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Find video protocols related to scientific articles indexed in Pubmed.
Relationship Between Male Pattern Baldness and the Risk of Aggressive Prostate Cancer: An Analysis of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.
J. Clin. Oncol.
PUBLISHED: 09-17-2014
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Male pattern baldness and prostate cancer appear to share common pathophysiologic mechanisms. However, results from previous studies that assess their relationship have been inconsistent. Therefore, we investigated the association of male pattern baldness at age 45 years with risks of overall and subtypes of prostate cancer in a large, prospective cohort-the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.
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Sex steroid hormone metabolism in relation to risk of aggressive prostate cancer.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 09-01-2014
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The combined action of androgens and estrogens-specifically their balance-may play a role in prostate carcinogenesis, but existing evidence is sparse and inconsistent. We investigated associations between serum sex steroid hormones, including estrogen metabolites, and risk of aggressive prostate cancer.
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.
Zhaoming Wang, Bin Zhu, Mingfeng Zhang, Hemang Parikh, Jinping Jia, Charles C Chung, Joshua N Sampson, Jason W Hoskins, Amy Hutchinson, Laurie Burdette, Abdisamad Ibrahim, Christopher Hautman, Preethi S Raj, Christian C Abnet, Andrew A Adjei, Anders Ahlbom, Demetrius Albanes, Naomi E Allen, Christine B Ambrosone, Melinda Aldrich, Pilar Amiano, Christopher Amos, Ulrika Andersson, Gerald Andriole, Irene L Andrulis, Cecilia Arici, Alan A Arslan, Melissa A Austin, Dalsu Baris, Donald A Barkauskas, Bryan A Bassig, Laura E Beane Freeman, Christine D Berg, Sonja I Berndt, Pier Alberto Bertazzi, Richard B Biritwum, Amanda Black, William Blot, Heiner Boeing, Paolo Boffetta, Kelly Bolton, Marie-Christine Boutron-Ruault, Paige M Bracci, Paul Brennan, Louise A Brinton, Michelle Brotzman, H Bas Bueno-de-Mesquita, Julie E Buring, Mary Ann Butler, Qiuyin Cai, Géraldine Cancel-Tassin, Federico Canzian, Guangwen Cao, Neil E Caporaso, Alfredo Carrato, Tania Carreon, Angela Carta, Gee-Chen Chang, I-Shou Chang, Jenny Chang-Claude, Xu Che, Chien-Jen Chen, Chih-Yi Chen, Chung-Hsing Chen, Constance Chen, Kuan-Yu Chen, Yuh-Min Chen, Anand P Chokkalingam, Lisa W Chu, Francoise Clavel-Chapelon, Graham A Colditz, Joanne S Colt, David Conti, Michael B Cook, Victoria K Cortessis, E David Crawford, Olivier Cussenot, Faith G Davis, Immaculata De Vivo, Xiang Deng, Ti Ding, Colin P Dinney, Anna Luisa Di Stefano, W Ryan Diver, Eric J Duell, Joanne W Elena, Jin-Hu Fan, Heather Spencer Feigelson, Maria Feychting, Jonine D Figueroa, Adrienne M Flanagan, Joseph F Fraumeni, Neal D Freedman, Brooke L Fridley, Charles S Fuchs, Manuela Gago-Dominguez, Steven Gallinger, Yu-Tang Gao, Susan M Gapstur, Montserrat Garcia-Closas, Reina Garcia-Closas, Julie M Gastier-Foster, J Michael Gaziano, Daniela S Gerhard, Carol A Giffen, Graham G Giles, Elizabeth M Gillanders, Edward L Giovannucci, Michael Goggins, Nalan Gokgoz, Alisa M Goldstein, Carlos González, Richard Gorlick, Mark H Greene, Myron Gross, H Barton Grossman, Robert Grubb, Jian Gu, Peng Guan, Christopher A Haiman, Göran Hallmans, Susan E Hankinson, Curtis C Harris, Patricia Hartge, Claudia Hattinger, Richard B Hayes, Qincheng He, Lee Helman, Brian E Henderson, Roger Henriksson, Judith Hoffman-Bolton, Chancellor Hohensee, Elizabeth A Holly, Yun-Chul Hong, Robert N Hoover, H Dean Hosgood, Chin-Fu Hsiao, Ann W Hsing, Chao Agnes Hsiung, Nan Hu, Wei Hu, Zhibin Hu, Ming-Shyan Huang, David J Hunter, Peter D Inskip, Hidemi Ito, Eric J Jacobs, Kevin B Jacobs, Mazda Jenab, Bu-Tian Ji, Christoffer Johansen, Mattias Johansson, Alison Johnson, Rudolf Kaaks, Ashish M Kamat, Aruna Kamineni, Margaret Karagas, Chand Khanna, Kay-Tee Khaw, Christopher Kim, In-Sam Kim, Jin Hee Kim, Yeul Hong Kim, Young-Chul Kim, Young Tae Kim, Chang Hyun Kang, Yoo Jin Jung, Cari M Kitahara, Alison P Klein, Robert Klein, Manolis Kogevinas, Woon-Puay Koh, Takashi Kohno, Laurence N Kolonel, Charles Kooperberg, Christian P Kratz, Vittorio Krogh, Hideo Kunitoh, Robert C Kurtz, Nilgun Kurucu, Qing Lan, Mark Lathrop, Ching C Lau, Fernando Lecanda, Kyoung-Mu Lee, Maxwell P Lee, Loic Le Marchand, Seth P Lerner, Donghui Li, Linda M Liao, Wei-Yen Lim, Dongxin Lin, Jie Lin, Sara Lindstrom, Martha S Linet, Jolanta Lissowska, Jianjun Liu, Börje Ljungberg, Josep Lloreta, Daru Lu, Jing Ma, Nuria Malats, Satu Mannisto, Neyssa Marina, Giuseppe Mastrangelo, Keitaro Matsuo, Katherine A McGlynn, Roberta Mckean-Cowdin, Lorna H McNeill, Robert R McWilliams, Beatrice S Melin, Paul S Meltzer, James E Mensah, Xiaoping Miao, Dominique S Michaud, Alison M Mondul, Lee E Moore, Kenneth Muir, Shelley Niwa, Sara H Olson, Nick Orr, Salvatore Panico, Jae Yong Park, Alpa V Patel, Ana Patiño-García, Sofia Pavanello, Petra H M Peeters, Beata Peplonska, Ulrike Peters, Gloria M Petersen, Piero Picci, Malcolm C Pike, Stefano Porru, Jennifer Prescott, Xia Pu, Mark P Purdue, You-Lin Qiao, Preetha Rajaraman, Elio Riboli, Harvey A Risch, Rebecca J Rodabough, Nathaniel Rothman, Avima M Ruder, Jeong-Seon Ryu, Marc Sanson, Alan Schned, Fredrick R Schumacher, Ann G Schwartz, Kendra L Schwartz, Molly Schwenn, Katia Scotlandi, Adeline