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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 | Radioembolization for the treatment of unresectable hepatocellular carcinoma:A clinical review显示文摘Hepatocellular carcinoma(HCC)is the sixth most common cancer in the world.The majority of patients with HCC present with unresectable disease.These patients have historically had limited treatment options secondary to HCC demonstrating chemoresistance to the currently available systemic therapies.Additionally, normal liver parenchyma has shown intolerance to tumoricidal radiation doses,limiting the use of external beam radiation.Because of these limitations,novel percutaneous liver-directed therapies have emerged. The targeted infusion of radioactive microspheres (radioembolization)represents one such therapy. Radioembolization is a minimally invasive transcatheter therapy through which radioactive microspheres are infused into the hepatic arteries that supply tumor. Once infused,these microspheres traverse the hepatic vascular plexus and selectively implant within the tumor arterioles.Embedded within the arterioles, the 90Y impregnated microspheres emit high energy and low penetrating radiation doses selectively to the tumor.Radioembolization has recently shown promise for the treatment of patients with unresectable HCC. The objective of this review article is to highlight twocurrently available radioembolic devices(90Y,188Rh)and provide the reader with a recent review of the literature. | Saad M Ibrahim Robert J Lewandowski Kent T Sato Vanessa L Gates Laura Kulik Mary F Mulcahy Robert K Ryu Reed A Omary Riad Salem | 2008 | World Journal of Gastroenterology2008，14，11： | 14 |
| 3 | Diffusion-weighted magnetic resonance imaging to predict response of hepatocellular carcinoma to chemoembolization显示文摘AIM: To investigate whether intra-procedural diffusion- weighted magnetic resonance imaging can predict response of hepatocellular carcinoma (HCC) during trans- catheter arterial chemoembolization (TACE). METHODS: Sixteen patients (15 male), aged 59 ±11 years (range: 42-81 years) underwent a total of 21 separate treatments for unresectable HCC in a hybrid magnetic resonance/interventional radiology suite. Ana- tomical imaging and diffusion-weighted imaging (b = 0, 500 s/mm2) were performed on a 1.5-T unit. Tumor enhancement and apparent diffusion coefficient (ADC, mm2/s) values were assessed immediately before and at 1 and 3 mo after TACE. We calculated the percent change (PC) in ADC values at all time points. We compared follow-up ADC values to baseline values using a paired t test (α = 0.05). RESULTS: The intra-procedural sensitivity, specificity, and positive and negative predictive values (%) for detecting a complete or partial 1-mo tumor response using ADC PC thresholds of ±5%, ±10%, and ±15% were 77, 67, 91, and 40; 54, 67, 88, and 25; and 46, 100, 100, and 30, respectively. There was no clear predictive value for the 3-mo follow-up. Compared to baseline, the immediate post-procedure and 1-mo mean ADC values both increased; the latter obtaining statistical significance (1.48 ± 0.29 mm2/s vs 1.65 ± 0.35 × 10-3 mm2/s, P < 0.014). CONCLUSION: Intra-procedural ADC changes of > 15% predicted 1-mo anatomical HCC response with the greatest accuracy, and can provide valuable feedback at the time of TACE. | Johnathan C Chung Neel K Naik Robert J Lewandowski Mary F Mulcahy Laura M Kulik Kent T Sato Robert K Ryu Riad Salem Andrew C Larson Reed A Omary | 2010 | World Journal of Gastroenterology2010，16，25： | 13 |
| 4 | Gastroenteropancreatic neuroendocrine tumours显示文摘 | Irvin M Modlin Kjell Oberg Daniel C Chung Robert T Jensen Wouter W de Herder Rajesh V Thakker Martyn Caplin Gianfranco Delle Fave Greg A Kaltsas Eric P Krenning Steven F Moss Ola Nilsson Guido Rindi Ramon Salazar Philippe Ruszniewski Anders Sundin | 2008 | Lancet Oncology2008，，1： | 8 |
