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Find video protocols related to scientific articles indexed in Pubmed.
Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer.
Brian M Wolpin, Cosmeri Rizzato, Peter Kraft, Charles Kooperberg, Gloria M Petersen, Zhaoming Wang, Alan A Arslan, Laura Beane-Freeman, Paige M Bracci, Julie Buring, Federico Canzian, Eric J Duell, Steven Gallinger, Graham G Giles, Gary E Goodman, Phyllis J Goodman, Eric J Jacobs, Aruna Kamineni, Alison P Klein, Laurence N Kolonel, Matthew H Kulke, Donghui Li, Nuria Malats, Sara H Olson, Harvey A Risch, Howard D Sesso, Kala Visvanathan, Emily White, Wei Zheng, Christian C Abnet, Demetrius Albanes, Gabriella Andreotti, Melissa A Austin, Richard Barfield, Daniela Basso, Sonja I Berndt, Marie-Christine Boutron-Ruault, Michelle Brotzman, Markus W Büchler, H Bas Bueno-de-Mesquita, Peter Bugert, Laurie Burdette, Daniele Campa, Neil E Caporaso, Gabriele Capurso, Charles Chung, Michelle Cotterchio, Eithne Costello, Joanne Elena, Niccola Funel, J Michael Gaziano, Nathalia A Giese, Edward L Giovannucci, Michael Goggins, Megan J Gorman, Myron Gross, Christopher A Haiman, Manal Hassan, Kathy J Helzlsouer, Brian E Henderson, Elizabeth A Holly, Nan Hu, David J Hunter, Federico Innocenti, Mazda Jenab, Rudolf Kaaks, Timothy J Key, Kay-Tee Khaw, Eric A Klein, Manolis Kogevinas, Vittorio Krogh, Juozas Kupcinskas, Robert C Kurtz, Andrea LaCroix, Maria T Landi, Stefano Landi, Loic Le Marchand, Andrea Mambrini, Satu Mannisto, Roger L Milne, Yusuke Nakamura, Ann L Oberg, Kouros Owzar, Alpa V Patel, Petra H M Peeters, Ulrike Peters, Raffaele Pezzilli, Ada Piepoli, Miquel Porta, Francisco X Real, Elio Riboli, Nathaniel Rothman, Aldo Scarpa, Xiao-Ou Shu, Debra T Silverman, Pavel Soucek, Malin Sund, Renata Talar-Wojnarowska, Philip R Taylor, George E Theodoropoulos, Mark Thornquist, Anne Tjønneland, Geoffrey S Tobias, Dimitrios Trichopoulos, Pavel Vodicka, Jean Wactawski-Wende, Nicolas Wentzensen, Chen Wu, Herbert Yu, Kai Yu, Anne Zeleniuch-Jacquotte, Robert Hoover, Patricia Hartge, Charles Fuchs, Stephen J Chanock, Rachael S Stolzenberg-Solomon, Laufey T Amundadottir.
Nat. Genet.
PUBLISHED: 02-26-2014
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We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 × 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 × 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 × 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 × 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 × 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 × 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.
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Peroxisome proliferator-activated receptor ?-mediated induction of microRNA-145 opposes tumor phenotype in colorectal cancer.
Biochim. Biophys. Acta
PUBLISHED: 02-19-2014
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MicroRNAs (miRNAs) regulate diverse biological processes by inhibiting translation or inducing degradation of target mRNAs. miR-145 is a candidate tumor suppressor in colorectal carcinoma (CRC). Colorectal carcinogenesis involves deregulation of cellular processes controlled by a number of intertwined chief transcription factors, such as PPAR? and SOX9. Since PPAR family members are able to modulate complex miRNAs networks, we hypothesized a role of miRNA-145 in the interaction between PPAR? and SOX9 in colorectal carcinogenesis. To address this issue, we evaluated gene expression in tissue specimens of CRC patients and we took advantage of invitro models represented by CRC derived cell lines (CaCo2, SW480, HCT116, and HT-29), employing PPAR? activation and/or miRNA-145 ectopic overexpression to analyze how their interplay impact the expression of SOX9 and the development of a malignant phenotype.
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Circadian clock circuitry in colorectal cancer.
World J. Gastroenterol.
