Search PubMed⌕ Search

Biomedical subjects

G Daxenbichler

Publications and source records attributed to G Daxenbichler.

At least 37 records · Page 2Linked to original sources
PubMed1996

Circulating immunostimulatory protein 90K and soluble interleukin-2-receptor in human ovarian cancer.

The tumor-associated antigen 90K is thought to play an important role in cellular immune defense against malignant cells. It is therefore of interest to investigate whether circulating 90K could be used as a prognostic variable in ovarian cancer, and whether this immunostimulatory antigen is related to other parameters known to be involved in the cellular immune response. In the present retrospective study, circulating levels of antigen 90K were measured before primary surgery in 152 ovarian-cancer patients. A very close association between antigen 90K and s-IL-2R concentrations was pointed out in a stepwise logistic regression model. Univariate analysis of overall survival revealed that antigen 90K and s-IL-2R were associated with poor prognosis. In the multivariate Cox regression, however, neither antigen 90K nor s-IL-2R retained independent prognostic significance. Urinary neopterin was shown to be the only independent prognostic variable among the "immunological parameters" investigated. Additionally, residual disease after primary tumor debulking and histopathologic tumor grade were the most prominent clinico-pathologic parameters for the independent prediction of poor clinical outcome in ovarian-cancer patients.

Adult↗
PubMed1996

Different effects of interferons, interleukin-1beta and tumor necrosis factor-alpha in normal (OSE) and malignant human ovarian epithelial cells.

Ovarian cancer arises mostly from the ovarian surface epithelium. The aim of our study was to compare the effects of cytokines in ovarian surface epithelial (OSE) cells and in ovarian carcinoma cells. Proliferation and expression of surface antigens (CA-125 and classes I and II antigens of the major histocompatibility complex [MHC]) were measured in OSE cells obtained from 7 different patients and 7 ovarian carcinoma cell lines. Proliferation of OSE cells remained unaffected by interferon (IFN)-alpha or IFN-gamma, whereas interleukin-1 (IL-1) and tumor necrosis factor (TNF) increased cell growth. Proliferation of ovarian carcinoma cells was reduced by both types of IFN as well as TNF but was not affected by IL-1. Expression of the tumor marker CA-125 was increased by IFN-gamma in ovarian carcinoma cells but not by any other treatment. None of the cytokines affected CA-125 surface expression in OSE cells. Expression of MHC-I was augmented in OSE and in carcinoma cells by both IFNs but not by the other cytokines. Both types of cell were negative for MHC-II, but IFN-gamma induced its expression in both OSE and carcinoma cells. Significant concentrations of the cytokines evaluated here have been measured in blood and follicular fluid by several authors. The different actions of these cytokines in OSE and carcinoma cells could therefore be important in understanding the role of such molecules in the regulation of physiological and pathological processes in the ovary, such as ovulation or malignant proliferation.

Antigens, Neoplasm↗
PubMed1996

Increased radiosensitivity by a combination of 9-cis-retinoic acid and interferon-y in breast cancer cells.

Interferons (IFNs) and retinoic acid (RA) are known to possess antiproliferative effects in various human cancer cell lines, including squamous cervix carcinoma and breast cancer cell lines. Frequently synergistic effects could be observed by the combination of both, and in clinical trials high response rates could be achieved by IFN-alpha in combination with 13-cis-RA in patients with squamous carcinoma of the uterine cervix. Since radiation-potentiating effects of IFNs and RA were described, we evaluated the additional impact of irradiation on three human breast cancer cell lines and investigated the antiproliferative effects of single, double, or triple treatments with IFN-gamma, 9-cis-RA, and irradiation. Antiproliferative effects were observed in all cell lines by any single treatment. When combining IFN-gamma with 9-cis-RA, synergism could be observed in all experiments. The combination of either IFN-gamma or 9-cis-RA with irradiation resulted mostly in additive effects. Irradiation contributed additive or further synergistic effects to the already synergistic effects of the combination of these two drugs. Thus synergism of IFN-gamma and 9-cis-RA always at least persisted fully. These results suggest that a regimen of IFN, RA, and radiotherapy (RT) might be a promising combination in the therapy of solid tumors, where RT is part of the conventional treatment.

Antineoplastic Agents↗
PubMed1996

Human peritoneal mesothelial cells are more potent than ovarian cancer cells in producing tumor marker CA-125.

