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| 1 | Bioreductive prodrugs as cancer therapeutics:targeting tumor hypoxia显示文摘Hypoxia, a state of low oxygen, is a common feature of solid tumors and is associated with disease progression as well as resistance to radiotherapy and certain chemotherapeutic drugs. Hypoxic regions in tumors, therefore, represent attractive targets for cancer therapy. To date, five distinct classes of bioreactive prodrugs have been developed to target hypoxic cells in solid tumors. These hypoxia-activated prodrugs, including nitro compounds, N-oxides, quinones, and metal complexes, generally share a common mechanism of activation whereby they are reduced by intracellular oxidoreductases in an oxygensensitive manner to form cytotoxins. Several examples including PR-104, TH-302, and EO9 are currently undergoing phase II and phase III clinical evaluation. In this review, we discuss the nature of tumor hypoxia as a therapeutic target, focusing on the development of bioreductive prodrugs. We also describe the current knowledge of how each prodrug class is activated and detail the clinical progress of leading examples. | Christopher P.Guise Alexandra M.Mowday Amir Ashoorzadeh Ran Yuan Wan-Hua Lin Dong-Hai Wu Jeff B.Smaill Adam V.Patterson Ke Ding | 2014 | Chinese Journal of Cancer2014，33，2： | 9 |
| 2 | Comparison of postoperative complications between internal and external pancreatic duct stenting during pancreaticoduodenectomy: a meta-analysis显示文摘Background:Two types of pancreatic duct stents are used to improve postoperative outcomes of pancreatic anastomosis.The aim of this meta-analysis was to evaluate and compare the postoperative outcomes of patients with internal or external stenting during pancreaticoduodenectomy(PD).Methods:We searched Pub Med,EMBASE,the Cochrane Library and Web of Science databases until the end of December,2014.Studies comparing outcomes of external vs.internal stent placement in PD were eligible for inclusion.Included literature was extracted and assessed by two independent reviewers.Results:Seven articles were identified for inclusion:three randomized controlled trials(RCTs)and four observational clinical studies(OCS).The meta-analyses revealed that use of external stents had advantage on reducing the incidences of pancreatic fistula(PF)in total[odds ratio(OR)=0.69;95%confidence interval(CI),0.48-0.99;P=0.04],PF in soft pancreas(OR=0.30;95%CI,0.16-0.56;P=0.0002)and delayed gastric emptying(DGE)(OR=0.58;95%CI,0.38-0.89;P=0.01)compared with internal stents.There were no significant differences in other postoperative outcomes between two stenting methods,including postoperative morbidity(OR=0.93;95%CI,0.39-2.23;P=0.88),overall mortality(OR=0.70;95%CI,0.22-2.25;P=0.55),and intra-abdominal collections(OR=0.67;95%CI,0.26-1.71;P=0.40).Conclusions:Based upon this meta-analysis,the use of external pancreatic stents might have potential benefit in reducing the incidence of PF and DGE.Due to the limited number of original studies,more RCTs are needed to further support our result and clarify the issue. | Fa-Yong Ke Xiang-Song Wu Yong Zhang Hong-Cheng Zhang Ming-Zhe Weng Ying-Bin Liu Christopher Wolfgang Wei Gong | 2015 | Chinese Journal of Cancer Research2015，27，4： | 4 |