| 5 | High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes显示文摘Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening(HTS) data for 3 762 distinct global gene knockout(KO) mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type(WT) cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging,ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass: 23 previously reported genes(Calcr, Cebpb, Crtap, Dcstamp, Dkk1, Duoxa2, Enpp1, Fgf23, Kiss1/Kiss1 r, Kl(Klotho),Lrp5, Mstn, Neo1, Npr2, Ostm1, Postn, Sfrp4, Slc30a5, Slc39a13, Sost, Sumf1, Src, Wnt10b), five novel genes extensively characterized(Cldn18, Fam20 c, Lrrk1, Sgpl1, Wnt16), five novel genes with preliminary characterization(Agpat2, Rassf5, Slc10a7, Slc26a7, Slc30a10) and three novel undisclosed genes coding for potential osteoporosis drug targets. | Robert Brommage Jeff Liu Gwenn M Hansen Laura L Kirkpatrick David G Potter Arthur T Ss Brian Zambrowicz David R Powell Peter Vogel | 2014 | Bone Research2014，2，3： | 7 |
| 6 | Clinical outcomes following salvage Gamma Knife radiosurgery for recurrent glioblastoma显示文摘Glioblastoma multiforme(GBM) is the most common malignant primary brain tumor with a survival prognosis of 14-16 mo for the highest functioning patients. Despite aggressive, multimodal upfront therapies, the majority of GBMs will recur in approximately six months. Salvage therapy options for recurrent GBM(r GBM) are an area of intense research. This study compares recent survival and quality of life outcomes following Gamma Knife radiosurgery(GKRS) salvage therapy. Following a Pub Med search for studies usingGKRS as salvage therapy for malignant gliomas, nine articles from 2005 to July 2013 were identified which evaluated rG BM treatment. In this review, we compare overall survival following diagnosis, overall survival following salvage treatment, progression-free survival, time to recurrence, local tumor control, and adverse radiation effects. This report discusses results for rG BM patient populations alone, not for mixed populations with other tumor histology grades. All nine studies reported median overall survival rates(from diagnosis, range:16.7-33.2 mo; from salvage, range:9-17.9 mo). Three studies identified median progression-free survival(range:4.6-14.9 mo). Two showed median time to recurrence of GBM. Two discussed local tumor control. Six studies reported adverse radiation effects(range:0%-46% of patients). The greatest survival advantages were seen in patients who received GKRS salvage along with other treatments, like resection or bevacizumab, suggesting that appropriately tailored multimodal therapy should be considered with each rG BM patient. However, there needs to be a randomized clinical trial to test GKRS for rG BM before the possibility of selection bias can be dismissed. | Erik W Larson Halloran E Peterson Wayne T Lamoreaux Alexander R MacKay Robert K Fairbanks Jason A Call Jonathan D Carlson Benjamin C Ling John J Demakas Barton S Cooke Christopher M Lee | 2014 | World Journal of Clinical Oncology2014，5，2： | 5 |
| 7 | Is it possible to stop nucleos(t)ide analogue treatment in chronic hepatitis B patients?显示文摘Chronic hepatitis B(CHB) remains a challenging global health problem, with nearly one million related deaths per year. Nucleos(t)ide analogue(NA) treatment suppresses viral replication but does not provide complete cure of the hepatitis B virus(HBV) infection. The accepted endpoint for therapy is the loss of hepatitis B surface antigen(HBs Ag), but this is hardly ever achieved. Therefore, indefinite treatment is usually required. Many different studies have evaluated NA therapy discontinuation after several years of NA treatment and before HBs Ag loss. The results have indicated that the majority of patients can remain off therapy, with some even reaching HBs Ag seroconversion. Fortunately, this strategy has proved to be safe, but it is essential to consider the risk of liver damage and other comorbidities and to ensure aclose follow-up of the candidates before considering this strategy. Unanswered questions remain, namely in which patients could this strategy be effective and what is the optimal time point at which to perform it. To solve this enigma, we should keep in mind that the outcome will ultimately depend on the equilibrium between HBV and the host's immune system. Viral parameters that have been described as good predictors of response in HBe Ag(+) cases, have proven useless in HBe Ag(-) ones. Since antiviral immunity plays an essential role in the control of HBV infection, we sought to review and explain potential immunological biomarkers to predict safe NA discontinuation in both groups. | Elia Moreno-Cubero Robert T Sánchez del Arco Julia Pena-Asensio Eduardo Sanz de Villalobos Joaquín Míquel Juan Ramón Larrubia | 2018 | World Journal of Gastroenterology2018，24，17： | 5 |
