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Pre-diagnostic levels of adiponectin and soluble vascular cell adhesion molecule-1 are associated with colorectal cancer risk

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World Journal of Gastroenterology 2012年第22期18卷 2805-2812页

作者： Mathilde Touvier Léopold Fezeu Namanjeet Ahluwalia Chantal Julia Nathalie Charnaux Angela Sutton Caroline Méjean Paule Latino-Martel Serge Hercberg Pilar Galan Sébastien Czernichow inserm u577(National Institute of Health and Medical Research) Inra Cnam University of Paris 13 (UREN) SMBH 74 rue Marcel Cachin F-93017 Bobigny France Department of Biochemistry Jean Verdier Hospital F-93140 Bondy France inserm u698 University of Paris 13 F-93017 Bobigny France Department of Public Health Avicenne Hospital (AP-HP) University of Paris 13 F-93017 Bobigny France Department of Nutrition Ambroise Paré Hospital (AP-HP) University of Versailles Saint Quentin F-92100 Boulogne-Billancourt France

AIM： To examine the relationships between pre-diag- nostic biomarkers and colorectal cancer risk and assess their relevance in predictive ***： A nested case-control study was designed to include all first primary incident colorectal cancer cases diagnosed between inclusion in the Supplemen- tation en VItamines et Min^raux AntioXydants cohort in 1994 and the end of follow-up in 2007. Cases （n = 50） were matched with two randomly selected con- trols （n = 100）. Conditional logistic regression models were used to investigate the associations between pre- diagnostic levels of hs-CRP, adiponectin, leptin, soluble vascular cell adhesion molecule-1 （sVCAM-1）, soluble intercellular adhesion molecule-I, E-selectin, monocyte chemoattractant protein-1 and colorectal cancer risk. Area under the receiver operating curves （AuC） and relative integrated discrimination improvement （RIDI） statistics were used to assess the discriminatory poten- tial of the models. RESuLTS： Plasma adiponectin level was associated with decreased colorectal cancer risk （P for linear trend -- 0.03）. Quartiles of sVCAM-1 were associated with increased colorectal cancer risk （P for linear trend = 0.02）. No association was observed with any of the other biomarkers. Compared to standard models with known risk factors, those including both adiponectin and sVCAM-1 had substantially improved performance for colorectal cancer risk prediction （P for AuC improve- ment = 0.01, RIDI = 26.5%）. CONCLuSION： These results suggest that pre-diag- nostic plasma adiponectin and sVCAM-1 levels are as- sociated with decreased and increased colorectal cancer risk, respectively. These relationships must be confirmed in large validation studies.

关键词： Colorectal cancer Adiponectin Soluble vascu-lar cell adhesion molecule-l Nested case-control study Prospective study

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Mechanisms of regulation of PFKFB expression in pancreatic and gastric cancer cells

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World Journal of Gastroenterology 2014年第38期20卷 13705-13717页

作者： Oleksandr H Minchenko Katsuya Tsuchihara Dmytro O Minchenko Andreas Bikfalvi Hiroyasu Esumi Department of Molecular Biology Palladin Institute of Biochemistry Department of Innovative Oncology National Cancer Center Department of Pediatrics Bogomolets National Medical University inserm u1029 Molecular Angiogenesis and Cancer Microenvironment Laboratory University Bordeaux I

Enzymes 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 and -4 (PFKFB-3 and PFKFB-4) play a significant role in the regulation of glycolysis in cancer cells as well as its proliferation and survival. The expression of these mRNAs is increased in malignant tumors and strongly induced in different cancer cell lines by hypoxia inducible factor (HIF) through active HIF binding sites in promoter region of PFKFB-4 and PFKFB-3 genes. Moreover, the expression and hypoxia responsibility of PFKFB-4 and PFKFB-3 was also shown for pancreatic (Panc1, PSN-1, and MIA PaCa-2) as well as gastric (MKN45 and NuGC3) cancer cells. At the same time, their basal expression level and hypoxia responsiveness vary in the different cells studied: the highest level of PFKFB-4 protein expression was found in NuGC3 gastric cancer cell line and lowest in Panc1 cells, with a stronger response to hypoxia in the pancreatic cancer cell line. Overexpression of different PFKFB in pancreatic and gastric cancer cells under hypoxic condition is correlated with enhanced expression of vascular endothelial growth factor (VEGF) and Glut1 mRNA as well as with increased level of HIF-1α protein. Increased expression of different PFKFB genes was also demonstrated in gastric, lung, breast, and colon cancers as compared to corresponding non-malignant tissue counterparts from the same patients, being more robust in the breast and lung tumors. Moreover, induction of PFKFB-4 mRNA expression in the breast and lung cancers is stronger than PFKFB-3 mRNA. The levels of both PFKFB-4 and PFKFB-3 proteins in non-malignant gastric and colon tissues were more pronounced than in the non-malignant breast and lung tissues. It is interesting to note that Panc1 and PSN-1 cells transfected with dominant/negative PFKFB-3 (dnPFKFB-3) showed a lower level of endogenous PFKFB-3, PFKFB-4, and VEGF mRNA expressions as well as a decreased proliferation rate of these cells. Moreover, a similar effect had dnPFKFB-4. In conclusi

