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Biomedical subjects

Lukas Hefler

Publications and source records attributed to Lukas Hefler.

29 records · Page 2Linked to original sources
PubMed2003

Role of p53 in G2/M cell cycle arrest and apoptosis in response to gamma-irradiation in ovarian carcinoma cell lines.

We investigated the cell cycle and apoptotic response to irradiation in 4 human ovarian carcinoma cell lines, i.e., PA-1, Caov-3, SK-OV-3, and ES-2. Cell lines were also analysed for their p53 and Bax expression to address the relationship with cell cycle and apoptotic response. Apoptosis was examined by flow cytometric measurement of annexin V binding and by determination of cytoplasmic histone-associated DNA fragments with a photometric enzyme immunoassay. Cell cycle analyses were performed on the basis of flow cytometry. p53 and Bax protein expression was examined by immunocytochemistry in untreated cells and after irradiation. p53 cDNA sequencing and a functional yeast-based assay (FASAY) were performed to determine the p53 mutational status. All cell lines exhibited a dose-dependent G2/M arrest. No arrest in G1 was seen. A strong correlation was found between the G2/M arrest and the induction of apoptosis. PA-1, the only cell line found to express wild-type p53, showed the highest susceptibility to accumulate in G2/M and the strongest apoptotic response after irradiation. In this cell line irradiation resulted in an unequivocal accumulation of p53 protein and in an increased expression of Bax protein. Caov-3, lacking wild-type p53, showed upregulation of Bax expression after irradiation. Caov-3 proved to be relative sensitive to apoptosis compared to SK-OV-3 and ES-2. These two cell lines were found to be p53 mutated in sequence analysis and irradiation had no effect on the expression of p53. No change in Bax expression was seen in ES-2, while SK-OV-3 exhibited decreased Bax protein levels after irradiation. Our data suggest that the G2/M arrest is an important component of the pathway leading from irradiation-induced DNA damage to apoptosis in the examined cell lines. The G2/M arrest and associated apoptosis found in the examined cell lines does not necessarily require wild-type p53, although wild-type p53 and possibly Bax may contribute to a maximum response to irradiation. Two independent mechanisms, p53-dependent and p53-independent, are suggested in the examined cell lines.

Apoptosis↗
PubMed2002

Mental well-being in 5000 women participating in the 'Women-Plus' preventive medicine program.

In the present study, we report on an additive evaluation of mental well-being in an established program of preventive medicine including general and gynecologic examination, and screening mammography. An easy-to-use questionnaire including 19 questions was completed by 5247 women. Answers were grouped into mental well-being, zest for living, sexuality, and self-assessment of psychic disorders. A risk score for the presence of major depression was calculated. Women with high and intermediate risk for major depression were found in 5.0-7.2% and 15.4-19.8% depending on age, respectively. Seven to 9.2% and 19.2-26.5% of women suspected themselves to be at a high and intermediate risk for psychic disorders, respectively. Deterioration of well-being as well as the risk of developing depression is mostly overlooked in a general preventive medicine setting. We conclude that problems involving mental well-being seem to affect a significant number of women. The incorporation of easy-to-use questionnaires able to screen for mental problems to general preventive medicine programs must be strongly recommended.

Adult↗
PubMed2002

Serum vascular endothelial growth factor and serum leptin in patients with cervical cancer.

