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| 1 | Emerging role of Hippo pathway in gastric and othergastrointestinal cancers显示文摘More evidence has underscored the importance of Hippo signaling pathway in gastrointestinal tissue homeostasis, whereas its deregulation induces tumorigenesis. Yes-associated protein 1(YAP1) and its close paralog TAZ, transcriptional co-activator with a PDZbinding motif, function as key effectors negatively controlled by the Hippo pathway. YAP1/TAZ exerts oncogenic activities by transcriptional regulation via physical interaction with TEAD transcription factors. In various cancers, Hippo pathway cross-talks with pro- or anti-tumorigenic pathways such as GPCR, Wnt/β-catenin, Notch and TGF-β signaling and is deregulated by multiple factors including cell density/junction and micro RNAs. As YAP1 expression is significantly associated with poor prognosis of gastric and other gastrointestinal cancers, detailed delineation of Hippo regulation in tumorigenesis provides novel insight for therapeutic intervention. In current review, we summarized the recent research progresses on the deregulation of Hippo pathway in the gastrointestinal tract including stomach and discuss the molecular consequences leading to tumorigenesis. | Wei Kang Alfred SL Cheng Jun Yu Ka Fai To | 2016 | World Journal of Gastroenterology2016，22，3： | 11 |
| 2 | Cell cycle-related kinase reprograms the liver immune microenvironment to promote cancer metastasis显示文摘The liver is an immunologically tolerant organ and a common metastatic site of multiple cancer types.Although a role for cancer cell invasion programs has been well characterized,whether and how liver-intrinsic factors drive metastatic spread is incompletely understood.Here,we show that aberrantly activated hepatocyte-intrinsic cell cycle-related kinase(CCRK)signaling in chronic liver diseases is critical for cancer metastasis by reprogramming an immunosuppressive microenvironment.Using an inducible liverspecific transgenic model,we found that CCRK overexpression dramatically increased both B16F10 melanoma and MC38 colorectal cancer(CRC)metastasis to the liver,which was highly infiltrated by polymorphonuclear-myeloid-derived suppressor cells(PMNMDSCs)and lacking natural killer T(NKT)cells.Depletion of PMN-MDSCs in CCRK transgenic mice restored NKT cell levels and their interferon gamma production and reduced liver metastasis to 2.7% and 0.7%(metastatic tumor weights)in the melanoma and CRC models,respectively.Mechanistically,CCRK activated nuclear factor-kappa B(NF-κB)signaling to increase the PMN-MDSC trafficking chemokine C-X-C motif ligand 1(CXCL1),which was positively correlated with liver-infiltrating PMN-MDSC levels in CCRK transgenic mice.Accordingly,CRC liver metastasis patients exhibited hyperaaivation of hepatic CCRK/NF-κB/CXCL1 signaling,which was associated with accumulation of PMN-MDSCs and paucity of NKT cells compared to healthy liver transplantation donors.In summary,this study demonstrates that immunosuppressive reprogramming by hepatic CCRK signaling undermines antimetastatic immunosurveillance.Our findings offer new mechanistic insights and therapeutic targets for liver metastasis intervention. | Xuezhen Zeng Jingying Zhou Zhewen Xiong Hanyong Sun Weiqin Yang Myth T.S.Mok Jing Wang Jingqing Li Man Liu Wenshu Tang Yu Feng Hector Kwong-Sang W ang Shun-Wa Tsang King-Lau Chow Philip Chun Yeung John Wong Paul Bo-San Lai Anthony Wing-Hung Chan Ka Fai To Stephen Lam Chan Qiang Xia Jing Xue Xiao Chen Jun Yu Sui Peng Joseph Jao-Yiu Sung Ming Kuang Alfred Sze-Lok Cheng | 2021 | Cellular & Molecular Immunology2021，18，4： | 5 |
| 3 | Aberrant cholesterol metabolic signaling impairs antitumor immunosurveillance through natural killer T cell dysfunction in obese liver显示文摘Obesity is a major risk factor for cancers including hepatocellular carcinoma(HCC)that develops from a background of non-alcoholic fatty liver disease(NAFLD).Hypercholesterolemia is a common comorbidity of obesity.Although cholesterol biosynthesis mainly occurs in the liver,its role in HCC development of obese people remains obscure.Using high-fat high-carbohydrate diet-associated orthotopic and spontaneous NAFLD-HCC mouse models,we found that hepatic cholesterol accumulation in obesity selectively suppressed natural killer T(NKT)cell-mediated antitumor immunosurveillance.Transcriptome analysis of human liver revealed aberrant cholesterol metabolism and NKT cell dysfunction in NAFLD patients.Notably,cholesterol-lowering rosuvastatin restored NKT expansion and cytotoxicity to prevent obesogenic diet-promoted HCC