PubMed Health⌕ Search

Biomedical subjects

S Leodolter

Publications and source records attributed to S Leodolter.

At least 55 records · Page 3Linked to original sources
PubMed1999

Monocyte chemoattractant protein-1 serum levels in ovarian cancer patients.

The chemokine monocyte chemoattractant protein (MCP)-1 is an important mediator of monocyte infiltration in various solid tumours of epithelial origin. The aim of the present study was to evaluate the role of MCP-1 in the natural history of ovarian cancer and to determine its value as differentiation marker and prognostic marker regarding disease free and overall survival. This retrospective study comprises 86 patients with ovarian cancer, 48 with primary ovarian cancer and 38 with recurrent ovarian cancer, 67 patients with benign ovarian cysts and 42 healthy women. Median serum levels in patients with primary ovarian cancer, recurrent ovarian cancer, benign ovarian cysts and in healthy women were 535.6 (range 129.6-1200) pg ml(-1), 427.3 (range 193.4-1101) pg ml(-1), 371.2 (range 222-986.8) pg ml(-1) and 318.7 (range 241.3-681.4) pg ml(-1) respectively (Mann-Whitney U-test, P < 0.001). Univariate logistic regression models revealed a significant influence of MCP-1 serum levels on the odds of presenting with primary ovarian cancer versus benign cysts and versus healthy women respectively (univariate logistic regression, P < 0.001 and P < 0.001 respectively). In a multivariate logistic regression model considering MCP-1 and CA 125 serum levels simultaneously, both MCP-1 and CA 125 revealed statistical significance on the odds of presenting with primary ovarian cancer versus benign cysts (multivariate logistic regression, P = 0.05 and P < 0.001 respectively). In ovarian cancer patients, MCP-1 serum levels showed a statistically significant correlation with histological grade (Mann-Whitney U-test, P = 0.02) and age at the time of diagnosis (Mann-Whitney U-test, P = 0.03). Elevated MCP-1 serum levels prior to therapy were not associated with disease-free and overall survival (log-rank test, P = 0.2 and P = 0.7 respectively). In summary these data indicate that MCP-1 might play a functional role in the natural history of ovarian cancer and might serve as differentiation marker between benign ovarian cysts and ovarian cancer, providing additional information to the established tumour marker CA 125.

Adult↗
PubMed1999

BRCA1 gene mutations in sporadic ovarian carcinomas: detection by PCR and reverse allele-specific oligonucleotide hybridization.

BACKGROUND: Although germline mutations in BRCA1 play a central role in familial breast and ovarian cancers, to date, no somatic mutations in BRCA1 have been reported in sporadic breast cancer, and only five somatic mutations have been identified in the sporadic ovarian carcinomas. Because loss of heterozygosity appears frequently at the BRCA1 locus in nonfamilial breast and ovarian carcinomas, we searched for mutations in the BRCA1 gene in sporadic ovarian tumors. METHODS: We developed a detection system based on PCR and reverse allele-specific oligonucleotide hybridization on membrane strips for the simultaneous detection of 17 frequently occurring mutations in the BRCA1 gene. RESULTS: As little as 2% mutant DNA in a sample could be detected. Two of 122 DNA samples isolated from sporadic ovarian tumor biopsies contained the Cys61Gly mutation. Both mutations were germline mutations. One of these was an ovarian metastasis of a primary fallopian tube carcinoma. The tubal carcinoma was also confirmed to contain the Cys61Gly mutation. CONCLUSIONS: This is the first report that a germline BRCA1 mutation is associated with primary tubal carcinoma. The 17 specific mutations in the BRCA1 gene do not play a major role in the tumorigenesis and progression of sporadic ovarian cancer.

Alleles↗
PubMed1999

Messenger RNA determination of estrogen receptor, progesterone receptor, pS2, and plasminogen activator inhibitor-1 by competitive reverse transcription-polymerase chain reaction in human breast cancer.