OBJECTIVE: Serum levels of vascular endothelial growth factor (VEGF) can be seen as surrogate markers of angiogenesis. Recently, leptin, which is involved in the control of satiety and energy expenditure, was also shown to modulate angiogenesis. As angiogenesis plays an abundant role in cervical carcinogenesis, we evaluated serum VEGF and leptin in patients with cervical intraepithelial neoplasia (CIN) and cervical cancer. METHODS: Serum VEGF and leptin were measured in 84 patients with cervical cancer, in 28 patients with CIN I-III, and in 35 healthy women, using a commercially available enzyme-linked immunosorbent assay and radioimmunoassay, respectively. RESULTS: Serum VEGF was significantly elevated in patients with cervical cancer and in patients with CIN I-III compared to healthy women. In patients with cervical cancer serum VEGF was significantly correlated with tumor stage, but not with lymph node involvement and histological grade. Univariate and multivariate analyses showed that elevated pretreatment serum VEGF was not associated with the duration of disease-free and overall survival. Serum leptin did not differ among patients with cervical cancer, patients with CIN I-III, and healthy women. Serum leptin was significantly correlated with body mass index (BMI). All further analyses were performed with absolute and serum leptin corrected by BMI. No differences in serum leptin could be ascertained between patients with cervical cancer and patients with CIN I-III. Serum leptin was not associated with any clinicopathological parameter and patients' survival. No correlation between serum VEGF and leptin was found. CONCLUSIONS: It can be speculated that serum VEGF might be used as a surrogate marker of angiogenesis in patients with cervical cancer. Our data support the concept that VEGF plays a role in malignant transformation and tumor growth, but not in the lymphatic spread of cervical cancer. This is the first report on leptin in a gynecological malignancy. Our results show that serum leptin falls short of being a useful marker in patients with cervical cancer.

Adult↗
PubMed2002

Transforming growth factor-beta 1 serum levels in pregnancy and pre-eclampsia.

BACKGROUND: Isoforms of transforming growth factor-beta (TGF-beta1) are thought to be involved in the pathogenesis of pre-eclampsia. Data with respect to TGF-beta1 are controversial. We examined the correlation between TGF-beta1 serum levels and the occurrence and severity of pre-eclampsia. METHODS: Transforming growth factor-beta 1 serum levels were measured using a commercially available enzyme-linked immunosorbent assay in 44 women with pre-eclampsia and 44 healthy pregnant women. Results were correlated with clinical data. RESULTS: No difference in TGF-beta1 serum levels was assessed between women with pre-eclampsia and healthy pregnant women. Transforming growth factor-beta 1 serum levels were not associated with the severity of the disease and were not correlated with clinical maternal (blood pressure, proteinuria) and fetal (5-min APGAR score, umbilical cord pH values, birth weight) parameters. CONCLUSIONS: Our data support the assumption that in contrast to other isoforms, TGF-beta1, as evidenced by serum TGF-beta1 levels, does not seem to be involved in the pathogenesis of pre-eclampsia.

Adult↗
PubMed2002

Serum levels of squamous cell carcinoma antigen as a predictor of inguinofemoral lymph node metastasis in patients with vulvar cancer.

OBJECTIVE: To evaluate the predictive value of preoperatively determined squamous cell carcinoma antigen (SCC-Ag) serum levels for the risk of inguinofemoral lymph node metastasis. STUDY DESIGN: In this retrospective trial, preoperative serum levels of SCC-Ag in 29 patients with invasive squamous cell vulvar cancer (pT1 + 2) were evaluated and compared with nodal status. RESULTS: Twenty patients had negative inguinofemoral nodes, whereas in nine an inguinofemoral lymph node metastasis could be observed. The median SCC-Ag in women with negative nodes was 1.3 micrograms/L (0.2-11.5) and with positive nodes, 2.7 micrograms/L (0.4-9.1) (P = .35). CONCLUSION: Measurement of the serum level of SCC-Ag cannot be used for preoperative evaluation of the risk of lymph node metastasis in patients with clinically localized tumors since there is a significant overlap between both cohorts.

Adult↗
PubMedDate not supplied

Monocyte chemoattractant protein-1 serum levels in patients with breast cancer.