PUBLISHED: 01-06-2014
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Colorectal cancer is the most prevalent among digestive system cancers. Carcinogenesis relies on disrupted control of cellular processes, such as metabolism, proliferation, DNA damage recognition and repair, and apoptosis. Cell, tissue, organ and body physiology is characterized by periodic fluctuations driven by biological clocks operating through the clock gene machinery. Dysfunction of molecular clockworks and cellular oscillators is involved in tumorigenesis, and altered expression of clock genes has been found in cancer patients. Epidemiological studies have shown that circadian disruption, that is, alteration of bodily temporal organization, is a cancer risk factor, and an increased incidence of colorectal neoplastic disease is reported in shift workers. In this review we describe the involvement of the circadian clock circuitry in colorectal carcinogenesis and the therapeutic strategies addressing temporal deregulation in colorectal cancer.
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Loss of connectivity in cancer co-expression networks.
PLoS ONE
PUBLISHED: 01-01-2014
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Differential gene expression profiling studies have lead to the identification of several disease biomarkers. However, the oncogenic alterations in coding regions can modify the gene functions without affecting their own expression profiles. Moreover, post-translational modifications can modify the activity of the coded protein without altering the expression levels of the coding gene, but eliciting variations to the expression levels of the regulated genes. These considerations motivate the study of the rewiring of networks co-expressed genes as a consequence of the aforementioned alterations in order to complement the informative content of differential expression. We analyzed 339 mRNAomes of five distinct cancer types to find single genes that presented co-expression patterns strongly differentiated between normal and tumor phenotypes. Our analysis of differentially connected genes indicates the loss of connectivity as a common topological trait of cancer networks, and unveils novel candidate cancer genes. Moreover, our integrated approach that combines the differential expression together with the differential connectivity improves the classic enrichment pathway analysis providing novel insights on putative cancer gene biosystems not still fully investigated.
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The circadian clock and the hypoxic response pathway in kidney cancer.
Tumour Biol.
PUBLISHED: 06-28-2013
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The most frequent malignant tumor of the kidney in adults is represented by renal cell carcinoma characterized by high lethality related to presence of metastatic disease at the time of diagnosis. The main characteristic molecular feature of most sporadic renal cell carcinomas is the mutation of the tumor suppressor gene encoding the von Hippel-Lindau protein, with alteration of regulated pathways and activation of hypoxia-inducible transcription factors. Hypoxia-inducible transcription factors are transcriptional regulators of genes controlling mammalian oxygen homeostasis, energy metabolism, neovascularisation, internal pH, cell survival, and migration and are considered powerful promoters of tumor growth. Tight interrelationships have been evidenced between hypoxic response pathway and circadian pathway. Severe deregulation of genes involved in the circadian clock circuitry and response to hypoxia has been found in patients affected by kidney cancer, influencing the process of carcinogenesis, as well as disease progression and outcome. The study of alterations of clock gene expression and hypoxia correlated pathway in kidney cancer may promote the comprehension of pathophysiological mechanisms involved in renal cell carcinoma onset and evolution and may help to exploit more effective therapeutic approaches.
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Interplay between SOX9, ?-catenin and PPAR? activation in colorectal cancer.
Biochim. Biophys. Acta
PUBLISHED: 04-03-2013
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Colorectal carcinogenesis relies on loss of homeostasic mechanisms regulating cell proliferation, differentiation and survival. These cell processes have been reported to be influenced independently by transcription factors activated downstream of the Wnt pathway, such as SOX9 and ?-catenin, and by the nuclear receptor PPAR?. The purpose of this study was to explore the expression levels and functional link between SOX9, ?-catenin and PPAR? in the pathogenesis of colorectal cancer (CRC). We evaluated SOX9, ?-catenin and PPAR? expression levels on human CRC specimens by qPCR and immunoblot detection. We tested the hypothesis that PPAR? activation might affect SOX9 and ?-catenin expression using four colon cancer cell lines (CaCo2, SW480, HCT116, and HT29 cells). In CRC tissues SOX9 resulted up-regulated at both mRNA and protein levels when compared to matched normal mucosa, ?-catenin resulted up-regulated at protein levels, while PPARG mRNA and PPAR? protein levels were down-regulated. A significant relationship was observed between high PPARG and SOX9 expression levels in the tumor tissue and female gender (p=0.005 and p=0.04, respectively), and between high SOX9 expression in the tumor tissue and age (p=0.04) and microsatellite instability (MSI), in particular with MSI-H (p=0.0002). Moreover, treatment with the synthetic PPAR? ligand rosiglitazone induced different changes of SOX9 and ?-catenin expression and subcellular localization in the colon cancer cell lines examined. In conclusion, SOX9, ?-catenin and PPAR? expression levels are deregulated in the CRC tissue, and in colon cancer cell lines ligand-dependent PPAR? activation unevenly influences SOX9 and ?-catenin expression and subcellular localization, suggesting a variable mechanistic role in colon carcinogenesis.
