Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prognostic significance of the inactivation of the p16, p15, and p14 genes has been reported in lymphoid malignancies in humans. To evaluate the relationship between inactivation of the p16, p15, and p14 genes and prognosis in canine high-grade lymphoma, primary tumor cell samples obtained from 71 dogs with high-grade lymphoma were examined for the expression levels of these genes. Quantitative and conventional reverse transcriptase-polymerase chain reaction (RT-PCR) analyses were used to measure the amounts of p16, p15, and p14 mRNAs. The methylation status of the CpG island of the p16 gene was evaluated using methylation-specific PCR. Overall survival (OS) was compared using the Kaplan-Meier method. The log-rank test and Cox proportional hazard model were used to evaluate factors that influenced OS. Of 62 dogs examined, p16, p15, and p14 mRNA levels were found to be undetectable in 21, 18, and 10 dogs, respectively. In 20/68 dogs analyzed, the CpG island of the p16 gene was shown to be methylated. The prognostic significance of inactivation of the p16, p15, and p14 genes as well as various conventional factors obtained from medical records was examined. p16 expression status and anatomic form/immunophenotype were found to correlate with OS in the dogs with high-grade lymphoma. p16 mRNA level over its cut-off value correlated with a poor prognosis; however, the expression levels of p15 and p14 mRNAs and p16 methylation status did not influence the prognosis in dogs with high-grade lymphoma.
...
PMID:Prognostic significance of the expression levels of the p16, p15, and p14 genes in dogs with high-grade lymphoma. 2436 70

Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is recognized as a distinct disease entity associated with improved survival. DNA hypermethylation profiles differ significantly by HPV status suggesting that a specific subset of methylated CpG loci could give mechanistic insight into HPV-driven OPSCC. We analyzed genome-wide DNA methylation of primary tumor samples and adjacent normal mucosa from 46 OPSCC patients undergoing treatment at Montefiore Medical Center, Bronx, NY using the Illumina HumanMethylation27 beadchip. For each matched tissue set, we measured differentially methylated CpG loci using a change in methylation level (M value). From these analyses, we identified a 22 CpG loci panel for HPV+ OPSCC that included four CDKN2A loci downstream of the p16(INK4A) and p14(ARF) transcription start sites. This panel was significantly associated with overall HPV detection (P < 0.05; ROC area under the curve = 0.96, 95% CI: 0.91-1.0) similar to the subset of four CDKN2A-specific CpG loci (0.90, 95% CI: 0.82-0.99) with equivalence to the full 22 CpG panel. DNA hypermethylation correlated with a significant increase in alternative open reading frame (ARF) expression in HPV+ OPSCC primary tumors, but not to the other transcript variant encoded by the CDKN2A locus. Overall, this study provides evidence of epigenetic changes to the downstream region of the CDKN2A locus in HPV+ oropharyngeal cancer that are associated with changes in expression of the coded protein products.
 ...
PMID:Epigenetic changes in the CDKN2A locus are associated with differential expression of P16INK4A and P14ARF in HPV-positive oropharyngeal squamous cell carcinoma. 2561 63

Chromodomain helicase DNA-binding protein 5 (CHD5) plays a crucial tumor suppressor role in multiple types of tumors. For this study, we investigated its clinical significance and the molecular mechanism(s) underlying tumorigenesis in renal cell carcinoma (RCC). Initially, CHD5 expression was assessed in primary tumor tissue and in tissue array. Correlations among CHD5 expression and clinicopathological characteristics were analyzed. Next, lentivirus-mediated CHD5 overexpression in the ACHN and 769-P cells was used to assess effects on proliferation, migration, invasion ability, and the regulation of the p14ARF/p53 and p16INK4a/RB signaling pathways. Finally, a xenograft mouse model was used to verify its impact on tumor growth in vivo. Results demonstrated that CHD5 was downregulated in tumor tissues and that low CHD5 expression was correlated with advanced TNM stage, high Fuhrman grade, lymph node metastasis, and poor survival. Overexpression of CHD5 inhibited proliferation, migration, and invasion in vitro; prompted cell cycle G1 phase arrest; induced apoptosis; and suppressed tumor growth in vivo. Furthermore, we confirmed that CHD5 activates the p53 and RB pathways to inhibit tumorigenesis in RCC. In summary, CHD5 is involved in the initiation and progression of RCC and may serve as a diagnostic biomarker and a potential therapeutic target for RCC.
 ...
PMID:Chromodomain Helicase DNA-Binding Protein 5 Inhibits Renal Cell Carcinoma Tumorigenesis by Activation of the p53 and RB Pathways. 3306 82


<< Previous 1 2