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A Obermair

Publications and source records attributed to A Obermair.

At least 37 records · Page 2Linked to original sources

DNA repair-redox enzyme apurinic endonuclease in cervical cancer: evaluation of redox control of HIF-1alpha and prognostic significance.

The multifunctional apurinic/apyrimidinic endonuclease (Ape1/ref-1) plays a key role in the human DNA base excision repair pathway. Ape1/ref-1 has also been shown to be involved in the redox control of transactivation activities of hypoxia-inducible factor (HIF)-1alpha. The aim of our study was to investigate the expression of these proteins in early stage invasive cervical cancer. Expression of Ape1/ref-1 and HIF-1alpha was detected immunohistochemically in 88 samples of cervical cancer stage pT1b. The levels of the proteins were compared and the prognostic influence of Ape1/ref-1 expression was investigated. Strong nuclear expression of Ape1/ref-1 was observed in 9 cases (10.2%), moderate in 22 cases (25%), weak in 17 cases (19.3%), and absent in 40 cases (45.5%). Furthermore, no correlation between Ape1/ref-1 and HIF-1alpha expression was observed (p=0.864). We also found no relationship of Ape1/ref-1 expression and survival (p>0.05, log-rank test). From these studies, we have concluded that in cervical cancer there is no correlation between the upstream redox regulatory protein of HIF-1, i.e., Ape1/ref-1, and HIF-1alpha expression. However, these studies do not address any functional relationship between the two proteins.

Carbon-Oxygen Lyases↗

Selective immunohistochemical staining of blood and lymphatic vessels reveals independent prognostic influence of blood and lymphatic vessel invasion in early-stage cervical cancer.

Lymphovascular space invasion was shown to play a key role in the progression of cervical cancer. Because of the absence of a specific marker for lymphatic vessels, earlier studies could not reliably distinguish between blood and lymphatic vessel invasion. By immunostaining for podoplanin, a novel marker for lymphatic endothelium, and for factor VIII-related antigen, we determined lymphatic and blood vessel invasion in tissue samples of 98 patients with cervical cancer pT1b treated by radical hysterectomy. Eleven (11.2%) specimens showed invasion of blood vessels, 20 (20.4%) showed invasion of lymphatic vessels, and 15 (15.3%) showed invasion of blood and lymphatic vessels. There was a strong association of lymphatic vessel invasion and lymph node involvement (P < 0.001). In univariate analysis, both blood and lymphatic vessel invasion failed to reach a statistically significant influence on overall survival, but a significant influence on disease-free survival was found (P = 0.0002 and P < 0.0001, respectively). In multivariate analysis of disease-free survival, only blood vessel invasion remained statistically significant (P = 0.0457). Lymphatic vessel invasion reached significance when lymph node status was excluded from the model (P = 0.0025). Both lymphatic vessel and blood vessel invasion occur frequently in early-stage cervical cancer. Determination of the vessel status may be of clinical importance because it signifies the risk of recurrent disease.

Adult↗

Impact of second look laparotomy and secondary cytoreductive surgery at second-look laparotomy in ovarian cancer patients.

OBJECTIVE: Currently, no prospective study supports or refutes the value of secondary cytoreductive surgery in patients with ovarian cancer. We therefore reviewed the surgical data of patients who underwent second-look laparotomy (SLL) with or without secondary cytoreductive surgery at our department. METHODS: Analysis is based on the data of 179 patients who had FIGO stage II (suboptimally staged), stage III or IV ovarian cancer, who received a platinum-based first-line chemotherapy, who were clinically considered to be tumor-free or had at least a clinically partial response to first-line chemotherapy, and who underwent SLL. In patients with macroscopic tumor the diagnostic SLL was followed by a secondary cytoreductive surgery in order to remove as much tumor as possible. Patients with a positive SLL were given second-line chemotherapy. Survival from SLL until death was considered the primary statistical endpoint. RESULTS: In 78 out of 179 (43.5%) a negative SLL could be confirmed pathologically. Patients with negative findings, with microscopic, and macroscopic disease at SLL had a median survival of 66.6, 57.2, and 19.0 months, respectively (p=0.0001). In patients who underwent a secondary cytoreductive operation and in whom residual tumor was none, less than 2 cm, or more than 2 cm, the median survival was 22.9, 17.8, and 15.5 months, respectively (p=0.325). CONCLUSIONS: The presence of macroscopic tumor at SLL is an adverse prognostic factor whereas the role of secondary cytoreductive surgery at SLL appears to be limited in the routine management of ovarian cancer patients.