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Cancer risk associated with STK11/LKB1 germline mutations in Peutz-Jeghers syndrome patients: results of an Italian multicenter study.
Dig Liver Dis
PUBLISHED: 02-15-2013
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Germline mutations in the STK11/LKB1 gene cause Peutz-Jeghers syndrome, an autosomal-dominantly inherited condition characterized by mucocutaneous pigmentation, hamartomatous gastrointestinal polyposis, and an increased risk for various malignancies. We here report the results of the first Italian collaborative study on Peutz-Jeghers syndrome.
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SIRT1 and the clock gene machinery in colorectal cancer.
Cancer Invest.
PUBLISHED: 12-13-2011
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SIRT1 and the clock genes are involved in carcinogenesis. We evaluated SIRT1 expression in 19 human colorectal cancer (CRC) specimens and clock gene expression in SIRT1-overexpressing CaCo2 and SW480 cells. In CRC, SIRT1 mean expression level was decreased. Compared to CaCo2 cells, SW480 cells displayed lower levels of SIRT1 and PER3 and higher levels of ARNTL1, CLOCK, PER1, PER2, CRY1, TIPIN, and CSNKIE. SIRT1 overexpression induced PER1 upregulation in CaCo2 and downregulation in SW480 cells. SIRT1 expression was heterogeneous in human CRC and in CRC cell lines. These results might have relevant implications for a better understanding of colorectal carcinogenesis.
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Altered expression of the clock gene machinery in kidney cancer patients.
Biomed. Pharmacother.
PUBLISHED: 09-18-2011
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Kidney cancer is associated with alteration in the pathways regulated by von Hippel-Lindau protein and hypoxia inducible factor ?. Tight interrelationships have been evidenced between hypoxia response pathways and circadian pathways. The dysregulation of the circadian clock circuitry is involved in carcinogenesis. The aim of our study was to evaluate the clock gene machinery in kidney cancer.
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ARNTL2 and SERPINE1: potential biomarkers for tumor aggressiveness in colorectal cancer.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 08-23-2011
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Cathepsin and plasmin may favor cancer cell invasion degrading extracellular matrix. Plasmin formation from plasminogen is regulated by plasminogen activator inhibitor type-1 (PAI-1). ARNTL2 activates the promoters of the PAI-1 gene, officially called SERPINE1, driving the circadian variation in circulating PAI-1 levels.
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Alteration of hypothalamic-pituitary-thyroid axis function in non-small-cell lung cancer patients.
Integr Cancer Ther
PUBLISHED: 08-23-2011
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The aim of this study was to evaluate the hypothalamic-pituitary-thyroid (HPT) axis function in patients suffering from lung cancer. Thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), free thyroxine (FT4), interleukin (IL)-2, and melatonin serum levels were measured in blood samples collected every 4 hours for 24 hours from 11 healthy participants (H; ages 35-53 years) and 9 patients suffering from non-small-cell lung cancer (C; ages 43-63 years). Relationships between hormone levels overall and over time of day were evaluated within and among groups. A prominent circadian rhythm with peaks near midnight was present for TSH and melatonin serum levels in both H and C, indicating similar synchronization of the main body clock to the 24-hour environmental light-dark cycle. As regards 24-hour means in H and C, TSH was lower in C, whereas TRH, FT4, and IL-2 were higher in C, with no difference in melatonin levels. Simple linear regression, FT4 versus TRH, showed a positive correlation in H and a negative correlation in C, whereas FT4 versus TSH showed a negative correlation in both groups. For FT4 versus IL-2, a negative correlation was found in C but not for H, whereas TSH versus TRH showed no correlation for either group. Both groups were found to be similarly synchronized to the 24-hour sleep-wake schedule, but HPT axis function was altered in patients suffering from lung cancer. When compared with healthy controls, cancer patients showed modifications of hormone serum levels overall and a negative correlation between individual TRH and FT4 levels.
