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| 1 | Sorafenib inhibits growth and metastasis of hepatocellular carcinoma by blocking STAT3显示文摘AIM: To investigate the inhibitory role and the underlying mechanisms of sorafenib on signal transducer and activator of transcription 3 (STAT3) activity in hepatocellular carcinoma (HCC).METHODS: Human and rat HCC cell lines were treated with sorafenib. Proliferation and STAT3 dephosphorylation were assessed. Potential molecular mechanisms of STAT3 pathway inhibition by sorafenib were evaluated. In vivo antitumor action and STAT3 inhibition were investigated in an immunocompetent orthotopic rat HCC model.RESULTS: Sorafenib decreased STAT3 phosphorylationat the tyrosine and serine residues (Y705 and S727), but did not affect Janus kinase 2 (JAK2) and phosphatase shatterproof 2 (SHP2), which is associated with growth inhibition in HCC cells. Dephosphorylation of S727 was associated with attenuated extracellular signal-regulated kinase (ERK) phosphorylation, similar to the effects of a mitogen-activated protein kinase (MEK) inhibitor U0126, suggesting that sorafenib induced S727 dephosphorylation by inhibiting MEK/ERK signaling. Meanwhile, sorafenib could also inhibit Akt phosphorylation, and both the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 and Akt knockdown resulted in Y705 dephosphorylation, indicating that Y705 dephosphorylation by sorafenib was mediated by inhibiting the PI3K/Akt pathway. Finally, in the rat HCC model, sorafenib signifi cantly inhibited STAT3 activity, reducing tumor growth and metastasis.CONCLUSION: Sorafenib inhibits growth and metastasis of HCC in part by blocking the MEK/ERK/STAT3 and PI3K/Akt/STAT3 signaling pathways, but independent of JAK2 and SHP2 activation. | Fang-Ming Gu, Quan-Lin Li, Qiang Gao, Jia-Hao Jiang, Xiao-Yong Huang, Jin-Feng Pan, Jia Fan, Jian ZhouFang-Ming Gu, Quan-Lin Li, Qiang Gao, Jia-Hao Jiang, Xiao-Yong Huang, Jin-Feng Pan, Jia Fan, Jian Zhou, Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Shanghai 200032, China Author contributions: Gu FM, Li QL and Gao Q contributed equally to this work Gu FM and Li QL performed the experi- ments and interpretation of the data and statistical analysis Zhou J and Gao Q contributed to the conception and design of the study Gu FM, Gao Q, Li QL and Zhou J wrote the manuscript Jiang JH, Huang XY, Pan JF and Fan J made substantial contri- bution to the design and conception of the study and interpreta- tion of data all authors read and approved the f inal manuscript. | 2011 | World Journal of Gastroenterology2011，17，34： | 18 |
| 2 | Big Data Thinking and Its Biomedical Application显示文摘Big data thinking gradually rise with the coming era of big data. Big data characteristics could be summarized with 4V: volume, variety, velocity and value. The characteristics of big data thinking could be summed up in integrity, fault tolerance, correlation and intelligence. These characteristics were also the primary differences between big data thinking and small data thinking. The application of big data thinking in biomedical field became more and more widely, and the most commonly used was NCBI database. The process of mining valuable information in NCBI database was big data thinking. And the rise of Meta analysis and TCGA database would illustrate the huge application value of big data thinking in the biomedical field. | Petar Melih INAL Nikhil Vishnu | 2018 | Biomed Communication2018，2，1： | 5 |
| 3 | General characteristics of patients with electrolyte imbalance admitted to emergency department显示文摘BACKGROUND:Fluid and electrolyte balance is a key concept to understand for maintaining homeostasis,and for a successful treatment of many metabolic disorders.There are various regulating mechanisms for the equilibrium of electrolytes in organisms.Disorders of these mechanisms result in electrolyte imbalances that may be life-threatening clinical conditions.In this study we defined the electrolyte imbalance characteristics of patients admitted to our emergency department.METHODS:This study was conducted in the Emergency Department(ED) of Uludag University Faculty of Medicine,and included 996 patients over 18 years of age.All patients had electrolyte imbalance,with various etiologies other than traumatic origin.Demographic and clinical parameters were collected