Estrogen receptor (ER), progesterone receptor (PR), the estrogen-inducible protein pS2, and plasminogen activator inhibitor-1 (PAI-1) are important prognostic factors in primary breast cancer. The protein concentrations of these factors in breast tumors have been well documented. However, few data about the mRNA expression of ER, PR, pS2, and PAI-1 in breast cancer are available, which is mostly due to the limitations of conventional techniques for mRNA analysis. We have described a competitive reverse transcription-PCR system for the simultaneous quantification of ER, PR, pS2, and PAI-1 mRNA in tumor samples. Here, we evaluated 100 tumor biopsies from breast cancer patients for the mRNA expression of ER, PR, pS2, and PAI-1. The results were analyzed for correlations with protein status and with clinical data. Significant correlations between mRNA expression levels and protein concentrations of all tested markers were found. In only a few cases was there an obvious discordance between the measurable amounts of mRNA and protein, especially for ER and PR. In addition, ER, PR, and pS2 mRNA levels correlated significantly with each other. No correlation between PAI-1 mRNA amount and the expression of the other markers was found. With respect to clinical data, ER and PR mRNA levels were found to be inversely correlated to tumor size and histological grade but not to the lymph node status. pS2 and PAI-1 mRNA expression were not correlated with tumor size, grade, or lymph node involvement. In conclusion, competitive reverse transcription-PCR may be used as an alternative for the study of prognostic factors in human breast cancer and other malignancies. However, before mRNA expression is measured for diagnostics, a presumed concordance of mRNA and protein expression must be evaluated very carefully for every gene.

Adult↗
PubMed1999

Serum levels of leukocyte functional antigen-3 in pregnancy and preeclampsia.

BACKGROUND: Adhesion molecules have been demonstrated to be involved in placental growth and development in normal pregnancy. Experimental evidence indicates that adhesion molecules are key factors of endothelial activation in preeclampsia. The aim of our study was to evaluate serum levels of the adhesion molecule Leukocyte Functional Antigen (LFA)-3 in healthy, non pregnant, female controls, healthy pregnant women, and preeclamptic women. METHODS: In our study we included 45 healthy, non pregnant, female controls, 45 healthy pregnant women, and 45 preeclamptic women. An enzyme-linked immunosorbent assay was used to determine serum levels of LFA-3. Results were correlated to clinical data. RESULTS: The median LFA-3 serum level in healthy, non pregnant, female controls was 0.2 (range 0 to 8.6) ng/mL. LFA-3 serum levels in healthy pregnant women were 4.8 (range 0 to 18) ng/mL and were significantly elevated compared to healthy, non pregnant, female controls (Mann-Whitney U-test, p=0.004). A cut-off level of 4.8 ng/mL was selected according to the 75th quantile of serum levels measured in the panel of healthy, non pregnant, female controls. In preeclamptic women, whose pregnancies had to be terminated due to exacerbation of preeclamptic symptoms, LFA-3 serum levels above the cut-off level were seen in 14/27 (52%) cases. In contrast, preeclamptic women, who went into spontaneous labor showed elevated LFA-3 serum levels in 17/18 (95%) cases (chi-square test, p=0.002). LFA-3 serum levels revealed a statistically significant influence on the odds of termination of pregnancy due to exacerbation of preeclamptic symptoms (unconditional logistic regression, p=0.02) with an odds ratio of 0.1 (95% CI, 0.006 to 0.7) by every doubling of LFA-3 values. CONCLUSIONS: Our results suggest that LFA-3 expression is upregulated in healthy pregnant women compared to healthy, non pregnant, female controls. Failure of LFA-3 upregulation in preeclampsia is associated with an increased risk for termination of pregnancy due to exacerbation of preeclamptic symptoms.

CD58 Antigens↗
PubMed1999

Serum concentrations of vascular endothelial growth factor in vulvar cancer.