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Antiphase signalling in the neuroendocrine-immune system in healthy humans.
Biomed. Pharmacother.
PUBLISHED: 02-08-2011
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Any quantity varying in the spatial-temporal dimension may be considered as a signal. Human lymphocyte cell surface molecules and subsets present circadian variation and this variation may represent a kind of signalling in the neuroendocrine-immune system. We have analyzed the dynamics of variation of specific lymphocyte subsets in healthy humans.
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Circadian aspects of growth hormone-insulin-like growth factor axis function in patients with lung cancer.
Clin Lung Cancer
PUBLISHED: 01-16-2011
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Insulin-like growth factor 1 (IGF1) promotes cell cycle progression and inhibition of apoptosis and may have a role in carcinogenesis and cancer promotion. Growth hormone (GH) stimulates IGF1 production in liver and other tissues. The aim of our study was to evaluate differences between healthy subjects and patients with lung cancer in the GH-IGF1 axis function.
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Stage dependent destructuration of neuro-endocrine-immune system components in lung cancer patients.
Biomed. Pharmacother.
PUBLISHED: 09-24-2010
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Close relationships among the nervous, endocrine and immune system components maintain body homeostasis. Alteration of time-related prophile of variation of system components and loss of integrated function may favour the developing of cancer and may be aggravated in the presence of neoplastic disease. The aim of our study was to evaluate the prophiles of time-related variation of neuro-endocrine-immune system components in lung cancer patients.
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On the reproducibility of results of pathway analysis in genome-wide expression studies of colorectal cancers.
J Biomed Inform
PUBLISHED: 06-26-2009
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One of the major problems in genomics and medicine is the identification of gene networks and pathways deregulated in complex and polygenic diseases, like cancer. In this paper, we address the problem of assessing the variability of results of pathways analysis identified in different and independent genome wide expression studies, in which the same phenotypic conditions are assayed. To this end, we assessed the deregulation of 1891 curated gene sets in four independent gene expression data sets of subjects affected by colorectal cancer (CRC). In this comparison we used two well-founded statistical models for evaluating deregulation of gene networks. We found that the results of pathway analysis in expression studies are highly reproducible. Our study revealed 53 pathways identified by the two methods in all the four data sets analyzed with high statistical significance and strong biological relevance with the pathology examined. This set of pathways associated to single markers as well as to whole biological processes altered constitutes a signature of the disease which sheds light on the genetics bases of CRC.
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Promoter methylation correlates with reduced NDRG2 expression in advanced colon tumour.
BMC Med Genomics
PUBLISHED: 03-03-2009
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Aberrant DNA methylation of CpG islands of cancer-related genes is among the earliest and most frequent alterations in cancerogenesis and might be of value for either diagnosing cancer or evaluating recurrent disease. This mechanism usually leads to inactivation of tumour-suppressor genes. We have designed the current study to validate our previous microarray data and to identify novel hypermethylated gene promoters.
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Molecular pathways undergoing dramatic transcriptomic changes during tumor development in the human colon.
BMC Cancer
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The malignant transformation of precancerous colorectal lesions involves progressive alterations at both the molecular and morphologic levels, the latter consisting of increases in size and in the degree of cellular atypia. Analyzing preinvasive tumors of different sizes can therefore shed light on the sequence of these alterations.
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Genetic susceptibility to pancreatic cancer and its functional characterisation: the PANcreatic Disease ReseArch (PANDoRA) consortium.
Dig Liver Dis
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Pancreatic cancer is the fourth leading cause of cancer deaths in the European Union and in the USA, but little is known about its genetic susceptibility. The PANcreatic Disease ReseArch (PANDoRA) consortium was established to unite the efforts of different research groups; its aim is to create a large bio-database to uncover new genetic factors for pancreatic cancer risk, response to treatment, and patient survival. So far 2220 cases of pancreatic adenocarcinoma, a smaller number of cases of endocrine pancreatic tumours (n=86), chronic pancreatitis (n=272) and 3847 healthy controls have been collected. As a collective effort of the consortium, SNPs associated with pancreatic adenocarcinoma risk from a genome-wide association study performed in Caucasians were replicated. The possibility that the same genetic polymorphisms may influence patient survival as well was also addressed. This collective effort is particularly important for pancreatic cancer because it is a relatively rare disease for which little is known about aetiopathogenesis and risk factors. The recruitment of additional collaborators and partner institutions is continuously on-going.
