Preoperative measurement of methylated DAPK and APC promoter DNA in peripheral blood may contribute to better estimate postoperative survival chances of patients with esophageal carcinoma, especially adenocarcinoma. The postoperative detection of methylated APC in peripheral blood might provide crucial information on apparent residual tumor and might be used as a "molecular" R0-Marker in addition to the pathologic examination.
This is the first report showing that direct quantitative real-time RT-PCR analysis of survivin mRNA expression in peripheral blood of patients with gastrointestinal cancers is technically feasible. Survivin mRNA levels fall significantly following complete resection and might become a molecular marker for the completeness of surgical resection.
The TIG3 gene is a retinoic acid inducible class II tumor suppressor gene downregulated in several human tumors and malignant cell lines. Diminished TIG3 expression correlates with decreased differentiation whereas forced expression of TIG3 suppresses oncogenic signaling pathways and subsequently induces differentiation or apoptosis in tumor cells. Analysis of TIG3 mRNA expression in a large set of cDNA pools derived from matched tumor and normal human tissues showed a significant downregulation of TIG3 in 29% of the cDNA samples obtained from ovarian carcinomas. Using in situ hybridization, we demonstrated expression of TIG3 in the epithelial lining of 7 normal ovaries but loss of TIG3 expression in 15/19 of human ovarian carcinoma tissues. In SKOV-3, CAOV-3 and ES-2 ovarian carcinoma cell lines, downregulation of TIG3 mRNA was reversible and dependent on an activated MEK-ERK signaling pathway. Re-expression of TIG3 mRNA in these cells upon specific interference with the MEKpathway was correlated with growth inhibition of the cells. In OVCAR-3 and A27/80 ovarian carcinoma cells, TIG3 suppression is MEK-ERK independent, but expression could be reconstituted upon interferon gamma (IFNc) induction. Overexpression of TIG3 in A27/80 ovarian carcinoma cells significantly impaired cell growth and despite increased mRNA levels, TIG3 protein was hardly detectable. These results suggest that TIG3 is negatively regulated by an activated MEK-ERK signaling pathway. Further mechanisms must interfere with TIG3 expression that are independent of MEK and partially include interferon-responsive components. ' 2005 Wiley-Liss, Inc.
166 Background: miR-210 is a known transcriptional target of the hypoxia-responsive HIF-1α signaling pathway. However, the association between the expression of miR-210 and the tumor progression in prostate cancer (PCa) remains unclear. Methods: We isolated miRNA by miRNeasy FFPE kit (Qiagen, Hilden, Germany) from paraffin-embedded tissues of 87 prostate specimens with adenocarcinoma of the prostate cancer in different tumor stages, with high-grade prostatic intraepithelial neoplasia (HGPIN) and normal tissues. Organ-confined PCa was defined as PCa with pT2 tumor stage, Gleason score ≤ 7a and PSA level < 10 ng/ml. PCa with pT3/4 or Gleason > 7a was defined as advanced PCa. PCa with pN1 were considered as metastatic diseases. Additionally, 3 cases with castration-resistant prostate cancer (CRPC) were considered. Quantitative miR-210 expression data were acquired and analyzed using a real-time TaqMan-based PCR with the ABI Prism 7900HT (Life Technologies, Darmstadt, Germany). ANOVA and post hoc analysis according to Turkey were performed using SPSS 22 (IBM, Armonk, USA). For silico analysis, Diana tools were applied to determine target genes of miR-210 and related functions and pathways. All the statistical tests were two-sided, and the level of statistical significance was set at P < 0.05. The small nuclear U6 RNA was used as an endogenous control. Results: ANOVA revealed significant differences in expression levels of miR-210 according to the tumor progression. Interestingly, organ-confined PCa showed the lowest expression level of miR-210 in our analysis. No sig. differences in miR-210 expression between normal tissues, HGPIN and organ-confined PCa and between advanced PCa, metastatic diseases and CRPC were observed. However, miR-210 expression was significantly higher in metastatic diseases and CRPC in comparison to organ-confined PCa. The silico analysis showed that genes regulated by miR-210 were associated with homologous recombination, non-homologous end-joining, the cell cycle regulation and synthesis of DNA. Conclusions: We observed an enhanced overexpression of hypoxia-related miRNA-210 in primary tumor of metastatic prostate cancer and CRPC in comparison to organ-confined PCa.
miR-210 was significantly higher in N1 PCa compared with nonmetastatic PCa, whereas the metastatic tumor revealed a lower expression level of miR-210 than the primary tumor.
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