The aim of the present study was to evaluate serum concentrations of vascular endothelial growth factor (VEGF) in patients with vulvar cancer and healthy female controls with respect to correlation of VEGF with clinicopathological parameters and impact on the patients' prognosis. Serum concentrations of VEGF were measured using a commercially available ELISA. Results were correlated to clinical data. Median serum concentrations of VEGF in patients with vulvar cancer (n = 41) and healthy female controls (n = 130) were 260 (range, 33-1216) pg/ml and 216 (range, 0-777) pg/ml, respectively (Mann-Whitney U test, P = 0.048). Serum concentrations of VEGF significantly correlated with tumor stage (Mann-Whitney U test, P = 0.02) but not with histological grade (Mann-Whitney U test, P = 0.2). In a univariate analysis, elevated pretreatment serum concentrations of VEGF were significantly correlated with a shortened disease-free and overall survival (Wilcoxon test, P = 0.03; and Wilcoxon test, P = 0.04, respectively). A multivariate Cox regression model considering tumor stage and serum concentrations of VEGF revealed, however, that serum concentrations of VEGF did not confer additional prognostic information to that already obtained by the established prognosticator tumor stage (multivariate Cox regression model: P = 0.9 and P = 0.8, respectively). Our data indicate that angiogenesis, as reflected by serum concentrations of VEGF, plays a functional role in vulvar carcinogenesis. VEGF seems to be a mediator of vulvar tumor growth but not of tumor cell dedifferentiation. Although associated with impaired disease-free and overall survival, pretreatment serum concentrations of VEGF are not an independent predictor of outcome in patients with vulvar cancer.

Adult↗
PubMed1999

Comparison of flow cytometry and RT-PCR for the detection of ovarian cancer cells in peripheral blood.

Recently, there has been significant effort in developing techniques designed to detect disseminated tumor cells in the peripheral blood (PB). These techniques include immunocytochemical staining of cytocentrifuge slides, flow cytometry, and RT-PCR. Several authors reported various results concerning the sensitivity of the detection limit when applying these methods. The aim of this study was to assess the value of two methods in the detection of ovarian carcinoma cells in the PB. For tumor cell detection we compared RT-PCR to immunomagnetic enrichment followed by flow cytometric analysis. In a model system, single cell suspensions of ovarian cancer cell lines were mixed with full blood samples from healthy donors in order to determine the sensitivity limit of the two methods and to analyze the reproducibility of each. In a multiparameter flow cytometric analysis, tumor cells were defined as cytokeratin 7/8 positive and CD45 negative. RNA was screened for MUC1 mRNA by RT-PCR. MUC1 mRNA expression turned out not to be a specific marker of disseminated ovarian cancer cells, because a weak expression was also found in samples of healthy persons. Using immunomagnetic enrichment followed by flow cytometry, one carcinoma cell per 1 x 10(6) leukocytes was detectable. However, a minimum of 10 ml blood had to be analyzed in order to clearly distinguish real positive tumor cells from false-positive signals.

Biomarkers, Tumor↗
PubMed1998

The influence of vascular space involvement on the prognosis of patients with stage IB cervical carcinoma: correlation of results from hematoxylin and eosin staining with results from immunostaining for factor VIII-related antigen.

BACKGROUND: There is controversy over the question of whether the involvement of vascular spaces influences the prognosis of patients with carcinoma of the uterine cervix. The aim of the current study was to compare patterns of vascular space involvement determined by hematoxylin and eosin (H & E) staining with those patterns determined by immunostaining for factor VIII-related antigen (F8-RA) with regard to their prognostic impact on the disease free survival (DFS) and overall survival (OS) of patients with clinical Stage IB cervical carcinoma. Staining for F8-RA is known to highlight blood vessels predominantly, whereas the presence of tumor cell emboli in vascular spaces of H & E-stained sections mainly indicates lymphatic vessel invasion. METHODS: The authors analyzed data on 163 patients for whom vascular space involvement (VSI) was determined by H & E (VSI/H & E) and F8-RA (VSI/F8) staining from the same block in two separate runs. RESULTS: The median follow-up period was 85 months (range, 5-170 months). The 25% quantile for OS was 109 months (median not reached; range, 5-170 months). The overall rates of VSI/H & E and VSI/F8 were 29.4% and 24.5%, respectively. The findings obtained by H & E and F8-RA staining were concurrent in 60.7% of cases. Lymph node involvement and VSI/F8 remained independent prognostic factors for DFS and OS. Due to a highly significant correlation of pelvic lymph node status with both VSI/H & E and tumor size, the last two parameters failed to retain a significant value. For lymph node negative patients, the estimated OS probability was 92% for those without VSI/F8 and 62% for those with VSI/F8. CONCLUSIONS: VSI/F8 may provide additional information on the outcome of clinical Stage IB cervical carcinoma. Lymph node negative patients with VSI/F8 positive tumors may benefit from more intense postsurgical treatment. Further trials involving larger series of patients are necessary to confirm these findings.