| 8 | Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial显示文摘 | Kris V Kowdley Eric Lawitz Israel Crespo Tarek Hassanein Mitchell N Davis Michael DeMicco David E Bernstein Nezam Afdhal John M Vierling Stuart C Gordon Jane K Anderson Robert H Hyland Hadas Dvory-Sobol Di An Robert G Hindes Efsevia Albanis William T Symo | 2013 | The Lancet2013，，9883： | 3 |
| 9 | Approximate analysis of shear and normal stress concentration in the adhesive layer of plated RC beams 显示文摘 | Roberts T M | 1989 | Structural Engineering1989，67，12： | 2 |
| 10 | Mutifactorial analysis of risk factors for reduced bone mineral density in patients with Crohn’s disease显示文摘AIM: To determine the prevalence of osteoporosis in a cohort of patients with Crohn’s disease (CD) and to identify the relative significance of risk factors for osteoporosis. METHODS: Two hundred and fifty-eight unselected patients (92 M, 166 F) with CD were studied. Bone mineral density (BMD) was measured at the lumbar spine and hip by dual X-ray absorptiometry. Bone formation was assessed by measuring bone specific alkaline phosphatase (BSAP) and bone resorption by measuring urinary excretion of deoxypyridinoline (DPD) and N-telopeptide (NTX). RESULTS: Between 11.6%-13.6% patients were osteoporotic (T score < -2.5) at the lumbar spine and/or hip. NTX levels were significantly higher in the patients with osteoporosis (P < 0.05) but BSAP and DPD levels were not significantly different. Independent risk factors for osteoporosis at either the lumbar spine or hip were a low body mass index (P < 0.001), increasing corticosteroid use (P < 0.005), and male sex (P < 0.01). These factors combined accounted for 23% and 37% of the reduction in BMD at the lumbar spine and hip respectively. CONCLUSION: Our results confirm that osteoporosis is common in patients with CD and suggest that increased bone resorption is the mechanism responsible for thebone loss. However, less than half of the reduction in BMD can be attributed to risk factors such as corticosteroid use and low BMI and therefore remains unexplained. | Sarah A Bartram Robert T Peaston David J Rawlings David Walshaw Roger M Francis Nick P Thompson | 2006 | World Journal of Gastroenterology2006，12，35： | 2 |
| 11 | New directions in management accounting research 显示文摘 | Atkinson A A Balakrishnan P B Cote J M Grout T M Roberts H Ulan E Wu A | | Journal of Management Accounting Research0，997，： | 1 |
| 12 | Targeting the phosphoinositide 3- kinase pathway in cancer 显示文摘 | Liu P Cheng H Roberts T M | 2009 | Nat Rev Drug Discov2009，8，8： | 1 |
| 13 | Mul- tialternative decision field theory: a dynamic connec- tionist model of decision making显示文摘 | ROBERT M R JEROME R B JAMES T T | 2001 | Psychological Review2001，108，2： | 1 |
| 14 | Lateral pedestrian excitation of footbridge 显示文摘 | Roberts T M | 2005 | Journal of Bridge Engineering ASCE2005，9，2： | 1 |
| 15 | Diverticulitis in California from 1995 to 2006: Increased Rates of Treatment for Younger Patients显示文摘 | Etzioni David A Cannom Rebecca R Ault Glenn T Beart Robert W Kaiser Andreas M | 2009 | The American Surgeon2009，，10： | 1 |
| 16 | Exploring Variation in Active Network Size: Constraints and Ego Characteristics 显示文摘 | Roberts S G B Dunbar R I M Pollet T V | 2009 | Social Networks2009，31，2： | 1 |
| 17 | Plasma uric acid remains a marker of poor outcome in hypertensive pregnancy: a retrospective cohort study 显示文摘 | HAWKINS T L ROBERTS J M MANGOS G J | 2012 | B JOG- An International Journal of Obstetrics and Gynaecology2012，119，4： | 1 |
| 18 | Standardised growth curves for optical dating of sediment using multiple-grain aliquots 显示文摘 | Roberts H M Duller G A T | 2004 | Radiation Measurements2004，38，： | 1 |
| 19 | Further genetic studies ofresistance to Helminthosporium turcicum Psaa:in maizeby means of chromosomal translocation显示文摘 | JENKINS M T ROBERT A L | 1961 | Crop Scien-ce1961，1，： | 1 |
| 20 | Syn- thesis of Isoambrettolide and Its Isomers from 1,9-cy- clohexadecadiene显示文摘 | BRAJA D M ROBERT W T RAMAN R P | 1972 | J Org Chem1972，37，24： | 1 |
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