Seow, Consol Serra, Massimo Serra, Howard D Sesso, Gianluca Severi, Hongbing Shen, Min Shen, Sanjay Shete, Kouya Shiraishi, Xiao-Ou Shu, Afshan Siddiq, Luis Sierrasesúmaga, Sabina Sierri, Alan Dart Loon Sihoe, Debra T Silverman, Matthias Simon, Melissa C Southey, Logan Spector, Margaret Spitz, Meir Stampfer, Pär Stattin, Mariana C Stern, Victoria L Stevens, Rachael Z Stolzenberg-Solomon, Daniel O Stram, Sara S Strom, Wu-Chou Su, Malin Sund, Sook Whan Sung, Anthony Swerdlow, Wen Tan, Hideo Tanaka, Wei Tang, Ze-Zhang Tang, Adonina Tardón, Evelyn Tay, Philip R Taylor, Yao Tettey, David M Thomas, Roberto Tirabosco, Anne Tjonneland, Geoffrey S Tobias, Jorge R Toro, Ruth C Travis, Dimitrios Trichopoulos, Rebecca Troisi, Ann Truelove, Ying-Huang Tsai, Margaret A Tucker, Rosario Tumino, David Van Den Berg, Stephen K Van Den Eeden, Roel Vermeulen, Paolo Vineis, Kala Visvanathan, Ulla Vogel, Chaoyu Wang, Chengfeng Wang, Junwen Wang, Sophia S Wang, Elisabete Weiderpass, Stephanie J Weinstein, Nicolas Wentzensen, William Wheeler, Emily White, John K Wiencke, Alicja Wolk, Brian M Wolpin, Maria Pik Wong, Margaret Wrensch, Chen Wu, Tangchun Wu, Xifeng Wu, Yi-Long Wu, Jay S Wunder, Yong-Bing Xiang, Jun Xu, Hannah P Yang, Pan-Chyr Yang, Yasushi Yatabe, Yuanqing Ye, Edward D Yeboah, Zhihua Yin, Chen Ying, Chong-Jen Yu, Kai Yu, Jian-Min Yuan, Krista A Zanetti, Anne Zeleniuch-Jacquotte, Wei Zheng, Baosen Zhou, Lisa Mirabello, Sharon A Savage, Peter Kraft, Stephen J Chanock, Meredith Yeager, Maria Terese Landi, Jianxin Shi, Nilanjan Chatterjee, Laufey T Amundadottir.
Hum. Mol. Genet.
PUBLISHED: 07-15-2014
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Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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Generalizability of established prostate cancer risk variants in men of African ancestry.
Int. J. Cancer
PUBLISHED: 05-16-2014
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Genome-wide association studies have identified more than eighty risk variants for prostate cancer, mainly in European or Asian populations. The generalizability of these variants in other racial/ethnic populations needs to be understood before the loci can be utilized widely in risk modeling. In this study, we examined 82 previously reported risk variants in 4,853 prostate cancer cases and 4,678 controls of African ancestry. We performed association testing for each variant using logistic regression adjusted for age, study, and global ancestry. Of the 82 known risk variants, 68 (83%) had effects that were directionally consistent in their association with prostate cancer risk and 30 (37%) were significantly associated with risk at p<0.05, with the most statistically significant variants being rs116041037 (p=3.7×10(-26) ) and rs6983561 (p=1.1×10(-16) ) at 8q24, as well as rs7210100 (p=5.4×10(-8) ) at 17q21. By exploring each locus in search of better markers, the number of variants that captured risk in men of African ancestry (p<0.05) increased from 30 (37%) to 44 (54%). An aggregate score comprised of these 44 markers was strongly associated with prostate cancer risk (per-allele odds ratio (OR)=1.12, p=7.3×10(-98) ). In summary, the consistent directions of effects for the vast majority of variants in men of African ancestry indicate common functional alleles that are shared across populations. Further exploration of these susceptibility loci is needed to identify the underlying biologically relevant variants to improve prostate cancer risk modeling in populations of African ancestry. © 2014 Wiley Periodicals, Inc.
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High prevalence of screen detected prostate cancer in West Africans: implications for racial disparity of prostate cancer.
J. Urol.
PUBLISHED: 04-10-2014
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To our knowledge the reasons for the high rates of prostate cancer in black American men are unknown. Genetic and lifestyle factors have been implicated. Better understanding of prostate cancer rates in West African men would help clarify why black American men have such high rates since the groups share genetic ancestry and yet have different lifestyles and screening practices. To estimate the prostate cancer burden in West African men we performed a population based screening study with biopsy confirmation in Ghana.
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Role of Casein Kinase 1A1 in the Biology and Targeted Therapy of del(5q) MDS.
Cancer Cell
PUBLISHED: 04-01-2014
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The casein kinase 1A1 gene (CSNK1A1) is a putative tumor suppressor gene located in the common deleted region for del(5q) myelodysplastic syndrome (MDS). We generated a murine model with conditional inactivation of Csnk1a1 and found that Csnk1a1 haploinsufficiency induces hematopoietic stem cell expansion and a competitive repopulation advantage, whereas homozygous deletion induces hematopoietic stem cell failure. Based on this finding, we found that heterozygous inactivation of Csnk1a1 sensitizes cells to a CSNK1 inhibitor relative to cells with two intact alleles. In addition, we identified recurrent somatic mutations in CSNK1A1 on the nondeleted allele of patients with del(5q) MDS. These studies demonstrate that CSNK1A1 plays a central role in the biology of del(5q) MDS and is a promising therapeutic target.
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A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.
