Biomedical subjects

T Bauknecht

Publications and source records attributed to T Bauknecht.

At least 73 records · Page 4Linked to original sources

PubMed1990

[Detection of epidermal growth factor-like factors in various skin tumors].

EGF-like factors (EGF-F) in tissue extracts make use of the EGF receptor system (EGF-R) in order to transmit biological signals. EGF-F, which partly show transforming activities, can be detected with the help of an EGF receptor assay. We measured the EGF concentrations in extracts of 25 benign, 5 semi-malignant, and 13 malignant skin tumors, as well as in 5 biopsies of normal skin. The highest amounts of EGF-F were found in malignant melanoma (10 ng/mg) and in squamous cell carcinoma (7 ng/mg). The EGF-F concentrations in benign and semi-malignant tumors, in contrast, were similar to those found in normal skin (up to 4 ng/mg). Isoelectric focusing (IEF) revealed that the activity of EGF-F malignant tumors consists of various components.

Biomarkers, Tumor↗

PubMed1989

Localization of human epidermal growth factor receptor in cervical intraepithelial neoplasias.

Immunohistochemical staining of epidermal growth factor receptor (EGF-R) with a monoclonal antibody was performed in 43 biopsies of cervical tissue. The distribution of the receptors in normal cervical tissue differs from that of cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma of the cervix. Whereas the staining reaction in normal squamous epithelium was confined to the basal and deep parabasal cell layer, in all cervical intraepithelial neoplasias, with or without human papilloma virus association, a homogeneous EGF-R staining reaction could be observed throughout the entire lesion. This means that the dysplasia cells of a CIN I-III, like the tumor cells of a squamous cell carcinoma, have a raised EGF-R content, which in the normal squamous epithelium is usually only found in the basal and deep parabasal cells that are capable of dividing. No EGF-R staining reaction could be detected in the higher, differentiated cell layers of the normal squamous epithelium of the cervix.

Adult↗

PubMed1989

The occurrence of epidermal growth factor receptors and the characterization of EGF-like factors in human ovarian, endometrial, cervical and breast cancer. EGF receptors and factors in gynecological carcinomas.

In this study we investigated the presence of epidermal growth factor receptors (EGF-R) and the tissue levels of EGF-like factors (EGF-F) in ovarian, endometrial, cervical and breast carcinomas. EGF-R were found in 33/40 (83%) cervical, 15/26 (58%) endometrial, 64/141 (45%) ovarian, and 19/59 (33%) breast carcinomas. The highest number of EGF-R binding sites was detected in cervical carcinomas followed by endometrial, breast and ovarian carcinomas. The tissue concentrations of EGF-like factors, were investigated in extracts of 63 ovarian, 25 breast, 12 cervical, 14 endometrial carcinomas and in 21 biopsies of nonmalignant tissue such as myometrium and ovaries. The extracts of nonmalignant tissues had a mean EGF-F level of 1.5 +/- 0.7 ng/mg with a concentration range from 0 to 4 ng/mg. The mean EGF-F levels of malignant tissues were: ovarian carcinomas 4.2 +/- 1.5 ng/mg (range 0-15 ng), endometrial carcinomas 4.5 +/- 1.7 ng/mg (range 0-12 ng), cervical carcinomas 4.15 +/- 1.1 ng/mg (range 0-8) and breast carcinomas 3.16 +/- 1.1 ng/mg (range 0-10 ng). About 30% ovarian, endometrial and cervical carcinomas and 16% breast carcinomas, respectively, had enhanced EGF levels from 5 ng/mg to 15 ng/mg compared to nonmalignant tissues. The EGF-F of tissue extracts consists of EGF and transforming growth factor TGF alpha) as shown by the results of EGF and TGF alpha radioimmunoassays. It is assumed that in some tumors the EGF-F tissue levels influence the number of biochemically detectable EGF binding sites.

Binding Sites↗

PubMed1989

Human ovarian carcinomas: correlation of malignancy and survival with the expression of epidermal growth factor receptors (EGF-R) and EGF-like factors (EGF-F).