The aim of the present study was to investigate the extent to which human peritoneal mesothelial cells (HPMCs) are able to participate in the release of tumor marker CA-125 in ovarian cancer and other conditions associated with an involvement of the peritoneum. For this purpose CA-125 shedding was measured in the supernatant culture medium of HPMCs obtained from various donors and seven well-established ovarian cancer cell lines (OVCAR-3, 2780, 2774, SKOV-6, SKOV-8, HOC-7, HTB-77). Furthermore, the influence of inflammatory cytokines [interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma)] on CA-125 release in normal and malignant cells was also studied. Constitutive CA-125 shedding was found to be about five times higher in HPMCs as compared with the investigated ovarian cancer cell lines. IL-1 beta and TNF-alpha treatment of HPMCs resulted in a significant reduction in CA-125 release; however, no consistent pattern in CA-125 secretion was found during incubation with either IL-1 beta or TNF-alpha in the various malignant cell lines. IFN-gamma, on the other hand, induced a highly significant increase in CA-125 secretion in ovarian cancer cells, but did not influence the shedding of CA-125 in HPMCs.

CA-125 Antigen↗
PubMed1996

Effects of sex- and glucocorticoid steroids on breast cancer cells grown as either multicellular tumor spheroids or monolayers.

The effects of estradiol, medroxyprogesterone acetate (MPA) dexamethasone, dihydrotestosterone and the antihormones 4-OH tamoxifen and RU 38486 were studied in two established breast carcinoma cell lines, the estrogen-sensitive ZR-75-1 and the estrogen-independent BT 20 cells applying two different in vitro systems, spheroid and monolayer cell culture in steroid deprived medium. Growth of ZR-75-1 spheroids was dramatically stimulated by the addition of estradiol, an effect which was neutralized by the simultaneous addition of 4-OH tamoxifen. The antiestrogen alone as well as dihydrotestosterone and MPA reduced ZR-75-1 spheroid growth significantly. While growth of BT 20 spheroids was only transiently inhibited by tamoxifen and dihydrotestosterone, a persistent increase in BT 20 spheroid growth was observed under MPA treatment in a concentration of 1 microM. This effect, although statistically significant, was very moderate. With the exception of this finding, growth effects of the different test compounds were similar in both in vitro systems, tumor spheroids and monolayer cell cultures.

Breast Neoplasms↗
PubMed1996

[Immunostimulating protein 90K in ovarian carcinoma].

Protein 90K is a tumor-associated antigen, which is able to enhance the cytotoxic activity in lymphokine-activated and natural killer cells as well as the IL-2 release in peripheral blood lymphocytes. In our in vitro experiences we observed a stimulatory effect by IFN-alpha and IFN-gamma on 90K-specific mRNA expression and protein release in ovarian cancer cells, and 90K was furthermore found to be a potent stimulator of macrophage activity. Protein 90K seems to be involved in tumor immunology; it may represent a critical link between tumor and immune system.

Adjuvants, Immunologic↗
PubMed1996

Tissue polypeptide antigen during parturition and puerperium.

The tumour and cytoskeleton protein tissue polypeptide antigen (TPA) was determined in maternal serum taken during the second stage of labour and on the 4th postpartum day. Pregnant women at term (weeks 38-42) served as a control group. TPA levels of women during parturition (median 169 U/l) were higher than those of the control group (median 108.5 U/l) and those of women on the 4th postpartum day (median 66.5 U/l); p < 0.0001 in each case. The correlation between duration of labour and TPA concentration was positive and significant (rs = 0.3; p = 0.03). A significant negative correlation was found between placental weight and maternal serum TPA levels during parturition (rs = -0.3; p = 0.03). The decline of TPA after delivery indicated a serum half-life for TPA of less than 4 days.

Female↗
PubMed1995

Effects of retinoic acid and gamma-interferon on expression of retinoic acid receptor and cellular retinoic acid-binding protein in breast cancer cells.

Retinoids and gamma-interferon (IFN-gamma) have been demonstrated to synergistically amplify growth inhibition in cultured breast cancer cells. Since IFN-gamma enhances effects mediated by retinoids more than vice versa, we focused our investigations on the mRNA expression of cellular retinoic acid-binding proteins (CRABPs) and retinoic acid receptors (RARs), since these are the key molecules that mediate retinoid action. Synergistic inhibition of cell proliferation under treatment with 9-cis-retinoic acid and IFN-gamma was detected in the three breast cancer cell lines MCF-7, SKBR-3, and even in the RA-resistant BT-20 cells. RAR-alpha and RAR-gamma mRNA were observed in all cell lines, whereas RAR-beta was not detectable. CRABP I message was expressed in MCF-7 cells only, but CRABP II was found in all three breast cancer cell lines. IFN-gamma (10 ng/ml) increased RAR-gamma expression but had no influence on RAR-alpha, whereas RAR-beta was not detectable in any of the cell lines. RA (1 microM)-mediated CRABP II increase was suppressed by IFN-gamma (10 ng/ml). These observations indicate that IFN-gamma-mediated increase in RAR-gamma and suppression of RA-mediated CRABP II activation may play a role in synergistic inhibition of proliferation in breast cancer cell lines.

Breast Neoplasms↗
PubMed1995

Effects of Taxol on choriocarcinoma cells.

