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Biomedical subjects

G Daxenbichler

Publications and source records attributed to G Daxenbichler.

At least 55 records · Page 3Linked to original sources
PubMed1993

Progesterone receptors in routinely paraffin-embedded primary breast carcinomas and lymph node metastases.

Described here is an immunohistochemical technique using the commercially available monoclonal progesterone receptor (PR) antibody KD 68 in routinely fixed and paraffin-embedded breast carcinomas and lymph node metastases. The authors' technique is compared with several incubation variations. The method applying the primary antibody in a dilution of 1:10 overnight followed by a biotinylated second antibody showed the best results when Triton X-100 was added to the buffer. Using this method, comparison with the results on frozen sections of 34 breast carcinomas yielded a significant concordance of 94%. Correlation between the results on paraffin sections and those obtained by the standard dextran-coated charcoal cytosol assay was 80%. The value of the method for predicting endocrine therapy response was shown in 20 patients. Thus the reliability of the method has been demonstrated and was applied on 151 lymph node metastases and the corresponding primary breast carcinomas from 50 patients. Generally PR content in the metastases was lower than in the primary tumors (p < 0.001). This finding indicates that evaluation of PR in lymph node metastases should be included in the decision for endocrine therapy of breast cancer.

Breast Neoplasms↗
PubMed1993

Relationship between quantity of silver stained nucleolar organizer region associated proteins (Ag-NORs) and growth rate suppression of breast cancer cell lines after interferon-gamma and 4-hydroxy-tamoxifen treatment.

The correlation between the silver-stained nucleolar organizer region associated proteins (Ag-NORs) and the growth rate suppression (GRS) of ten established breast cancer cell lines which were treated with 4-hydroxy-tamoxifen (OHT) and interferon-gamma (g-IFN), respectively, was investigated by means of automated image analysis. Previous studies have shown a statistically significant relationship between the Ag-NOR quantity and the population doubling time (PDT) of these cell clones. The results of the present study showed a highly significant correlation between the GRS and the Ag-NOR quantity in estrogen receptor (ER) positive tumour cell lines after OHT treatment (P < 0.001) whereas no strict correlation of these parameters could be demonstrated after g-IFN treatment in both ER positive and negative cell lines. Our results suggest a different behaviour of NOR-proteins in breast cancer cell lines if treated either with g-IFN or OHT, probably reflecting the different mechanism of cell suppression mediated by OHT and g-IFN. It is concluded that quantitative assessment of Ag-NORs is not as suitable for the determination of the GRS as it is for the determination of cell duplication rates obtained on untreated tumour cell lines.

Breast Neoplasms↗
PubMed1993

The prognostic value of nuclear roundness and neopterin in ovarian cancer.

The prognostic value of clinical factors, morphometric features and neopterin, a marker for macrophage activation, was investigated retrospectively in 68 ovarian carcinoma patients. Nuclear roundness was a good predictor of patient survival. About 50% of our patients showed neopterin concentrations above the cut-off level of 275 mumol/mol creatinine. Interestingly, those patients with elevated urinary neopterin concentration, and thus displaying a sign of activation of cell-mediated immunity, had a shorter survival than those with normal concentration. Applying a multivariate Cox regression analysis, the only independent parameters predicting patient survival were FIGO stage, residual disease, nuclear roundness and neopterin.

Adult↗
PubMed1993

Mechanism of synergistic action of all-trans- or 9-cis-retinoic acid and interferons in breast cancer cells.

Combination of all-trans-retinoic acid (RA) with either interferon-alpha or -gamma resulted in a synergistic amplification of the anti-proliferative effect on cultured breast cancer cells. RA could be replaced by other biologically active retinoids. The synergism was also observed for the induction of 2'-5'-oligoadenylate synthetase, an enzyme which is involved in anti-viral activity of interferons and possibly in growth regulation of tumor cells. Combination of RA with interferon-gamma increased the down-regulation of specific binding sites for [125I]interferon-gamma. On the other hand interferons had no effect on the cytoplasmic binding protein for RA. Comparing all-trans- with 9-cis-RA, the latter was more effective in inhibiting tumor cell growth and in inducing synergism with interferon-gamma. This would indicate that retinoic X receptors are more important in mediating these effects than the RA receptors (RARs). This assumption is also supported by the failure of Ro-415253, a specific RAR-alpha antagonist, to reduce the synergistic interaction of RA with interferon with respect to growth inhibition.

Breast Neoplasms↗
PubMed1993

Tumor marker CA-125 in tissues of the female reproductive tract and in serum during the normal menstrual cycle.