Ali Amin Al Olama, Zsofia Kote-Jarai, Sonja I Berndt, David V Conti, Fredrick Schumacher, Ying Han, Sara Benlloch, Dennis J Hazelett, Zhaoming Wang, Ed Saunders, Daniel Leongamornlert, Sara Lindstrom, Sara Jugurnauth-Little, Tokhir Dadaev, Malgorzata Tymrakiewicz, Daniel O Stram, Kristin Rand, Peggy Wan, Alex Stram, Xin Sheng, Loreall C Pooler, Karen Park, Lucy Xia, Jonathan Tyrer, Laurence N Kolonel, Loic Le Marchand, Robert N Hoover, Mitchell J Machiela, Merideth Yeager, Laurie Burdette, Charles C Chung, Amy Hutchinson, Kai Yu, Chee Goh, Mahbubl Ahmed, Koveela Govindasami, Michelle Guy, Teuvo L J Tammela, Anssi Auvinen, Tiina Wahlfors, Johanna Schleutker, Tapio Visakorpi, Katri A Leinonen, Jianfeng Xu, Markus Aly, Jenny Donovan, Ruth C Travis, Tim J Key, Afshan Siddiq, Federico Canzian, Kay-Tee Khaw, Atsushi Takahashi, Michiaki Kubo, Paul Pharoah, Nora Pashayan, Maren Weischer, Borge G Nordestgaard, Sune F Nielsen, Peter Klarskov, Martin Andreas Røder, Peter Iversen, Stephen N Thibodeau, Shannon K McDonnell, Daniel J Schaid, Janet L Stanford, Suzanne Kolb, Sarah Holt, Beatrice Knudsen, Antonio Hurtado Coll, Susan M Gapstur, W Ryan Diver, Victoria L Stevens, Christiane Maier, Manuel Luedeke, Kathleen Herkommer, Antje E Rinckleb, Sara S Strom, Curtis Pettaway, Edward D Yeboah, Yao Tettey, Richard B Biritwum, Andrew A Adjei, Evelyn Tay, Ann Truelove, Shelley Niwa, Anand P Chokkalingam, Lisa Cannon-Albright, Cezary Cybulski, Dominika Wokołorczyk, Wojciech Kluźniak, Jong Park, Thomas Sellers, Hui-Yi Lin, William B Isaacs, Alan W Partin, Hermann Brenner, Aida Karina Dieffenbach, Christa Stegmaier, Constance Chen, Edward L Giovannucci, Jing Ma, Meir Stampfer, Kathryn L Penney, Lorelei Mucci, Esther M John, Sue A Ingles, Rick A Kittles, Adam B Murphy, Hardev Pandha, Agnieszka Michael, Andrzej M Kierzek, William Blot, Lisa B Signorello, Wei Zheng, Demetrius Albanes, Jarmo Virtamo, Stephanie Weinstein, Barbara Nemesure, John Carpten, Cristina Leske, Suh-Yuh Wu, Anselm Hennis, Adam S Kibel, Benjamin A Rybicki, Christine Neslund-Dudas, Ann W Hsing, Lisa Chu, Phyllis J Goodman, Eric A Klein, S Lilly Zheng, Jyotsna Batra, Judith Clements, Amanda Spurdle, Manuel R Teixeira, Paula Paulo, Sofia Maia, Chavdar Slavov, Radka Kaneva, Vanio Mitev, John S Witte, Graham Casey, Elizabeth M Gillanders, Daniella Seminara, Elio Riboli, Freddie C Hamdy, Gerhard A Coetzee, Qiyuan Li, Matthew L Freedman, David J Hunter, Kenneth Muir, Henrik Grönberg, David E Neal, Melissa Southey, Graham G Giles, Gianluca Severi, , Michael B Cook, Hidewaki Nakagawa, Fredrik Wiklund, Peter Kraft, Stephen J Chanock, Brian E Henderson, Douglas F Easton, Rosalind A Eeles, Christopher A Haiman.
Nat. Genet.
PUBLISHED: 03-26-2014
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Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.
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Csnk1a1 inhibition has p53-dependent therapeutic efficacy in acute myeloid leukemia.
J. Exp. Med.
PUBLISHED: 03-10-2014
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Despite extensive insights into the underlying genetics and biology of acute myeloid leukemia (AML), overall survival remains poor and new therapies are needed. We found that casein kinase 1 ? (Csnk1a1), a serine-threonine kinase, is essential for AML cell survival in vivo. Normal hematopoietic stem and progenitor cells (HSPCs) were relatively less affected by shRNA-mediated knockdown of Csnk1a1. To identify downstream mediators of Csnk1a1 critical for leukemia cells, we performed an in vivo pooled shRNA screen and gene expression profiling. We found that Csnk1a1 knockdown results in decreased Rps6 phosphorylation, increased p53 activity, and myeloid differentiation. Consistent with these observations, p53-null leukemias were insensitive to Csnk1a1 knockdown. We further evaluated whether D4476, a casein kinase 1 inhibitor, would exhibit selective antileukemic effects. Treatment of leukemia stem cells (LSCs) with D4476 showed highly selective killing of LSCs over normal HSPCs. In summary, these findings demonstrate that Csnk1a1 inhibition causes reduced Rps6 phosphorylation and activation of p53, resulting in selective elimination of leukemia cells, revealing Csnk1a1 as a potential therapeutic target for the treatment of AML.
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A genome-wide association study of prostate cancer in West African men.
Hum. Genet.
PUBLISHED: 08-21-2013
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Age-adjusted mortality rates for prostate cancer are higher for African-American men compared with those of European ancestry. Recent data suggest that West African men also have elevated risk for prostate cancer relative to European men. Genetic susceptibility to prostate cancer could account for part of this difference. We conducted a genome-wide association study (GWAS) of prostate cancer in West African men in the Ghana Prostate Study. Association testing was performed using multivariable logistic regression adjusted for age and genetic ancestry for 474 prostate cancer cases and 458 population-based controls on the Illumina HumanOmni-5 Quad BeadChip. The most promising association was at 10p14 within an intron of a long non-coding RNA (lncRNA RP11-543F8.2) 360 kb centromeric of GATA3 (p = 1.29E-7). In sub-analyses, SNPs at 5q31.3 were associated with high Gleason score (?7) cancers, the strongest of which was a missense SNP in PCDHA1 (rs34575154, p = 3.66E-8), and SNPs at Xq28 (rs985081, p = 8.66E-9) and 6q21 (rs2185710, p = 5.95E-8) were associated with low Gleason score (<7) cancers. We sought to validate our findings in silico in the African Ancestry Prostate Cancer GWAS Consortium, but only one SNP, at 10p14, replicated at p < 0.05. Of the 90 prostate cancer loci reported from studies of men of European, Asian or African-American ancestry, we were able to test 81 in the Ghana Prostate Study, and 10 of these replicated at p < 0.05. Further genetic studies of prostate cancer in West African men are needed to confirm our promising susceptibility loci.
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CT of acute appendicitis: can diagnostic accuracy serve as a practical performance metric for readers specialized in abdominal imaging?
Clin Imaging
PUBLISHED: 08-11-2013
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To investigate diagnostic accuracy for acute appendicitis at computed tomography (CT) as a performance metric for radiologists specialized in abdominal imaging.