Adult↗

Expression of hypoxia-inducible factor 1alpha in epithelial ovarian tumors: its impact on prognosis and on response to chemotherapy.

PURPOSE: To investigate the impact of expression of hypoxia-inducible factor (HIF)-1alpha on prognosis and on response to chemotherapy in epithelial ovarian tumors. EXPERIMENTAL DESIGN: Expression of HIF-1alpha protein was studied by immunohistochemistry in 102 specimens of epithelial ovarian cancers, in 50 borderline tumors, and in 20 cystadenomas. Results were correlated with p53, p21, and bcl-2 expression, microvessel density (MVD), apoptotic rate of tumor cells, and survival. RESULTS: In 68.6% of ovarian cancers and 88% of borderline tumors, expression of HIF-1alpha was observed. There was a significant correlation of HIF-1alpha protein expression and MVD (P < 0.001). HIF-1alpha overexpression alone and MVD showed no impact on survival of cancer patients. Furthermore, the response to platinum-based chemotherapy was independent from HIF-1alpha expression. Expression of HIF-1alpha correlated with apoptotic rate in the majority of cases, especially in low malignant potential tumors. In contrast, in cancer patients with strong expression of HIF-1alpha and p53 protein overexpression, not only a significantly increased MVD (P = 0.032, Mann-Whitney test) but also a significantly shorter overall survival was observed (P < 0.0001, Cox regression). The apoptotic rate was very low in these tumors. CONCLUSIONS: HIF-1alpha protein overexpression alone has no impact on the prognosis of ovarian cancer. The combination of HIF-1alpha protein overexpression with nonfunctional p53, however, indicates a dismal prognosis.

Cell Survival↗

Quality of life changes during conformal radiation therapy for prostate carcinoma.

BACKGROUND: The objective of this study was to describe prospectively quality of life (QOL) before and after radiotherapy for patients with prostate carcinoma. METHODS: Forty-three patients with T1-T3 prostate carcinoma who underwent conformal external beam radiation therapy were randomized either to the complete European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaire (EORTC QLQ-C30) or the Medical Outcomes Study Group Short Form Health Survey (SF-36) at baseline, at 3 weeks and 6 weeks after initial treatment, and at 6 weeks and 5 months after the completion of radiotherapy. The measures were self-reported patient QOL, and values are given as the mean +/- standard error of the mean. Changes in QOL are described from baseline to the end of treatment in both questionnaire groups. RESULTS: Emotional role functioning, as measured with the SF-36 questionnaire, significantly improved from 68.2 +/- 9.9 at baseline to 93.3 +/- 5.2 at the end of therapy (P = 0.02). The EORTC QLQ-C30 questionnaire revealed consistent values of emotional functioning during treatment (72.7 +/- 5.9 at baseline) but showed a significant improvement 6 weeks after therapy (89.0 +/- 4.4; P = 0.01). Role functioning deteriorated from 80.1 +/- 6.5 at baseline to 62.5 +/- 8.8 at the end of radiotherapy (P = 0.02). Symptoms of fatigue were shown to increase significantly from 26.9 +/- 6.0 at baseline to 37.7 +/- 7.6 at the end of therapy (P = 0.02). No significant changes in the other dimensions were observed in either questionnaire. CONCLUSIONS: After radiotherapy for prostate carcinoma, patients experience a temporary deterioration of fatigue and role functioning, as measured with the EORTC QLQ-C-30. Despite physical deterioration, the authors observed an improvement in emotional functioning scores with both questionnaires. This may have been due to psychological adaptation and coping.

Aged↗

Overexpression of hypoxia-inducible factor 1alpha is a marker for an unfavorable prognosis in early-stage invasive cervical cancer.

Hypoxia-inducible factor 1alpha (HIF-1alpha) is a transcriptional factor that regulates genes involved in response to hypoxia and promotes neoangiogenesis, which are considered essential for tumor growth and progression. Using immunohistochemistry, we investigated the influence of HIF-1alpha expression on prognosis in 91 patients with cervical cancer stage pT1b. In univariate and multivariate analysis, patients with strong expression of HIF-1alpha had a significantly shorter overall survival time (P = 0.0307, log-rank test) and disease-free survival time (P < 0.0001, log-rank test) compared with those with moderate to absent HIF-1alpha expression. HIF-1alpha expression is a strong independent prognostic marker in early stage cervical cancer.

Adult↗

Does hysteroscopy facilitate tumor cell dissemination? Incidence of peritoneal cytology from patients with early stage endometrial carcinoma following dilatation and curettage (D & C) versus hysteroscopy and D & C.

