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| 1 | Role of ion channels in gastrointestinal cancer显示文摘In their seminal papers Hanahan and Weinberg described oncogenic processes a normal cell undergoes to be transformed into a cancer cell.The functions of ion channels in the gastrointestinal(GI)tract influence a variety of cellular processes,many of which overlap with these hallmarks of cancer.In this review we focus on the roles of the calcium(Ca^2+),sodium(Na^+),potassium(K^+),chloride(Cl^-)and zinc(Zn^2+)transporters in GI cancer,with a special emphasis on the roles of the KCNQ1 K+channel and CFTR Cl-channel in colorectal cancer(CRC).Ca^2+is a ubiquitous second messenger,serving as a signaling molecule for a variety of cellular processes such as control of the cell cycle,apoptosis,and migration.Various members of the TRP superfamily,including TRPM8,TRPM7,TRPM6 and TRPM2,have been implicated in GI cancers,especially through overexpression in pancreatic adenocarcinomas and down-regulation in colon cancer.Voltage-gated sodium channels(VGSCs)are classically associated with the initiation and conduction of action potentials in electrically excitable cells such as neurons and muscle cells.The VGSC NaV1.5 is abundantly expressed in human colorectal CRC cell lines as well as being highly expressed in primary CRC samples.Studies have demonstrated that conductance through NaV1.5 contributes significantly to CRC cell invasiveness and cancer progression.Zn2+transporters of the ZIP/SLC39A and ZnT/SLC30A families are dysregulated in all major GI organ cancers,in particular,ZIP4 up-regulation in pancreatic cancer(PC).More than 70 K+channel genes,clustered in four families,are found expressed in the GI tract,where they regulate a range of cellular processes,including gastrin secretion in the stomach and anion secretion and fluid balance in the intestinal tract.Several distinct types of K+channels are found dysregulated in the GI tract.Notable are hERG1 upregulation in PC,gastric cancer(GC)and CRC,leading to enhanced cancer angiogenesis and invasion,and KCNQ1 down-regulation in CRC,where KCNQ1 expression is associated with enhanced disease-free survival in stage II,III,and IV disease.Cl-channels are critical for a range of cellular and tissue processes in the GI tract,especially fluid balance in the colon.Most notable is CFTR,whose deficiency leads to mucus blockage,microbial dysbiosis and inflammation in the intestinal tract.CFTR is a tumor suppressor in several GI cancers.Cystic fibrosis patients are at a significant risk for CRC and low levels of CFTR expression are associated with poor overall disease-free survival in sporadic CRC.Two other classes of chloride channels that are dysregulated in GI cancers are the chloride intracellular channels(CLIC1,3&4)and the chloride channel accessory proteins(CLCA1,2,4).CLIC1&4 are upregulated in PC,GC,gallbladder cancer,and CRC,while the CLCA proteins have been reported to be down-regulated in CRC.In summary,it is clear,from the diverse influences of ion channels,that their aberrant expression and/or activity can contribute to malignant transformation and tumor progression.Further,because ion channels are often localized to the plasma membrane and subject to multiple layers of regulation,they represent promising clinical targets for therapeutic intervention including the repurposing of current drugs. | Kyle J Anderson Robert T Cormier Patricia M Scott | 2019 | World Journal of Gastroenterology2019，25，38： | 19 |
| 2 | Evaluation of the safety and effectiveness of direct oral anticoagulants and low molecular weight heparin in gastrointestinal cancer-associated venous thromboembolism显示文摘BACKGROUND Gastrointestinal cancer(GICA)is associated with a higher incidence of venous thromboembolism(VTE)compared to other solid tumors,moreover,recurrent VTE and major bleeding(MB)complications during anticoagulation treatment have an associated increase rate.GICA-VTE remains a challenging clinical scenario with MB concerns for utilization of direct oral anticoagulants(DOAC),especially with active cancer therapies.AIM To evaluate patient risk factors,effectiveness(VTE)and safety(MB)of DOACs and low molecular weight heparin(LMWH)in patients with active GICA-VTE.METHODS A retrospective chart review of patients receiving DOACs and LMWH with GICA and symptomatic or incidental VTE treated at comprehensive cancer center from November 2013 to February 2017 was