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Prospective evaluation of serum sarcosine and risk of prostate cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.
Carcinogenesis
PUBLISHED: 05-22-2013
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Metabolomic profiling has identified, sarcosine, a derivative of the amino acid glycine, as an important metabolite involved in the etiology or natural history of prostate cancer. We examined the association between serum sarcosine levels and risk of prostate cancer in 1122 cases (813 non-aggressive and 309 aggressive) and 1112 controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Sarcosine was quantified using high-throughput liquid chromatography-mass spectrometry. A significantly increased risk of prostate cancer was observed with increasing levels of sarcosine (odds ratio [OR] for the highest quartile of exposure [Q4] versus the lowest quartile [Q1] = 1.30, 95% confidence interval [CI]: 1.02, 1.65; P-trend 0.03). When stratified by disease aggressiveness, we observed a stronger association for non-aggressive cases (OR for Q4 versus Q1 = 1.44, 95% CI: 1.11, 1.88; P-trend 0.006) but no association for aggressive prostate cancer (OR for Q4 versus Q1 = 1.03, 95% CI: 0.73, 1.47; P-trend 0.89). Although not statistically significant, temporal analyses showed a stronger association between sarcosine and prostate cancer for serum collected closer to diagnosis, suggesting that sarcosine may be an early biomarker of disease. Interestingly, the association between sarcosine and prostate cancer risk was stronger among men with diabetes (OR = 2.66, 95% CI: 1.04, 6.84) compared with those without reported diabetes (OR = 1.23, 95% CI: 0.95-1.59, P-interaction = 0.01). This study found that elevated levels of serum sarcosine are associated with an increased prostate cancer risk and evidence to suggest that sarcosine may be an early biomarker for this disease.
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Variants in CCK and CCKAR genes to susceptibility to biliary tract cancers and stones: a population-based study in Shanghai, China.
J. Gastroenterol. Hepatol.
PUBLISHED: 05-06-2013
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Altered motility of the gallbladder is associated with an increased risk of gallstones and can result in biliary tract cancers. Cholecystokinin (CCK) is an important modulator of gallbladder motility which functions by activating CCK type-A receptor (CCKAR). The aim of this study was to determine whether genetic variants in CCK and CCKAR are associated with the risk of biliary tract cancers and stones.
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A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry.
Keri L Monda, Gary K Chen, Kira C Taylor, Cameron Palmer, Todd L Edwards, Leslie A Lange, Maggie C Y Ng, Adebowale A Adeyemo, Matthew A Allison, Lawrence F Bielak, Guanjie Chen, Mariaelisa Graff, Marguerite R Irvin, Suhn K Rhie, Guo Li, Yongmei Liu, Youfang Liu, Yingchang Lu, Michael A Nalls, Yan V Sun, Mary K Wojczynski, Lisa R Yanek, Melinda C Aldrich, Adeyinka Ademola, Christopher I Amos, Elisa V Bandera, Cathryn H Bock, Angela Britton, Ulrich Broeckel, Quiyin Cai, Neil E Caporaso, Chris S Carlson, John Carpten, Graham Casey, Wei-Min Chen, Fang Chen, Yii-Der I Chen, Charleston W K Chiang, Gerhard A Coetzee, Ellen Demerath, Sandra L Deming-Halverson, Ryan W Driver, Patricia Dubbert, Mary F Feitosa, Ye Feng, Barry I Freedman, Elizabeth M Gillanders, Omri Gottesman, Xiuqing Guo, Talin Haritunians, Tamara Harris, Curtis C Harris, Anselm J M Hennis, Dena G Hernandez, Lorna H McNeill, Timothy D Howard, Barbara V Howard, Virginia J Howard, Karen C Johnson, Sun J Kang, Brendan J Keating, Suzanne Kolb, Lewis H Kuller, Abdullah Kutlar, Carl D Langefeld, Guillaume Lettre, Kurt Lohman, Vaneet Lotay, Helen Lyon, JoAnn E Manson, William Maixner, Yan A Meng, Kristine R Monroe, Imran Morhason-Bello, Adam B Murphy, Josyf C Mychaleckyj, Rajiv Nadukuru, Katherine L Nathanson, Uma Nayak, Amidou N'Diaye, Barbara Nemesure, Suh-Yuh Wu, M Cristina Leske, Christine Neslund-Dudas, Marian Neuhouser, Sarah Nyante, Heather Ochs-Balcom, Adesola Ogunniyi, Temidayo O Ogundiran, Oladosu Ojengbede, Olufunmilayo I Olopade, Julie R Palmer, Edward A Ruiz-Narváez, Nicholette D Palmer, Michael F Press, Evandine Rampersaud, Laura J Rasmussen-Torvik, Jorge L Rodriguez-Gil, Babatunde Salako, Eric E Schadt, Ann G Schwartz, Daniel A Shriner, David Siscovick, Shad B Smith, Sylvia Wassertheil-Smoller, Elizabeth K Speliotes, Margaret R Spitz, Lara Sucheston, Herman Taylor, Bamidele O Tayo, Margaret A Tucker, David J Van Den Berg, Digna R Velez Edwards, Zhaoming Wang, John K Wiencke, Thomas W Winkler, John S Witte, Margaret Wrensch, Xifeng Wu, James J Yang, Albert M Levin, Taylor R Young, Neil A Zakai, Mary Cushman, Krista A Zanetti, Jing Hua Zhao, Wei Zhao, Yonglan Zheng, Jie Zhou, Regina G Ziegler, Joseph M Zmuda, Jyotika K Fernandes, Gary S Gilkeson, Diane L Kamen, Kelly J Hunt, Ida J Spruill, Christine B Ambrosone, Stefan Ambs, Donna K Arnett, Larry Atwood, Diane M Becker, Sonja I Berndt, Leslie Bernstein, William J Blot, Ingrid B Borecki, Erwin P Bottinger, Donald W Bowden, Gregory Burke, Stephen J Chanock, Richard S Cooper, Jingzhong Ding, David Duggan, Michele K Evans, Caroline Fox, W Timothy Garvey, Jonathan P Bradfield, Hakon Hakonarson, Struan F A Grant, Ann Hsing, Lisa Chu, Jennifer J Hu, Dezheng Huo, Sue A Ingles, Esther M John, Joanne M Jordan, Edmond K Kabagambe, Sharon L R Kardia, Rick A Kittles, Phyllis J Goodman, Eric A Klein, Laurence N Kolonel, Loic Le Marchand, Simin Liu, Barbara McKnight, Robert C Millikan, Thomas H Mosley, Badri Padhukasahasram, L Keoki Williams, Sanjay R Patel, Ulrike Peters, Curtis A Pettaway, Patricia A Peyser, Bruce M Psaty, Susan Redline, Charles N Rotimi, Benjamin A Rybicki, Michèle M Sale, Pamela J Schreiner, Lisa B Signorello, Andrew B Singleton, Janet L Stanford, Sara S Strom, Michael J Thun, Mara Vitolins, Wei Zheng, Jason H Moore, Scott M Williams, Shamika Ketkar, Xiaofeng Zhu, Alan B Zonderman, , Charles Kooperberg, George J Papanicolaou, Brian E Henderson, Alex P Reiner, Joel N Hirschhorn, Ruth J F Loos, Kari E North, Christopher A Haiman.