BACKGROUND: In several case reports, distension and irrigation of the uterine cavity during fluid hysteroscopy was suspected to cause tumor cell dissemination into the abdominal cavity in patients with endometrial carcinoma. It was the aim of this study to compare the incidence of positive peritoneal cytology in patients who underwent dilatation and curettage (D & C) with or without previous hysteroscopy. METHODS: The authors conducted a multicentric, retrospective cohort analysis. One hundred thirteen consecutive patients with endometrial carcinoma treated between 1996 and 1997 were included. Endometrial carcinoma had to be limited to the inner half or less than the inner half of the myometrium (pathologic Stage IA,B). Positive peritoneal cytology was obtained during staging laparotomy. Patients underwent D & C either with or without prior diagnostic fluid hysteroscopy. No selection or randomization was applied to the two groups. Positive peritoneal cytology, defined as malignant or suspicious, was considered the primary statistical endpoint. RESULTS: Peritoneal cytology was suspicious or positive in 10 of 113 patients (9%). The presence of suspicious or positive peritoneal cytology was associated with a history of hysteroscopy (P = 0.04) but not with myometrial invasion (P = 0.57), histologic subtype (P = 1.00) or grade (r = 0.16, P = 0.10), or the time between D & C and staging laparotomy (r = 0.04, P = 0.66). CONCLUSIONS: Based on the limited extent of endometrial carcinoma in the current analysis, our data strongly suggest dissemination of endometrial carcinoma cells after fluid hysteroscopy. Determining whether a positive peritoneal cytology affects the prognoses of patients without further evidence of extrauterine disease will require longer follow-up.

Adult↗

Multiple myeloma with deletion of chromosome 13q is characterized by increased bone marrow neovascularization.

Anti-angiogenesis therapy with thalidomide has been reported to have marked activity in multiple myeloma (MM). As cytogenetics is an independent prognostic factor in MM, we analysed bone marrow (BM) angiogenesis and cytogenetic abnormalities in 34 patients with active MM. BM microvessel density (MVD), as determined by staining with anti-CD34, was significantly higher in MM (MVD: 221 +/- 94 per mm2) than in controls (80 +/- 36; P < 0.0001). In patients with the presence of at least one unfavourable cytogenetic abnormality (deletion of 13q14, deletion of 17p13, aberrations of 11q), a significantly increased BM MVD was observed (254 +/- 93 vs. 160 +/- 60 in patients with absence of these abnormalities; P = 0.0035). Further analyses indicated that increased BM MVD was significantly correlated with deletion of 13q14 (259 +/- 96 vs. 188 +/- 80; P = 0. 026), but not with other cytogenetic, clinical and laboratory MM parameters. We conclude that BM neovascularization is particularly high in MM with deletion of 13q14, which provides a rationale for use of anti-angiogenic strategies in the treatment of MM with high-risk cytogenetics.

Adult↗

Austrian women's attitudes toward and knowledge of breast self-examination.

BACKGROUND: Education of women to perform breast self-examination is a main objective of cancer societies worldwide. METHODS: By means of a questionnaire, 975 healthy women in an Austria-wide population-based cross-sectional study were asked about their knowledge of breast self-examination (BSE) and mammography, and their cancer histories. RESULTS: 92% of the women knew BSE but only 31% practiced it thoroughly. Women living in rural communities with a life companion and younger women were more likely to practice BSE. Women who had family histories of cancer, especially older women, performed BSE significantly more often. There was a trend towards increasing BSE with increasing personal perception of the risk of cancer, especially among older women. The study showed a positive association between BSE and screening mammography. CONCLUSIONS: Although knowledge of BSE is widespread, it is actually practiced by only one third of women. Older women but not young women carry out BSE significantly more often when they have family histories of cancer. Information campaigns should target specific groups and emphasize the effectiveness of properly done BSE.

Adult↗

Expression of mucins and cytokeratins in ovarian cancer cell lines.