The chemokine monocyte chemoattractant protein (MCP)-1 is thought to be involved in breast carcinogenesis. We evaluated MCP-1 serum levels in patients with breast cancer (n = 135), ductal carcinoma in situ (DCIS) I-III (n = 30), benign breast lesions (n = 143) and in healthy women (n = 27). We determined the value of MCP-1 serum levels as a differentiation marker between malignant, preinvasive and benign breast diseases and as a predictive marker for the biological phenotype of breast carcinoma. Median (range) MCP-1 serum levels in patients with breast cancer, DCIS I-III, benign breast lesions and healthy women were 200 (57-692) pg/ml, 194 (58-525) pg/ml, 174 (39-529) pg/ml and 175 (67-425) pg/ml, respectively. No differences were ascertained between the patient groups. In patients with breast cancer, increased MCP-1 serum levels were correlated with advanced tumor stage (p = 0.04) and lymph node involvement (p = 0.04). We were not able to establish MCP-1 as a differentiation marker between malignant and benign breast diseases. Our data might indicate that MCP-1 influences breast carcinogenesis by facilitating tumor growth and metastatic spread, thus altering the biological phenotype of the disease.

Adult↗
PubMedDate not supplied

Histological category and expression of hormone receptors in ductal carcinoma in situ of the breast.

BACKGROUND: While the role of estrogen receptor (ER) and progesterone receptor (PR) status in invasive breast cancer has been clinically established, data with respect to their role in ductal carcinoma in situ of the breast (DCIS) are sparse. PATIENTS AND METHODS: We reviewed 120 consecutive patients with DCIS I-III. Detailed histological categorization and immunohistochemical staining for ER and PR were performed and correlated with clinical data. RESULTS: DCIS I, DCIS II, and DCIS III were found in 51, 36 and 33 patients, respectively. Comedo-type tumors (p<0.001), presence of tumor necrosis (p<0.001) and absence of ER (p=0.005) were significantly associated with poorly-differentiated DCIS. No association was ascertained between PR expression and grade of DCIS. Hormone receptor expression was independent of the patients' menopausal status. CONCLUSION: We support the assumption that DCIS I-III is morphologically and biologically heterogeneous. Our results contribute further data on the role of ER and PR in the pathogenesis and progression of DCIS.

Adult↗
PubMedDate not supplied

The correlation between immunohistochemically-detected markers of angiogenesis and serum vascular endothelial growth factor in patients with breast cancer.

BACKGROUND: As angiogenesis is known to be a crucial factor in breast cancer growth, numerous studies have examined angiogenic markers in breast cancer. Their definite role, however, has not been fully elucidated. MATERIALS AND METHODS: We investigated intratumoral microvessel density (MVD), Vascular Endothelial Growth Factor (VEGF) and its receptor flk-1, and serum VEGF in 46 patients with breast cancer prior to surgery. RESULTS: Median serum VEGF in patients with breast cancer was 257.5 pg/mL (range, 21.9 to 899.6). Serum VEGF showed a significant correlation with tumor stage, but not with lymph node involvement, histological grade, estrogen and progesterone receptor status. Increased MVD was associated with advanced tumor stage (p=0.05) and high tumor grade (p<0.001). A linear significant correlation between elevated serum VEGF and increased MVD was ascertained (p=0.02). CONCLUSION: Our results suggested that angiogenesis as reflected by immunohistochemically-detected MVD and serum VEGF, is involved in breast cancer growth and lymphatic spread.

Biomarkers, Tumor↗
PubMedDate not supplied

Thrombocytosis and anaemia in women with recurrent ovarian cancer prior to a second-line chemotherapy.

BACKGROUND: To investigate the incidence and the prognostic value of platelet count and serum haemoglobin (Hb) in patients with recurrent ovarian cancer prior to second-line chemotherapy. MATERIALS AND METHODS: Clinical records were reviewed for 31 patients with recurrent ovarian cancer. Survival analysis was evaluated by univariate (Kaplan-Meier product limit method and log-rank test) analysis. We analysed the results for the overall survival. Anaemia and thrombocytosis were defined as a serum Hb level < 12 g/dl and as platelet count > 300,000/microL, respectively. RESULTS: Thrombocytosis and tumour anaemia were present in 55% and 42% of the patients, respectively. Tumour anaemia was of no prognostic value with respect to overall survival in our series. In patients with thrombocytosis, the median survival rate was reduced (p = 0.05). CONCLUSION: Our data suggest that a platelet count > 300,000/microL appears to be an adverse prognostic parameter in patients with recurrent ovarian cancer prior to a second-line chemotherapy.

Adult↗