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Biomedical subjects

G Sliutz

Publications and source records attributed to G Sliutz.

At least 37 records · Page 2Linked to original sources
PubMed1997

Serum M3/M21 in ovarian cancer patients.

Cytokeratins are polypeptides that constitute a subclass of intermediate filaments in epithelial cells. The aim of the present study was to evaluate the clinical usefulness of the serum evaluation of M3/M21 in patients with ovarian cancer. This retrospective study comprises 75 patients suffering from ovarian cancer FIGO stages Ia-III. M3/M21 reached a sensitivity of 78%, a specificity of 85%, a PPV of 89% and a NPV of 83% using a cut-off level of 45 U 1(-1). Forty-four women developed recurrent disease after complete remission during the observation period. M3/M21 showed lead time effects in 19 patients, ranging from 2 to 8 months (median 3.2 months). Elevated M3/M21 serum levels before therapy were associated with a poor overall survival (log-rank test, P = 0.02). Considering these preliminary results, the value of M3/M21 as a serum tumour marker, i.e. to evaluate the tumour burden, seems promising.

Adult↗
PubMed1996

HSP70 overexpression mediates the escape of a doxorubicin-induced G2 cell cycle arrest.

The stress inducible heat shock protein 70 (hsp70) confers resistance to a variety of adverse environmental conditions including certain anticancer drugs. In the present study we explored cellular consequences of hsp70 overexpression with respect to genotoxic stress. Employing an isogenic set of stable transfectant cells, one overexpressing hsp70 and the other serving as control, we found that a high hsp70 expression level is sufficient to provide protection against the cytotoxicity of doxorubicin. In addition, hsp70-protected cells showed the capability to restart cell proliferation at concentrations where control cells arrested. However, the DNA lesion density was comparable in the lines used. Recording the cell cycle control revealed a dramatic shortening of the doxorubicin-mediated cell cycle arrest in the G2 phase upon hsp70 overexpression. Our data suggest an involvement of hsp70 in the regulation of the cell cycle.

Animals↗
PubMed1996

Influence of microvessel density and vascular permeability factor/vascular endothelial growth factor expression on prognosis in vulvar cancer.

Microvessel density (MVD) and expression of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), acting as a highly specific inducer of angiogenesis, were evaluated in tissue specimens of 25 patients with squamous cell cancer of the vulva. MVD was quantified by immunostaining for factor VIII-related antigen at one field of 0.25 mm2. VPF/VEGF expression was evaluated immunohistochemically using a monoclonal anti-VEGF antibody. FIGO stages I, II, and III were diagnosed in 12, 7, and 6 patients, respectively. MVD >20/field was found in 10 of 25 tumors and moderate or strong expression of VPF/VEGF in 10 of 25 tumors. High MVD was significantly more frequent in tumors with moderate or strong VPF/VEGF expression compared to tumors with no or weak VPF/VEGF expression (P = 0.01). Overall survival rates of patients with tumors of high MVD (P = 0.01) and strong VPF/VEGF expression (P < 0.01) were significantly poorer compared to those patients with low MVD or poor VPF/VEGF expression. Strong VPF/VEGF expression and high MVD are considered important parameters of tumor angiogenesis and therefore are related to poor survival probability in vulvar cancer patients.

Adult↗
PubMed1996

Simultaneous expression of nitric oxide synthase and estrogen receptor in human breast cancer cell lines.

For various human tumor cell lines (neuroblastoma, cervix carcinoma) the presence of constitutive nitric oxide synthase (cNOS) has been documented. Here, for the first time, we report about cNOS expression in 10 of 16 human breast cancer cell lines. cNOS expression correlates strongly with expression of estrogen receptor (ER). Competitive reverse transcription-polymerase chain reaction (cRT-PCR) was used to detect cNOS and ER mRNA expression. Our findings suggest that estradiol could stimulate constitutive NO release in breast tissue, where it acts as a free radical.

Breast Neoplasms↗
PubMed1996

Quantification of uPA receptor expression in human breast cancer cell lines by cRT-PCR.

