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Biomedical subjects

G Sliutz

Publications and source records attributed to G Sliutz.

At least 55 records · Page 3Linked to original sources

Immunohistochemical and serological evaluation of CD44 splice variants in human ovarian cancer.

The surface glycoprotein CD44 is widely distributed in different tissues. In contrast to healthy tissue, tumour samples show a more complex pattern of CD44 expression, indicating a loss of splice control. Beside cell-surface expression, the measurement of soluble CD44 in serum of cancer patients could be useful in early diagnosis and assessment of disease status. We evaluated the surface expression of CD44 isoforms in 22 ovarian cancer patients by means of immunohistochemistry. Additionally, we investigated 134 serological samples of these patients for the occurrence of CD44 isoform expression. For CD44 standard, CD44v5 and CF44v6 mean serum levels in patients with clinically detectable or non-detectable ovarian cancer were 422.4 +/- 143.8 ng ml-1 and 547.4 +/- 148.2 ng ml-1, 12.3 +/- 7.9 ng ml-1 and 21.9 +/- 12.2 ng ml-1 and 105.5 +/- 37.9 ng ml-1 and 144.9 +/- 50.9 ng ml-1 respectively (P-values not significant). CD44 surface proteins containing epitopes encoded by splice variants CD44v5, CD44v6 and CD44v7-8 were immunohistochemically detected in 9% (n = 2), 13% (n = 3) and 4% (n = 1) of the 22 tumour samples respectively. In the present study we showed that in ovarian cancer CD44 isoforms CD44v5 and CD44v6 are expressed in very low amounts by the tumours. In accordance with this, we found that the presence of tumour is not associated with higher serum levels of CD44standard, CD44v5 and CD44v6 in preoperative serum samples in ovarian cancer patients.

Adult↗

[The Bethesda system--an improvement in classification of cervix cytology?].

Cervical cytology screening programmes have significantly reduced cervical cancer mortality. In 1988 the National Cancer Institute developed a new classification for reporting cervical cytology--"The Bethesda System". The aim of our study was to compare the clinical usefulness of this new classification with the classification used in German-speaking countries (which discriminates cytologically between moderate and severe dysplasia) including a verbal classification predicting the histological grade of cervical intraepithelial neoplasia (CIN I, II, III). 671 patients with abnormal cervical cytology results and subsequent conisation or hysterectomy were included. We correlated cytological and histological diagnosis (gold standard). In cases of cytologically suggested moderate dysplasia we found histologically CIN I, CIN II and CIN III in 11%, 41% and 42%, respectively. Our results show that discrimination of CIN II and CIN III by means of cytology is limited. Using our therapy schedules we found that adequate therapy is possible by each of the cytological classification systems. The cervical smear is used as a screening test to determine which women require further examination using colposcopy. Under these circumstances an adequate therapy is possible with both classifications. The results underline the importance of colposcopy in the management of cervical dysplasia. As long as conisation is commonly used in German-speaking countries as the only diagnostic tool after an abnormal cervical smear the Bethesda System increases the risk of overtreatment.

Adult↗

Proto-oncogenes and oncogenes in epidermal neoplasia.

This review briefly will focus on the role of selected proto-oncogenes and their activated forms during the regulation of cell proliferation, cell death and tumor formation in the epidermis. In addition, the multiple and complex functions of these proteins in normal as well as transformed cells will be discussed.

Animals↗

Microsurgical treatment of tubal sterility using the CO2 laser: a reasonable alternative to IVF in cases of tubal sterility.