performed.Inclusion criteria included active GI cancer diagnosed at any stage or treatment+/-6 mo of VTE diagnosis,whom were prescribed 6 mo or more of DOACs or LMWH.The Chi-squared test was used for overall and the Fisher exact test for pairwise comparisons of the proportions of patients experiencing recurrent VTE and MB events.Odds ratios were used to compare the relative odds of the occurrence of the outcome given exposure to the risk factor.RESULTS A total of 144 patients were prescribed anticoagulation,in which 106 fulfilled inclusion criteria apixaban(27.3%),rivaroxaban(34.9%)and enoxaparin(37.7%),and 38 were excluded.Patients median age was 66.5 years at GICA diagnosis and 67 years at CAVTE event,with 62%males,80%Caucasian,70%stage IV,pancreatic cancer(40.5%),30%Khorana Score(≥3 points),and 43.5%on active chemotherapy.Sixty-four percent of patients completed anticoagulation therapy(range 1 to 43 mo).Recurrent VTE at 6 mo was noted in 7.5%(n=3),6.8%(n=2)and 2.7%(n=1)of patients on enoxaparin,apixaban and rivaroxaban,respectively(all P=NS).MB at 6 mo were 5%(n=2)for enoxaparin,6.8%(n=2)for apixaban and 21.6%(n=8)for rivaroxaban(overall P=0.048;vs LMWH P=0.0423;all other P=NS).Significant predictors of a primary or secondary outcome for all anticoagulation therapies included:Active systemic treatment(OR=5.1,95%CI:1.3-19.3),high Khorana Score[≥3 points](OR=5.5,95%CI:1.7-17.1),active smoker(OR=6.7,95%CI:2.1-21.0),pancreatic cancer(OR=6.8,95%CI:1.9-23.2),and stage IV disease(OR=9.9,95%CI:1.2-79.1).CONCLUSION Rivaroxaban compared to apixaban and enoxaparin had a significantly higher risk of MB on GICA-VTE patients with equivocal efficacy. | Alejandro Recio-Boiles Sumana Veeravelli Jessica Vondrak Hani M Babiker Aaron J Scott Rachna T Shroff Hitendra Patel Emad Elquza Ali McBride | 2019 | World Journal of Gastrointestinal Oncology2019，11，10： | 3 |
| 3 | A comparison of the relative efficiency of ICSI and extended culture with epididymal sperm versus testicular sperm in patients with obstructive azoospermia显示文摘This is a retrospective cohort study comparing blastocyst transfer outcomes following intracytoplasmic sperm injection utilizing epididymal versus testicular sperm for men with obstructive azoospermia.All cases at a single center between 2012 and 2016 were included.Operative approach was selected at the surgeon’s discretion and included microepididymal sperm aspiration or testicular sperm extraction.Blastocyst culture was exclusively utilized prior to transfer.The primary outcome was live birth rate.Secondary outcomes included fertilization rate,blastulation rate,euploidy rate,and implantation rate.A mixed effects model was performed.Seventy-six microepididymal sperm aspiration cases and 93 testicular sperm extraction cases were analyzed.The live birth rate was equivalent(48.6%vs 50.5%,P=0.77).However,on mixed effects model,epididymal sperm resulted in a greater likelihood of fertilization(adjusted OR:1.37,95%CI:1.05–1.81,P=0.02)and produced a higher blastulation rate(adjusted OR:1.41,95%CI:1.1–1.85,P=0.01).As a result,the epididymal sperm group had more supernumerary blastocysts available(4.3 vs 3,P<0.05).The euploidy rate was no different.Pregnancy rates were no different through the first transfer cycle.However,intracytoplasmic sperm injection following microepididymal sperm aspiration resulted in a greater number of usable blastocysts per patient.Thus,the true benefit of epididymal sperm may only be demonstrated via a comparison of cumulative pregnancy rates after multiple transfers from one cohort. | Scott J Morin Brent M Hanson Caroline R Juneau Shelby A Neal Jessica N Landis Richard T Scott Jr James M Hotaling | 2020 | Asian Journal of Andrology2020，22，2： | 2 |
| 4 | Survival after inflammatory bowel disease-associated colorectal cancer in the Colon Cancer Family Registry显示文摘AIM: To investigate the survival of individuals with colorectal cancer (CRC) with inflammatory bowel disease (IBD-associated CRC) compared to that of individuals without IBD diagnosed with CRC. METHODS: Epidemiologic, clinical, and follow-up data were obtained from the Colon Cancer Family Registry (Colon CFR). IBD-associated cases were identified from self-report of physician diagnosis. For a subset of participants, medical records were examined to confirm self-report of IBD. Cox proportional hazards regression was applied to estimate adjusted hazard ratios (aHR) and 95%CI of mortality, comparing