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  • 1
    Keywords: EXPRESSION ; CELL-PROLIFERATION ; RISK ; PROTEIN ; MESSENGER-RNA ; COLON-CANCER ; STABILITY ; LIVER METASTASES ; POLYPS ; FALSE DISCOVERY RATE
    Abstract: Deregulation of apoptosis is a frequent alteration in early benign lesions of the colon mucosa and is thought to be a major contributor to tumor progression and cancer. Single nucleotide polymorphisms (SNPs) within apoptosis-related genes could affect apoptotic responses and their identification might provide a basis to assess individual risk for development of early lesions. To investigate a possible association between genetic polymorphisms and the occurrence of hyperplastic polyps (HP), we developed a custom DNA chip assay for 1,536 SNPs in the coding and flanking regions of 826 genes with known functional roles in apoptosis or apoptosis-associated (e. g., stress-related) pathways. During a first round of screening, genotypes were determined for 272 endoscopy patients harboring hyperplastic colorectal polyps and for 512 sex and aged-matched controls. A set of 14 candidate SNPs associated with HP (P 〈 0.01) was then evaluated in an independent cohort of patients (n = 38) and controls (n = 38). Following meta-analysis of Stages I and II, a false discovery rate approach was applied. Among the 14 candidate SNPs, eight showed significant association (combined P 〈 0.01) with the occurrence of HP. The SNPs rs4709583 (PARK2) and rs10476823 (HDAC3) were analyzed for potential functional effects on RNA splicing and RNA half-life. Despite its location near a splice site, alternative splicing was not detected for rs4709583 (PARK3). By contrast, cDNA analysis revealed use of a cryptic polyadenylation signal in the 3'UTR of HDAC3 mRNA and a longer mRNA half-life in a cell line heterozygous for rs10476823.
    Type of Publication: Journal article published
    PubMed ID: 24861865
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  • 2
    Keywords: COLON-CANCER ; PROGNOSTIC-SIGNIFICANCE ; PANCREATIC-CANCER ; ANTI-P53 ANTIBODIES ; HUMORAL IMMUNE-RESPONSE ; PROTEOMICS-BASED IDENTIFICATION ; SERUM P53 ANTIBODIES ; CIRCULATING ANTIBODIES ; CANCER/TESTIS ANTIGEN ; AUTOIMMUNE-RESPONSE
    Abstract: Multiple studies have shown that cancer patients produce detectable autoantibodies against certain tumor-associated antigens, which might be promising blood biomarkers for early detection of colorectal cancer (CRC). We aimed to provide an overview of published studies on blood autoantibody markers for early detection of CRC and to summarize their diagnostic performance. A systematic literature search was performed in PubMed, ISI Web of Knowledge and EMBASE to find relevant studies published until 23 July 2013. Relevant information, such as study population characteristics, autoantibodies studied, analytical methods and diagnostic performance characteristics was independently extracted by two reviewers. Overall, 67 studies evaluating 109 autoantibody markers were included. Most individual markers showed low sensitivity (below 25%) for detecting CRC, along with high specificity close to 100%. Occasionally reported higher sensitivities for specific antibodies are yet to be replicated in independent studies. Generally, more promising results were seen for combinations of multiple autoantibody markers. But again, these promising results are yet to be replicated in other samples. In conclusion, autoantibody signatures may become a promising approach to noninvasive CRC screening. Optimized marker panels are yet to be developed, and promising results require validation in large screening populations.
    Type of Publication: Journal article published
    PubMed ID: 24462820
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