| 3 | Nature’s marvels endowed in gaseous molecules Ⅰ:Carbon monoxide and its physiological and therapeutic roles显示文摘Nature has endowed gaseous molecules such as O_(2),CO_(2),CO,NO,H2 S,and N2 with critical and diverse roles in sustaining life,from supplying energy needed to power life and building blocks for life ’s physical structure to mediating and coordinating cellular functions.In this article,we give a brief introduction of the complex functions of the various gaseous molecules in life and then focus on carbon monoxide as a specific example of an endogenously produced signaling molecule to highlight the importance of this class of molecules.The past twenty years have seen much progress in understanding CO’s mechanism(s) of action and pharmacological effects as well as in developing delivery methods for easy administration.One remarkable trait of CO is its pleiotropic effects that have few parallels,except perhaps its sister gaseous signaling molecules such as nitric oxide and hydrogen sulfide.This review will delve into the sophistication of CO-mediated signaling as well as its validated pharmacological functions and possible therapeutic applications. | Xiaoxiao Yang Wen Lu Christopher P.Hopper Bowen Ke Binghe Wang | 2021 | Acta Pharmaceutica Sinica B2021，11，6： | 3 |
| 4 | Smoking and respiratory conditions in pregnancy: associations with adverse pregnancy outcomes显示文摘 | Kitsantas P Christopher KE | 2013 | South Med J2013，106，5： | 1 |
| 5 | Household catastrophic health expenditure: a multi-cotuatry analysis显示文摘 | Ke Xu David B Evans Kei Kawabata Riadh Zeramdini Jan Klavus Christopher J L Murray | 2003 | The lancet2003，，362： | 1 |
| 6 | Nerve Growth Factor and Its High-Affinity Receptor in Chronic Pancreatitis显示文摘 | Helmut Friess Zhao-Wen Zhu Fabio F. di Mola Christoph Kulli Hans U. Graber ?ke Andren-Sandberg Arthur Zimmermann Murray Korc Max Reinshagen Markus W. Büchler | 1999 | Annals of Surgery1999，，5： | 1 |
| 7 | Hepatitis C Virus Infection of Neuroepithelioma Cell Lines显示文摘 | Nicola F. Fletcher Jian Ping Yang Michelle J. Farquhar Ke Hu Christopher Davis Qiuchen He Kimberly Dowd Stuart C. Ray Sophie E. Krieger Johan Neyts Thomas F. Baumert Peter Balfe Jane A. McKeating Flossie Wong–Staal | 2010 | Gastroenterology2010，，4： | 1 |
| 8 | Nerve Growth Factor and Its High-Affinity Receptor in Chronic Pancreatitis显示文摘 | Helmut Friess Zhao-Wen Zhu Fabio F. di Mola Christoph Kulli Hans U. Graber ?ke Andren-Sandberg Arthur Zimmermann Murray Korc Max Reinshagen Markus W. Büchler | 1999 | Annals of Surgery1999，，5： | 1 |
| 9 | Intermediate maple syrup urine disease: neuroimaging observations in 3 patients from South India 显示文摘 | Bindu PS Shehanaz KE Christopher R | 2007 | J Child Neurol2007，22，7： | 1 |
| 10 | Survival Outcomes in Resected Extrahepatic Cholangiocarcinoma: Effect of Adjuvant Radiotherapy in a Surveillance, Epidemiology, and End Results Analysis显示文摘 | Tamara Z. Vern-Gross Anand T. Shivnani Ke Chen Christopher M. Lee Jonathan D. Tward O. Kenneth MacDonald Christopher H. Crane Mark S. Talamonti Louis L. Munoz William Small | 2011 | International Journal of Radiation Oncology Biology Physics2011，，1： | 1 |
| 11 | Relationship Between Intravascular Ultrasound Guidance and Clinical Outcomes After Drug-Eluting Stents: The Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) Study显示文摘 | Bernhard Witzenbichler Akiko Maehara Giora Weisz Franz-Josef Neumann Michael J. Rinaldi D. Christopher Metzger Timothy D. Henry David A. Cox Peter L. Duffy Bruce R. Brodie Thomas D. Stuckey Ernest L. Mazzaferri Ke Xu Helen Parise Roxana Mehran Gary S. Min | 2014 | Circulation2014，，4： | 1 |
| 12 | Role of Fat Hydrolysis in Regulating Glucagon-Like Peptide-1 Secretion显示文摘 | Svetlana Beglinger Juergen Drewe Joerg Schirra Burkhard G?ke Massimo D?Amato Christoph Beglinger | 2010 | The Journal of Clinical Endocrinology & Metabolism2010，，2： | 1 |