Adenocarcinoma↗
PubMed1998

Absence of p53 protein overexpression in precancerous lesions of the vulva.

BACKGROUND: Recently the authors reported the prognostic value of p53 protein overexpression in invasive squamous cell carcinoma of the vulva. The aim of this study was to evaluate the status of p53 overexpression and human papillomavirus (HPV) infection in patients with precancerous lesions of the vulva. METHODS: Biopsy specimens of 28 women (mean age, 44.2 years; range, 19-71 years) with warty and/or basaloid type vulvar intraepithelial neoplasia (VIN) of Grade 1 to 3 were examined retrospectively for p53 protein overexpression by immunohistochemistry. The presence of the HPV genome was assessed using a nested polymerase chain reaction (PCR) method with consensus primers directed against the L1 coding region. RESULTS: Neither the preoperative punch biopsy specimen nor the subsequent surgical specimen contained immunohistochemically detectable levels of p53 in this study of a group of younger women with preinvasive vulvar lesions. These results are in contrast to those obtained previously in older women with keratinizing squamous cell carcinoma demonstrating p53 protein overexpression in approximately 50% of patients. HPV DNA was detected in the vast majority of VIN cases (92.8%) using a highly sensitive nested PCR method. The current data indicate that p53 protein is not overexpressed in basaloid/warty VIN when evaluated by immunohistochemistry. In addition, this study confirms previous reports demonstrating the presence of HPV DNA in the majority of these lesions. CONCLUSIONS: These data suggest that p53 protein overexpression is not an early event in the pathogenesis of basaloid/warty type vulvar dysplasia and that HPV infection may contribute to the development of VIN.

Adolescent↗
PubMed1998

Tumor angiogenesis in stage IB cervical cancer: correlation of microvessel density with survival.

OBJECTIVE: Because angiogenesis is considered essential for tumor growth and the development of metastasis, we assessed the correlation of microvessel density with overall survival in patients with clinical stage IB carcinoma of the uterine cervix. STUDY DESIGN: Histologic slides were immunostained for factor VIII-related antigen. Microvessel density was determined within each tumor by enumeration under a light microscope at 200x magnification and an examination area of 0.25 mm2. The Cox proportional hazards model was used for multivariate analysis. RESULTS: In 166 patients with stage IB cervical cancer the 5-year survival was as follows: 89.7% in 102 patients whose tumors had a microvessel density < or =20/field, and 63.0% in 64 patients whose tumors had a microvessel density >20/field (log rank p < 0.0001). In the multivariate Cox model microvessel density, lymph node involvement, tumor size, and the application of radiation therapy remained independent prognostic factors for survival, whereas lymphatic vascular space involvement failed to retain a significant value. CONCLUSION: High microvessel density adversely influences patients' survival in clinical stage IB cervical cancer and identifies patients with negative nodes at risk for relapse.

Adult↗
PubMed1998

Concentration of vascular endothelial growth factor (VEGF) in the serum of patients with suspected ovarian cancer.

As a promoter of angiogenesis, vascular endothelial growth factor (VEGF) is believed to play a pivotal role in tumour growth and metastasis. The aim of this study was to determine the value of preoperative serum VEGF levels in the early diagnosis of ovarian cancer and in the differential diagnosis of adnexal masses. We examined preoperative serum VEGF levels in healthy women (n = 131), patients with benign ovarian cysts (n = 81) and in ovarian cancer patients (n = 44) by using an ELISA (R&D Systems, Minneapolis, MN, USA). A logistic regression model was carried out to determine the influence of VEGF and CA 125 on the probability of malignancy. VEGF revealed a significant influence on the odds of presenting with malignancy vs healthy women (P = 0.001). At 363.7 pg ml(-1), VEGF achieved a sensitivity of 54% and a specificity of 77%. With respect to the differentiation between benign cysts and ovarian cancer, CA 125 (P < 0.0001) but not VEGF (P = 0.229) predicts the presence of malignancy in a multivariate model. In conclusion, VEGF does not appear to be a useful tool in the early diagnosis of ovarian cancer or for indicating the absence or presence of malignancy in patients with an adnexal mass.