We have studied the concentration of epidermal growth factor receptors (EGF-R) in 115 different malignant ovarian tumors (101 ovarian carcinomas) and EGF-like factors (EGF-F) in tissue extracts of 63 different ovarian carcinomas and 20 non-malignant tissues. 36% of ovarian carcinomas are EGF-R positive. The calculated mean EGF-F level of 4.2 +/- 1.5 ng mg-1 (range: 0-15 ng mg-1) in ovarian carcinomas is significantly enhanced compared to 1.5 +/- 0.7 ng mg-1 (range: 0-4 ng mg-1) of non-malignant tissue extracts. The correlation between EGF-R positive as well as negative ovarian carcinomas and the results of a primary chemotherapy of advanced ovarian carcinomas (n = 92) revealed a significantly higher remission rate of EGF-R positive tumors (66%) compared to EGF-R negative cases (23%). 84% of tumors with progressive disease were EGF-R negative. The mean EGF-F levels were calculated for prognostic subgroups of ovarian carcinomas. Increased EGF-F levels are significantly associated with progressive disease compared to all patients or the remission group. 15/16 cases with EGF-F levels greater than 5 ng mg-1 showed progressive disease. The overall survival time of patients with tumor tissue EGF-F levels greater than 3.5 ng mg-1 was worse than that of patients with low EGF-F levels. Multivariate analysis showed that the EGF-F level was, after grading, the second most important factor for predicting overall survival.

Epidermal Growth Factor↗

PubMed1988

Occurrence of epidermal growth factor receptors in human adnexal tumors and their prognostic value in advanced ovarian carcinomas.

Ninety-eight different malignant adnexal tumors were analyzed for the presence of epidermal growth factor (EGF)-specific binding sites and binding parameters were calculated by Scatchard plot analysis [G. Scatchard, Ann. N.Y. Acad. Sci. 51, 660-672 (1949)]. Thirty-four biopsies were EGF receptor (EGF-R) positive with dissociation constants (KD) of 0.5-12 X 10(-9) M and binding capacities (Bmax) of 2-250 fmol/mg. One tumor had a KD of 60 X 10(-9) M and a Bmax of 1660 fmol/mg. The correlation of EGF-R status with clinical parameters showed no significant differences in primary, metastatic, or recurrent tumors, histological subtype, tumor differentiation, and tumor residual after primary surgery. As an inverse correlation, EGF-R-positive tumors are 39% and EGF-R-negative tumors 60% progesterone receptor positive. A response to chemotherapy was noticed in 50% of EGF-R-positive ovarian carcinomas with a mean survival time of patients of 28 months. The response rate of EGF-R negative ovarian carcinomas was 12% with a mean survival time of 16 months. Regarding the treatment schedule the major differences were noticed in the cis-platinum plus cyclophosphamide treatment group. These results suggest that the biology of ovarian carcinomas is influenced by growth factors and their receptors, which can be used as prognostic factors.

Adnexa Uteri↗

PubMed1987

[Torre-Muir syndrome].

The Torre-Muir syndrome is a tumour syndrome characterized by multiple cutaneous and extracutaneous primary carcinomas and different sebaceous neoplasias. The visceral adenocarcinomas are mainly found in the gastrointestinal and urogenital tract. A case of Torre-Muir syndrome is described in a female patient and the different tumour localizations are demonstrated.

Biopsy↗

PubMed1986

Role of prostaglandins on the regulation of macrophage proliferation and cytotoxic functions.

The data presented show different effects of prostaglandins on proliferation and cytotoxic effector functions of murine bone-marrow derived mononuclear cells. Colony stimulating factor (CSF)-dependent proliferation of colony forming unit-cells (CFU c) was inhibited by PGE1, PGE2 and PGB2. Lymphokine induced cytotoxicity and antibody mediated cytotoxicity (ADCC) of monocytes and macrophages were also affected by PG. We conclude that PGE2 may regulate macrophage mediated tumorcell-lysis mainly at the induction phase. If these processes function in vivo, one would therefore expect high affinity binding sites for PGE2 on macrophages. The existence of a receptor for PGE2 one murine bone marrow derived macrophages is described.

Alprostadil↗

PubMed1986

Growth patterns and hormonal sensitivity of primary tumor, abdominal metastasis and ascitic fluid from human epithelial ovarian carcinomas in the tumor colony-forming assay.

The human tumor colony forming assay was used to evaluate the response of ovarian carcinoma cells from primary tumors, ascitic fluids and metastasis to hormonal treatment. In 12/35 patients a sufficient colony formation (greater than 30 colonies/dish) was obtained in order to perform a simultaneous drug testing. The plating efficiency of the metastatic samples (0.12%) was significantly higher (P less than 0.053) than those from the primary tumor (0.076%) or those that were derived from the ascitic fluid (0.082%). Colonies from the metastatic tissues could be evaluated 2-4 days earlier than those from primary tumors. These discrepancies may be due to a heterogeneity in the clonable tumor cell compartment of primary tumor and metastasis. The antiproliferative properties of the antiestrogen tamoxifen and the progestin gestoneron were studied. In 9/12 cases a significant, dose-dependent reduction of colony formation (greater than 70-90% of the controls) was observed after continuous exposure to 1 mumole tamoxifen. No correlation between the dose response and the content of steroid receptors was found. Even estrogen receptor negative tumor samples showed a maximal antiproliferative effect of tamoxifen.

