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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 | Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance显示文摘 | Rajkumar S V Kyle R A Therneau T M | 2005 | Blood2005，106，3： | 1 |
| 3 | Review of 1027 patients with newly diagnosed multiple myeloma显示文摘 | KYLE R A GERTZ M A WITZIG T E | 2003 | Mayo Clin Proc2003，78，1： | 1 |
| 4 | Rb-Sr dating of sphalerites from MVT ore deposits显示文摘 | Nakai S Halliday A N Kesler S E Jones H D Kyle J R Lane T E | 1993 | Geochimica et Cosmochimica Acta1993，57，： | 1 |
| 5 | Incidence of multiple myeloma in Olmsted County, Minnesota: trend over 6 decades 显示文摘 | Kyle R A Therneau T M Rajkumar S V | 2004 | Cancer2004，101，26： | 1 |
| 6 | Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma 显示文摘 | Kyle R A Remstein E Therneau T M | 2007 | New Engl J Med2007，356，25： | 1 |
| 7 | An examination of the relationship between leisure activity involvement and place attachment among hikers along the Appalachian 显示文摘 | Kyle G T Graefe A R Manning R Bacon J | 2003 | Journal of Leisure Research2003，35，3： | 1 |
| 8 | Surgical treatment of intertrochanteric hip fractures with associated femoral neck fractures using a sliding hip screw显示文摘 | Kyle R Ellis T Templeman D | 2005 | J Orthop Trauma2005，19，： | 1 |
| 9 | Screw position affects dynamic compression plate strain in an in vitro fracture model 显示文摘 | Ellis T Bourgeault C A Kyle R F | 2001 | J Orthop Trauma2001，15，5： | 1 |
| 10 | A Disintegin and Metalloproteinase 10 - Mediated Cleavage and Shedding Regulates the Cell Surface Expression of CXC Chemokine Ligand 16显示文摘 | Peter J Kyle J Paul T | 2004 | J Immunol2004，172，： | 1 |
| 11 | Linking place preferences with place meaning: an examination of the relationship between place motivation and place attachment 显示文摘 | Kyle G T Mowen A J Tarrant M | 2004 | Journal of Environmental Psy- chology2004，24，4： | 1 |
| 12 | The differentiation of CD4(+) T-helper cell subsets in the context of helminth parasite infection显示文摘 | Bouchery T Kyle R Ronchese F et ol | 2014 | Front Immunol2014，5，： | 1 |
| 13 | Surgical treatment of intertochanteric hip fractures with associated femoral neck fractures using a siliding hip screw显示文摘 | Kyle RF Ellis T J | 2005 | J Orthop Trauma2005，19，1： | 1 |
| 14 | Screw position affects dy- namic compression plate strain in an in vitro fracture model 显示文摘 | Ellis T Bourgeault CA Kyle RF | 2001 | J Orthop Trauma2001，15，5： | 1 |
| 15 | Rb-Sr dating of sphalerites from Mississippi Valley (MVT) ore deposits显示文摘 | Nakai S Halliday A N Kesler S E Jones H D Kyle J R and Lane T E | | 0，，： | 1 |
| 16 | Hybrid cartesian and orbit element feedback law for formation flying spacecraft显示文摘 | Schaub H Kyle T Alfriend | 2002 | Journal of Guidance Navigation and Control2002，25，2： | 1 |
| 17 | Surgical treatment of intertrochanteric hip fractures with associated femoral neck fractures using a sliding hip screw 显示文摘 | Kyle R F Ellis T J Templeman D C | 2005 | J Orthop Trauma2005，19，1： | 1 |
| 18 | Cont inuous Auctions and Insider Trading显示文摘 | Kyle Alber t S | 1985 | Econometrica1985，53，6： | 1 |
| 19 | Linking place preferences with place meaning: an examination of the relationship between place motivation and place attachment显示文摘 | Kyle G T Mowen A J Tarrant M | 2004 | Journal of Environmental Psy- chology2004，24，： | 1 |
| 20 | Dashing away hypertension: Evaluating the efficacy of the dietary approaches to stop hypertension diet in controlling high blood pressure显示文摘The dietary approaches to stop hypertension(DASH) diet has been developed and popularized as a nonpharmaceutical intervention for high blood pressure reduction since 1995.However,to date,a comprehensive description of the biochemical rationale behind the diet's principal guidelines has yet to be compiled.With rising interest for healthy and reliable life-style modifications to combat cardiovascular disease,this review aims to compile the most recent and relevant studies on this topic and make an informed assessment as to the efficacy of and underlying mechanisms operant in the DASH diet.Specifically,the merits of lowering dietary intake of sodium and saturated fat,as well as increasing the intake of fruits,vegetables,fiber,and dairy,have been shown to attenuate hypertension individually.Upon review of this evidence,we conclude that the combination of dietary patterns proposed in the DASH diet is effective in attenuating high blood pressure.We also suggest that efforts to more widely implement adoption of the DASH diet would be beneficial to public health. | Preeya T Shah Kyle D Maxwell Joseph I Shapiro | 2015 | World Journal of Hypertension2015，5，4： | 1 |
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