A retrospective analysis of women treated microsurgically using the CO2 laser in sterility treatment was performed. The aim of the study was to determine women's personal feeling about the procedure, prognostic factors, success rates, and complications. Included were 192 patients with tubal occlusions or pelvic adhesions treated by means of CO2 laser microsurgery between February 1984 and July 1992. A standardized questionnaire was used to evaluate women's procedure-related stress, extrauterine and intrauterine pregnancy rates, pregnancy complications, and postoperative complaints. In 75 cases, records and questionnaires contained sufficient data and were included for further analysis. Adhesiolysis alone, unilateral neosalpingostomy, bilateral neosalpingostomy, or new implantation was done in 7%, 52%, 33%, and 8%, respectively. In the range of 1-10, a medium degree procedure-related stress (mean 4.3, range 1-10) was expressed by the treated women. No surgery-related complications were observed. The overall pregnancy rate was 37.3%, and 10.7% were tubal pregnancies. In 26.7%, fertility surgery resulted in intrauterine pregnancies, and 21.3% of the treated women delivered living children. Three women had two consecutive pregnancies after surgery. Women with intrauterine pregnancy, extrauterine pregnancy, and no pregnancy had a mean age of 29.5 +/- 3.8, 27.3 +/- 5.3, and 32.3 +/- 4.2 years, respectively (p = NS). Mean duration of infertility before start of surgical treatment was 42.4 +/- 34.6, 41.6 +/- 25.8, and 48.8 +/- 33.2 months, respectively (p = NS). Intraabdominal instillation of streptokinase to prevent reformation of adhesions had no significant impact on tubal patency results or pregnancy rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Fallopian Tube Diseases↗

Does cord blood contain enough progenitor cells for transplantation?

We analyzed 125 blood samples obtained from umbilical cord immediately after delivery of full-term neonates. Between 0.1 and 10.4% (mean 1.13%, SD 1.34) of the density-separated glycophorin A (GPA)-negative mononuclear cells (MNC) expressed CD34 as analyzed by flow cytometry. These hematopoietic progenitor cells did not coexpress CD19, and the majority were negative for CD45RA. The number of MNC determined per ml cord blood ranged from 1 x 10(5) to 200 x 10(5) (mean 20.2 x 10(5), SD 24.7). Regression analysis revealed that a mean of 56% (n = 26, R = 0.8) and 120% (n = 35, R = 0.94) of the analyzed CD34+ MNC gave rise to day 14 colonies in the clonogenic assay when cultured without or with stem cell factor (SCF). The number and the exact phenotype of progenitor cells required for successful transplantation are not known. If the transplantation of 5 x 10(5) CD34% cells/kg body weight is required for engraftment and one-third of the progenitor cells are lost to cell processing, and if 180 ml blood can be collected from a single umbilical cord (and placenta), our data suggest that 90% of the collections do not contain enough precursors to transplant a 25 kg recipient. To meet these conditions, an average of 1439 ml cord blood would be necessary for transplantation.

Colony-Forming Units Assay↗

EGF-R and steroid receptors in breast cancer: a comparison with tumor grading, tumor size, lymph node involvement, and age.

In this study epidermal growth factor receptor (EGF-R), estrogen receptor (ER), and progesterone receptor (PR) status was evaluated in 326 primary breast carcinomas. Nineteen percent of samples were EGF-R positive, 63% were positive for ER, and 54% for PR. In 46% of the tumors both ER and PR were positive. These data are presented together, with grading, size of tumor, lymph node involvement, histological subtype, and age. Sixty-nine percent of EGF-R negative tumors were ER-positive and 51% were positive for ER as well as PR. In particular, negative correlation between EGF-R and steroid receptor status was found. A quantitative correlation was also shown. A combination of negative steroid receptor and positive EGF-R was found more often in the population of poorly differentiated tumors. Tumors bigger than 5 cm were related to a positive EGF-R status. No correlation between nodal status and any receptor status was found. Intraductal carcinomas were more often EGF-R positive than infiltrating ductal (NOS) or infiltrating lobular lesions. The age of patients correlated with the concentration of ER only. In our study we reaffirmed the negative correlation between steroid receptor status and the overexpression of EGF-R; furthermore the combination of EGF-R+ and ER- tumors was observed more often in histological high-risk tumors. Patient outcome did not show statistically significant differences concerning the EGF-R status, but was associated with the steroid receptor status.

Adult↗

Agnus castus extracts inhibit prolactin secretion of rat pituitary cells.