关键词： 6-phosphofructo-2-kinase/fructose-2 6-bisphosphatase-3 6-phosphofructo-2-kinase/fructose-2 6-bisphosphatase-4 Hypoxia Hypoxia inducible factor Panc1 PST-1 MKN45 NuGC3 Gastric cancer Lung cancer

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Region 2 of 8q24 is associated with the risk of aggressive prostate cancer in Caribbean men of African descent from Guadeloupe （French West Indies）

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Asian Journal of Andrology 2015年第1期17卷 117-119,I0010页

作者： Geraldine Cancel-Tassin Marc Romana Cecile Gaffory Pascal Blanchet Olivier Cussenot Luc Multigner CeRePP Pitie-Salpetriere Hospital Paris 75013 France ER2 UPMC Univ Paris 6 Paris 75020 France 3u665 Inserm Pointe a Pitre 97159 Guadeloupe French West Indies Department of urology Assistance Publique Hopitaux de Paris Tenon Hospital GHU Est Paris 75020 France u1085 - IRSET Inserm Pointe Pitre 97154 Guadeloupe French West Indies Department of urology CHU Pointe--Pitre/Abymes Pointe Pitre 97159 Guadeloupe French West Indies.

Multiple regions of the genome have been associated with the risk of prostate cancer in Caucasians, particularly including several polymorphisms located at 8q24. Region 2 of 8q24 has been repeatedly found to be associated with the risk of prostate cancer among men of African descent, although one study performed in the Caribbean island of Jamaica did not report this finding. In this study, the single nucleotide polymorphism rs16901979, located in region 2 of 8q24, was genotyped in 498 cases of histologically confirmed prostate cancer and 541 controls from the French Caribbean islands of Guadeloupe, where the population is largely of African descent. The AA genotype and the A allele at rs16901979 were associated with elevated risks of prostate cancer （odds ratios [ORs] = 1.84, 95% confidence interval [95% CI] = 1.26-2.69, P= 0.002 and OR = 1.36, 95% CI = 1.13-1.64, P= 0.001, respectively）. Following stratification of the patients by disease aggressiveness, as defined by the Gleason score, the pooled genotypes AC ＋ AA were associated with a higher risk of a Gleasen score 〉7 at diagnosis （OR = 1.79, 95% CI = 1.17-2.73, P= 0.007）. In summary, the A allele at rs16901979 was associated with the risk of prostate cancer in the Caribbean population of Guadeloupe, confirming its involvement in populations of African descent. Moreover, our study provides the first evidence of an association between this variant and the risk of aggressive prostate cancer.

关键词： African Continental Ancestry Group aggressiveness Caribbean region genetic predisposition to disease prostaticneoplasms

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Identification and characterization of a novel bipartite nuclear localization signal in the hepatitis B virus polymerase

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World Journal of Gastroenterology 2013年第44期19卷 8000-8010页

作者： Joachim Lupberger Stephanie Schaedler Alexander Peiran Eberhard Hildt Department of Medicine Ⅱ University of Freiburg D-79106 Freiburg Germany inserm U748 Strasbourg France Division of Virology University Goettingen37073 Goettingen Germany Division of Virology Paul-Ehrlich-InstituteD-63325 Langen Germany

AIM: To characterize the nuclear import of hepatitis B virus (HBV) polymerase (P) and its relevance for the viral life cycle.METHODS: Sequence analysis was performed to predict functional motives within P. Phosphorylation of P was analyzed by in vitro phosphorylation. Phosphorylation site and nuclear localization signal (NLS) were destroyed by site directed mutagenesis. Functionality of the identified NLS was analyzed by confocal fluorescence microscopy and characterizing the karyopherin binding. Relevance of the structural motives for viral life cycle was studied by infection of primary Tupaia hepatocytes with HBV.RESuLTS: We identified by sequence alignment and functional experiments a conserved bipartite NLS containing a casein kinase II (CKII) phosphorylation site located within the terminal protein domain (TP) of the HBV polymerase. Inhibition of CKII impairs the functionality of this NLS and thereby prevents the nuclear import of the polymerase. Binding of the import factor karyopherin-α2 to the polymerase depends on its CKII-mediated phosphorylation of the bipartite NLS. In HBV-infected primary Tupaia hepatocytes CKII inhibition in the early phase (post entry phase) of the infection process prevents the establishment of the infection.CONCLuSION: Based on these data it is suggested that during HBV infection the final import of the genome complex into the nucleus is mediated by a novel bipartite NLS localized in the TP domain of HBV polymerase.

