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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 | 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 |
| 3 | Brain MRI of hippocampal volumetry in patients with refractory temporal lobe epilepsy显示文摘Objective To detect for hippocampal sclerosis presurgically in a group of patients with refractory temporal lobe epilepsy Methods Eighty four consecutive patients with refractory temporal lobe epilepsy were subjected to brain MRI of hippocampal volumetry A ratio of smaller to larger hippocampal volume was determined and unilateral hippocampal atrophy (HA) was diagnosed if the ratio is less than 0 91 Results Unilateral HA was diagnosed in 42 patients (50%) and bilateral HA in 1 patient Other MRI abnormalities were detected in 18 patients with or without coexisting HA Conclusions Hippocampal sclerosis can be detected presurgically in many patients by brain MRI Additional abnormalities not detected by brain CT can also be | Ka Kui Philip Ng, Kwok Wing Tang, Yuk Ling James Cheung and Patrick Chung Ki Li | 2000 | Chinese Medical Journal2000，，3： | 3 |
| 4 | HBsAg Seroclearance in Chronic Hepatitis B in Asian Patients: Replicative Level and Risk of Hepatocellular Carcinoma显示文摘 | Man–Fung Yuen Danny Ka–Ho Wong James Fung Philip Ip David But Ivan Hung Kevin Lau John Chi–Hang Yuen Ching–Lung Lai | 2008 | Gastroenterology2008，，4： | 2 |
| 5 | 轻型缺血性卒中或短暂性脑缺血发作的早期双联抗血小板治疗显示文摘王拥军及同事探讨了应用双联抗血小板治疗预防卒中复发或短暂性脑缺血发作的最新证据。轻型缺血性卒中和短暂性脑缺血发作(TIA)患者在头几周内有较高的卒中及其他血管事件的复发风险(5%~11.7%严。双联抗血小板治疗,包括氯吡格雷和阿司匹林,是减少卒中复发的有效治疗策略Magic Group的专家小组(http://gffzz25d7f5dd9bdf4c9ehc09p5upf5wp96650.ffgz.tsg.suse.edu.cn/)最近在The BMJ中发表了一个强烈的快速推荐建议,即对于轻型缺血性卒中和TIA患者应在症状出现24小时内开始双联抗血小板治疗,并持续10~21天3。 | 王拥军 S. Claiborne Johnston Philip M Bath James C. Grotta 潘岳松 Pierre Amarenco 王伊龙 Tabassome Simon Jong Sung Kim Jiann-Shing Jeng 刘丽萍 林毅 Ka Sing Lawrence Wong David Wang 李昊 | 2019 | 英国医学杂志中文版2019，22，5： | 2 |
| 6 | Randomized Trial of Endoscopic Sphincterotomy With Balloon Dilation Versus Endoscopic Sphincterotomy Alone for Removal of Bile Duct Stones显示文摘 | Anthony Yuen Bun Teoh Frances Ka Yin Cheung Bing Hu Ya Min Pan Larry Hin Lai Philip Wai Yan Chiu Simon Kin Hung Wong Francis Ka Leung Chan James Yun Wong Lau | 2013 | Gastroenterology2013，，： | 2 |
| 7 | A Bub-l-V 15×10 6/C CMOS Bandgap Voltage Reference without Requiring Low Threshold Voltage Device 显示文摘 | Leung Ka Nang Mork Philip K T | 2002 | IEEE J Solid-State Circuits2002，37，4： | 1 |
| 8 | A sub-l-V 15-ppm/℃ CMOS bandgap voltage reference without requiring low threshold voltage device显示文摘 | Ka Nang Leung Mok Philip K T | 2002 | IEEE J Solid-State Circuites2002，37，4： | 1 |
| 9 | A low- voltage CMOS low - dropout regulator with enhanced loop response显示文摘 | Ka Nang Leung Philip K T Mok Sai Kit Lau | 2004 | IEEE ISCAS2004，，12： | 1 |
| 10 | Design Considerations of Recent Advanced Low-voltage Low-temperature-coefficient CMOS Bandgap Voltage Reference显示文摘 | Philip K T Mok Ka Nang Leung | 2004 | IEEE CICC2004，，： | 1 |
| 11 | Prevalence of diagnosed atrial fib rillation in adults: national implications for rhythm management and stroke prevention: the anticoagulation and lnsk factors in atrial fibrillation (ATRIA) study显示文摘 | Go AS Hylek EM Philips KA | 2001 | JAMA2001，285，18： | 1 |
| 12 | Randomized Trial of Endoscopic Sphincterotomy With Balloon Dilation Versus Endoscopic Sphincterotomy Alone for Removal of Bile Duct Stones显示文摘 | Anthony Yuen Bun Teoh Frances Ka Yin Cheung Bing Hu Ya Min Pan Larry Hin Lai Philip Wai Yan Chiu Simon Kin Hung Wong Francis Ka Leung Chan James Yun Wong Lau | 2013 | Gastroenterology2013，，： | 1 |
| 13 | A Voltage-Mode PWM Buck Regulator with End-Point Prediction显示文摘 | Man Siu Philip K T Mok Ka Nang Leung | 2006 | IEEE Transaction on Circuits and Systems-Ⅱ:Express Briefs2006，53，4： | 1 |
| 14 | Automated microaneurysm detection using local contrast normalization and local vessel detection 显示文摘 | Fleming AD Philip S Goatman KA | 2006 | IEEE Transactions on Medical Imaging2006，25，9： | 1 |
| 15 | The new concept of ' interventional heart failure therapy':part 2--inotropes,valvular disease,pumps,and transplantation显示文摘 | Thompson KA Philip KJ Simsir S | | 0，，03： | 1 |
| 16 | A Sub - 1 - V 15 ppm/℃ CMOS Bandgap Voltage Reference without Requiring Low Threshold Voltage Device显示文摘 | Ka Nang Leung Philip K T Mok | 2002 | IEEE Journal of Solid - state Circuits2002，37，4： | 1 |
| 17 | Analysis of multistage amplifier-frequency compensation显示文摘 | Ka Nang Leung Philip K T Mok | 2001 | IEEE Transactions on Circuits and Systems- I :Fundamental Theory and Applications2001，48，9： | 1 |
| 18 | A CMOS voltage reference based on weighted-VGS for CMOS low- dropout linear regulators显示文摘 | Ka Nang Leung Philip K T Mok | 2003 | IEEE J Solid- State Circuits2003，38，1： | 1 |
| 19 | An integrated CMOS current- sensing circuit for low- Voltage current--mode buck regulator显示文摘 | Chi Yat Leung Philip K T Mok Ka Nang Leung | 2005 | IEEE Trans- actions on Circuits and Systems Ⅱ Express Briefs2005，52，7： | 1 |
| 20 | A Voltage-Mode PWM Buck Regulator with End-Point Pre- diction 显示文摘 | SIU Man MOK Philip K T LEUNG Ka Nang | 2006 | IEEE Trans Circuits Syst II Expr Briefs2006，53，4： | 1 |
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