OBJECTIVE: Taxol (Bristol-Myers Squibb) (paclitaxel) has been shown to be a potent inhibitor of cell growth for a variety of tumors. We were interested in the antiproliferative efficacy and biologic properties of this novel antineoplastic agent in choriocarcinoma cells. STUDY DESIGN: Human choriocarcinoma cell lines JAR and BeWo were cultured as monolayers and treated with Taxol. RESULTS: Proliferation of JAR and BeWo cells was inhibited by Taxol in a dose-related manner and 1 to 3 nmol/L was sufficient to achieve 50% growth reduction. This effect was accompanied by a marked induction of human chorionic gonadotropin secretion. The effect on human chorionic gonadotropin secretion was dependent on intact protein biosynthesis but not mediated by augmented messenger ribonucleic acid expression. In these choriocarcinoma cells Taxol promoted differentiation as shown by an increase in syncytiotrophoblastic-like cells. Combination of Taxol with either etoposide or methotrexate resulted in antagonistic growth inhibition. CONCLUSION: Taxol is a highly effective antineoplastic agent in choriocarcinoma cells, and clinical trials in refractory disease would therefore be warranted. However, substances other than etoposide or methotrexate should be evaluated for combined treatment. In addition to growth inhibition, differentiation is also induced by Taxol, as shown by increased human chorionic gonadotropin secretion and changed morphologic features.

Antineoplastic Agents, Phytogenic↗
PubMed1995

[Value of the TAG-72 (CA 72-4) tumor marker in primary diagnosis of ovarian carcinoma. A comparison with the established CA-125 marker].

The value of the TAG-72 (CA 72-4) serum marker in primary diagnosis was investigated in 110 patients with histologically diagnosed ovarian cancer. A reference group consisted of 103 patients with benign pelvic masses. Compared to the well-established CA-125, TAG-72 showed a low sensitivity of 42% in the detection of ovarian cancer. By contrast, when the cut-off level for TAG-72 was set at 6 U/ml, it showed a very high specificity of 99%. When the measurement of TAG-72 was combined to that of CA-125, improvements in both the specificity (as compared to a single CA-125 determination) and the sensitivity (as compared to a single TAG-72 assay) were observed. In such a combined assay, our results suggest that the best predictive value (positive and negative) was obtained if CA-125 is assigned a relatively high cut-off value (65 U/ml) in conjunction with a low cut-off level (3.2 U/ml or 4 U/ml) for TAG-72. In the present study, at threshold values of 65 U/ml respectively, a sensitivity of 86%, a specificity of 83% and a positive and negative predictive value of 85% were obtained. In mucinous carcinomas of the ovary, however, the additional TAG-72 determination did not lead to a better predictive power than did CA-125 measurement alone.

Adenocarcinoma, Clear Cell↗
PubMed1995

[Kallikrein (urine) in pregnancy-induced hypertension].

Total, active and inactive renal kallikrein were compared between 25 patients with hypertensive disorders of pregnancy and 25 healthy pregnant women of corresponding gestational age. Values of all three fractions were twice as high in healthy women than in hypertensive patients and differed with statistical significance. A longitudinal examination of renal kallikrein during pregnancy showed a physiological decrease of values from the 16th-20th week until term. Asymptomatic women, who developed hypertension later on, showed decreased renal kallikrein values.

Adult↗
PubMed1995

[Modification of chorionic carcinoma cells by immunomodulators. Cytokines and chorionic carcinoma cells].

OBJECTIVES: The role of inflammatory cytokines on regulation of hCG biosynthesis was studied. METHODS: JAR choriocarcinoma cells were cultured and treated with interleukin-1 (IL-1), IL-3. IL-4, stem cell factor (SCF), tumor necrosis factor (TNF), and granulocyte or granulocyte-macrophage-colony stimulating factor. hCG concentration was determined by immunoradiometric methods and cell number was enumerated by means of an electronic particle counter. RESULTS: Il-1 and TNF increased biosynthesis of holo-hCG as well as the free alpha- and free beta-subunit and the beta-core protein. Proliferation was not affected by any cytokine tested. CONCLUSION: Inflammatory cytokines are able to increase the biosynthesis of hCG.

Cell Division↗
PubMed1994

Effects of type-I and -II interferons on 90K antigen expression in ovarian carcinoma cells.

Antigen 90K is produced by several tumor-cell lines and by patients with cancer. Its function has not yet been clarified, although recent reports suggest that it plays a role in the tumor-host relationship--for example by stimulation of natural killer and lymphokine-activated killer-cell activity. Previous studies have indicated that 90K expression may be under the influence of interferon-alpha. Here, we provide evidence that both interferon-alpha and -gamma can enhance the secretion of 90K and augment the level of specific mRNA expression in 3 ovarian carcinoma cell lines (OVCAR-3, HTB-77 and SKOV-6). However, interferon-gamma leads to depletion of cellular 90K whereas interferon-alpha increases both secreted and cellular 90K levels. In equimolar concentrations, Interferon-alpha was always superior to interferon-gamma in augmenting 90K protein or mRNA levels. Combinations of TNF with interferon-gamma were highly synergistic both in reducing cell proliferation and in increasing 90K secretion and mRNA expression. This synergism was seen to a lesser extent with interferon-alpha.