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Differential patterns in the periodicity and dynamics of clock gene expression in mouse liver and stomach.
Chronobiol. Int.
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The rhythmic recurrence of biological processes is driven by the functioning of cellular circadian clocks, operated by a set of genes and proteins that generate self-sustaining transcriptional-translational feedback loops with a free-running period of about 24?h. In the gastrointestinal apparatus, the functioning of the biological clocks shows distinct patterns in the different organs. The aim of this study was to evaluate the time-related variation of clock gene expression in mouse liver and stomach, two components of the digestive system sharing vascular and autonomic supply, but performing completely different functions. The authors analyzed the periodicity by cosinor analysis and the dynamics of variation by computing the fractional variation to assess the rate of change in gene expression. Five-week-old male Balb/c mice were exposed to 2 wks of 12-h light/12-h dark cycles, then kept in complete darkness for 3 d as a continuation of the dark span of the last light-dark cycle. The authors evaluated the expression of Bmal1, Clock, Cry1, Cry2, Per1, Per2, Per3, Rev-erb?, Rev-erb?, Npas2, Timeless, Dbp, Csnk1d, and Csnk1e by using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in mouse liver and stomach. A significant 24-h rhythmic component was found for 10 genes in the liver (Bmal1, Clock, Cry1, Per1, Per2, Per3, Rev-erb?, Rev-erb?, Npas2, and Dbp), and for 9 genes in the stomach (Bmal1, Cry1, Per1, Per2, Per3, Rev-erb?, Rev-erb?, Npas2, and Dbp). In particular, Clock showed marked rhythm differences between liver and stomach, putatively due to some compensation by Npas2. The acrophase of the original values of Bmal1, Per2, Per3, Rev-erb?, Rev-erb?, Npas2, and Dbp expression was delayed in the stomach, and the average delay expressed as mean?±?SD was 14.30?±?7.94 degrees (57.20?±?31.78 minutes). A statistically significant difference was found in the acrophases of Bmal1 (p?=?.015) and Npas2 (p?=?.011). Fractional variations provided significant circadian rhythms for nine genes in the liver (Bmal1, Per1, Per2, Per3, Rev-erb?, Rev-erb?, Npas2, Timeless, and Dbp), and for seven genes in the stomach (Bmal1, Clock, Per2, Rev-erb?, Npas2, Dbp, and Csnk1e). The acrophase of the fractional variations of Bmal1, Per2, Per3, Rev-erb?, Rev-erb?, and Dbp expression was delayed in the stomach, and the average delay expressed as mean?±?SD was 19.10?±?9.39 degrees (76.40?±?37.59 minutes). A significantly greater fractional variation was found in the liver for Clock at 06:00?h (p?= .034), Per1 at 02:00?h (p?=?.037), and Per3 at 02:00?h (p?=?.029), whereas the fractional variation was greater in the stomach for Clock at 10:00?h (p?=?.016), and for Npas2 at 02:00?h (p?=?.029) and at 06:00?h (p?=?.044). In conclusion, liver and stomach show different phasing and dynamics of clock gene expression, which are probably related to prevailing control by different driving cues, and allow them to keep going the various metabolic pathways and diverse functional processes that they manage.
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The expression of leucine-rich repeat gene family members in colorectal cancer.
Exp. Biol. Med. (Maywood)
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This study was conducted to evaluate the association of the leucine-rich repeat (LRR) gene family with colorectal cancer (CRC). The expression of members of the LRR gene family were analyzed in 17 CRC specimens and in 59 healthy colorectal tissues by using Human Exon1.0ST microarray, and in 25 CRC specimens and 32 healthy colorectal tissues by U133Plus2.0 microarray. An association was found for 25 genes belonging to the plant-specific (PS) class of LRR genes (P = 0.05 for Exon1.0 ST and P = 0.04 for U133Plus2.0). In both data-sets, in CRC, we found down-regulation of SHOC2 (P < 0.00003) and LRRC28 (P < 0.01) and up-regulation of LRSAM1 (P < 0.000001), while up-regulation of MFHAS1 (P = 0.0005) and down-regulation of WDFY3 (P = 0.026) were found only in the Exon1.0 ST data-set. The PS LLR gene class encodes proteins that activate immune cells and might play a key role in programmed cell death and autophagy. SHOC2 and LRRC28 genes involved in RAS-mediated signaling, which hinders nutrient deprivation-induced autophagy, might be a possible link between the negative control of autophagy and tumorigenesis.
