G. Daxenbichler

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).

Transforming growth factor-beta and ovarian carcinoma cells: regulation of proliferation and surface antigen expression

Transforming growth factor-beta (TGF-beta) is a multifunctional peptide regulating several processes in ovarian cells. The growth of ovarian carcinoma cell lines (OVCAR-3, HTB-77, 2780 and CRL-1572) was reduced by TGF-beta in a dose related manner. The antiproliferative activity was not improved by combination with other biological response modifiers. Treatment with TGF-beta augmented the expression of interferon-gamma induced class I and II antigens of the major histocompatibility complex. The presentation of another antigen namely the tumor marker CA-125 on the cell surface was markedly reduced by TGF-beta.

Correlation of Biochemical (Receptors, Endogenous Tissue Hormones) and Quantitative Morphologic (Stereologic) Findings in Normal and hyperplastic Human Prostates

In previous light and electron-microscopic analyses human benign prostatic hyperplasia was shown to be predominantly a stromal disease; the aim of the present study was to correlate the stereological data with the levels of the endogenous tissue hormones (androgens, estrogens, progesterone) in normal (N) and hyperplastic human prostatic tissues (BPH). BPH tissue specimens were obtained by open prostatectomy (n = 25); normal prostatic tissue was obtained from kidney donors (n = 5). No statistically significant difference was found between normal and hyperplastic tissue. Testosterone BPH 0.69 +/- 0.44, N 0.25 +/- 0.12; 5 alpha-dihydrotestosterone BPH 7.0 +/- 2.9, N 4.2 +/- 0.7; progesterone BPH 0.059 +/- 0.022, N 0.058 +/- 0.005; estrone BPH 0.10 +/- 0.03, N 0.14 +/- 0.03; estradiol BPH 0.07 +/- 0.02, N 0.05 +/- 0.02; estriol BPH 0.02 +/- 0.01, N 0.04 +/- 0.02. Using a Spearman rank correlation coefficient a statistical analysis was performed for age, weight of the prostate, absolute stereological data and the endogenous prostatic hormones. As can be seen from the statistical analysis there is a poor correlation for 5 alpha-dihydrotestosterone and the amount of the glandular epithelium; otherwise no correlation of the endogenous tissue hormones with the stereological data investigated was found. These data show that the stromal overgrowth of benign hyperplasia is not reflected in the tissue hormone levels.

High serum levels of soluble CD44 variant isoform v5 are associated with favourable clinical outcome in ovarian cancer

In 96 ovarian cancer patients, the present study investigates the clinical significance of pretreatment concentrations of soluble CD44 standard (CD44s) and its isoforms v5 and v6 determined in the serum and the ascitic fluid by means of recently developed enzyme-linked immunosorbent assays (ELISAs). Furthermore, CD44 serum concentrations in the ovarian cancer patients were compared with circulating CD44 levels in 50 healthy age-matched female blood donors. Whereas CD44s was found to be higher and CD44v5 to be lower in ovarian cancer patients than healthy control subjects, no statistical difference between the two cohorts was revealed for CD44 isoform v6. In the ascitic fluid samples, variant isoform v5 and v6 were demonstrated at lower concentrations than serum. Multivariate analysis of overall survival demonstrated that a high pretreatment serum level of soluble CD44 isoform v5 is independently associated with favourable clinical outcome in ovarian cancer. When circulating CD44 isoforms were compared with a panel of serum parameters known to be involved in the immunological network, an inverse correlation between serum CD44v5 levels and indicators of cellular immune system activation, such as soluble interleukin 2 receptor, immunostimulatory protein 90K and neopterin, became apparent.

Correlation between Steroid Hormone Receptors, Histological and Clinical Parameters in Ovarian Carcinoma

Estrogen (ER) and progesterone (PR) receptors in ovarian tumors of 62 patients (51 carcinomas, 11 benign tumors) were estimated by the dextran-coated charcoal method using Scatchard plot analyses. 63% of carcinomas were ER-positive (greater than 10 fmol/mg cytosol), 38% were PR-positive (greater than 25 fmol/mg cytosol), whereas in benign tumors only 45% were ER-positive and 36% were PR-positive. We found no statistically significant correlation between receptor content and stage of disease, menopausal status or age of the patient. The highest concentration of ER and PR was observed in patients between 61 and 70 years of age. Life table analysis for patients with advanced ovarian carcinomas showed no significant difference in survival time in the group with higher ER and PR content. This study also reports the results obtained in a group of patients with receptor-positive ovarian carcinomas treated with a combination of chemotherapy and antiestrogen therapy. In comparison to treatment with cytotoxic chemotherapy alone, no significant difference in the time of survival or duration of remission could be found.

