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Find video protocols related to scientific articles indexed in Pubmed.
The 19q12 Bladder Cancer GWAS Signal: Association with Cyclin E Function and Aggressive Disease.
Yi-Ping Fu, Indu Kohaar, Lee E Moore, Petra Lenz, Jonine D Figueroa, Wei Tang, Patricia Porter-Gill, Nilanjan Chatterjee, Alexandra Scott-Johnson, Montserrat Garcia-Closas, Brian Muchmore, Dalsu Baris, Ashley Paquin, Kris Ylaya, Molly Schwenn, Andrea B Apolo, Margaret R Karagas, McAnthony Tarway, Alison Johnson, Adam Mumy, Alan Schned, Liliana Guedez, Michael A Jones, Masatoshi Kida, Gm Monawar Hosain, Nuria Malats, Manolis Kogevinas, Adonina Tardón, Consol Serra, Alfredo Carrato, Reina Garcia-Closas, Josep Lloreta, Xifeng Wu, Mark Purdue, Gerald L Andriole, Robert L Grubb, Amanda Black, Maria T Landi, Neil E Caporaso, Paolo Vineis, Afshan Siddiq, H Bas Bueno-de-Mesquita, Dimitrios Trichopoulos, Börje Ljungberg, Gianluca Severi, Elisabete Weiderpass, Vittorio Krogh, Miren Dorronsoro, Ruth C Travis, Anne Tjønneland, Paul Brennan, Jenny Chang-Claude, Elio Riboli, Jennifer Prescott, Constance Chen, Immaculata De Vivo, Edward Govannucci, David Hunter, Peter Kraft, Sara Lindstrom, Susan M Gapstur, Eric J Jacobs, W Ryan Diver, Demetrius Albanes, Stephanie J Weinstein, Jarmo Virtamo, Charles Kooperberg, Chancellor Hohensee, Rebecca J Rodabough, Victoria K Cortessis, David V Conti, Manuela Gago-Dominguez, Mariana C Stern, Malcolm C Pike, David Van Den Berg, Jian-Min Yuan, Christopher A Haiman, Olivier Cussenot, Géraldine Cancel-Tassin, Morgan Rouprêt, Eva Compérat, Stefano Porru, Angela Carta, Sofia Pavanello, Cecilia Arici, Giuseppe Mastrangelo, H Barton Grossman, Zhaoming Wang, Xiang Deng, Charles C Chung, Amy Hutchinson, Laurie Burdette, William Wheeler, Joseph Fraumeni, Stephen J Chanock, Stephen M Hewitt, Debra T Silverman, Nathaniel Rothman, Ludmila Prokunina-Olsson.
Cancer Res.
PUBLISHED: 10-17-2014
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A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) ? 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 × 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (Ptrend = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models. Cancer Res; 74(20); 5808-18. ©2014 AACR.
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A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus.
Nat. Genet.
PUBLISHED: 01-06-2013
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Chronic infection with hepatitis C virus (HCV) is a common cause of liver cirrhosis and cancer. We performed RNA sequencing in primary human hepatocytes activated with synthetic double-stranded RNA to mimic HCV infection. Upstream of IFNL3 (IL28B) on chromosome 19q13.13, we discovered a new transiently induced region that harbors a dinucleotide variant ss469415590 (TT or ?G), which is in high linkage disequilibrium with rs12979860, a genetic marker strongly associated with HCV clearance. ss469415590[?G] is a frameshift variant that creates a novel gene, designated IFNL4, encoding the interferon-?4 protein (IFNL4), which is moderately similar to IFNL3. Compared to rs12979860, ss469415590 is more strongly associated with HCV clearance in individuals of African ancestry, although it provides comparable information in Europeans and Asians. Transient overexpression of IFNL4 in a hepatoma cell line induced STAT1 and STAT2 phosphorylation and the expression of interferon-stimulated genes. Our findings provide new insights into the genetic regulation of HCV clearance and its clinical management.
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Common genetic variants in the PSCA gene influence gene expression and bladder cancer risk.
Proc. Natl. Acad. Sci. U.S.A.
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Genome-wide association studies have identified a SNP, rs2294008, on 8q24.3 within the prostate stem cell antigen (PSCA) gene, as a risk factor for bladder cancer. To fine-map this region, we imputed 642 SNPs within 100 Kb of rs2294008 in addition to 33 markers genotyped in one of the reported genome-wide association study in 8,652 subjects. A multivariable logistic regression model adjusted for rs2294008 revealed a unique signal, rs2978974 (r(2) = 0.02, D = 0.19 with rs2294008). In the combined analysis of 5,393 cases and 7,324 controls, we detected a per-allele odds ratio (OR) = 1.11 [95% confidence interval (CI) = 1.06-1.17, P = 5.8 × 10(-5)] for rs2294008 and OR = 1.07 (95% CI = 1.02-1.13, P = 9.7 × 10(-3)) for rs2978974. The effect was stronger in carriers of both risk variants (OR = 1.24, 95% CI = 1.08-1.41, P = 1.8 × 10(-3)) and there was a significant multiplicative interaction (P = 0.035) between these two SNPs, which requires replication in future studies. The T risk allele of rs2294008 was associated with increased PSCA mRNA expression in two sets of bladder tumor samples (n = 36, P = 0.0007 and n = 34, P = 0.0054) and in normal bladder samples (n = 35, P = 0.0155), but rs2978974 was not associated with PSCA expression. SNP rs2978974 is located 10 Kb upstream of rs2294008, within an alternative untranslated first exon of PSCA. The non-risk allele G of rs2978974 showed strong interaction with nuclear proteins from five cell lines tested, implying a regulatory function. In conclusion, a joint effect of two PSCA SNPs, rs2294008 and rs2978974, suggests that both variants may be important for bladder cancer susceptibility, possibly through different mechanisms that influence the control of mRNA expression and interaction with regulatory factors.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.