Nat. Genet.
PUBLISHED: 03-18-2013
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Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one new locus at 5q33 (GALNT10, rs7708584, P = 3.4 × 10(-11)) and another at 7p15 when we included data from the GIANT consortium (MIR148A-NFE2L3, rs10261878, P = 1.2 × 10(-10)). We also found suggestive evidence of an association at a third locus at 6q16 in the African-ancestry sample (KLHL32, rs974417, P = 6.9 × 10(-8)). Thirty-two of the 36 previously established BMI variants showed directionally consistent effect estimates in our GWAS (binomial P = 9.7 × 10(-7)), five of which reached genome-wide significance. These findings provide strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations.
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Niche-based screening identifies small-molecule inhibitors of leukemia stem cells.
Nat. Chem. Biol.
PUBLISHED: 03-13-2013
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Efforts to develop more effective therapies for acute leukemia may benefit from high-throughput screening systems that reflect the complex physiology of the disease, including leukemia stem cells (LSCs) and supportive interactions with the bone marrow microenvironment. The therapeutic targeting of LSCs is challenging because LSCs are highly similar to normal hematopoietic stem and progenitor cells (HSPCs) and are protected by stromal cells in vivo. We screened 14,718 compounds in a leukemia-stroma co-culture system for inhibition of cobblestone formation, a cellular behavior associated with stem-cell function. Among those compounds that inhibited malignant cells but spared HSPCs was the cholesterol-lowering drug lovastatin. Lovastatin showed anti-LSC activity in vitro and in an in vivo bone marrow transplantation model. Mechanistic studies demonstrated that the effect was on target, via inhibition of HMG-CoA reductase. These results illustrate the power of merging physiologically relevant models with high-throughput screening.
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In Vivo RNAi screening identifies a leukemia-specific dependence on integrin beta 3 signaling.
Cancer Cell
PUBLISHED: 02-19-2013
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We used an in vivo small hairpin RNA (shRNA) screening approach to identify genes that are essential for MLL-AF9 acute myeloid leukemia (AML). We found that Integrin Beta 3 (Itgb3) is essential for murine leukemia cells in vivo and for human leukemia cells in xenotransplantation studies. In leukemia cells, Itgb3 knockdown impaired homing, downregulated LSC transcriptional programs, and induced differentiation via the intracellular kinase Syk. In contrast, loss of Itgb3 in normal hematopoietic stem and progenitor cells did not affect engraftment, reconstitution, or differentiation. Finally, using an Itgb3 knockout mouse model, we confirmed that Itgb3 is dispensable for normal hematopoiesis but is required for leukemogenesis. Our results establish the significance of the Itgb3 signaling pathway as a potential therapeutic target in AML.
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Individual Variations in Serum Melatonin Levels through Time: Implications for Epidemiologic Studies.
PLoS ONE
PUBLISHED: 01-01-2013
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Melatonin, a marker for the circadian rhythm with serum levels peaking between 2AM and 5AM, is hypothesized to possess anti-cancer properties, making it a mechanistic candidate for the probable carcinogenic effect of circadian rhythm disruption. In order to weigh epidemiologic evidence on the association of melatonin with cancer, we must first understand the laboratory and biological sources of variability in melatonin levels measured in samples. Participants for this methodological study were men enrolled in the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO). We measured serum melatonin levels over a five year period in 97 individuals to test if melatonin levels are steady over time. The Pearson correlation coefficient between two measures separated by 1 year was 0.87, while the correlation between two measures separated by 5 years was to 0.70. In an additional cross-sectional study of 292 individuals, we used Analysis of Variance to identify differences in melatonin levels between different lifestyle and environmental characteristics. Serum melatonin levels were slightly higher in samples collected from 130 individuals during the winter, (6.36±0.59 pg/ml) than in samples collected from 119 individuals during the summer (4.83±0.62 pg/ml). Serum melatonin levels were lowest in current smokers (3.02±1.25 pg/ml, p?=?0.007) compared to never (6.66±0.66 pg/ml) and former (5.59±0.50 pg/ml) smokers whereas BMI did not significantly affect serum melatonin levels in this study. In conclusion, the high 5 year correlation of melatonin levels implies that single measurements may be used to detect population level associations between melatonin and risk of cancer. Furthermore, our results reiterate the need to record season of sample collection, and individual characteristics in order to maximize study power and prevent confounding.
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Replication and cumulative effects of GWAS-identified genetic variations for prostate cancer in Asians: a case-control study in the ChinaPCa consortium.
Carcinogenesis
PUBLISHED: 11-23-2011
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A recent genome-wide association study has identified five new genetic variants for prostate cancer susceptibility in a Japanese population, but it is unknown whether these newly identified variants are associated with prostate cancer risk in other populations, including Chinese men. We genotyped these five variants in a case-control study of 1524 patients diagnosed with prostate cancer and 2169 control subjects from the Chinese Consortium for Prostate Cancer Genetics (ChinaPCa). We found that three of the five genetic variants were associated with prostate cancer risk (P = 4.33 × 10(-8) for rs12653946 at 5p15, 4.43 × 10(-5) for rs339331 at 6q22 and 8.42 × 10(-4) for rs9600079 at 13q22, respectively). A cumulative effect was observed in a dose-dependent manner with increasing numbers of risk variant alleles (P(trend) = 2.58 × 10(-13)), and men with 5-6 risk alleles had a 2-fold higher risk of prostate cancer than men with 0-2 risk alleles (odds ratio = 2.26, 95% confidence interval = 1.78-2.87). Furthermore, rs339331 T allele was significantly associated with RFX6 and GPRC6A higher messenger RNA expression, compared with the C allele. However, none of the variants was associated with clinical stage, Gleason score or family history. These results provide further evidence that the risk loci identified in Japanese men also contribute to prostate cancer susceptibility in Chinese men.