after obtaining informed consent from the patients.The ethical committee of the university approved this study.RESULTS:The mean age of the patients was 59.28±16.79,and 55%of the patients were male.The common symptoms of the patients were dyspnea(14.7%),fever(13.7%),and systemic deterioration(11.9%);but the most and least frequent electrolyte imbalances were hyponatremia and hypermagnesemia,respectively.Most frequent findings in physical examination were confusion(14%),edema(10%) and rales(9%);and most frequent pathological findings in ECG were tachycardia in24%,and atrial fibrillation in 7%of the patients.Most frequent comorbidity was malignancy(39%).Most frequent diagnoses in the patients were sepsis(11%),pneumonia(9%),and acute renal failure(7%).CONCLUSIONS:Electrolyte imbalances are of particular importance in the treatment of ED patients.Therefore,ED physicians must be acknowledged of their fluid-electrolyte balance dynamics and general characteristics. | Arif Kadri Balci Ozlem Koksal Ataman Kose Erol Armagan Fatma Ozdemir Taylan Inal Nuran Oner | 2013 | World Journal of Emergency Medicine2013，4，2： | 3 |
| 4 | Antioxidant enzyme activities and malondialdehyde levels related to aging显示文摘 | Kanbak G Sunal E | 2001 | Clin Chim Acta2001，305，1： | 1 |
| 5 | Peanut/maize intercropping induced changes in rhizosphere and nutrient concentrations in shoots 显示文摘 | INAL A GUNES A ZHANG F | 2007 | Plant Physiology and Biochemistry2007，45，： | 1 |
| 6 | Sternocleidomastoid muscle flap reconstruction during parotidectomy to prevent Frey's syndrome and facial contour deformity显示文摘 | Asal K Ksybasioglu A Inal E | 2005 | Ear Nose Throat J2005，84，3： | 1 |
| 7 | Percutaneous placement of biliary metallic stents in patients with malignant biliary obstruction:unilobar versus bilobar drainage显示文摘 | Inal M Akgui E Aksungur E | 2003 | J Vasc Interv Radio12003，14，11： | 1 |
| 8 | Biochemical indicators and cardiac function tests in chronic alcohol abusers显示文摘 | Avsaroglu D Inal TC Demir M | 2005 | Croat Med J2005，46，2： | 1 |
| 9 | Percutaneous Placement of biliary metallic stents in patients with maligant hiliar obstruction:unilobar versus bilobar drainage显示文摘 | Inal M Akgül E Aksungur E et a1 | 2003 | J Vase interv Radiol2003，14，11： | 1 |
| 10 | The prognostic value of D-dimer in lung cancer 显示文摘 | INAL T ANAR C POLAT G | 2015 | Clin Respir J2015，9，3： | 1 |
| 11 | Factors determining self - effica- cy in chronic obstructive pulmonary disease显示文摘 | Inal - Ince D Savci S Coplu L | 2005 | Saudi Med J2005，26，4： | 1 |
| 12 | Performance prediction of a ground-coupled heat pump system using artificial neural networks 显示文摘 | HikmetEsen Mustafa Inalli Abdulkadir Sengur | 2008 | Expert Systems with Applications2008，35，4： | 1 |
| 13 | A large seminal vesicle cyst with contralateral agenesis显示文摘 | Kosan M Tul M Inal G | 2006 | Int Urol Nephrol2006，38，34： | 1 |
| 14 | Reducing nitrate content of NET grown winter onion plants by partial replacement of NO3^- with aminoacid in nutrient solution 显示文摘 | GUNES A INAL A AKTAS M | 1996 | Scientia Horticulturae1996，65，： | 1 |
| 15 | Forecasting of a ground-coupled heat pump performance using neural networks with statistical data weighting pre-processing 显示文摘 | Hikmet Esen Mustafa Inalli Abdulkadir Sengur | 2008 | International Journal of Thermal Sciences2008，47，4： | 1 |
| 16 | Thermal and economic comparisons of solar heating systems with seasonal storage used in building heating 显示文摘 | UCAR A INALLI M | 2008 | Renewable Energy2008，33，12： | 1 |
| 17 | Antioxidant enzy me activities and malondial dehyde levels related to aging 显示文摘 | Inal ME Kanbak G Surtal E | 2001 | Clin Chim Acta2001，305，12： | 1 |
| 18 | Effect of the subdermalcontraceptive etonogestrel implant (Implanon) on biochemical andhormonal parameters (three years follow-up)显示文摘 | Inal MM Yildirim Y Ertopcu K | 2008 | Eur J ContraceptReprod Health Care2008，13，3： | 1 |
| 19 | Prosthetic repair of acutely incar- cerated groin hernias: a prospective clinical observational cohort study 显示文摘 | Atria K Guler S Inal A | 2010 | Langenbecks Arch Surg2010，395，5： | 1 |
| 20 | Artificial neural networks and adaptive neuro-fuzzy assessments for groundcoupled heat pump system 显示文摘 | Hikmet Esen Mustafa Inalli Abdulkadir Sengur | 2008 | Energy and Buildings2008，40，6： | 1 |
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