CA 125 in the Serum and Tissue of Patients with Gynecological Disease

SummarySerum levels of CA 125 were determined in 239 patients suffering from gynecological malignancies. The upper limit for normal was 35 U/ml. Raised levels were found in 82% of patients with primary ovarian carcinoma, and in 29% of those with benign ovarian tumors. The values from patients with ovarian carcinomas in partial or complete remission were compared with those from patients with progressive disease. The former group had elevated levels in 19% compared to 89% in the latter group. Fifty-four percent of the values in progressive cervical carcinoma and 41% of the levels in progressive endometrial carcinoma were greater than 35 U/ml. High CA 125 levels were found in the cytosol of placenta, ovarian carcinoma, cervical carcinoma, and in ascitic fluid; correlation with serum levels was satisfactory. Even though CA 125 is of limited specificity for ovarian cancer, serum levels are important for follow up care and for the early detection of recurrences.

Childbirth as a Biological Model for Stress

Objective: The aims of this investigation were to measure corticotropin-releasing hormone (CRH), corticotropin (ACTH) and cortisol before, during and after delivery searching for an endocrine intercorrelation of the hypothalamic-pituitary-adrenal (HPA) axis and to correlate these findings with obstetrical variables. Methods: Blood was sampled from 50 women with singleton pregnancies at term without uterine contractions, during delivery (after full cervical dilatation) and on the 4th postnatal day. Hormones were measured by radioimmunoassay (RIA). The correlation between obstetric variables, sociodemographic and endocrine data were evaluated using the Spearman rank coefficient. Group comparisons for continuous variables were calculated using the Mann-Whitney U test and Kruskal-Wallis test. Results: Maternal plasma ACTH and cortisol increased significantly during labor, declining toward the 4th postnatal day (p < 0.001) and showing a significant intercorrelation (p < 0.01). Compared to women without uterine contractions CRH rose during labor (p < 0.05) and decreased rapidly to the 4th postnatal day (p < 0.001). No correlations between CRH and ACTH or cortisol were observed. None of the obstetrical variables (parity, newborn’s weight, duration of delivery) revealed any significant correlation with ACTH. Analgetic medication (pethidine hydrochloride) was not able to influence the endocrine response to labor stress. Conclusions: Stressful experience during childbirth has an impact on endocrine response. However, this is not fully evident along the HPA axis in a simple biological model with monocausal dependencies. This ‘biological stress model’ is not sensitive enough to detect different childbirth conditions and the hormones in the maternal compartment have partially fetal (placental) origin.

Inhibition of the estradiol-induced growth of cultured human breast cancer cells by the anti-estrogens tamoxifen, desmethyl-tamoxifen, 4-hydroxy-tamoxifen and enclomiphene

The growth effects of tamoxifen (T), desmethyl-tamoxifen (dMeT), 4-hydroxy-tamoxifen (OHT) and enclomiphene (Clo) on cultured human breast cancer cell lines have been related to published binding affinities for the estrogen receptor. Only in cells which were stimulated by estrogens did these anti-estrogens markedly inhibit growth. In both estrogen sensitive cell lines tested, 734 B and ZR 75.1, the anti-estrogen activity showed the identical rank: OHT much greater than Clo approximately equal to T = dMeT; this anti-proliferative potency agrees with reported affinities of these compounds for the estrogen receptor. In culture media containing defined amounts of estradiol we observed that a 10,000-fold molar excess of OHT was required to inhibit the estradiol-induced growth, but the estradiol-independent proliferation was not affected.

Regulation of CA 125 expression in cultured human carcinoma cells

CA 125 shedding is not a constitutive and stable process but may be affected by cell cycle and cell proliferation as well as by various growth factors and cytokines. Interferons, interleukin-1β, tumor necrosis factor-α and transforming growth factor-α have been shown to induce while glucocorticoids and transforming growth factor-β have been shown to suppress the release of the tumor marker CA 125 from ovarian carcinoma cells. Several endogenous as well as exogenous factors may affect CA 125 biosynthesis; however, a major question remains whether this observed modulation of CA 125 expression in vitro is of clinical importance.

Vitamin A Status and Retinoid-Binding Proteins in Carcinomas of the Head and Neck Region

The serum levels of retinol, RBP (retinol-binding protein) and PALB (prealbumin) were found to be significantly lower in patients with malignant tumors of the head and neck region than in controls. In tumor tissues as well as in normal laryngeal mucosa, specific binding sites for retinol and retinoic acid were found. Whereas retinol-binding (CRBP = cellular retinol-binding protein) could only be detected in a few cases, binding for retinoic acid (CRABP = cellular retinoic acid-binding protein) was present in all specimens investigated. The presence or lack of binding sites was not dependent on the actual serum retinol levels. With regard to the antineoplastic role of vitamin A, the reduced serum levels are considered as a possible factor in tumor development and growth. CRBP and CRABP are assumed to be mediating factors for the retinol and retinoic acid action. Since the presence of CRABP is a constant finding, we propose that retinoic acid and its synthetic derivatives with high affinity for CRABP could be appropriate antineoplastic drugs in these tissues.