The conversion of plasminogen to active plasmin is thought to be a crucial step in the process of extracellular matrix degradation associated with metastatic spread. Activation of plasminogen is initiated by urokinase plasminogen activator (uPA). The binding of uPA to the uPA cell surface receptor (uPA-R) accelerates plasmin generation from plasminogen and localizes uPA activity to the cell surface. We investigated the mRNA-expression of uPA-R in 19 different human breast cancer cell lines. In a competitive reverse transcription polymerase chain reaction (cRT-PCR) we simultaneously co-amplified two different RNA templates bearing the same primer recognition sequences, the cell line RNA and a known amount of an in vitro synthesized uPA-R-RNA internal standard. We analyzed the two PCR products differing 50 bp in size by agarose gel electrophoresis and calculated the initial uPA-R-RNA template concentration from the relative intensities of the bands quantified by video densitometry. We grouped the investigated cell lines according to their in vitro invasiveness according to literature. Cell lines with a high potential of invasiveness showed a higher expression of uPA-R compared to those with a low potential of invasiveness (Student's t-test, p 0.04). In addition to that we compared the uPA-R mRNA levels with uPA-R, uPA, and PAI-1 protein levels in culture supernatants and cell lysates. The obtained results in breast cancer cell lines with different invasiveness and in benign epithelial cell lines revealed the complex cooperation of the urokinase type proteolytic pathway. uPA, uPA-R, and PAI-1 are to be considered as a diagnostic tool rather than assaying a particular molecule alone. Our findings support the hypothesis that the urokinase proteolytic pathway plays a central role in the acquisition of an invasive phenotype and favors its potential use as a prognostic marker in patients with breast cancer.

Binding, Competitive↗
PubMed1996

Drug resistance against gemcitabine and topotecan mediated by constitutive hsp70 overexpression in vitro: implication of quercetin as sensitiser in chemotherapy.

Heat shock proteins have been reported to confer resistance to certain antineoplastic drugs. We investigated the impact of hsp70 overexpression on the efficacy of two new anti-cancer drugs, topotecan and gemcitabine. We used the fibrosarcoma WEHI-S cells stably transfected to overexpress the hsp70 cDNA from the constitutive SV40 promoter and appropriate control cells. After topotecan and gemcitabine treatment hsp70-overexpressing cells showed a marked elevation in cell survival, suggesting that hsp70 overexpression was sufficient to confer resistance to the drugs. In addition, hsp70-overexpressing cells were capable of starting cell proliferation after treatment with drug dosages that were lethal to control cells. Our results demonstrate that hsp70 overexpression represents a possible cause of drug resistance. In order to transfer these data to tumour cells constitutively expressing stress hsp70 due to the constitutive activity of the original hsp70 promoter we sought to supress the heat shock response pathway by the natural flavonoid quercetin, known to inactivate the heat shock transcription factor (HSF). Using a suitable cell line, we demonstrated the sensitising activity of quercetin. We found that antineoplastic drug concentrations exerting cytotoxic activity were markedly lower when cells were pretreated with quercetin. Concomitantly, hsp70 expression was strongly down-regulated under quercetin treatment. Our data indicate that quercetin may be useful as a sensitiser in chemotherapeutically treated patients suffering from hsp70-overexpressing tumours.

Animals↗
PubMed1996

Quantitative immunohistochemistry of factor VIII-related antigen in breast carcinoma: a comparison of computer-assisted image analysis with established counting methods.