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Human polymorphisms at long non-coding RNAs (lncRNAs) and association with prostate cancer risk.
Carcinogenesis
PUBLISHED: 08-19-2011
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Long non-coding RNAs (lncRNAs), representing a large proportion of non-coding transcripts across the human genome, are evolutionally conserved and biologically functional. At least one-third of the phenotype-related loci identified by genome-wide association studies (GWAS) are mapped to non-coding intervals. However, the relationships between phenotype-related loci and lncRNAs are largely unknown. Utilizing the 1000 Genomes data, we compared single-nucleotide polymorphisms (SNPs) within the sequences of lncRNA and protein-coding genes as defined in the Ensembl database. We further annotated the phenotype-related SNPs reported by GWAS at lncRNA intervals. Because prostate cancer (PCa) risk-related loci were enriched in lncRNAs, we then performed meta-analysis of two existing GWAS for discovery and an additional sample set for replication, revealing PCa risk-related loci at lncRNA regions. The SNP density in regions of lncRNA was similar to that in protein-coding regions, but they were less polymorphic than surrounding regions. Among the 1998 phenotype-related SNPs identified by GWAS, 52 loci were located directly in lncRNA intervals with a 1.5-fold enrichment compared with the entire genome. More than a 5-fold enrichment was observed for eight PCa risk-related loci in lncRNA genes. We also identified a new PCa risk-related SNP rs3787016 in an lncRNA region at 19q13 (per allele odds ratio = 1.19; 95% confidence interval: 1.11-1.27) with P value of 7.22 × 10(-7). lncRNAs may be important for interpreting and mining GWAS data. However, the catalog of lncRNAs needs to be better characterized in order to fully evaluate the relationship of phenotype-related loci with lncRNAs.
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Systematic confirmation study of reported prostate cancer risk-associated single nucleotide polymorphisms in Chinese men.
Cancer Sci.
PUBLISHED: 08-10-2011
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More than 30 prostate cancer (PCa) risk-associated loci have been identified in populations of European descent by genome-wide association studies. We hypothesized that a subset of these loci might be associated with PCa risk in Chinese men. To test this hypothesis, 33 single nucleotide polymorphisms (SNP), one each from the 33 independent PCa risk-associated loci reported in populations of European descent, were investigated for their associations with PCa risk in a case-control study of Chinese men (1108 cases and 1525 controls). We found that 11 of the 33 SNP were significantly associated with PCa risk in Chinese men (P < 0.05). The reported risk alleles were associated with increased risk for PCa, with allelic odds ratios ranging from 1.12 to 1.44. The most significant locus was located on 8q24 region 2 (rs16901979, P = 5.14 × 10(-9)) with a genome-wide significance (P < (-8) ), and three loci reached the Bonferroni correction significance level (P < 1.52 × 10(-3)), including 8q24 region 1 (rs1447295, P = 7.04 × 10(-6)), 8q24 region 5 (rs10086908, P = 9.24 × 10(-4)) and 8p21 (rs1512268, P = 9.39 × 10(-4)). Our results suggest that a subset of the PCa risk-associated SNP discovered by genome-wide association studies among men of European descent is also associated with PCa risk in Chinese men. This finding provides evidence of ethnic differences and similarity in genetic susceptibility to PCa. Genome-wide association studies in Chinese men are needed to identify Chinese-specific PCa risk-associated SNP.
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A reproducible and high-throughput HPLC/MS method to separate sarcosine from ?- and ?-alanine and to quantify sarcosine in human serum and urine.
Anal. Chem.
PUBLISHED: 06-21-2011
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While sarcosine was recently identified as a potential urine biomarker for prostate cancer, further studies have cast doubt on its utility to diagnose this condition. The inconsistent results may be due to the fact that alanine and sarcosine coelute on an HPLC reversed-phase column and the mass spectrometer cannot differentiate between the two isomers, since the same parent/product ions are generally used to measure them. In this study, we developed a high-throughput liquid chromatography-mass spectrometry (LC-MS) method that resolves sarcosine from alanine isomers, allowing its accurate quantification in human serum and urine. Assay reproducibility was determined using the coefficient of variation (CV) and intraclass correlation coefficient (ICC) in serum aliquots from 10 subjects and urine aliquots from 20 subjects across multiple analytic runs. Paired serum/urine samples from 42 subjects were used to evaluate sarcosine serum/urine correlation. Both urine and serum assays gave high sensitivity (limit of quantitation of 5 ng/mL) and reproducibility (serum assay, intra- and interassay CVs < 3% and ICCs > 99%; urine assay, intra-assay CV = 7.7% and ICC = 98.2% and interassay CV = 12.3% and ICC = 94.2%). In conclusion, this high-throughput LC-MS method is able to resolve sarcosine from ?- and ?-alanine and is useful for quantifying sarcosine in serum and urine samples.
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Clinical management of the physically active patient with type 1 diabetes.
Phys Sportsmed
PUBLISHED: 06-16-2011
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The prevalence and incidence of type 1 diabetes continues to increase worldwide. Most patients with type 1 diabetes are young at the time of diagnosis and wish to continue leading a physically active life. Although regular exercise, insulin therapy, and proper nutrition are the cornerstone of treatment, there are considerable challenges in managing the active individual with type 1 diabetes. The current recommendation for diabetes management is intensive glycemic control for all patients when possible to help prevent secondary complications. Both insulin pump therapy and multiple daily injections are beneficial treatment options to lower average glucose levels; however, without continuous glucose monitoring, these treatment options typically increase the risk of hypoglycemia. In active patients with type 1 diabetes, the challenges of maintaining good glycemia are complicated by the inability to regulate insulin concentrations during and after exercise. Physiological and psychosocial factors during growth and maturation also provide additional challenges. This article highlights challenges and key strategies for diabetes management in the active individual with type 1 diabetes, including the application of the most recent diabetes technologies.
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Genome-wide copy-number variation analysis identifies common genetic variants at 20p13 associated with aggressiveness of prostate cancer.