| 13 | Aspirin inhibits cell viability and mTOR downstream signaling in gastroenteropancreatic and bronchopulmonary neuroendocrine tumor cells显示文摘AIM:To investigate the effect of aspirin on neuroendocrine tumor(NET)cell growth and signaling in vitro.METHODS:Human pancreatic BON1,bronchopulmonary NCI-H727 and midgut GOT1 neuroendocrine tumor cells were treated with different concentrations of aspirin(from 0.001 to 5 mmol/L),and the resulting effects on metabolic activity/cell proliferation were measured using cell proliferation assays and SYBR-DNAlabeling after 72,144 and 216 h of incubation.The effects of aspirin on the expression and phosphorylation of several critical proteins that are involved in the most common intracellular growth factor signaling pathways(especially Akt protein kinase B)and mammalian target of rapamycin(mTOR)were determined by Western blot analyses.Propidium iodide staining and flow cytometry were used to evaluate changes in cell cycle distribution and apoptosis.Statistical analysis was performed using a 2-tailed Student’s t-test to evaluate the proliferation assays and cell cycle analyses.The results are expressed as the mean±SD of 3 or 4 independently performed experiments.Statistical significance was set at P<0.05.RESULTS:Treatment with aspirin suppressed the viability/proliferation of BON1,NCI-H727 and GOT1 cells in a time-and dose-dependent manner.Significant effects were observed at starting doses of 0.5-1 mmol/L and peaked at 5 mmol/L.For instance,after treatment with 1 mmol/L aspirin for 144 h,the viability of pancreatic BON1 cells decreased to 66%±13%(P<0.05),the viability of bronchopulmonary NCI-H727 cells decreased to 53%±8%(P<0.01)and the viability of midgut GOT1 cells decreased to 89%±6%(P<0.01).These effects were associated with a decreased entry into the S phase,the induction of the cyclin-dependent kinase inhibitor p21 and reduced expression of cyclindependent kinase 4 and cyclin D3.Aspirin suppressed mTOR downstream signaling,evidenced by the reduced phosphorylation of the mTOR substrates 4E binding protein 1,serine/threonine kinase P70S6K and S6 ribosomal protein and inhibited glycogen synthase kinase3 activity.We observed the(compensatory)activation of tuberous sclerosis 2,the serine/threonine specific protein kinase AKT and extracellular signal-regulated kinases.CONCLUSION:Aspirin demonstrates promising anticancer properties for NETs in vitro.Further preclinical and clinical studies are needed. | Matilde Spampatti George Vlotides Gerald Spttl Julian Maurer Burkhard Gke Christoph J Auernhammer | 2014 | World Journal of Gastroenterology2014，20，29： | 1 |
| 14 | Urodynamic effects of the K+channel(KCNQ)opener retigabine in freely moving,consciousrats显示文摘 | Streng T Christoph T Andersson KE | 2007 | J Urol2007，172，51： | 1 |
| 15 | Mechanisms of distal axonal degeneration in peripheral neuropathies显示文摘 | Christopher R. Cashman Ahmet H?ke | 2015 | Neuroscience Letters2015，，： | 1 |
| 16 | Nodular regenerative hyperplasia: a reversible entity associated with azathioprine therapy显示文摘 | Julia Seiderer Christoph J. Zech Joachim Diebold Stefan O. Schoenberg Stephan Brand Cornelia Tillack Burkhard G?ke Thomas Ochsenkühn | 2006 | European Journal of Gastroenterology & Hepatology2006，，5： | 1 |
| 17 | Multifocal intraocular lens implantation in prepresbyopic patients with unilateral cataract显示文摘 | Philipp C Jacobi Thomas S Dietlein Christoph Lüke Felix K Jacobi | 2002 | Ophthalmology2002，，4： | 1 |
| 18 | In silico directed mutagenesis identifies the CD 81/claudin‐1 hepatitis C virus receptor interface显示文摘 | Christopher Davis Helen J. Harris Ke Hu Heidi E. Drummer Jane A. McKeating Jonathan G. L. Mullins Peter Balfe | 2012 | Cell Microbiol2012，，12： | 1 |
| 19 | Household catastrophic health expenditure: a multicountry analysis显示文摘 | Ke Xu David B Evans Kei Kawabata Riadh Zeramdini Jan Klavus Christopher JL Murray | 2003 | The Lancet2003，，9378： | 1 |
| 20 | Nerve Growth Factor and Its High-Affinity Receptor in Chronic Pancreatitis显示文摘 | Helmut Friess Zhao-Wen Zhu Fabio F. di Mola Christoph Kulli Hans U. Graber ?ke Andren-Sandberg Arthur Zimmermann Murray Korc Max Reinshagen Markus W. Büchler | 1999 | Annals of Surgery1999，，5： | 1 |
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