Microvessel density in the area of the most intense neovascularization in invasive breast carcinoma is reported to be an independent prognostic factor. The established method of enumeration of microvessel density is to count the vessels using an ocular raster (counted microvessel density [CMVD]). The vessels were detected by staining endothelial cells using Factor VIII-related antigen. The aim of the study was to compare the CMVD results with the percentage of factor VIII-related antigen-stained area using computer-assisted image analysis. A true color red-green-blue (RGB) image analyzer based on a morphologically reduced instruction set computer processor was used to evaluate the area of stained endothelial cells. Sixty invasive breast carcinomas were included in the analysis. There was no significant correlation between the CMVD and the percentage of factor VIII-related antigen-stained area (Spearman correlation coefficient = 0.24, confidence interval = 0.02-0.46). Although high CMVD was significantly correlated with poorer recurrence free survival (P = .024), percentage of factor VIII-related antigen-stained area showed no prognostic value. Counted microvessel density and percentage of factor VIII-related antigen-stained area showed a highly significant correlation with vessel invasion (P = .0001 and P = .02, respectively). There was no correlation between CMVD and percentage of factor VIII-related antigen-stained area with other prognostic factors. In contrast to the CMVD within malignant tissue, the percentage of factor VIII-related antigen-stained area is not suitable as an indicator of prognosis in breast cancer patients.

Breast Neoplasms↗
PubMed1996

Radiosurgery in the management of cervical intraepithelial neoplasia.

OBJECTIVE: To evaluate the loop electrosurgical excision procedure (LEEP) and large loop excision of the transformation zone-conization (LLETZ-conization) in the management of cervical intraepithelial dysplasia using high-frequency, filtered waveform energy (radiosurgery). STUDY DESIGN: Two hundred thirteen women attending the outpatient cervical colposcopy clinic with smears consistent with an epithelial abnormality, but macroscopically or colposcopically not consistent with invasive carcinoma, were included in the study. LEEP and LLETZ-conization were performed in 72 and 141 women, respectively. A matched pair group of patients undergoing cold knife conization was used for the comparison with LLETZ-conization. Using LEEP, in 83% a clear resection margin of the biopsy specimen was achieved. In this subset, diagnosis and therapy were achieved in a single visit. No complications, such as hemorrhage, occurred during the operation or postoperative period. RESULTS: Comparison of LLETZ-conization with the matched-pair group undergoing cold knife conization showed a significantly shorter duration of surgery for LLETZ-conization (mean, 10.8 vs. 16.5 minutes, P < .001). We found no differences concerning posttreatment bleeding complications (2.8% vs. 3.3%) or clear resection margins (92% vs. 86%). Patients undergoing LLETZ-conization needed significantly less analgesic (P < .01). CONCLUSION: Radiosurgical loop excision is a safe and cost-effective method in the diagnosis and treatment of cervical intraepithelial neoplasia.

Biopsy↗
PubMed1996

[Prognostic factors in ovarian carcinoma].

The prognosis in ovarian cancer remains poor, and there is a need to identify patients who are less likely to respond to treatment or are suffering from low stage disease and have a worse prognosis. Stage, presence of ascites, age of patient, histologic type and grade, as well as cellular DNA content or ploidy and mitotic activity index are of prognostic value. In addition to that halftime of CA 125 is also a prognostic indicator. Recently expression of receptors, growth factors and the expression of several oncogenes revealed to have a prognostic significance in ovarian cancer. An overview of the most important prognostic factors is presented.

DNA, Neoplasm↗
PubMed1995

Prognostic value of immunohistochemically detected p53 expression in vulvar carcinoma.

BACKGROUND: Overexpression of the p53 protein has been reported to correlate with poor prognosis in several types of tumors. To the authors' knowledge, there are no studies concerning the prognostic value of p53 protein overexpression in squamous cell vulvar carcinoma. METHODS: Twenty-five cases of squamous cell carcinoma of the vulva with International Federation of Gynecology and Obstetrics (FIGO) Stage I-II were examined for p53 protein overexpression using immunohistochemistry. The correlation of p53 protein overexpression with clinical stage, histologic grade, and overall survival was investigated. Follow-up ranged from 36 to 120 months. RESULTS: Clinical stage and histologic grade did not correlate with p53 protein overexpression. p53 protein overexpression was associated with poorer overall survival (log rank: P < 0.05). CONCLUSION: Immunohistochemically detected p53 protein overexpression is significantly correlated with a reduced overall survival rate for patients with vulvar carcinoma.

Adult↗
PubMed1995

Serum evaluation of basic fibroblast growth factor in cervical cancer patients.