In our studies on prolactin inhibition by plant extracts we focused on the effects of extracts of Vitex agnus castus and its preparations on rat pituitary cells under basal and stimulated conditions in primary cell culture. Both extracts from Vitex agnus castus as well as synthetic dopamine agonists (Lisuride) significantly inhibit basal as well as TRH-stimulated prolactin secretion of rat pituitary cells in vitro and as a consequence inhibition of prolactin secretion could be blocked by adding a dopamine receptor blocker. Therefore because of its dopaminergic effect Agnus castus could be considered as an efficient alternative phytotherapeutic drug in the treatment of slight hyperprolactinaemia.

Animals↗

Expression of cathepsin D in head and neck cancer.

To determine overexpression of cathepsin D in head and neck tumours we examined cytosols from 53 primary tumours, nine cytosols of lymph node metastases and 12 cytosols from adjacent normal tissue. We found a significantly lower concentration in normal tissue compared with tumour cytosol as well as with metastases, even when we compared tumours and corresponding metastases pairwise. In addition, we found a significantly higher concentration of cathepsin D in five lymph node metastases than in the corresponding tumours. We conclude that the reported role of cathepsin D is not restricted to breast cancer but could also be important in head and neck cancer.

Biomarkers, Tumor↗

[Epidermal growth factor receptor in human breast cancer: correlation with steroid receptors, tumor stage, grading and menopausal status].

In this study, correlations between the epidermal growth factor receptor (EGF-R), steroid receptors, and other prognostic parameters (grading, pTNM-status, menopausal status) were analysed in 326 primary breast carcinomas. 19% of the tumour samples were EGF-R positive, 63% were estrogen receptor (ER) and 54% progesteron receptor (PR) positive. Both steroid receptors were positive in 46% of all samples. We found a highly significant inverse correlation between EGF-R and steroid receptors. 88% of the ER positive tumours were EGF-R negative (p less than 5 x 10(-5)), 90% of the PR positive tumours were EGF-R negative (p less than 5 x 10(-5)) and 91% of the ER plus PR positive tumours were ERF-R negative (p less than 1 x 10(-6)). Grading was available in 170 cases. Six (4%) of the carcinomas were highly differentiated (G1), 82 (48%) were classified as G2, and another 82 (48%) were poorly differentiated (G3). A combination of negative ER and positive EGF-R was found more often in the population of G3 tumours. EGF-R was also positively correlated to tumour size. With regard to receptor status, we did not find a correlation with lymph node involvement. The ER correlated negatively (p less than 1.3 x 10(-5) and the EGF-R positively (p less than 0.042) with menopausal status. Thus, EGF-R overexpression seems to be a marker of morphological and functional dedifferentiation which is associated with a loss of steroid dependency and an increase of an autostimulatory-paracrine growth control. These changes seem to be related to poor prognosis.

Breast↗

HER-2 oncogene amplification and overall survival of breast carcinoma patients.

DNA was extracted from tumour samples of 77 patients with primary breast carcinoma and HER-2 proto-oncogene amplification was assessed. Prognostic indices such as number of positive lymph nodes, tumour size and histological grading were strongly associated with overall survival. No statistically significant correlation between amplification of HER-2 and overall survival was observed. In addition, prognostic indices, HER-2 amplification and disease-free interval was not correlated. Analysis of HER-2 amplification alone is not a useful guide in the management of patients with mammary carcinoma.

Breast Neoplasms↗

Determination of HER-2/neu amplification and expression in tumor tissue and cultured cells using a simple, phenol free method for nucleic acid isolation.