The expression pattern of the epithelial cell markers MUC1 (CA15-3, EMA), CA125 (OC125), human epithelial antigen HEA (Ber-EP4) and cytokeratins (Ck7, Ck8, Ck7/8, Ck8/18/19) was studied in seven human ovarian cancer cell lines. We analyzed the cell lines by immunofluorescence to determine the surface as well as cytoplasmic expression. Furthermore, we evaluated the mRNA expression of MUC1, Ck18 and Ck19 by reverse transcriptase-polymerase chain reaction (RT-PCR). All cell lines were positive for MUC1. However, expression patterns and staining intensity depended on the different epitope-specific antibodies. CA125, a typical serum marker for ovarian carcinomas, was positive only in two cell lines. HEA was strongly positive in three cell lines, whereas the others expressed the antigen only weakly in the cytoplasm. Ck7 was not expressed in three of the seven cell lines. Ck7/8 was detectable in all cell lines and was strongly expressed in four of them. MUC1 mRNA was expressed by all cell lines as detected by RT-PCR. These findings permit selection of a suitable marker for the detection of disseminated ovarian cancer cells.

Antigens, Neoplasm↗

Prognostic significance of tumor angiogenesis in primary fallopian tube cancer.

Tumor angiogenesis has been found to be prognostically significant in many types of malignant tumors. We assessed tumor vascularity in 43 cases of histologically proven primary fallopian tube cancer, FIGO stage I-IV, using the highly specific endothelial cell marker CD34. Microvessel count was determined by counting CD34-positive cells at 200 x magnification. The 5-year disease-free survival probability was 43.8% (+/- 11.5%) in 24 patients whose tumors had a microvessel count < or = 19 microvessels/field and 19.7% (+/- 9.5%) in the > 19 microvessels/field group (P = 0.046). Stage and microvessel count were statistically significant for disease-free survival in univariate analysis. Therefore, a larger sample size would be required to detect an independent and statistically significant prognostic effect of microvessel density in primary fallopian tube cancer in multivariate analysis.

Adult↗

Serum concentrations of squamous cell carcinoma antigen in patients with vulvar intraepithelial neoplasia and vulvar cancer.

Our aim was to evaluate whether serum concentrations of squamous cell carcinoma antigen (SCC-Ag) are an independent prognostic factor in patients with vulvar cancer. We measured SCC-Ag in pretreatment serum samples of 55 patients with squamous cell vulvar cancer, 30 patients with vulvar intraepithelial neoplasia (VIN) grade III and 50 healthy female controls. The results were compared with clinical data. Median serum concentrations of SCC-Ag in healthy female controls, patients with VIN III, and patients with invasive vulvar cancer were 0.5 (range 0.1 to 3.8) ng/mL, 0.5 (range 0 to 4.1) ng/mL and 1.6 (range 0.3 to 65) ng/mL, respectively (Mann-Whitney U test, p < 0.001). The 75% quantile of serum concentrations of SCC-Ag in patients with vulvar cancer was defined as cut-off level. Elevated pretreatment serum concentrations of SCC-Ag were significantly correlated with a shorter disease-free and overall survival (log-rank test, p=0.002; and p<0.001, respectively). A multivariate Cox regression model showed that serum concentrations of SCC-Ag are a prognostic factor of disease-free and overall survival independent of tumour stage (multivariate Cox regression model, p=0.03; and p=0.048, respectively). Pre-treatment serum concentrations of SCC-Ag were not correlated with tumour stage, histological grade and patients' age. In summary, our data indicate that serum concentrations of SCC-Ag may be an additional independent prognostic factor of disease-free and overall survival in patients with vulvar cancer.

Adult↗

Prognostic significance of tumor angiogenesis in epithelial ovarian cancer.

Since angiogenesis is considered essential for tumor growth and the development of metastasis, we assessed the correlation of microvessel density (MVD) with overall survival in patients with epithelial ovarian cancer. Histologic slides were immunostained for CD34-antigen. MVD 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. In 63 patients with epithelial ovarian cancer the 5-year survival rate (OS-%) was as follows: 55.0% (+/-12.5) in 18 patients whose tumors had an MVD < 10/field, and 23.6% (+/-6.7) in 45 patients whose tumors had an MVD(10/field (log-rank P = 0.038). MVD showed a significant influence on survival in univariate analysis, but failed to attain a significant value after adjustment for established prognostic parameters such as patients' age at diagnosis, stage of disease, and histologic grading. High MVD was significantly associated with advanced patients' age at diagnosis. This and a considerable heterogenity in the vascular architecture of ovarian carcinoma tissue might be the reasons why MVD did not reveal prognostic significance in multivariate analysis. In contrast to a variety of solid neoplasms, MVD does not seem to be a useful predictor of survival in patients with epithelial ovarian cancer.

Adult↗

[Angiogenesis in gynecology and obstetrics].