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Changes in miR-143 and miR-21 expression and clinicopathological correlations in pancreatic cancers.
Pancreas
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Despite advances in clinical management of pancreatic cancer (PC), there is still room for improvement in early detection, diagnosis, and treatment strategies. The role of microRNAs (miRNAs) in tumor biology might pinpoint an alteration in expression of miRNAs as new diagnostic/prognostic biomarkers.
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A unifying working hypothesis for juvenile polyposis syndrome and Ménétriers disease: specific localization or concomitant occurrence of a separate entity?
Dig Liver Dis
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Juvenile polyposis syndrome with gastric involvement may mimic Ménétriers disease, which is correlated to transforming growth factor (TGF)? overproduction and PDX1 upregulation in the gastric fundus.
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BEAT: Bioinformatics Exon Array Tool to store, analyze and visualize Affymetrix GeneChip Human Exon Array data from disease experiments.
BMC Bioinformatics
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It is known from recent studies that more than 90% of human multi-exon genes are subject to Alternative Splicing (AS), a key molecular mechanism in which multiple transcripts may be generated from a single gene. It is widely recognized that a breakdown in AS mechanisms plays an important role in cellular differentiation and pathologies. Polymerase Chain Reactions, microarrays and sequencing technologies have been applied to the study of transcript diversity arising from alternative expression. Last generation Affymetrix GeneChip Human Exon 1.0 ST Arrays offer a more detailed view of the gene expression profile providing information on the AS patterns. The exon array technology, with more than five million data points, can detect approximately one million exons, and it allows performing analyses at both gene and exon level. In this paper we describe BEAT, an integrated user-friendly bioinformatics framework to store, analyze and visualize exon arrays datasets. It combines a data warehouse approach with some rigorous statistical methods for assessing the AS of genes involved in diseases. Meta statistics are proposed as a novel approach to explore the analysis results. BEAT is available at http://beat.ba.itb.cnr.it.
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DNA methyltransferases 1 and 3b expression in Huh-7 cells expressing HCV core protein of different genotypes.
Dig. Dis. Sci.
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Hepatitis C virus infects ~3% of the population and it is a risk factor for hepatocarcinogenesis. The epigenetic mechanisms of HCV-induced hepatocyte transformation towards malignancy in this context are unclear.
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Mirna expression profiles identify drivers in colorectal and pancreatic cancers.
PLoS ONE
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Altered expression of microRNAs (miRNAs) hallmarks many cancer types. The study of the associations of miRNA expression profile and cancer phenotype could help identify the links between deregulation of miRNA expression and oncogenic pathways.
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MUTYH-associated polyposis (MAP): evidence for the origin of the common European mutations p.Tyr179Cys and p.Gly396Asp by founder events.
Eur. J. Hum. Genet.
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MUTYH-associated polyposis (MAP) is an autosomal recessive adenomatous polyposis caused by biallelic germline mutations of the base-excision-repair gene MUTYH. In MAP patients of European origin, the combined allele frequency of the mutations p.Tyr179Cys and p.Gly396Asp ranges between 50 and 82%, while these mutations have not been identified in Far Eastern Asian populations, supporting the hypothesis that a founder effect has occurred at some point in European history. To investigate the natural history of the two common European MUTYH alleles, we genotyped six gene-flanking microsatellite markers in 80 unrelated Italian and German MAP patients segregating one or both mutations and calculated their age in generations (g) by using DMLE+2.2 software. Three distinct common haplotypes, one for p.Tyr179Cys and two for p.Gly396Asp, were identified. Estimated mutation ages were 305?g (95% CS: 271-418) for p.Tyr179Cys and 350?g (95% CS: 313-435) for p.Gly396Asp. These results provide evidence for strong founder effects and suggest that the p.Tyr179Cys and p.Gly396Asp mutations derive from ancestors who lived between 5-8 thousand years and 6-9 thousand years B.C., respectively.European Journal of Human Genetics advance online publication, 30 January 2013; doi:10.1038/ejhg.2012.309.
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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.