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| 1 | 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 |
| 2 | 澳大利亚个人理财业的发展与启示显示文摘20世纪80年代以来,个人理财业的迅速扩张使得澳大利亚个人理财业发生了根本的变化。与澳大利亚相比,中国个人理财业正处于早期形成阶段,加强理财的教育培训,构建合理的理财经营模式,进行严格的金融监管对个人理财业健康发展十分重要。 | 陈兵 Alfred Wong | 2007 | 金融教学与研究2007，，1： | 4 |
| 3 | Non-invasive versus invasive mechanical ventilation for respiratory failure in severe acute respiratory syndrome显示文摘Background Severe acute respiratory syndrome is frequently complicated by respiratory failure requiringventilatory support.We aimed to compare the efficacy of non-invasive ventilation against invasive mechanicalventilation treating respiratory failure in this disease.Methods Retrospective analysis was conducted on all respiratory failure patients identified from the HongKong Hospital Authority Severe Acute Respiratory Syndrome Database.Intubation rate, mortality and secondaryoutcome of a hospital utilizing non-invasive ventilation under standard infection control conditions ( NIVHospital) were compared against13 hospitals using solely invasive ventilation (IMVHospitals).Multiple logisticregression analyses with adjustments for confounding variables were performed to test for association betweenoutcomes and hospital groups.Results Both hospital groups had comparable demographics and clinical profiles, but NIV Hospital (42patients) had higher lactate dehydrogenase ratio and worse radiographic score on admission and ribavirin-corticosteroid commencement.Compared to IMV Hospitals (451 patients), NIV Hospital had lower adjustedodds ratios for intubation (0.36, 95% CI 0.164 -0.791,P=0.011) and death (0.235, 95% CI 0.077 -0.716,P=0.011), and improved earlier after pulsed steroid rescue.There were no instances of transmission ofsevere acute respiratory syndrome among health care workers due to the use of non-invasive ventilation.Conclusion Compared to invasive mechanical ventilation, non-invasive ventilation as initial ventilatory supportfor acute respiratory failure in the presence of severe acute respiratory syndrome appeared to be associated withreduced intubation need and mortality. | Loretta YC Yam Alfred YF Chan Thomas MT Cheung Eva LH Tsui Jane CK Chan Vivian CW Wong | 2005 | Chinese Medical Journal2005，，17： | 3 |
| 4 | 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 |
| 5 | Collectivist values for learning in organizational relationships in China: the role of trust and vertical coordination显示文摘 | Alfred Wong Dean Tjosvold | 2006 | Asia Pacific Journal of Management2006，，3： | 2 |
| 6 | Determinants of angle closure in older Singa- poreans显示文摘 | LAVANYA R WONG TY FRIEDMAN DS AUNG HT ALFRED T GAO H | | Arch Ophthalmol0，126，5： | 1 |
| 7 | Developing relationships in strategic alliances: commitment to quality and cooperative interdependence 显示文摘 | ALFRED WONG DEAN TJOSVOLD PENGZHU ZHANG | 2005 | Industrial Marketing Management2005，34，3： | 1 |
| 8 | Determinants of angle closure in older Singaporeans 显示文摘 | Lavanya R Wong TY Friedman DS Aung T Alfred T Gao H et a/ | 2008 | Arch Ophthalmol2008，126，5： | 1 |
| 9 | Cooperative and Competitive Conflict for Quality Supply Partnerships between China and Hong Kong 显示文摘 | Alfred Wong Dean Tjosvold Winnie Y L Wong C K Liu | 1999 | International Journal of Physical Distribution & Logistics Management1999，29，1： | 1 |
| 10 | Signet-ring cell carcinoma of the colon and rectum显示文摘 | Aviram Nissan M.D. Jose G. Guillem M.D. Phillip B. Paty M.D. W. Douglas Wong M.D. Dr. Alfred M. Cohen M.D | 1999 | Diseases of the Colon & Rectum1999，，9： | 1 |
| 11 | Social Face for Innovation in Strategic Alliances in China: The Mediating Roles of Resource Exchange and Reflexivity 显示文摘 | Wong Alfred Dean Tjosvold and Fang Su | 2007 | Journal of Or?ganization Behavior2007，28，8： | 1 |
| 12 | Partnering through cooperative goals in supply chain relationships 显示文摘 | WONG ALFRED | 1999 | Total Quality Management1999，，10： | 1 |
| 13 | Risk factors for complications after performance of ERCP显示文摘 | Jo Vandervoort Roy M. Soetikno Tony C.K. Tham Richard C.K. Wong Angelo P. Ferrari Henry Montes Alfred D. Roston Adam Slivka David R. Lichtenstein Frederick W. Ruymann Jacques Van Dam Mike Hughes David L. Carr-Locke | 2002 | Gastrointestinal Endoscopy2002，，5： | 1 |
| 14 | RNA interference targeting HBx suppresses tumor growth and enhances cisplatin chemosensitivity in human hepatocellular carcinoma显示文摘 | Alfred S.L. Cheng Nathalie Wong Ada M.Y. Tse Kathy Y.Y. Chan Kai K. Chan Joseph J.Y. Sung Henry L.Y. Chan | 2007 | Cancer Letters2007，，1： | 1 |
| 15 | Rectus Flap Reconstruction Decreases Perineal Wound Complications After Pelvic Chemoradiation and Surgery: A Cohort Study显示文摘 | David B. Chessin MD John Hartley MD Alfred M. Cohen MD Madhu Mazumdar PhD Peter Cordeiro MD Joseph Disa MD Babek Mehrara MD Bruce D. Minsky MD Philip Paty MD Martin Weiser MD W. Douglas Wong MD Jose G. Guillem MD MPH | 2005 | Annals of Surgical Oncology2005，，2： | 1 |
| 16 | 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 |
| 17 | Surgical Salvage of Recurrent Rectal Cancer After Transanal Excision显示文摘 | Martin R. Weiser M.D. Ron G. Landmann M.D. W. Douglas Wong M.D. Jinru Shia M.D. José G. Guillem M.D. M.P.H. Larissa K. Temple M.D. Bruce D. Minsky M.D. Alfred M. Cohen M.D. Philip B. Paty M.D | 2005 | Diseases of the Colon & Rectum2005，，6： | 1 |
| 18 | Partnering Through Cooperative Goals in Supply Chain Relationships显示文摘 | Wong Alfred | 1999 | Total Quality Management1999，，10： | 1 |
| 19 | Adequacy of 1-cm Distal Margin After Restorative Rectal Cancer Resection With Sharp Mesorectal Excision and Preoperative Combined-Modality Therapy显示文摘 | Harvey G. Moore Elyn Riedel Bruce D. Minsky Leonard Saltz Philip Paty Douglas Wong Alfred M. Cohen Jose G. Guillem | 2003 | Annals of Surgical Oncology2003，，1： | 1 |
| 20 | Determinants of angle closure in older Singa- poreans 显示文摘 | LAVANYA R WONG TY FRIEDMAN DS AUNG HT ALFRED T GAO H | 2008 | Arch Ophthalmol2008，126，5： | 1 |
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