Peripheral blood lymphocytes (PBL) from patients with ovarian or breast cancer or benign lesions of the breast, respectively, have been analysed for expression of phenotypic and activation markers by flow cytometry. The results were compared with those of a control group of healthy women. The relative proportion as well as the absolute counts of B lymphocytes were similar in both groups and in the control group. The absolute number of T cells was decreased in breast cancer patients (p < 0.05). The CD4+/CD8+ ratio was significantly depressed in ovarian cancer patients (p < 0.05), but not in breast cancer patients. In the ovarian cancer group, the percentage of CD3+ T cells expressing HLA-DR (p < 0.05) as well as CD3+ T cells expressing CD16 and CD56 (p < 0.05) was significantly higher. The relative proportion as well as the absolute counts of CD3+ T cells expressing the IL-2 receptor (CD25) were significantly higher (p < 0.001), respectively, in breast cancer patients (p < 0.05). These results suggest that gynaecological cancer is associated with specific alterations in the T cell population.

MSA (Mammary Serum Antigen) concentration was measured in serum samples from patients with diagnosed mammary carcinom (n = 50) in different stages. The normal serum levels of the new tumor marker were determined in 100 healthy women in the age of 18-65 years and 20 healthy men (20-60 years old). In the group of healthy women the mean concentration for MSA was 28 U/ml whereas healthy men had a mean MSA concentration of 7.5 U/ml. For breast cancer patients the sensitivity of MSA was 73% at a specifity of 95%. The MSA concentration were between 17.5 U/ml and 485 U/ml. The stability of the MSA antigen in serum samples stored at 2 degrees C -8 degrees C can be guaranted for 48 hours. For longer periods storage of serum samples at -20 degrees C is recommended.

The treatment of female stress- and urge incontinence has changed during the last years. The most important trend is the increasing importance of conservative treatment modalities (estrogen replacement, pelvic training) in case of stress incontinence grade 1. In case of stress incontinence grade II and grade Ill there is a trend towards abdominal suspension procedures (f. i. Burch operation). The vaginal operative procedures are the method of choice in case of descensus uteri or cysto-rektocele without major urine incontince. Even of the abdominal suspension procedures are limited with a succes in about 80%, when patients were controlled 3 years later.

Proteases are involved in the invasion and metastasis of tumours by destruction of the basal membrane and connective tissue. As levels in malignant tissue have both prognostic and therapeutic implications, we examined 318 frozen samples from malignant tumours and comparable non-malignant tissue looking for urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) levels with ELISA, as well as cathepsin D with RIA. Oestrogen receptor (ER) levels, progesterone receptor (PrgR) levels and epidermal growth factor receptors (EGFR) were measured by biochemical methods at the same time. Significantly raised levels of uPA, PAI-1 and cathepsin D were found in malignant tissue, with PAI-1 particularly high in carcinoma of the cervix. Significantly raised tPA levels were found in breast cancer tissue with a more favourable clinical prognosis, with a positive correlation between tPA and ER. No correlation could be shown between uPA, PAI-1 and cathepsin D with other prognostic factors for breast cancer. It could be that routine, uncomplicated estimation of tumour-associated proteases such as uPA, tPA, PAI-1 and cathepsin D will provide an independent prognostic marker for therapeutic decisions with regard to gynaecological tumours and breast cancer.

In the athymic nude mice model with xenotransplanted human carcinomas, the effect of a monoclonal antibody (MAb 425), directed against the human epidermal growth factor (EGFR), on tumour growth was studied. Five different solid human breast carcinomas and one vulvar epidermoid cancer cell line (A431) were transplanted in nude mice, and treated with MAb 425 2.2 mg intraperitoneally (i.p.) on day 7 post-transplantation. Tumours with EGFR concentrations of ⩾ 16 fmol/mg soluble cytosolic protein showed growth inhibition, whereas the growth pattern of EGFR-negative tumours was unaffected. Variation of MAb 425 dosage (1.1 versus 2.2 mg) revealed no difference in the growth inhibiting effect. Different application schedules (application on day 0, 12 or 26) showed different onsets and durations of tumour growth inhibition. Repeated application (1.1 mg, day 0 and 12) was followed by a prolonged inhibitory effect. Our results suggest that growth inhibition of EGFR-positive tumours by MAb 425 may lead to an additional treatment option for patients with EGFR-positive cancer.