We present the data of 105 serum samples from 20 patients suffering from cervical cancer. Mean serum levels of basic fibroblast growth factor (bFGF) in patients with or without tumor present were 31.3 +/- 32.1 (minimum 0, maximum 156.7) pg/ml and 4.8 +/- 6.8 (minimum 0, maximum 29.6) pg/ml, respectively (P = 0.0001). bFGF reached a sensitivity of 65.7% at a specificity of 91.5% when applying a cut-off level of 15 pg/ml. Four patients relapsed after complete remission. A continuous increase of bFGF serum levels before the clinical detection of relapse (lead time) was seen in two cases with a mean lead time of 4 months. Preoperative serum levels were not of prognostic value and showed no correlation with pelvic lymph node metastasis. These preliminary results indicate that in cervical cancer patients soluble bFGF may be useful in early detection of primary tumors, recurrences and monitoring of therapy.

Adenocarcinoma↗
PubMed1995

Serum CD44 splice variants in cervical cancer patients.

Aberrant expression of the cell adhesion molecule CD44 has been detected in human tumours and has been shown to be associated with metastasis and poor prognosis in human malignancies. We evaluated serum levels of different soluble CD44 molecules (CD44 standard form and CD44 splice variants v5 and v6) in cervical cancer patients stage IB to IIIB. Two-hundred three serum samples were analysed. Serum levels of CD44st and CD44v5 showed no significant correlation with the presence or absence of cervical cancer. The splice variant CD44v6 showed a mean concentration of 227.3 +/- 90.9 (minimum 71.4, maximum 543.9) ng/ml when tumour was present and a mean concentration of 198.7 +/- 135.4 (minimum 67.2, maximum 696.3) ng/ml in cases of complete remission (P-value = 0.0001). However, in this preliminary study the sensitivity/specificity characteristic of CD44v6 was poor.

Adenocarcinoma↗
PubMed1995

Cytokeratin subunit 19 measured by CYFRA 21-1 assay in follow-up of cervical cancer.

The purpose of this study was to evaluate the serum tumor markers CYFRA 21-1 and squamous-cell carcinoma antigen (SCC) in the follow-up of squamous-cell cervical cancer patients. One hundred-ninety-three serum samples, which were collected pretherapeutically and during follow-up of 30 patients suffering from squamous-cell cervical cancer FIGO stage III, were analyzed for SCC and CYFRA 21-1. Cutoff values for SCC and CYFRA 21-1 were 3 and 3.3 micrograms/liter, respectively. Fifteen cases were keratinizing and 15 nonkeratinizing squamous-cell carcinomas. Serum tumor marker results were correlated to the results of the clinical and radiologic examinations. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of serum SCC and serum CYFRA 21-1 for the whole study group and separately for the keratinizing and nonkeratinizing squamous-cell carcinoma group. Sensitivity, specificity, PPV, and NPV of serum SCC were 66, 91, 93, and 60%, respectively. Serum CYFRA 21-1 showed a sensitivity of 63%, specificity of 96%, PPV of 96%, and NPV of 59%. The combination of SCC and CYFRA 21-1 increased the sensitivity to 78%, with a specificity, PPV, and NPV of 87, 91, and 69%, respectively. In keratinizing squamous-cell carcinoma serum SCC, CYFRA 21-1 and the combination of both had a sensitivity of 76, 64, and 85%, respectively. In nonkeratinizing squamous-cell carcinoma sensitivity was 58, 61, and 72%, respectively. The detection of cervical cancer recurrences with SCC is improved by the combination with CYFRA 21-1. Especially in nonkeratinizing squamous-cell carcinoma CYFRA 21-1 showed promising results.

Antigens, Neoplasm↗
PubMed1995

Mutant p53 in patients with invasive cervical cancer stages IB to IIB.