Abdominal Neoplasms↗

PubMed1986

Characterization of growth factors in human ovarian carcinomas.

Epidermal growth factor (EGF)-like factors with EGF competing and cell growth stimulating activity were investigated in malignant and nonmalignant tissues. About 37% of ovarian carcinomas present an increased factor activity between 9.0 and 19.3 ng EGF units/mg protein. In one tumor 175.0 ng EGF units/mg protein were found. In extracts of nonmalignant tissues, the factor concentration was about 1.0-6.4 ng EGF units/mg protein. Isoelectric focusing was performed to characterize these factors. In normal ovaries and ovarian carcinomas, factors with EGF competing activity focus at pH 8.0-9.0, pH 5.7-6.3, and pH 3.6-4.9. In ovarian carcinomas, an additional peak with EGF competing and cell growth stimulating activity was found between pH 6.5 and 7.2. Similar results could be achieved in other malignant tissues investigated. These data indicate the presence of EGF-like factors. EGF itself focuses at pH 4.6 (G. Carpenter and S. Cohen, Annu. Rev. Biochem., 48: 193-216, 1979). Specific EGF binding was determined in 12 ovarian carcinomas. In five of these cases EGF receptors could be detected. In the EGF receptor positive carcinomas, the content of EGF-like growth factors varied between 0 and 9 ng EGF units/mg protein. In EGF receptor negative cases, the content of EGF-like growth factors varied between 0 and 19.3 ng EGF units/mg protein. The clinical data of 19 patients are also demonstrated.

Animals↗

PubMed1985

The influence of gonadotropic hormones on the EGF receptor regulation in the rat ovary.

Ovaries of immature rats are endowed with only a small number of EGF binding sites (59.2 X 10(-15) mol/mg protein). During development from day 20 to 28, the binding capacity increases 2.5 times, while the growth of the ovaries remains small. Treatment with FSH on day 20 advances the EGF binding capacity with a 4-fold increase in the number of binding sites within the first two days. HCG has no or only a slight effect on the EGF binding capacity. The EGF receptor formation after FSH treatment takes place before the ovaries begin to grow rapidly. Accelerated ovarian growth is associated with a decrease of EGF binding capacity reaching values below those of the control animals during the subsequent days. The dissociation constants (KD) of the FSH stimulated receptors and of receptors present during development are found in the order of 2.7 and 8.7 X 10(-9) M. The physiological function of the EGF receptor for ovarian cell proliferation and follicular growth is discussed.

Animals↗

PubMed1985

Formation of prostaglandins by ovarian carcinomas.

Tissue contents of prostaglandins (PG) PGE2, PGE2a and 6-keto-PGF1a (degradation product of PGI2) were determined in specimens of advanced human ovarian cancer (n = 11). The PG levels (ng/mg tissue protein) varied widley: PGE2 17-515; PGF2a 2-43 and 6-keto-PGF1a 5-105. Tumors of patients without response to chemotherapy contained more PGE2, PGF2a and 6-keto-PGF1a than did tumors responding to chemotherapy. PG production was investigated in two ovarian carcinoma-derived cell lines. The ability of these cells to synthesize PG varied depending on the cell density. An increase of cell number was associated with a decrease of PG yield. PG formation was inhibited by indomethacin in a concentration-dependent manner. The present study suggests that ovarian carcinoma cells form PG in vivo and vitro.

6-Ketoprostaglandin F1 alpha↗

PubMed1985

Epidermal growth factor receptors in different skin tumors.

Specific binding of 125I-labeled epidermal growth factor (EGF) was measured in 62 skin tumors of different severity. Within a group of 28 benign tumors, 11 of 15 condylomata acuminata were receptor positive, whereas the investigated mesenchymal tumors and normal skin as a control were receptor negative. 6 of 18 basal cell epitheliomas bound EGF specifically. In the group of precancerous and malignant skin tumors, 7 of 8 squamous cell carcinomas had the highest number of EGF binding sites and a high affinity state, whereas 5 malignant melanomas were receptor negative. The clinical relevance of these findings is not yet clear due to the short follow-up of the patients.

Binding Sites↗

PubMed1984

[Clinical significance of membrane receptors in ovarian carcinoma].