关键词： Hepatitis B virus Nuclear localization signal Casein kinase II Trafficking Replication

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Saccharomyces cerevisiae CNCM I-3856 in irritable bowel syndrome: An individual subject meta-analysis

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World Journal of Gastroenterology 2017年第2期23卷 336-344页

作者： Amélie Cayzeele-Decherf Fanny Pélerin Sébastien Leuillet Benoit Douillard Béatrice Housez Murielle Cazaubiel Gunnard K Jacobson Peter Jüsten Pierre Desreumaux Lesaffre Human Care Lesaffre Group Biofortis-Mérieux NutriS ciences Lesaffre Yeast Corporation Lesaffre Group CHu Lille Department of GastroenterologyClaude Huriez Hospital Lille university North of France inserm u995

AIMTo confirm previous conclusions on Saccharomyces cerevisiae (S. cerevisiae) CNCM I-3856 for irritable bowel syndrome (IBS) *** individual patient data meta-analysis was performed on two randomized clinical trials studying the effect of S. cerevisiae CNCM I-3856 supplementation on gastrointestinal (GI) symptoms in IBS subjects. A total of 579 IBS subjects were included. Outcomes were the daily Likert scale scores of abdominal pain/discomfort and bloating [area under the curve (AuC) and weekly means], responder status, and bowel movements (stool frequency and consistency). Statistical analyses were conducted in Intent to Treat (ITT) population, IBS-C subjects and IBS-C subjects with an abdominal pain/discomfort score higher than or equal to 2 at baseline (“IBS-C ≥ 2 subpopulation”).RESuLTSS. cerevisiae CNCM I-3856 significantly improved abdominal pain/discomfort and bloating during the second month of supplementation [AuC (W5-W8)] with improvement up to the minimal clinically relevant threshold of 10%: a 12.3% reduction of abdominal pain/discomfort in the ITT population compared to the Placebo group (P = 0.0134) has been observed. In the IBS-C ≥ 2 subpopulation, there were a 13.1% reduction of abdominal pain/discomfort and a 14.9% reduction of bloating compared to the Placebo group (P = 0.0194 and P = 0.0145, respectively). GI symptoms significantly decreased during supplementation but no statistical differences were reported between groups at the end of the supplementation period. Responder status was defined as a subject who experienced a decrease of 1 arbitrary unit (a.u.) or 50% of the abdominal discomfort score from baseline for at least 2 wk out of the last 4 wk of the study. A significant difference between groups was reported in the ITT population, when considering the first definition: subjects in the Active group had 1.510 higher odds to be a responder (reduction of 1 a.u. of abdominal pain/discomfort) comp

关键词： Irritable bowel syndrome Saccharomyces cerevisiae Constipation Abdominal pain Probiotics

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ACTIVITY OF PRESuMED HISTAMINE AND OREXIN NEuRONS ACROSS THE SLEEP-WAKING CYCLE IN FREELY BEHAVING CATS

ACTIVITY OF PRESUMED HISTAMINE AND OREXIN NEURONS ACROSS THE...

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The4thASRSCongress

作者： K.Sakai K. S.Crochet,S. inserm u480 Claude Bernard UniversityLyonFrance inserm u480 Claude Bernard UniversityLyonFrance

＜正＞Among the forebrain activating structures, the posterior hypothalamus appears to play a critical role in the initiation and maintenance of arousal through its widespread ascending and descending projections to brain structures implicated in the ascending arousal system. Indeed, previous pharmacological studies showed that inactivation of posterior hypothalamic neurons results in hypersomnia in normal cats and restores sleep in insomniac cats with lesions of the

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Deletion of the immunoglobulin heavy chain 3′ regulatory region super-enhancer affects somatic hypermutation in B1 B cells

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Cellular & Molecular Immunology 2019年第2期16卷 195-197页

作者： Issaoui Hussein Ghazzaui Nour Boyer François Denizot Yves Saintamand Alexis Centre National de la Recherche Scientifique unitéMixte de Recherche 7276 Institut National de la Santéet de la Recherche Médicale U1262CBRSrue du Pr.Descottes87025 LimogesFrance inserm u1236 UniversitéRennes 1RennesFrance

Mouse B1 B cells originate in the embryonic liver and are the major B-cell population in the peritoneal and pleural cavities.1–5 By contrast,mouse B2 B cells originate in the bone marrow and are the major B-cell population in the bone marrow,spleen,and blood.B1 and B2 B cells differ not only in their origin and locations,but also in their antigen specificity,cell surface markers,capacities for class-switch recombination(CSR)and somatic hypermutation(SHM).IgH cis-regulatory regions and,particularly,transcriptional super-enhancers are major locus regulators under both normal and pathological conditions.6,7 Important differences have been found regarding the ability of the IgH 3′regulatory region(3′RR)super-enhancer to control the B1 and B2 B-cell fate.

