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  • 1
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  129. Kongress der Deutschen Gesellschaft für Chirurgie; 20120424-20120427; Berlin; DOC12dgch298 /20120423/
    Publication Date: 2012-04-24
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 2
    Keywords: CELL LUNG-CANCER ; GENE ; PROTEINS ; BREAST-CANCER ; METASTASIS ; DISSEMINATED TUMOR-CELLS ; IMBALANCES ; METHYLATION ; TUMORIGENESIS ; CHROMOSOME 4Q
    Abstract: For better lung cancer diagnosis and therapy, early detection markers of tumor dissemination are urgently needed, as most lung cancers do not show symptoms until extensive metastasis formation has already taken place. Our previous studies showed that in non-small cell lung cancer (NSCLC) early tumor dissemination is associated with a loss of chromosome 4q12-q32 and the presence of disseminated tumor cells (DTC) in the bone marrow. In order to identify the potential target gene in this region, a screen for methylation-dependent expression was performed. Lung cancer cell lines showing a loss of 4q as well as a normal bronchial epithelial cell line as control were treated with 5-aza-2'-deoxycytidine (5-aza-CdR) followed by expression profiling. Seven genes within the 4q target region, which have been associated with a positive DTC status before were found to be regulated by hypermethylation. QRT-PCR in an independent sample set identified HERC5 as a potential target gene. Quantitative methylation analysis of these lung tissue samples revealed that HERC5 promoter hypermethylation was significantly associated with positive DTC status (p=0.020) and occurrence of brain metastases (p=0.015). In addition, hypermethylation of the HERC5 promoter in NSCLC was identified as a predictor for poor survival for Stage I adenocarcinoma patients (p=0.022) and also for poor overall survival in metastatic lung cancer patients (p=0.028). In conclusion, HERC5 may function as a prognostic marker and is associated with tumor dissemination in lung cancer. What's new? In order to improve the diagnosis and therapy of lung cancer, early biomarkers of tumor dissemination are urgently needed. In this study, the authors found that the HERC5 gene on chromosome 4 may be involved in regulating the spread of non-small cell lung cancer (NSCLC) tumors. In cases where the promoter region of HERC5 was hypermethylated, the number of disseminated tumor cells (DTC) and metastases increased, and survival decreased. HERC5 may thus be a new metastasis-suppressor gene, and its methylation and expression status may provide prognostic biomarkers for NSCLC.
    Type of Publication: Journal article published
    PubMed ID: 25353388
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  • 3
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  127. Kongress der Deutschen Gesellschaft für Chirurgie; 20100420-20100423; Berlin; DOC10dgch099 /20100517/
    Publication Date: 2010-05-17
    Keywords: ddc: 610
    Type: conferenceObject
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  • 4
    Publication Date: 2018-06-16
    Description: Purpose: Pancreatic cancer is one of the most devastating diseases with a 5-year survival rate of 3% to 5%. Here, we investigated whether circulating tumor cells (CTC) may predict metastatic spread and survival in pancreatic cancer patients. Experimental Design: In a prospective study, we enrolled 69 pancreatic cancer patients. In peripheral blood, CTCs were identified by MACS enrichment (anti-cytokeratin/anti-EpCam) and subsequent automated analysis after combined anti-cytokeratin/anti-CD45/DAPI staining. CTC results were correlated to established clinicopathologic risk factors, detection of disseminated tumor cells (DTC) in bone marrow, and clinical outcome (follow-up time: 48 months). Results: Median patient survival was 11 months (0–48 months). Thirty-eight patients were male and 31 were female, and the majority received gemcitabine (58/69). CTCs were present in 23 of 69 patients (33.3%) ranging from 1 to 19 cells (17 with 〉1 CTC). Although clinicopathologic parameters and DTC status did not correlate with CTC incidence, progression-free survival (PFS) and overall survival (OS) were significantly reduced in CTC-positive patients in univariate ( P = 0.009, PFS; P = 0.030, OS, both log rank) and multivariate analysis [HR = 4.543; confidence interval (CI), 1.549–13.329; P = 0.006, PFS; HR = 2.093; CI, 1.081–4.050; P = 0.028, OS, both Cox regression). Also within patients receiving chemotherapy, PFS was significantly reduced in CTC-positive patients in univariate ( P = 0.013) and multivariate (HR = 4.203; CI, 1.416–12.471; P = 0.010) analysis. Conclusions: CTCs affect the outcome of patients with pancreatic cancer independent from other risk factors, including patients receiving (adjuvant) cytotoxic therapy. CTC stratification may allow a better upfront identification of patients with a longer lifespan who might profit from new adjuvant therapies. Clin Cancer Res; 24(12); 2844–50. ©2018 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 5
    Publication Date: 2018-10-02
    Description: Background/Aim: The clinical significance of circulating tumor cells (CTC) in non-metastatic esophageal cancer (EC) remains controversial and the cellular and molecular characteristics of CTCs are poorly understood. Especially the frequency and oncological impact of HER2 expression in CTCs in patients with EC have not been evaluated until now. Materials and Methods: In this single-center, prospective study, peripheral blood samples were obtained preoperatively from 45 patients who were diagnosed with resectable EC. CTC detection and HER2 expression were performed using the CellSearch System. Data were correlated with clinicopathological parameters and patient outcomes. Results: The study included 13 patients with squamous cell carcinomas (SCC) and 32 patients with adenocarcinomas (AC). HER2 gene amplification in the primary tumor was detected in 9.1% of patients. One or more CTCs were detected in 15.6% (SCC 1/13; AC 6/32) of the patients. None of the detected CTCs showed HER2 expression. Patients with CTCs showed significantly shorter relapse-free (p〈0.001) and overall survival (p=0.015) than CTC-negative patients. Conclusion. This is the first study analyzing HER2 expression and the clinical significance of CTCs in patients with non-metastatic EC using an automated immunomagnetic detection system. HER2 expression in CTCs is very rare in patients with non-metastatic EC and seems to have a low clinical and oncological impact
    Print ISSN: 0250-7005
    Electronic ISSN: 1791-7530
    Topics: Medicine
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