OBJECTIVE: To further elucidate the origin of the physiological CA-125 amounts that lead to cyclic changes in CA-125 serum levels in normally menstruating women. DESIGN: Fifty-three normal endometria, 13 fallopian tubes, 25 ovaries, and nine isolated corpora lutea were prospectively investigated for their CA-125 content in a sandwich solid-phase RIA and by immunohistochemistry. In addition, endometrial CA-125 tissue content was compared with the actual CA-125 serum levels of the study patients. RESULTS: Cytosolic CA-125 concentrations were 20-fold and twofold higher in the endometrium than those measured in the ovary and the fallopian tube, respectively. Moreover, only in the endometrium did CA-125 content show significant cyclic changes, with the highest concentrations during the early proliferative and middle secretory phase. The lowest tissue concentrations were measured during the early secretory phase. Furthermore, during the early and middle secretory phases cytosolic CA-125 was negatively associated with CA-125 serum levels. In immunohistochemistry, marked distributional changes in OC-125 reactivity were revealed in the basalis and the functionalis throughout the menstrual cycle and the postovulatory loss of CA-125 expression was found to be strongly connected with early secretory transformation of glandular epithelium. CONCLUSION: Our findings indicate that the CA-125 amounts responsible for cyclic changes in serum levels in normally menstruating women seem to be a product of normal endometrium.

Adult↗
PubMed1993

Tumor markers in hypertensive disorders of pregnancy.

Plasma levels of tumor markers (CEA, TPA, CA 15.3, CA 125, alpha-fetoprotein) for 50 patients with hypertensive disorders of pregnancy were compared with those of 50 healthy women with singleton pregnancies and 50 healthy non-pregnant controls. With the exception of CEA all tumor marker values were higher in pregnant women, these differences being statistically significant (all p < 0.0001). Alpha-fetoprotein was lower in hypertensive than in healthy pregnant women (p = 0.0004), whereas CEA, CA 15.3 and CA 125 showed no statistically significant differences. TPA values in patients with hypertensive disorders of pregnancy (median 190 U/l) were 2.7 times higher than those of healthy pregnant controls (median 70.5 U/l) with a statistically significant difference (p < 0.0001). The individual degrees of disease severity demonstrated increasing TPA medians (pregnancy-induced hypertension: 106.5 U/l; pre-eclampsia: 200 U/l; HELLP syndrome: 339 U/l). TPA levels correlated positively with clinical severity of disease and negatively with fetal (rs = -0.58; p < 0.0001) and placental weight (rs = 0.44; p = 0.01).

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1992

Epidermal growth factor reduces HER-2 protein level in human ovarian carcinoma cells.

Over-expression of the proto-oncogene HER-2 (c-erbB-2/neu) in ovarian, endometrial, and mammary carcinoma is an indicator of poor prognosis. Interactions between the epidermal growth factor (EGF) receptor and the HER-2 protein have been described. The aim of this study was to elucidate the effects of EGF on HER-2 expression. In the human ovarian carcinoma cell lines HTB-77, OVCAR-3, 2780, SKOV-6, SKOV-8 and 2774, and the human mammary tumor cell line SKBR-3, total cellular p185HER-2 was determined by an ELISA, whereas the surface p185HER-2 was measured with a living-cell RIA. Stimulation of these cell lines with either EGF (0.1-30 nM) or TGF-alpha (0.1-30 nM) led to a significant reduction in p185HER-2 expression. The effect was more pronounced in cells with normal HER-2 expression. A reduction of mRNA levels for p185HER-2 by EGF was observed in OVCAR-3 cells but not in the over-expressing lines HTB-77 and SKBR-3. Interestingly, the EGF-induced effect was not always associated with growth stimulation and was not correlated with the number of EGF binding sites detected by a radioligand assay. Our data indicate that EGF treatment results in a down-regulation of p185HER-2.

Base Sequence↗
PubMed1992

Effects of interferons on the expression of the proto-oncogene HER-2 in human ovarian carcinoma cells.

The over-expression of the proto-oncogene HER-2 (c-erbB-2/neu) in ovarian, endometrial and mammary carcinoma is an important indicator for poor prognosis. We have previously shown in 3 out of 4 ovarian carcinoma cell lines an interferon-gamma (IFN-gamma)-mediated reduction in HER-2 specific protein and RNA levels. The oncogene expression was lowered only in the ovarian carcinoma cell lines but not in 3 IFN-gamma-sensitive human breast cancer cell lines. We extended our observations also to IFN type I, alpha and omega. The expression of the oncogene was measured by both the p185HER-2 ELISA and in selected cases by a living cell radioimmunoassay using the monoclonal antibody (MAb) 4D5 against the extracellular domain. Both IFN types reduced the expression of HER-2 in the ovarian carcinoma cell lines OVCAR-3, HTB-77, 2774 and SKOV-6, and in the SKUT-2 endometrial carcinoma cells. In contrast, SKOV-8 human ovarian carcinoma cells were sensitive for both IFN types regarding proliferation, but only IFN-gamma reduced proto-oncogene expression. In the SKBR-3 human mammary carcinoma cells, neither IFN type had an effect on HER-2 expression. The antibodies 4D5, 7C2, 3E8, and 3H4 which bind to the extracellular domain of p185HER-2 protein specifically inhibited anchorage-independent growth of SKBR-3 and HTB-77 cells. Expression of the oncogene HER-2 is the leading prognostic factor in ovarian cancer. Its modulation might represent a mechanism by which IFNs inhibit cell proliferation.