Carcinogenesis
PUBLISHED: 05-05-2011
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The genetic determinants for aggressiveness of prostate cancer (PCa) are poorly understood. Copy-number variations (CNVs) are one of the major sources for genetic diversity and critically modulate cellular biology and human diseases. We hypothesized that CNVs may be associated with PCa aggressiveness. To test this hypothesis, we conducted a genome-wide common CNVs analysis in 448 aggressive and 500 nonaggressive PCa cases recruited from Johns Hopkins Hospital (JHH1) using Affymetrix 6.0 arrays. Suggestive associations were further confirmed using single-nucleotide polymorphisms (SNPs) that tagged the CNVs of interest in an additional 2895 aggressive and 3094 nonaggressive cases, including those from the remaining case subjects of the JHH study (JHH2), the NCI Cancer Genetic Markers of Susceptibility (CGEMS) Study, and the CAncer of the Prostate in Sweden (CAPS) Study. We found that CNP2454, a 32.3 kb deletion polymorphism at 20p13, was significantly associated with aggressiveness of PCa in JHH1 [odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.01-1.68; P = 0.045]. The best-tagging SNP for CNP2454, rs2209313, was used to confirm this finding in both JHH1 (P = 0.045) and all confirmation study populations combined (P = 1.77 × 10(-3)). Pooled analysis using all 3353 aggressive and 3584 nonaggressive cases showed the T allele of rs2209313 was significantly associated with an increased risk of aggressive PCa (OR = 1.17, 95% CI: 1.07-1.27; P = 2.75 × 10(-4)). Our results indicate that genetic variations at 20p13 may be responsible for the progression of PCa.
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Predictive performance of prostate cancer risk in Chinese men using 33 reported prostate cancer risk-associated SNPs.
Prostate
PUBLISHED: 04-28-2011
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Genome-wide association studies (GWAS) have identified more than 30 single nucleotide polymorphisms (SNPs) that were reproducibly associated with prostate cancer (PCa) risk in populations of European descent. In aggregate, these variants have shown potential to predict risk for PCa in European men. However, their utility for PCa risk prediction in Chinese men is unknown.
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Prostate cancer incidence rates in Africa.
Prostate Cancer
PUBLISHED: 04-15-2011
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African American men have among the highest prostate cancer incidence rates in the world yet rates among their African counterparts are unclear. In this paper, we compared reported rates among black men of Sub-Saharan African descent using data from the International Agency for Research on Cancer (IARC) and the National Cancer Institute Surveillance, Epidemiology, and End Results Program for 1973-2007. Although population-based data in Africa are quite limited, the available data from IARC showed that rates among blacks were highest in the East (10.7-38.1 per 100,000 man-years, age-adjusted world standard) and lowest in the West (4.7-19.8). These rates were considerably lower than those of 80.0-195.3 observed among African Americans. Rates in Africa increased over time (1987-2002) and have been comparable to those for distant stage in African Americans. These patterns are likely due to differences between African and African American men in medical care access, screening, registry quality, genetic diversity, and Westernization. Incidence rates in Africa will likely continue to rise with improving economies and increasing Westernization, warranting the need for more high-quality population-based registration to monitor cancer incidence in Africa.
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The association between inflammation-related genes and serum androgen levels in men: the prostate, lung, colorectal, and ovarian study.
Prostate
PUBLISHED: 03-28-2011
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Androgens and inflammation have been implicated in the etiology of several cancers, including prostate cancer. Serum androgens have been shown to correlate with markers of inflammation and expression of inflammation-related genes.
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Carbohydrate intake reduces fat oxidation during exercise in obese boys.
Eur. J. Appl. Physiol.
PUBLISHED: 03-21-2011
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The recent surge in childhood obesity has renewed interest in studying exercise as a therapeutic means of metabolizing fat. However, carbohydrate (CHO) intake attenuates whole body fat oxidation during exercise in healthy children and may suppress fat metabolism in obese youth. To determine the impact of CHO intake on substrate utilization during submaximal exercise in obese boys, seven obese boys (mean age: 11.4 ± 1.0 year; % body fat: 35.8 ± 3.9%) performed 60 min of exercise at an intensity that approximated maximal fat oxidation. A CHO drink (CARB) or a placebo drink (CONT) was consumed in a double-blinded, counterbalanced manner. Rates of total fat, total CHO, and exogenous CHO (CHO(exo)) oxidation were calculated for the last 20 min of exercise. During CONT, fat oxidation rate was 3.9 ± 2.4 mg × kg fat-free mass (FFM)(-1 )× min(-1), representing 43.1 ± 22.9% of total energy expenditure (EE). During CARB, fat oxidation was lowered (p = 0.02) to 1.7 ± 0.6 mg × kg FFM(-1 )× min(-1), contributing to 19.8 ± 4.9% EE. Total CHO oxidation rate was 17.2 ± 3.1 mg × kg FFM(-1 )× min(-1) and 13.2 ± 6.1 mg × kg FFM(-1) × min(-1) during CARB and CONT, respectively (p = 0.06). In CARB, CHO(exo) oxidation contributed to 23.3 ± 4.2% of total EE. CHO intake markedly suppresses fat oxidation during exercise in obese boys.
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High prevalence of polyclonal hypergamma-globulinemia in adult males in Ghana, Africa.
Am. J. Hematol.
PUBLISHED: 03-17-2011
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Chronic antigenic stimulation is associated with hypergamma-globulinemia. Higher rates of hypergamma-globulinemia in tropical populations are maintained even with migration to temperate regions. We conducted a population-based screening study to assess the prevalence and risk factors for hypergamma-globulinemia in Ghana, Africa. 917 Ghanaian males (50-74 years) underwent in-person interviews and health examinations. Serum from all persons was analyzed by electrophoresis performed on agarose gel; serum with a discrete/localized band was subjected to immunofixation. 54 persons with monoclonal proteins were excluded and 17 samples were insufficient for analysis. Using logistic regression and Chi-square statistics we analyzed patterns of hypergamma-globulinemia. Among 846 study subjects, the median ?-globulin level was 1.86 g/dL. On the basis of a U.S. reference, 616 (73%) had hypergamma-globulinemia (>1.6 g/dL) and 178 (21%) had ?-globulin levels >2.17 gm/dl. On multivariate analyses, lower education status (P = 0.0013) and never smoking (P = 0.038) were associated with increased ?-globulin levels. Self-reported history of syphilis was associated with hypergamma-globulinemia. We conclude that three quarters of this population-based adult Ghanaian male sample had hypergamma-globulinemia with ?-globulin levels >1.6 g/dL. Future studies are needed to uncover genetic and environmental underpinnings of our finding, and to define the relationship between hypergamma-globulinemia, monoclonal gammopathy of undetermined significance (MGUS), and multiple myeloma.
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Colorectal cancer screening in women: an underutilized lifesaver.
AJR Am J Roentgenol
PUBLISHED: 01-25-2011
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Colorectal cancer (CRC) represents the third most common cancer diagnosed and a major cause of cancer-related deaths in women. Despite strong evidence that early screening decreases colorectal cancer incidence and mortality rates, colorectal cancer screening rates in women still lag significantly behind screening rates for breast and cervical cancers. Additionally, women have been found to be less likely than men to undergo CRC screening. This is despite the fact that the overall lifetime risk for the development of colorectal carcinoma is similar in both sexes. Barriers to screening have been found to be different for women compared with men. Screening adherence in women also appears to be associated with various social and demographic factors.