The exact knowledge of hormone receptor status is critical for therapeutic strategies in hormone-dependent tumors. The influence of tamoxifen on estrogen receptor concentration has to be taken into account when evaluating results in tamoxifen-treated patients. We studied the receptor modulation of tumors xenotransplanted into nude mice (one breast and one endometrial carcinoma) after injection of 50 μg tamoxifen/mouse. To differentiate between unoccupied and occupied receptors, determinations were done by an enzyme immunoassay for the estrogen receptor under low-and high-salt extraction. With low-salt extraction we found a temporary decrease of the estrogen receptor concentration within the first hours after tamoxifen treatment. This decrease lasted for several days before recovery to pretreatment levels occurred. The hormone-receptor complexes, tightly bound to acceptor sites of the DNA, increased more than 15 times within 24 h. These values remained at increased levels for 2–7 days, after which a decrease to initial levels was observed.

Antigestagene sind neue Substanzen, deren Einfluß in hormonabhängigen malignen Tumoren mit wachsendem Interessse erforscht wird. Die proliferationshemmende Wirkung der Antigestagene wurde bei drei Experimentaltumoren der Mamma auf Mäusen bzw. Ratten beschrieben (4). Onapristone wies eine dosisabhängige Wachstumsreduktion auf, die das Vorhandensein ausreichender Progesteronrezeptoren (PR) im Tumorgewebe voraussetzt (2).

The pre- and postnatal data of 20 pregnant heroin addicts and their neonates are described. 16 women were treated with methadone to prevent withdrawal symptoms. A relatively stabile prenatal condition with a decrease of complications was achieved. On the other hand, the neonates suffered from severe withdrawal symptoms including seizures in spite of intensive paediatric care and prophylactic treatment with barbiturates. After a mean follow-up of one to two years a relatively good neurological development of the children was observed.

The pre- and postnatal data of 20 pregnant heroin addicts and their neonates are described. 16 womens were treated with methadone to prevent withdrawal symptoms. A relatively stabile prenatal condition with a decrease of complications was achieved. On the other hand, the neonates suffered from severe withdrawal symptoms including seizures in spite of intensive paediatric care and prophylactic treatment with barbiturates. After a mean follow-up of one to two years a relatively good neurological development of the children was observed.

There is growing evidence that chemotherapy may influence the hormone receptor capacity in human carcinomas. The consideration of this assumption may be of importance for the therapeutic management of tumors with metastatic spread which underwent previous adjuvant chemotherapy. Therefore we investigated the influence of six different kinds of chemotherapy on the hormone receptor concentration and the percentage of receptorpositive cells in xenotransplanted endometrial cancer. Our results can be summarized as follows: (1) We find neither a significant decrease in hormone receptor capacity after chemotherapeutic treatment (biochemical determination), nor do we see a decrease in the percentage of ER/PR pos. cells (immunohistochemistry). (2) On the other hand, there is no increase in hormone receptor concentration induceable by chemotherapy and no increase in ER/PR pos. cells immunohistochemically.

Knowledge of receptor status is important for therapeutic strategies in hormone-dependent tumors. Therefore, methods specifically predicting biological response to endocrine therapy are essential. We investigated the receptor modulation of two breast tumors and one endometrial tumor in the nude mice model after injection of 20 micrograms 17 beta-estradiol. To differentiate the unoccupied and the occupied receptor sites, we used the enzyme immunoassay (EIA) for estrogen receptors (ER) under low- and high-salt conditions. With low-salt extraction we found a sharp decrease of the ER-EIA values within the first hour after estradiol treatment. This decrease continued for 24 hr until recovery to pretreatment levels occurred. In contrast, the ligand-receptor complexes tightly bound to acceptor sites on the DNA increased more than three times within 1 hr. These high levels could be measured for almost 12 hr, and then pretreatment levels were reestablished. The PgR-EIA values under low-salt conditions increased 10-fold within 12 hr, indicating an intact receptor mechanism. We conclude that this immunobiochemical method is a useful tool in determining receptor sites: those both unbound and those tightly bound to nuclear acceptors.

Der Epidermal Growth Factor-Receptor (EGF-R) ist in unterschiedlichen Prozentsätzen bei malignen Tumoren u.a. des Oesophagus, des Magens, der Harnblase, der Zervix uteri und der Mamma überexprimiert. Im Mammakarzinom-gewebe weisen biochemische Analysen in 10–54% bei unterschiedlichen „Cutoff“-Punkten einen positiven EGF-R-Gehalt aus, histochemische Untersuchungen zeigen in 20–60% einen positiven Nachweis. Der Gehalt an EGF-R korreliert negativ mit dem ER- und PR-Status und positiv mit einem hohen histologischen und nukleären Malignitätsgrad. Der EGF-R-Status wird auch als unabhängiger Prognoseparameter beschrieben (Sainsbury et al. 1987).