Adult↗
PubMed1998

[Epidemiologic considerations on the significance of hormones in carcinogenesis].

The incidence of gynecologic malignancies shows considerable regional differences which suggest a decisive role of environmental and endocrine factors in tumor genesis. The risk of developing breast cancer increases with increasing age, a positive family history, prolonged exposure to estrogens (early menarche, late menopause), nulliparity, alcohol consumption, and obesity. A relationship between a long exposure to estrogens and an increased risk of cancer may also be assumed in the case of endometrial cancer. Whether estrogens or their metabolites promote the initiation of cancer remains to be clarified. Endocrine monotherapy with only an estrogen, obesity, nulliparity/infertility as well as a late natural menopause are well-known risk factors of developing endometrial cancer. Whereas estrogens induce a hyperplasia of the endometrial mucosa, gestagens exert a protective effect on the endometrium. Old age, a family history of breast, endometrial and ovarian cancer as well as persistent or treated infertility are the established risk factors of ovarian cancer. Each pregnancy, the intake of oral contraceptives, a hysterectomy or tubal ligation are associated with a decreased risk of developing ovarian cancer; hormonal replacement therapy has no influence on the risk of ovarian cancer.

Adolescent↗
PubMed1997

Quantitative determination of gene expression by competitive reverse transcription-polymerase chain reaction in degraded RNA samples.

Quantitative competitive reverse transcription-polymerase chain reaction has become a powerful tool for determining the amount of mRNA in cultured cells as well as in tissue. To ensure the reliability of the analysis, RNA with high purity and integrity is needed. However, when analyzing RNA samples from tumor biopsies, RNA degradation is often an inevitable problem. This causes differences in sample quality and furthermore adversely affects the quantification of gene expression. Here, we demonstrate that in partially degraded RNA samples different mRNAs are degraded to the same extent. Normalizing the expression level of a specific gene to that of a constitutively expressed gene in the same sample allows the relative quantification of this specific gene. Thus, the comparison of gene expression in RNA samples with varying integrity is possible.

Gene Expression↗
PubMed1997

Vascular endothelial growth factor (VEGF) in human breast cancer: correlation with disease-free survival.

Studies have shown that microvessel density influences breast-cancer prognosis. Since tumor angiogenesis is considered to be substantially affected by the excretion of vascular endothelial growth factor (VEGF) from tumor cells, we examined whether VEGF concentration is different in malignant and in non-malignant breast tissue. It was also of interest to discover whether intratumoral VEGF concentration influences disease-free survival (DFS) of breast-cancer patients. Analysis is based on 120 tissue specimens taken from breast fibromas (n = 23), normal epithelial breast tissue adjacent to fibromas (n = 8) and invasive breast cancer (n = 89). VEGF concentration was quantified by using an immunoassay. Microvessel density was determined by immunostaining for factor-VIII-related antigen. Median VEGF concentration is given in pg/mg protein (25%-quantile-75%-quantile) and it was 0 (0-1.8) in normal breast tissue, 9.8 (0.52-43.0) in fibromas and 130.4 (50.8-362.2) in invasive carcinomas. A univariate Cox model revealed that node status, tumor size, estrogen-receptor concentration, histological grading and microvessel density were prognostic factors for disease-free survival in breast cancer. We found a significant correlation between VEGF concentration and microvessel count, but VEGF concentration did not significantly influence disease-free survival. Although VEGF protein was found at a significantly higher concentration in malignant than in non-malignant tissue, determination of intratumoral VEGF protein by an enzyme immunoassay was not prognostically relevant in our patient population.

Analysis of Variance↗
PubMed1997

Correlation of vascular endothelial growth factor expression and microvessel density in cervical intraepithelial neoplasia.

