturation curves in contrast to sparing procedures if parallel tissue probes were investigated. Therefore the application of a sparing homogenization seems to be an important precondition to get a correct determination of estradiol receptors in human breast cancer tissues.

Breast Neoplasms↗

PubMed1985

Clinical relevance of steroid hormone receptors.

Clinical parameters were reviewed by which it could be possible to predict a therapeutic success by an endocrine manipulation in breast cancer patients. During the last two decades this spectrum was supplied by determination of steroid hormone receptor binding ability of the tumour tissue. In the past there were given many reports representing high scattering results referring the predictive value of steroid receptor determinations. In our experience 60% of estradiol receptor positive and 42% of estradiol receptor negative patients with disseminated breast cancer benefited from therapy with tamoxifen or ethinylestradiol sulfonate with complete and partial remission or subjective clinical improvement. Clinical facts were discussed which could be responsible for unsatisfying results of therapy prediction on basis of receptor determinations, as well as hints from clinical points of view which confirm that sometimes endocrine treatment should be applied although the tumour shows a receptor negative status.

Adrenal Cortex Hormones↗