IBD-associated to non-IBD-associated CRC, adjusted for age at CRC diagnosis, sex, Colon CFR phase, and number of prior endoscopies. Following imputation to complete CRC stage information, adjustment for CRC stage was examined. RESULTS: A total of 7202 CRC cases, including 250 cases of IBD-associated CRC, were analyzed. Over a twelve year follow-up period following CRC diagnosis, 2013 and 74 deaths occurred among non-IBD associated CRC and IBD-associated CRC patients, respectively. The difference in survival between IBD-associated and non-IBD CRC cases was not statistically significant (aHR = 1.08; 95%CI: 0.85-1.36). However, the assumption of proportional hazards necessary for valid inference from Cox regression was not met over the entire follow-up period, and we therefore limited analyses to within five years after CRC diagnosis when the assumption of proportional hazards was met. Over this period, there was evidence of worse prognosis for IBD-associated CRC (aHR = 1.36; 95%CI: 1.05-1.76). Results were similar when adjusted for CRC stage, or restricted to IBD confirmed in medical records. CONCLUSION: These results support the hypothesis that IBD-associated CRC has a worse prognosis than non-IBD-associated CRC. | Scott V Adams Dennis J Ahnen John A Baron Peter T Campbell Steven Gallinger William M Grady Loic LeMarchand Noralane M Lindor John D Potter Polly A Newcomb | 2013 | World Journal of Gastroenterology2013，19，21： | 2 |
| 5 | MRI-based measurement of hippocampal volume in patients with ccrnhat- related posttraumatic stress disorder显示文摘 | BREMNER J D RANDALL P SCOTT T M | 1995 | Am J Psychiatry1995，152，7： | 2 |
| 6 | Effect of amphetamine precursors and by products on soil enzymes of two urban soils显示文摘 | Scott T L Janusz A Perkins M V | 2003 | Bull Environ Contam Toxical2003，70，： | 1 |
| 7 | Riak assessment of the mycotoxin zearalenone显示文摘 | Kuiper-Goodman T Scott P M Watanabe H | 1987 | Regulatory Toxicology and Pharmacology1987，，7： | 1 |
| 8 | Quantification of deoxynivalenol in wheat using an immunoaffinity column and liquid chromatography显示文摘 | Scott C Kruger Brian T McAlice | 1999 | Journal of Chromatography A1999，859，： | 1 |
| 9 | In vivo tumor imaging using a near-infrared-labeled endostatin molecule显示文摘 | Citrin D Scott T Sproull M | 2004 | Int J Radiation Oncology Biol Phys2004，58，2： | 1 |
| 10 | The general appli- cability of in situ transesterification for the production of fatty acid esters from a variety of feedstocks 显示文摘 | Haas M J Scott K M Foglia T A | 2007 | JAm Oil Chem Soc2007，84，10： | 1 |
| 11 | A pilot-scale continuous-jet hydrate reactor显示文摘 | Phillip S Scott D M Patricia T S | | 0，，： | 1 |
| 12 | Chemical Oxygen Demand Analysis of Waste Water Using Trivalent Mangunese Oxidant with Chloride Removal by Sodium Bismuthate Pretreatment显示文摘 | DONALD G M SCOTT V B WAYNE T B | 2001 | Water Environment Research2001，73，1： | 1 |
| 13 | Dynamics and availability of phosphorus in the rhizosphere of a temperate silvopastoral system显示文摘 | Scott J T Condron L M | 2003 | Biology Fertility of Soils2003，39，： | 1 |
| 14 | Predicting subcellular localization via protein motif co-occurrence 显示文摘 | SCOTT M S THOMAS D Y HALLETT M T | 2004 | Genome Res2004，14，： | 1 |
| 15 | Process requirements for achieving full-flow disinfection of recirculating water using ozonation and UV irradiation 显示文摘 | STEVEN T S MARK J S SCOTT M T | 2009 | Aquacuhural Engineering2009，40，1： | 1 |
| 16 | Factors predisposing to bacterial invasion and infection 显示文摘 | Heinzelmann M Scott M Lam T | 2002 | Am J Surg2002，183，2： | 1 |
| 17 | Chameleonic or consis- tent? A multilevel investigation of emotional labor variability and self-monitoring 显示文摘 | Scott B A Barnes C M Wagner D T | 2012 | Academy of management journal2012，55，4： | 1 |
| 18 | Revealing the vulnerabil- ity of people and places: a case study of georgetown county, south carolina 显示文摘 | Cutter S L Mitchell J T Scott M S | 2000 | Annals of the Association of American Ge- ographers2000，90，4： | 1 |
| 19 | A GIS - based Method to I- dentify Spatiotemporal Gaps in Public Service Delivery 显示文摘 | Neutens T Delafontaine M Scott D M | 2012 | Applied Geogra- phy2012，32，： | 1 |
| 20 | External fixationas a bridge to intramedullary nailing for patients with multi-ple jnjuries and with emur fractures:damage control ortho-pedics显示文摘 | Scalea T M Boswell S A Scott J D | 2000 | J Trauma2000，48，4： | 1 |
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