development.Moreover,suppression of hepatic cholesterol biosynthesis by a mammalian target of rapamycin(mTOR)inhibitor vistusertib preceded tumor regression,which was abolished by NKT inactivation but not CD8^(+)T cell depletion.Mechanistically,sterol regulatory element-binding protein 2(SREBP2)-driven excessive cholesterol production from hepatocytes induced lipid peroxide accumulation and deficient cytotoxicity in NKT cells,which were supported by findings in people with obesity,NAFLD and NAFLD-HCC.This study highlights mTORC1/SREBP2/cholesterol-mediated NKT dysfunction in the tumor-promoting NAFLD liver microenvironment,providing intervention strategies that invigorating NKT cells to control HCC in the obesity epidemic. | Wenshu Tang Jingying Zhou Weiqin Yang Yu Feng Haoran Wu Myth T.S.Mok Lingyun Zhang Zhixian Liang Xiaoyu Liu Zhewen Xiong Xuezhen Zeng Jing Wang Jiahuan Lu Jingqing Li Hanyong Sun Xiaoyu Tian Philip Chun Yeung Yong Hou Heung Man Lee Candice C.H.Lam Howard H.W.Leung Anthony W.H.Chan Ka Fai To John Wong Paul B.S.Lai Kelvin K.C.Ng Simon K.H.Wong Vincent W.S.Wong Alice P.S.Kong Joseph J.Y.Sung Alfred S.L.Cheng | 2022 | Cellular & Molecular Immunology2022，19，7： | 3 |
| 4 | A joint computational-experimental study of intracranial aneurysms:Importance of the aspect ratio显示文摘Rupture of a cerebral aneurysm(abnormal swelling of blood vessel in the brain) will cause subarachnoid hemorrhage, and will result in an alarming rate of mortality and morbidity. A joint computational-experimental study is conducted to assess the importance of the aspect ratio in the dynamics of blood flow. The aspect ratio is defined here to be the ratio of the height of the aneurysm to the linear dimension of the neck. Idealized models of such aneurysms located near a bifurcation point were investigated. Numerical simulations for hemodynamic properties like shear stress and flow rate were performed. The computational results were verified experimentally with specially fabricated phantoms, blood mimicking fluid and Doppler ultrasound imaging. Excellent agreements were obtained. Two features are highlighted, providing information in the intensely debated link between rupture risk and geometric factors. On increasing the aspect ratios, firstly, a jet impinging on the distal part of the neck can be observed, and secondly, a region of positive shear stress gradient can be found there. Furthermore, computational analyses for four patient-specific models were conducted to correlate with the results of idealized models and to provide further clinical insight. | Simon Sui-Man LAI Abraham Yik-Sau TANG Anderson Chun-On TSANG Gilberto Ka-Kit LEUNG Alfred Cheuk-Hang YU Kwok Wing CHOW | 2016 | Journal of Hydrodynamics2016，28，3： | 2 |
| 5 | Suppression of IL7Rα Transcription by IL-7 and Other Prosurvival Cytokines显示文摘 | Jung-Hyun Park Qing Yu Batu Erman Jacob S. Appelbaum Diego Montoya-Durango H.Leighton Grimes Alfred Singer | 2004 | Immunity2004，，2： | 1 |
| 6 | Comparative effectiveness of upfront treatment strategies in elderly women with ovarian cancer显示文摘 | Jason D. Wright Cande V. Ananth Jennifer Tsui Sherry A. Glied William M. Burke Yu‐Shiang Lu Alfred I. Neugut Thomas J. Herzog Dawn L. Hershman | 2014 | Cancer2014，，8： | 1 |
| 7 | Effect of laser in situ keratomileusis on tear stability显示文摘 | Edward Y.W Yu Alfred Leung Srinivas Rao Dennis S.C Lam | 2000 | Ophthalmology2000，，12： | 1 |
| 8 | Histone Deacetylase HDAC8 Promotes Insulin Resistance and β-Catenin Activation in NAFLD-Associated Hepatocellular Carcinoma显示文摘 | Tian Yuan Wong Vincent W.S. Wong Grace L.H. Yang Weiqin Sun Hanyong Shen Jiayun Tong Joanna H.M. Go Minnie Y.Y. Cheung Yue S. Lai Paul B.S. Zhou Mingyan Xu Gang Huang Tim H.M. Yu Jun To Ka F. Cheng Alfred S.L. Chan Henry L.Y | 2015 | Cancer Research2015，，22： | 1 |
| 9 | Arginine: New and Exciting Developments for an“Old”Amino Acid显示文摘Arginine (2-amino-5-guanidino pentanoic acid) was shown in 1895 by Hedin to be present in the proteins of horn. Metabolic nitrogen balance studies, conducted in 1957 by Rose in human adults and in 1959 by Snyderman and coworkers in young infants, revealed that a dietary source of this amino acid was not an obligatory requirement for growth and maintenance of nitrogen homeostasis in healthy individuals. Hence, It was initially classified as a non-essential (dispensable) amino acid and, perhaps, for reasons of this classification arginine did not receivc the earlier atteniion it now deserves, in relation to an understanding of the nutritional biochemistry and physiology of its metabolism in humans subjects. However, there is currently a considerable