The present study evaluates the prognostic value of mutant p53 protein overexpression in 109 surgically treated cervical cancer stages IB to IIB. Squamous cell carcinoma stages IB, IIA, and IIB were present in 52, 13, and 44 cases, respectively. We performed immunohistochemistry using a monoclonal antibody against the p53 suppressor gene product (clone BP53-12). Data were analyzed for the end points of disease-free survival and overall survival. In 109 tissue specimens we detected 22 cases of p53 expression. Six of 22 patients with p53 expression and 21 of 87 patients without p53 expression showed tumor recurrences. p53 expression showed no significant correlation to age, tumor stage or lymph node involvement. In the univariate analysis p53 expression showed no prognostic value for disease-free (P = 0.5) and overall survival (P = 0.6). Multivariate analysis showed a significant prognostic value for established prognostic parameters while p53 expression had no prognostic value for recurrence-free (P = 0.6) and overall survival (P = 0.5). In contrast to other malignancies mutant p53 overexpression showed no relation to prognosis in surgically treated cervical cancer stage IB to IIB.

Adult↗
PubMed1995

Splice variants of CD44 in human cervical cancer stage IB to IIB.

Aberrant expression of the cell adhesion molecule CD44 has been detected in human tumors and the expression of specific CD44 isoforms (splice variants) has been shown to be associated with metastasis and poor prognosis in human malignancies. We used three different variant exon sequence-specific murine monoclonal antibodies to epitopes encoded by exon v5, exon v6, or exon v7-v8 of human variant CD44 to study the expression of CD44 splice variants by immunohistochemistry in human cervical cancer. One-hundred five patients with surgically treated squamous cell carcinomas of the cervix stages IB to IIB were included in the study. CD44 splice variants CD44v5, CD44v6, and CD44v7-8 were detected in 70, 67, and 26%, respectively. Tumors expressing exon v6 had significantly more often metastasized to the pelvic nodes (58 vs 79%, P = 0.04). Expression of exon v6 was significantly correlated with a greater probability of vascular space invasion (73 vs 50%, P = 0.04) and a significantly lower rate of inflammatory stromal reaction (48 vs 78%, P = 0.004). Patients suffering from tumors expressing splice variant CD44v6 showed poorer overall survival (P = 0.03). In cases with negative pelvic lymph nodes we found a poorer prognosis when tumors expressed CD44v6 (P = 0.01) or CD44v7-8 (P = 0.02). Among the investigated CD44 splice variants expression of exon v6 is the most promising prognostic marker in surgically treated cervical cancer.

Adult↗
PubMed1995

A large hydatid cyst of the liver in pregnancy.

We report on a primigravida, who was admitted in the 14th week of pregnancy because of recurrent vomiting and upper abdominal pain. The diagnosis of a large 20 cm echinococcal cyst of the liver was confirmed by ultrasound and an indirect hemagglutination test (IHA). In the 19th week of pregnancy a subtotal cystectomy was performed under perioperative treatment with the anthelmintic drug Albendazole. The patient delivered a 1420 g, 41 cm premature boy in breech position at 33 weeks. The significance of echinococcal cysts in pregnancy is discussed.

Adult↗
PubMed1995

Prognostic value of CD44 splice variants in human stage III cervical cancer.

The expression of specific cell adhesion molecule CD44 isoforms (splice variants) has been shown to be associated with poor prognosis in human malignancies, such as breast cancer. We used three different variant exon sequence-specific murine monoclonal antibodies to epitopes encoded by exons v5, v6 or v7-v8 of human variant CD44, to study the expression of CD44 splice variants by immunohistochemistry in human stage III cervical cancer. We investigated 40 pretreatment punch biopsies of cervical cancer FIGO stage III. CD44 splice variants CD44v5, CD44v6 and CD44v7-8 were detected by means of immunohistochemistry in 90%, 55% and 25%, respectively. CD44 epitopes encoded by exon v5 were not correlated with prognosis. Expression of CD44 splice variants containing epitopes encoded by exon v6 were correlated with significantly poorer prognosis (Mantel test, P = 0.008). Five-year survival rates with or without CD44v6 expression were 20% versus 71%, respectively. Expression of CD44v7-8 was also correlated with significantly poorer overall survival (Mantel test, P = 0.02). Expression of CD44 splice variants containing epitopes encoded by exons v7-v8 and especially exon v6 is associated with significantly poorer prognosis in stage III cervical cancer patients.

Aged↗