关键词： spleen specificity peritoneal

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Role of Cholinergic Receptors in Colorectal Cancer: Potential Therapeutic Implications of Vagus Nerve Stimulation?

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Journal of Cancer Therapy 2013年第6期4卷 1116-1131页

作者： Marjolaine Pelissier-Rota Michèle Lainé Benjamin Ducarouge Bruno Bonaz Muriel Jacquier-Sarlin Centre de Recherche inserm u836 Institute of Neurosciences Grenoble France

Inflammatory Bowel Disease (IBD) patients, such as Crohn’s disease or ulcerative colitis suffer from chronic and relapsing intestinal inflammation that favours the development of colitis associated cancer (CAC). This inflammation is initiated by aberrant activations of the innate immune responses associated to intestinal barrier defects. The conventional medical therapies consist to decrease the inflammatory response, which also decrease the risk of colon carcinoma but lead to severe side-effects. Recently, a number of animal studies have demonstrated that innate immune responses are attenuated by stimulation of the efferent arm of vagus nerve (VN) through its neurotransmitter acetylcholine (ACh), that acts on resident macrophages α7 nicotinic receptor (α7 nAChR). ACh also acts as a signalling molecule in epithetlial cells through cholinergic receptors such as nAChR or muscarinic (mAChR) receptors. In the current study, we aimed to extend these findings to CAC prevention by treating human adenocarcinoma cell lines through targeting cholinergic receptors with nicotine (which binds nAChR) and ACh (which binds both cholinergic receptors). using HT-29 and Caco-2 cell lines, we demonstrated that ACh-induced activation of mAChR results in cell dissociation together with changes in expression and localization of intestinal tight and adherens junction proteins. ACh-induced modulation of cell adhesion proprieties correlates with the acquisition of invasive potential. By contrast, nicotine-mediated activation of nAChR maintains epithelial cell organisation. ACh-released by VN stimulation (VNS) could effectively preserve epithelium integrity thus limiting inflammatory response and tumor development. However, attention should be paid on the nature of the cholinergic receptor solicited. Indeed, regarding to the protective effects of nAChR signalling on epithelial cells, activation of mAChR would worsen the disease and led to increase inflammation. These data have important reper

关键词： Cell Adhesion Colorectal Cancer Tumor Progression Cholinergic Receptors Inflammation Vagus Nerve

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Folding-unfolding of 33-kDa protein from photosystem II explored by hydrostatic pressure perturbation

Folding-unfolding of 33-kDa protein from photosystem II expl...

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第九次全国生物物理大会学术会议

作者： Claude Balny inserm u 128 IFR 24 CNRS Montpellier

＜正＞ The 33-kDa protein isolated from the spinach photosystem Ⅱis an ideal model toexplore high-pressure *** protein has a very low free energy as previouslyreported by chemical unfolding studies, suggesting that it must be easy to modulate itsunfolding transition by rather mild pressure. Moreover, the protein molecule consists of onlyone tryptophan residue（Trp241） and 8 tyrosine residues, which can be conveniently used to

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Expression and role of nuclear receptor coregulators in colorectal cancer

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World Journal of Gastroenterology 2017年第25期23卷 4480-4490页

作者： Mouna Triki Marion Lapierre Vincent Cavailles Raja Mokdad-Gargouri IRCM Institut de Recherche en Cancérologie de Montpellier INSERM U1194 Université de Montpellier Institut régional du Cancer de Montpellier Centre de Biotechnologie de Sfax Université de Sfax

Colorectal cancer(CRC) is one of the most common human cancers and the cause of about 700000 deaths per year worldwide. Deregulation of the WNT/β-catenin pathway is a key event in CRC initiation. This pathway interacts with other nuclear signaling pathways, including members of the nuclear receptor superfamily and their transcription coregulators. In this review, we provide an overview of the literature dealing with the main coactivators(NCo A-1 to 3, NCo A-6, PGC1-α, p300, CREBBP and MED1) and corepressors(N-Co R1 and 2, NRIP1 and MTA1) of nuclear receptors and summarize their links with the WNT/β-catenin signaling cascade, their expression in CRC and their role in intestinal physiopathology.

关键词： Immunohistochemistry Colon cancer Nuclear receptors Transcription coregulators WNT signaling

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