interest in the cellular and tissue functions, as well as clinical, therapeutic significance, of arginine. In this paper we review the multiple functions of arginlne, including its role in the L-arginine-nitric oxide pathway,cellular regeneration, immune function, protein synthesis and protein breakdown. We then consider some in vivo aspects of the physiology of arginine metabolism, which varies greatly among eukaryotes, with particular reference to humans. Against this background, studies of arginine in the nutrition of humans under various pathophysiological conditions are reviewed briefly. Finally, a new, updated concept for the metabolic basis for the 'conditional essentiality' of arginine is | LOUIS BEAUMIER LETICIA CASTILLO YONG-MING YU ALFRED M. AJAMI AND VERNON R. YOUNG(Laboratory of Human Nutrition, School of Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA Shriners Burns Institute,Boston, MA, 02114 USA mass Tra | 1996 | Biomedical and Environmental Sciences1996，9，2： | 1 |
| 10 | Internet Tomography显示文摘 | Mark Coates Alfred Hero Robert Nowak Bin Yu | 2002 | IEEE Signal Processing Magazine2002，19，： | 1 |
| 11 | Mucoadhesive polymer films for tissue retraction in laparoscopic surgery: Ex-vivo study on their mechanical properties显示文摘 | Feng Liu Ali Goodarzi Haifeng Wang Joanna Stasiak Jianbo Sun Yu Zhou Zhigang Wang Lik-Ren Tai Donald McLean Emma J. Wright Gordon J. Florence Stuart I. Brown Pascal Andre Alfred Cuschieri | 2014 | Bio-Medical Materials and Engineering2014，，1： | 1 |
| 12 | Serum Vascular Endothelial Growth Factor C Correlates With Lymph Node Metastases and High-Risk Tumor Profiles in Papillary Thyroid Carcinoma显示文摘 | Xiao-Min Yu Chung-Yau Lo Alfred King-Yin Lam Pauline Leung John M. Luk | 2008 | Annals of Surgery2008，，： | 1 |
| 13 | Cell cycle-related kinase is a direct androgen receptor-regulated gene that drives [Beta]-catenin/T cell factor-dependent hepatocarcinogenesis显示文摘 | Feng Hai Cheng Alfred S L Tsang Daisy P Li May S Go Minnie Y Cheung Yue S Zhao Gui-jun Ng Samuel S Lin Marie C Yu Jun Lai Paul B To Ka F Sung Joseph J Y | 2011 | Journal of Clinical Investigation2011，，8： | 1 |
| 14 | The potential clinical relevance of serum vascular endothelial growth factor (VEGF) and VEGF-C in recurrent papillary thyroid carcinoma显示文摘 | Xiao-Min Yu Chung-Yau Lo Alfred King-Yin Lam Brian Hung-Hin Lang Pauline Leung John M. Luk | 2008 | Surgery2008，，： | 1 |
| 15 | A Numerical Understanding of Vertical Magnesium Thermal Reduction Processes显示文摘 | Henry Hu Alfred Yu Naiyi Li | 2002 | Magnesium Technology2002，2002，： | 1 |
| 16 | Exciton dynamics in luminescent carbon nanodots: Electron-hole exchange interaction显示文摘 | Bo Peng Xin Lu Shi Chen Cheng Hon Alfred Huan Qihua Xiong Evren Mutlugun Hilmi Volkan Demir Siu Fung Yu | 2016 | Nano Research2016，9，2： | 1 |
| 17 | Numerical simulation of natural convection in magnesium alloy squeeze casting显示文摘 | Yu Alfred Li Naiyi Hu Hernary | 2003 | The Minerals Metals and Materials Society2003，，： | 1 |
| 18 | Single-ensemble-based eigen-processing methods for color flow imaging显示文摘 | Alfred C H Yu R S C Cobbold | | 0，，03： | 1 |
| 19 | Intemet Tomography 显示文摘 | M Coates H Alfred Ill R Nowak B Yu | 2002 | IEEE Signal Processing Magazine: (S1053-5888)2002，19，3： | 1 |
| 20 | Effects of thinning on scatter-hoarding by rodents in temperate forest显示文摘Deforestation and thinning are human activities that can destabilize the forest ecological system and,consequently,impact significantly on habitat and behavior of forest-dwelling animals.This hypothesis was tested in Yugong in the Mount Taihangshan area by comparing the tracks of tagged seeds of Armeniaca sibirica.in sites of unthinned and thinned forests.Our results showed that:(i)the diversity of vegetation and rodents drastically reduced in sites with thinned forests,compared to unthinned sites;(ii)the amount of both removed and scatter-hoarded seeds significantly declined in sites with thinned forests,compared with the unthinned sites;(iii)there was no significant difference observed in the distance of seed dispersal between the thinned and unthinned areas;and(iv)the thinning did not show a significant change to the model of cache size.These results suggested that the thinning of forests negatively influenced the species richness and food-hoarding behavior of rodents.In addition,the results indicated that the weakened scattered-hoarding might be disadvantageous to seedling recruitment and forest restoration. | Yifeng ZHANG Jing YU Alfred M.SICHILIMA Weirui WANG Jiqi LU | 2016 | Integrative Zoology2016，11，3： | 0 |
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