The expression of membrane receptors was investigated at different human ovarian carcinomas. It could be demonstrated, that no specific binding sites of the gonadotropin hCG and the prostaglandins PGE2 and PGF2 alpha were found in the investigated specimens. However, 30% of ovarian carcinomas had receptors for the growth factor EGF. The determination of binding parameters resulted in an affinity constant (KD) between 1-6 X 10(-9)M, the number of binding sites (Bmax) varied between 5-250 fmol/mg). Further parameters such as histology, grade of differentiation, steroid hormone receptor status, stage and tumor rest after surgery were similar in the EGF receptor-positive and -receptor-negative groups. But, the response to chemotherapy was significant higher in the EGF receptor-positive group. The comparison of median survival time resulted in a better prognosis for patients with EGF receptor-positive carcinomas. Further investigations will clarify, if the EGF receptor status can be taken as a prognostic marker in the schedule of treatment in patients with ovarian carcinomas.

Age Factors↗

PubMed1983

Crosslinking of HCG to its specific receptor of porcine ovarian membranes.

HCG receptors of porcine ovarian plasma membranes were loaded with 125I-hCG and covalently crosslinked with glutaraldehyde. The plasma membranes were labeled with tritium. The hCG receptor complex was solubilized in 1% SDS and subsequently chromatographed on Biogel P 300. 40-50% of 125I-radioactivity eluted near the void volume. 3H radioactivity in these fractions indicated the presence of crosslinked hormone receptor complexes. A second minor peak of 125I-radioactivity appeared at 55000 d. A third peak represented subunits of 125I-hCG. Analysis of the Biogel P 300 purified 125I-hCG receptor complex by polyacrylamide gel electrophoresis in sodium dodecyl sulfate resulted in two radioactivity peaks. The main peak corresponded to 90 000-100 000 d, the second peak was calculated to approximately 140 000 d. As a result the majority of the hormone receptor complex has a molecular weight of 90 000-100 000 d. Existence of subunits is discussed.

Animals↗

PubMed1981

Development and regulation of the prostaglandin F2 alpha receptor in the rat ovary.

Ovaries of adult rats specifically bind PGF2 alpha while those of immature animals do not. Induction of luteinization by hCG in juvenile animals, however, results in specific binding of PGF2 alpha. It is suggested that luteal cells are the only cell type of the ovary, which is endowed with specific receptors for PGF2 alpha. The number of PGF2 alpha binding sites varies during the ovarian cycle. Most free receptors are detectable in early pro-oestrus, least in the oestrus stage. The oscillation of receptors disappears after inhibition of prostaglandin synthesis by indomethacin. Therefore the apparent cyclic variation of prostaglandin receptors must be ascribed to occupancy of the receptors by varying amounts of endogenous prostaglandin F2 alpha.

Animals↗

PubMed1981

Distribution of prostaglandin E2 and prostaglandin F2 alpha receptors in human myometrium.

Human myometrium was studied for specific binding of PGE2 and PGF2 alpha. PGF2 alpha-binding was almost undetectable, but specific binding sites for PGE2 with high affinity (KD = 2.7 +/- 0.4 x 10(-9) M were demonstrated. The binding capacity for PGE2 exhibited a topically different distribution pattern with the highest values in the central parts and low to undetectable levels in the cervical region. Binding characteristics were analyzed by receptor kinetics, revealing a homogeneous receptor population. Binding capacity in uteri obtained from post-menopausal women was of the order of 900-940 fmol/mg protein. Oestrogen pre-treatment and pregnancy were associated with a 3-fold reduction of the PGE2-binding capacity.

Cell Membrane↗

PubMed1980

In vitro inactivation of gonadotropin receptors, a membrane-associated action?

Under in vitro conditions the time-dependent inactivation process of LH/HCG receptors is nearly identical in ovarian and testicular homogenates but different in gonadal membrane preparations. In the ovarian membranes the loss of binding sites during the first preincubation time is faster than in testicular membranes, especially in membranes of luteinized rat ovaries. Compared with the homogenates, however, the receptor-inactivation in the membranes is generally delayed. The inhibitory effect of metabolic agents on receptor inactivation indicates that membrane-associated actions are involved in this process.

Animals↗

PubMed1980

Regulation of LH/HCG receptors during the ovarian cycle in rats.

The number of LH/HCG receptors varied during the ovarian cycle. Most 125I-HCG was bound in the diestrous II stage, least amounts of free binding sites were detectable in estrous. Bromocriptine, an inhibitor of prolactin secretion, suppressed the cyclic variations in free LH/HCG receptors. From this finding it is concluded that LH/HCG receptors of the corpus luteum of the cycle are occupied by LH just once and then degraded. The variations in the number of free LH/HCG receptors are probably due to the synthesis and degradation of only luteal receptors.

Animals↗