Antigens, Neoplasm↗
PubMed1994

Increased production of immune activation marker neopterin by colony-stimulating factors in gynecological cancer patients.

Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have recently been introduced in the treatment of chemotherapy-induced neutropenia. Effects of these CSFs on the cellular immune system were evaluated in 38 neutropenic gynecological cancer patients during chemotherapy. In addition to restoring the leukocyte count, GM-CSF--to a greater extent than G-CSF--also induced neopterin, a sensitive marker of macrophages activated by interferons. This effect was confirmed in vitro by investigating the effects of these CSFs on interferon-gamma-mediated pathways in THP-I human myelomonocytic cells. The results suggest activation of immune effector cells by GM-CSF.

Adult↗
PubMed1994

Immunocytochemical versus biochemical receptor determination in normal and tumorous tissues of the female reproductive tract and the breast.

The development of highly specific and sensitive monoclonal antibodies directed against human estrogen (ER) and progesterone receptors (PR) provides a new approach in precise histochemical receptor location independent of hormone binding. Over the years receptor determination was the domain of the radioligand-binding assay, in which receptors are measured by tritiated ligand and unbound ligand is removed by the dextran-coated charcoal (DCC) procedure. Presented here are the results and experiences obtained by the classic DCC and the immunocytochemical method in the different normal and tumorous tissues of the female reproductive tract and the breast. The results of both methods were compared, and overall concordance of the results was found to vary considerably among the different types of tissue analyzed. Best agreement (86%) was found for PR determination in breast cancer, and the lowest rate of concordance for ER determination in fibrocystic disease of the breast. Special attention was directed toward the heterogeneity of receptor distribution in the specimens examined. In all tissues investigated, ER and PR were located in the nuclei of cells in both paraffin and frozen sections. Staining intensity varied among different cell types and from cell to cell for a single cell type, as well as in tumorous and normal tissues. In breast cancer, randomly scattered single cell receptor positivity was distinguished from focal/clonal positivity. Paraffin-embedded lymph node metastases showed significantly weaker staining as compared with their respective primary tumors. In the normal ovary, the corpus luteum and the stromal layer of the outer cortex were revealed as highly receptive elements for progestins, whereas ER was barely demonstrable in the normal ovary. Benign serous and mucinous ovarian tumors showed opposite ER and PR distribution among the stromal and epithelial components. Of special interest were the highly significant changes in ER and PR content in the stromal and glandular cells of the different layers of the normal endometrium throughout the menstrual cycle.

Breast↗
PubMed1994

Significance of thrombocytosis in patients with epithelial ovarian cancer.

OBJECTIVES: Our objective was to determine the relevance of a preoperative platelet count in ovarian cancer. Special interest was directed to a possible prognostic significance of thrombocytosis in this disease. STUDY DESIGN: Charts of 130 patients with epithelial ovarian cancer were reviewed retrospectively. Survival analyses were performed with the Kaplan-Meier method. Differences in survival were examined according to Mantel and Breslow. Platelet counts were furthermore correlated to other clinical parameters. For this purpose the Spearman rank test and a stepwise logistic regression model were used. Data comparison was accomplished with the Mann-Whitney U test and the chi 2 test. RESULTS: Prevalence of thrombocytosis was 38%. No differences in survival between patients with or without thrombocytosis was found. Volume of ascites and hemoglobin concentrations were independently associated with thrombocytosis (p = 0.002 and p = 0.004, respectively). CONCLUSIONS: Thrombocytosis is not a useful prognostic factor in ovarian cancer. Elevated platelets are predominantly associated with the presence of ascites and marked anemia.

Adult↗
PubMed1994

[Interaction of interferon with retinoic acid].

Lippman and coworkers recently reported striking response rates achieved in patients with cervical cancer using a combined treatment with 13-cis-retinoic acid and interferon-alpha. In vitro studies demonstrated a synergistic amplification of proliferation inhibition by retinoids and interferon in malignant cells. Comparing all-trans- with 9-cis-retinoic acid, the latter was more effective in inhibiting tumor cell growth and in inducing synergism with interferon-gamma. Combination of retinoic acid with interferon-gamma increased the down-regulation of specific binding sites of interferon-gamma. Expression of MHC class II antigens induced by interferon-gamma was not further enhanced by retinoic acid. These results indicate that interferon seems to modulate the retinoic acid system.

Breast Neoplasms↗