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Cholesterol metabolism gene polymorphisms and the risk of biliary tract cancers and stones: a population-based case-control study in Shanghai, China.
Carcinogenesis
PUBLISHED: 11-09-2010
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Biliary tract cancers are rare but fatal malignancies, with increasing incidence in Shanghai, China. Gallstones, the primary risk factor for biliary tract cancer, typically result from oversaturation of cholesterol in bile. We examined the association of five variants in three lipid metabolism-related genes (CETP, ABCG8 and LRPAP1) and biliary tract cancers and stones in a population-based case-control study in Shanghai, China. We included 439 biliary tract cancer cases (253 gallbladder, 133 extrahepatic bile duct and 53 ampulla of Vater cancer cases), 429 biliary stone cases and 447 population controls. Carriers of the CG genotype of ABCG8 rs11887534 had higher risk of biliary stones [odds ratio (OR) = 2.3, 95% confidence interval (CI) 0.82-6.5), gallbladder cancer (OR = 4.3, 95% CI 1.7-10.4) and bile duct cancer (OR = 1.94, 95% CI 0.64-5.91), compared with carriers of the GG genotype. Analysis stratified by gender showed both male and female carriers of CG rs11887534 had higher risks of biliary stones and gallbladder cancer, although the association was statistically significant only for women and gallbladder cancer (OR = 6.3, 95% CI 1.86-22.3). Carriers of the ABCG8 haplotype C-C (rs4148217-rs11887534) had a 4.16-fold (95% CI 1.71-10.1) risk of gallbladder cancer compared with those carrying the C-G haplotype. Our findings suggest that ABCG8 rs11887534, identified as a gallstone risk single-nucleotide polymorphism by whole genome scan, is also associated with an increased risk of biliary tract cancer.
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Association between genetic variants in the 8q24 cancer risk regions and circulating levels of androgens and sex hormone-binding globulin.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 06-15-2010
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Genome-wide association studies have identified multiple independent regions on chromosome 8q24 that are associated with cancers of the prostate, breast, colon, and bladder.
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Urinary estrogen metabolites and prostate cancer risk: a pilot study.
Prostate
PUBLISHED: 06-14-2010
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The high incidence of and few identified risk factors for prostate cancer underscore the need to further evaluate markers of prostate carcinogenesis. The aim of this pilot study was to evaluate urinary estrogen metabolites as a biomarker of prostate cancer risk.
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Measuring serum melatonin in epidemiologic studies.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 03-23-2010
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Epidemiologic data on serum melatonin, a marker of circadian rhythms, and cancer are sparse due largely to the lack of reliable assays with high sensitivity to detect relatively low melatonin levels in serum collected during daylight, as commonly available in most epidemiologic studies.
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Maternal diet and risk of childhood acute lymphoblastic leukemia.
Public Health Rep
PUBLISHED: 07-22-2009
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Intrauterine environmental factors, including maternal diet, may play an etiologic role in acute lymphoblastic leukemia (ALL), a common childhood cancer. Expanding on previous findings from phase 1 of the Northern California Childhood Leukemia Study (NCCLS), a population-based case-control study, we sought to further elucidate and replicate the relationships between maternal diet and ALL risk.
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Revisiting the IspH catalytic system in the deoxyxylulose phosphate pathway: achieving high activity.
J. Am. Chem. Soc.
PUBLISHED: 07-09-2009
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From two C(5) isoprene building blocks, isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP), the more than 30 000 members of the isoprenoid family are constructed in nature using two biosynthetic pathways, the mevalonate (MVA) pathway and the deoxyxylulose phosphate (DXP) pathway. IspH of the DXP pathway is a protein containing an iron-sulfur cluster and catalyzes a reductive dehydration reaction of the DXP pathway. In the literature, a wide range of Escherichia coli IspH activities have been reported (2.0 nmol min(-1) mg(-1) to 3.4 micromol min(-1) mg(-1)). For such a broad range of activities, reaction assays were carried out under many different conditions, preventing direct comparison of the activities and determination of the key factor responsible for such a dramatic difference in IspH activities. In this work, we systematically examined the role of redox mediators in IspH catalysis using E. coli IspH as the enzyme and dithionite as the ultimate electron source. Our studies not only suggest the importance of the iron-sulfur cluster but also improve the E. coli IspH activity by nearly 97-fold relative to that from the E. coli NADPH-flavodoxin reductase-flavodoxin system.
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Impact of maternal physical activity and infant feeding practices on infant weight gain and adiposity.
Int J Endocrinol
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Increasing evidence supports the contribution of intrauterine environmental exposures on obesity risk in offspring. Few studies have included maternal and infant lifestyle factors. Our objective was to study the impact of maternal physical activity, infant feeding, and screen time on offspring weight gain and adiposity. In a prospective cohort study, 246 mothers underwent testing during pregnancy to assess glucose tolerance status and insulin sensitivity. Anthropometry and questionnaires on physical activity, infant feeding, and screen time were completed. Multiple-linear regression was performed to examine the impact of maternal and infant factors on infant weight gain and weight-for-length z-score at 1 year. Infant weight outcomes were negatively predicted by maternal pregravid vigorous/sport index and exclusive breastfeeding duration. After adjustment, each unit increase in maternal pregravid vigorous/sport index decreased infant weight gain by 218.6 g (t = 2.44, P = 0.016) and weight-for-length z-score by 0.20 (t = 2.17, P = 0.031). Each month of exclusive breastfeeding reduced infant weight gain by 116.4?g (t = 3.97, P < 0.001) and weight-for-length z-score by 0.08 (t = 2.59, P = 0.01). Maternal pregravid physical activity and exclusive breastfeeding duration are associated with weight gain and adiposity as early as 1 year of age.
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Associations of serum sex steroid hormone and 5?-androstane-3?,17?-diol glucuronide concentrations with prostate cancer risk among men treated with finasteride.
Cancer Epidemiol. Biomarkers Prev.
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Finasteride, an inhibitor of 5?-reductase (type II), lowers intraprostatic dihydrotestosterone (DHT), which is reflected in serum as reduced 5?-androstane-3?,17?-diol glucuronide (3?-dG). It also modestly increases serum testosterone (T), estrone (E(1)), and estradiol (E(2)). In this altered hormonal milieu, it is unknown whether serum concentrations of these hormones are associated with prostate cancer risk.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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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.