Antibodies, Monoclonal↗
PubMed1992

Modulation of tumour marker CA-125 expression in cultured ovarian carcinoma cells.

The aim of this study was to elucidate whether proliferation of ovarian carcinoma cells may affect the biosynthesis and release of CA-125. In a cell culture model the tumour marker CA-125 expression in cytosol, surface membrane, and release into culture medium was studied in six human carcinoma cell lines. Cell cycle analysis of propidium iodide stained nuclei was performed using a fluorescent activated cell sorter. The turnover of CA-125 is very rapid, within 24 h the equivalent amount found in each cell was also released in the supernatant culture medium. A good relation between cytosolic, membrane, and released CA-125 was observed. CA-125 expression was associated predominantly with the G0/G1 phase of the cell cycle and was dependent on cell density. The results presented here demonstrate that factors associated with tumour cell proliferation could influence the CA-125 serum level in ovarian cancer patients.

Antigens, Surface↗
PubMed1992

Relationship between quantity of silver stained nucleolar organizer regions associated proteins (Ag-NORs) and population doubling time in ten breast cancer cell lines.

Using a one-step silver staining technique ten human breast cancer cell lines were investigated, determining by means of automated image analysis the mean area of Ag-NORs per nucleus, the total number of Ag-NORs, and the so-called "scattered" and "clustered" Ag-NORs. These parameters were statistically correlated with the population doubling time (PDT) of the various carcinoma cell lines of this series. Our results show that the mean area of Ag-NORs per nucleus (p less than 0.001) is highly significantly correlated to the PDT, whereas all other parameters were less or not significant. It is concluded that the assessment of the area of Ag-NORs by automated image analysis is a simple and reliable method for the determination of cell duplication rates.

Breast Neoplasms↗
PubMed1992

[Placental protein 12 (PP 12) in pregnancy-induced hypertensive diseases].

Placental protein 12 (PP12) was measured in 30 patients with hypertensive disorders of pregnancy, 10 healthy pregnant and 10 healthy nonpregnant controls. Differences in PP12-concentrations of healthy nonpregnant (median 2.0 micrograms/l, range 1.0-5.5 micrograms/l) and healthy pregnant controls (median 110 micrograms/l, range 29-280 micrograms/l), as well as between healthy nonpregnant controls and hypertensive patients (median 125 micrograms/l, range 28-420 micrograms/l) were both statistically highly significant (p less than 0.001). The comparison between healthy pregnant and hypertensive women demonstrated no statistically significant differences. In coexistent intrauterine growth retardation (median 163 micrograms/l, range 60-400 micrograms/l), higher values could be observed in some patients, but this group showed no statistically significant difference compared to healthy pregnant controls with adequate fetal weight. PP12 does not seem to be a clinically usable parameter in the diagnosis of hypertensive disorders of pregnancy and fetal growth retardation, because of the widespread range of results.

Adult↗
PubMed1992

[Steroid and protein hormone concentrations in serum and follicular fluid after stimulation for in vitro fertilization].

Sixty patients with tubal infertility were stimulated for IVF with a fixed schedule consisting of clomiphene and pure follicle stimulating hormone. They responded with an optimal estradiol increase and 2 to 4 embryos were transferred. Conception cycles (n = 17) could be differentiated from non-conception cycles (n = 43) by serum estradiol, serum progesterone, the serum progesterone/estradiol-ratio and serum LH concentrations. Testosterone, androstenedione and FSH in serum and follicular fluid showed no significant relation to a possible therapy outcome. We conclude from our findings, that, during the peri-implantation period, certain LH patterns followed by an optimal progesterone/estradiol-ratio in the serum support an embryo survival after transfer to the uterus.

Androstenedione↗
PubMed1992

[Magnetic resonance tomography in follow-up of hydatidiform mole].

The value of magnetic resonance imaging (MRI) was studied in a case of a gestational trophoblastic tumour. In addition to the tumour size, MRI made it possible to measure necrotic areas, which are assumed to be a sign of response to chemotherapy. Moreover, uterine zonal anatomy and subserosal uterine veins yielded important information on tumour biology. Complete remission was induced in high-risk patients by etoposide, methotrexate, and actinomycin D treatment.

Adult↗
PubMed1992

Modulation of ovarian carcinoma OV632 antigen by interferons.

Interferons are known to modulate several cellular functions by the induction of different proteins. In our study interferon-gamma and -alpha augmented presentation of one specific ovarian cancer antigen recognized by the antibody OV632 on the cell surface on one of four ovarian carcinoma cell lines in vitro (HTB-77). The interferon-gamma effect reached a maximum after 24 of treatment. Both HLA-DR and OV632 antigen expression were increased by interferon-gamma on HTB-77 cells whereas the two cell lines OVCAR-3 and 2780, which respond to an interferon-gamma treatment with a reduced proliferation and induction of HLA-DR, and also the interferon-resistant CRL-1572 were found to be resistant regarding OV632 epitope modulation. The demonstration of OV632 expression provides an important insight into the potential regulatory mechanism governing this tumor marker.

Antigens, Neoplasm↗