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Biomedical subjects

H G Bender

Publications and source records attributed to H G Bender.

At least 73 records · Page 4Linked to original sources

Immuno-biochemical assay for determination of nuclear steroid receptors during tamoxifen therapy.

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 micrograms 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 level was observed.

Animals↗

[The erbB gene family: significance for tumor development, prognosis and new therapeutic modalities].

RNA and DNA viruses can be transforming and tumourigenic agents. The transformation is a consequence of the ability of viruses to integrate into the host cell's DNA and to produce transforming proteins. These proteins are mainly produced by specific integral parts of the viral genome, the oncogenes. Comparison between RNA/DNA sequence of viral oncogenes and normal human genome of non-transformed cells revealed high sequence similarities in specific genomic areas, which were named cellular proto-oncogens. They are important components of the growth regulatory pathways in normal cells. The accumulation of genetic alterations of some proto-oncogens, like the erbB-family, may be part of the mechanism, by which malignant cells can acquire a selective growth advantage. The epidermal growth factor receptor (EGF-R, c-erbB1), Her-2/neu (c-erbB2), and c-erbB3 are members of the erbB-family. The detection of increased abundance of EGF-R or Her-2/neu proteins in human tumours can provide additional information on the disease-free survival and overall survival for patients with breast, ovarian, endometrial or cervical cancer. Molecular and cell-physiological analyses have improved the understanding of tumour biology and provide the opportunity for new therapeutic approaches. Monoclonal antibody targeted therapy directed against EGF-R or Her-2/neu, the use of anti-sense oligonucleotides and oligodeoxynucleotides, and the application of tyrosine kinase and protein C-kinase inhibitors are currently being investigated.

Cell Division↗

Functional analysis of tumor-associated lymphocytes from gynecological tumors.

Tumor-Associated Lymphocytes (TAL) were isolated from peritoneal fluids of six ovarian cancer patients and pleural effusion from eight breast cancer patients, respectively. In one case we obtained ascitic fluid as well as pleural effusion because of intraabdominal metastatic breast carcinoma. The collected cells were cultured in a complete medium and supplemented with human interleukin-2 (nIL-2) in a concentration of 1000 Units/ml. Phenotyping was not always possible due to rapid decay of the cells. Cytotoxicity was determined with a fluorescence-based assay, in some cases at different stages of cell growth. In two cases TAL from ascitic fluids showed increased cytotoxic activity after a longer cultivation period. TAL from pleural effusions showed cytotoxic activity against the target cell lines in two cases only. Some of these TAL did not proliferate any more but died within 24 h. With the functional analysis we wanted to investigate the cytotoxic potential against natural killer (NK)-sensitive and NK-resistant (Raji) cell lines. The results demonstrate the ability of some of the TAL populations to destroy tumor cells.

Adult↗

Influence of chemotherapy on hormone receptor concentration in a xenotransplanted endometrial cancer.

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 receptor positive 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 inducible by chemotherapy and no increase in ER/PR pos. cells immunohistochemically.

Adenocarcinoma↗

Immunobiochemical assay for determination of nuclear steroid receptors.

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.

Adenocarcinoma↗

[Heroin abuse and methadone substitution in pregnancy].

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.

Asphyxia Neonatorum↗

Trophoblast tissue culture of human intrauterine and ectopic pregnancies and treatment with methotrexate.

The application of drugs for conservative treatment of patients with ectopic pregnancy has been used worldwide for several years. In-vitro studies, however, are very few. We therefore examined the effects of methotrexate on trophoblast tissue cultures derived from intrauterine and ectopic pregnancies. Methotrexate was administered either 12 h or 6 days after initiation of the culture. Human chorionic gonadotrophin (HCG) levels were measured in the culture medium. All cultures showed secretion of HCG within the first 16 days. Methotrexate concentrations less than 3.8 x 10(-4) mol/l had no effect on HCG secretion. Cultures of ectopic pregnancies required a concentration about 10x higher to induce an equivalent reduction of HCG levels compared to intrauterine pregnancies. A few intrauterine and ectopic pregnancies showed no reduction of HCG values after treatment. These results suggest that data obtained from studies on intrauterine pregnancies may not be transferable to ectopic pregnancies in all instances. In some regimens approximately 8 days are required before the effect becomes measurable. In combination with our clinical data, we therefore recommend not to repeat a methotrexate dose too early in treatment of patients with ectopic pregnancies. The possibility that non-responding patients could exist should be kept in mind.

Chorionic Gonadotropin↗