In current scientific discussion, increasing importance is being given to the clinical significance of the new formation of vessels (angiogenesis) in the course of physiological, inflammatory and neoplastic processes. Angiogenesis is best studied in the growth of malignant tumors, since cancer may be regarded as the most important angiogenesis-dependent disease in terms of social and economic aspects. The significance of angiogenesis in gynecological oncology is as follows: 1) Intratumoral vessel density is an indicator for the emergence and growth of malignant tumours and their precursor lesions, 2) intratumoral vessel density is an independent prognostic factor for solid malignancies and 3) the inhibition of tumor angiogenesis by means of anti-angiogenetic substances causes tumor growth to be suppressed. Angiogenesis also plays an important role in the regulation of the female menstrual cycle. Proliferation of the endometrium and the formation of the corpus luteum in the second half of the menstrual cycle are examples of angiogenesis in the physiological field. The function of angiogenetic factors in the emergence of endometriosis and in female and male infertility are currently under study. In obstetrics, the new formation of blood vessels is significant for the implantation of impregnated blastocysts and for the development and growth of the placenta. Preeclempsia (gestational toxicosis), for instance, is a typical pregnancy-related disease whose pathophysiological mechanism is attributed to a disturbed development and function of small placental vessels. The present paper is an overview of current knowledge and current approaches of research concerning angiogenesis in the field of gynecology and obstetrics. The paper is focused on the clinical significance of angiogenesis.

Angiogenesis Inducing Agents↗

Leiomyosarcoma of the uterus: a clinicopathologic multicenter study of 71 cases.

OBJECTIVE: The aim of this study was to evaluate the behavior of uterine leiomyosarcomas in relation to their clinical and pathologic features and to identify possible prognostic factors. METHODS: Seventy-one patients with histologically proven uterine leiomyosarcoma were included in the analysis. Leiomyosarcomas were defined as uterine smooth-muscle tumors with five or more mitoses per 10 high-power fields and cytologic atypia. Cox proportional hazards regression model was used to identify independent prognostic factors. RESULTS: The median follow-up time was 108 months; 5-year overall survival rate was 65%. Evaluating the correlation between several clinicopathologic parameters, tumors with vascular space involvement had a statistically significantly higher stage than tumors without vasular space involvement (P = 0.015). In a univariate Cox model early tumor stage (P < 0.0001), age <50 years (P < 0.0001), low mitotic count (P = 0.05), and the absence of vascular space involvement (P < 0.0005) were associated with good prognosis. In a multivariate analysis age (P = 0.002), tumor stage (P = 0.004), vascular space involvement (P = 0.003), and mitotic count in stage I tumors (P = 0.002) were found to be independent parameters for good prognosis in patients with uterine leiomyosarcoma. CONCLUSION: Early tumor stage, age <50 years, and absence of vascular space involvement were independently associated with good prognosis. Mitotic count was detected to be a strong prognostic parameter in early tumor stage, but failed to act as an independent prognostic parameter in patients with tumor stage II-IV disease.

Adult↗

Vascular endothelial growth factor and its receptors in male fertility.

OBJECTIVE: To determine the concentration of vascular endothelial growth factor in the seminal fluid, the presence of vascular endothelial growth factor receptors Flt-1 and KDR in spermatozoa, and the predictive value of seminal vascular endothelial growth factor on fertilization and the chance of pregnancy in patients undergoing intracytoplasmic sperm injection (ICSI) or IVF. DESIGN: Retrospective analysis. SETTING: Private institute (semen collection, IVF/ICSI) and academic research environment (analysis of seminal fluid and spermatozoa). PATIENT(S): Eighty men whose spermatozoa were subsequently used for IVF or ICSI. INTERVENTION(S): Seminal vascular endothelial growth factor was measured by an EIA. Spermatozoa were analyzed by fluorescence-activated cell sorter analysis and by immunocytochemistry. MAIN OUTCOME MEASURE(S): Oocyte fertilization rate, pregnancy rate, and presence of vascular endothelial growth factor receptors on spermatozoa. RESULT(S): Patients with a seminal concentration of vascular endothelial growth factor of 2-100 ng/mL had a sixfold increased chance of pregnancy. Vascular endothelial growth factor concentration and patient's age remained the only independent prognostic factors for pregnancy. The concentration of vascular endothelial growth factor did not correlate with indices of male factor infertility or with the oocyte fertilization rate. Expression of vascular endothelial growth factor receptors (Flt-1, KDR) on spermatozoa was demonstrated. CONCLUSION(S): The seminal concentration of vascular endothelial growth factor correlates with the chance of pregnancy in patients undergoing IVF or ICSI. Vascular endothelial growth factor receptors Flt-1 and KDR were detected on spermatozoa for the first time.

Adult↗