A rapid, simple and non-toxic procedure for the simultaneous isolation of DNA and RNA from tumor tissue and cells grown in vitro is described. Guanidinium isothiocyanate was used for homogenization of tumor tissue and for cell lysis. Separation of proteins, DNA and RNA was carried out by isopycnic centrifugation in cesium trifluoroacetate. DNA was further purified by salting out residual protein. Nucleic acids prepared by this method from 47 primary human carcinomas and 17 human cell lines were analysed for amplification and expression of the HER-2/neu proto-oncogene. 2- to 10-fold amplification of HER-2/neu was noted in 7/22 mammary carcinomas (32%) and in 4/14 ovarian carcinomas (28%). No amplification of the proto-oncogene was found in 4 laryngeal carcinomas, 1 pharyngeal carcinoma, 2 retrolingual carcinomas, 3 gastric carcinomas and 1 kidney carcinoma. HER-2/neu overexpression was observed in 6/22 of mammary carcinomas (27%) and 7/14 of ovarian carcinomas (50%). No overexpression was found in all other carcinomas studied. Concordance between amplification and overexpression was noted in 3 mammary and 4 ovarian carcinomas, respectively. 3 mammary and 3 ovarian carcinomas showed overexpression without amplification. 5 human mammary carcinoma cell lines showed both amplification and overexpression of HER-2/neu. In two mammary carcinoma cell lines (MDA MB-453 and ZR 75-1) overexpression was noted without amplification of the proto-oncogene. These data combine to suggest that mechanisms other than gene amplification may also lead to overexpression of the HER-2/neu protooncogene in cancer cells.

Blotting, Southern↗

HER-2 amplification, steroid receptors and epidermal growth factor receptor in primary breast cancer.

Amplification of HER-2 oncogene was analysed in DNAs obtained from 291 primary human mammary carcinomas. 52/291 (18%) were found to contain amplified HER-2 oncogene. Moderate amplification (2- to 5-fold) was noted in 36/291 (12%). Thirteen tumors (4.5%) had a copy number of 5 to 10. A 10- to 20-fold and greater than 20-fold amplification was observed in 2 and 1 patient, respectively. Sample sizes allowed the determination of estrogen receptor (ER) and progesterone receptor (PgR) levels in 253/291 primary breast cancers. HER-2 gene amplification was noted in 14% of ER+ patients and in 28% of ER- patients, respectively (P = 0.02). Similarly a significantly greater number of PgR- primary mammary carcinoma exhibited an amplification of the HER-2 gene compared to PgR+ cases (22% vs. 16%, P = 0.01). Although statistically not significant, tumors with HER-2 gene amplification were found to have lower levels of ER and PgR. No association of HER-2 amplification with the androgen receptor and EGF receptor was observed. Present data combine to suggest that tumor progression is more stringently controlled by the oncogene upon loss of hormone dependency. Differences found in HER-2 amplification between steroid receptor positive and negative tumors could be helpful to define a specific subset of women to whom adjuvant therapy should be directed.

Breast Neoplasms↗

Serum concentrations of tissue polypeptide antigen in patients with vulvar intraepithelial neoplasia and vulvar cancer.

The aim of the present study was to evaluate the clinical usefulness of the cytokeratin tumor marker tissue polypeptide antigen (TPA) in patients with vulvar cancer. This retrospective study comprises 41 patients with vulvar cancer FIGO stages I-III, 17 patients with vulvar intraepithelial neoplasia (VIN) III, and 40 healthy female controls. Serum concentrations of TPA were measured using a microparticle enzyme immunoassay. Results were correlated to clinical data. Median serum concentrations of TPA in healthy female controls, patients with VIN III, and patients with vulvar cancer were 42 U/l (range 12-192), 53 U/l (range 17-127.9) and 57 U/l (range 4.2-423), respectively (Mann-Whitney U test, p = 0.8). Serum concentrations of TPA were not associated with stage of disease, histological grade, and age at the time of diagnosis. In vulvar cancer patients, elevated serum concentrations of TPA prior to therapy were not associated with a shortened disease-free or overall survival (log-rank test: p = 0.5 and p = 0.9, respectively). In a multivariate Cox regression model comprising tumor stage and TPA, tumor stage, but not TPA revealed a statistically significant influence on disease-free (Cox proportional hazard regression model, p = 0.05 and p = 0.6, respectively) and overall (Cox proportional hazard regression model, p = 0.04 and p = 0.8, respectively) survival of patients with vulvar cancer. We conclude that cytokeratin expression, as reflected by serum concentrations of TPA, does not play a role in the natural history of vulvar cancer. The evaluation of serum concentrations of TPA prior to therapy is not recommended.

Age Factors↗

Humoral p53 antibody response is a prognostic parameter in ovarian cancer.