BACKGROUND: Angiogenesis (the formation of new blood vessels) appears to be required for the growth of invasive tumors, but little information exists about its role in the development of preinvasive lesions. We examined microvessel density and expression of vascular endothelial growth factor in specimens of cervical intraepithelial neoplasia (CIN), a preinvasive lesion of the uterine cervix, to determine whether a connection could be established between these parameters of angiogenesis and the grade of dysplasia (i.e., tissue abnormality). METHODS: Sections of biopsy specimens from 83 patients with grades I-III CIN were examined retrospectively. Microvessels were localized by use of a polyclonal antibody directed against factor VIII-related antigen; vascular endothelial growth factor was detected by means of a monoclonal antibody. Reported P values are two-sided. RESULTS: Highest microvessel densities and highest expression of vascular endothelial growth factor were found in a narrow border region between CIN lesions and the underlying stroma. A significant correlation was observed between high vascular endothelial growth factor expression and high microvessel density (Kendall's tau = 0.27; 95% confidence interval [CI] = 0.03-0.50; P = .018). Mean microvessel density values +/- standard deviations for CIN I, CIN II, and CIN III lesions were 19.4 +/- 5.8, 21.9 +/- 7.0, and 34.1 +/- 14.8, respectively (Kendall's tau = 0.46; 95% CI = 0.30-0.61; P<.0001). Corresponding values for vascular endothelial growth factor expression were 8.3 +/- 3.5, 8.4 +/- 2.0, and 12.2 +/- 3.6, respectively (Kendall's tau = 0.41; 95% CI = 0.20-0.60; P<.0001). CONCLUSIONS: Our results are consistent with the idea that progression of cervical dysplasia is dependent on angiogenesis.

Endothelial Growth Factors↗
PubMed1997

Angiogenesis in vulvar intraepithelial neoplasia.

Vulvar intraepithelial neoplasia (VIN) has been reported to be a precursor of invasive vulvar cancer. Switching to the angiogenic phenotype is considered a key step in tumor growth. Microvessel density (MVD) and vascular endothelial growth factor (VEGF), a highly angiogenic peptide, are important parameters of tumor angiogenesis. Forty-three histologic slides with 38 VIN I-III lesions were immunohistochemically stained for factor VIII-related antigen (F8-RA) and 44 slides with 37 VIN I-III for VEGF, since F8-RA reliably highlights tumor microvessels. Determination of MVD and VEGF expression was done by counting microvessels and VEGF-positive cells at a magnification of 200x and 400x. The highest concentration of F8-RA-stained MVD and VEGF expression was found at a small subepithelial area at the border of the VIN lesion to the stroma underneath but concentrations were low in all specimens of normal epithelium. High VEGF expression was significantly correlated to high MVD. For both MVD and VEGF expression the differences between VIN I and VIN III and between VIN II and VIN III were statistically significant (P < 0.0001). VIN III lesions are the clinical relevant precursors of invasive cancer of the vulva, as outlined by intense expression of VEGF protein and a highly dense network of microvessels underlying the dysplastic epithelium.

Adult↗
PubMed1997

Serum levels of the tumour-associated trypsin inhibitor in patients with endometriosis.

OBJECTIVE: To show that in patients with endometriosis a 6 kD polypeptide, the tumour-associated trypsin inhibitor (TATI), can occur at elevated concentrations in serum. DESIGN: In a prospective study TATI serum levels were assessed prior to surgery in 368 consecutive patients suffering from benign gynaecological diseases (e.g. pelvic pain, infertility, elective sterilisation, uterine fibroids and pelvic masses) with (n = 71) and without (n = 297) endometriosis, who underwent laparoscopy or laparotomy for diagnosis and/or treatment. RESULTS: The TATI serum levels of patients suffering from endometriosis were significantly different from those in the control group and showed a positive correlation with the stage of endometriosis. The sensitivity of TATI was 0.34 with a specificity of 0.85 for all cases of endometriosis, with an increase of sensitivity (0.67) and slight decrease of specificity (0.82), considering only a group of Stage III/IV patients. Excluding patients with benign ovarian cysts, the specificity of TATI was 0.91 and 0.85, respectively. The combination of TATI and CA125 showed an increase of sensitivity to 0.59 for all cases of endometriosis and 0.89 for patients with Stage III/IV endometriosis. CONCLUSIONS: The sensitivity of TATI as a screening method for endometriosis is too low, but considering its high specificity, TATI in combination with CA125 could provide an additional diagnostic tool in diagnosis and follow up of patients with endometriosis.

Biomarkers, Tumor↗