BACKGROUND: Mutant p53 protein may become the target of a tumor-specific humoral and cellular immune response. MATERIAL AND METHODS: We used a specific qualitative p53 antibody ELISA to investigate serum samples of 33 patients with ovarian cancer taken prior to therapy. Additionally, we sought to evaluate whether p53 antibodies are also present in the sera of 17 patients with benign ovarian tumors. RESULTS: p53 antibodies were detected in 36% of serum samples. There was a statistically significant association between p53 serum antibody response and poor overall survival (p < 0.006). No significant associations were found between p53 antibody status and histological type, histological grade, and tumor stage. In 81% of serum samples, no changes from p53 antibody negativity to positivity or vice versa during follow-up were observed. p53 antibodies were also detected in the sera of 18% of patients with benign ovarian tumors. CONCLUSIONS: The results of this preliminary study suggest that a p53 antibody response in patients with ovarian cancer is associated with poor prognosis. A qualitative method of p53 antibody detection cannot be used to monitor the clinical course of ovarian cancer.

Antibodies, Neoplasm↗

Prognostic value of tumour microvessel density in cancer of the uterine cervix stage IB to IIB.

High intensity of tumour angiogenesis has been correlated with an increased potential of metastasis and poor prognosis in human malignancies. We investigated 43 patients with cervical cancer stages IB (n = 13), IIA (n = 8) and IIB (n = 22). All patients were treated by radical hysterectomy and lymphadenectomy. In the tumour specimen blood vessels were highlighted by staining endothelial cells for factor VIII. Microvessels were counted on a 200x field (0.74 mm2) in the most active areas of neovascularisation. The mean microvessel counts per field for stage IB, IIA and IIB tumours were 59.6 +/- 28.1, 56.3 +/- 24.3 and 55.7 +/- 55.6, respectively (p-value = n.s.). We found no significant correlation of microvessel density and established prognostic factors like pelvic lymph node involvement, vascular space invasion and stromal reaction. Patients with tumours showing low microvessel density (< 40 microvessels per field) had a significantly poorer recurrence-free interval (log-rank test: p-value = 0.01).

Female↗

Tissue polypeptide specific antigen and cancer associated serum antigen in the follow-up of ovarian cancer.

420 clinical and serological examinations prior to surgery and during follow-up were performed in 30 patients suffering from ovarian cancer. The population consisted of three FIGO stage Ia, nine stage Ic, four stage II and fourteen stage III cases. Serous carcinoma of the ovary, mucinous carcinoma and other kinds of ovarian cancer were found in 16, 9 and 5 cases, respectively. The serum levels of the tumor markers tissue polypeptide specific antigen (TPS), cancer associated serum antigen (CASA) and carbohydrate antigen 125 (CA 125) were determined. Cut-off values of 97 U/l, 4 U/ml and 35mU/ml for TPS, CASA and CA 125, respectively, were selected according to the 95% of serum concentrations measured in healthy controls. Sensitivity, specificity, PPV and NPV of CA 125 were 75%/96%/69%/92%, respectively. Sensitivity, specificity, PPV and NPV of TPS were 67%/84%/59%/90%, respectively. CASA showed a sensitivity of 58%, specificity of 96% and a PPV and NPV of 73%/94%, respectively. The combination of TPS and CA125 increased the sensitivity to 81%, reaching a specificity of 82% and a PPV and NPV of 58/96%, respectively. The combination of CASA and CA125 showed a sensitivity, specificity, PPV and NPV of 88/85/65/96%, respectively. Twelve patients developed recurrence of disease after response to primary treatment. TPS, CASA and CA 125 detected recurrent disease in six, two and four cases, respectively. For TPS mean lead time was 4.6 months (range 2-18 months), for CASA 1.7 months (range 1-6 months), and for CA 125 3.5 months (range 1-24 months. As a matter of fact TPS never showed lead time effects in patients without elevated pretherapeutic levels. A combination of all makers showed a mean lead time of 6.72 months. Detection of recurrent disease by CA 125 is improved when CA 125 is used in combination with TPS, especially in those patients with pretherapeutically elevated TPS serum levels.

Biomarkers, Tumor↗