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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 | Correlation and prognostic significance of beta-galactoside alpha-2,6-sialyltransferase and serum monosialylated alpha-fetoprotein in hepatocellular carcinoma显示文摘AIM: To investigate the correlation between tissue ST6Gal I and serum msAFP in HCC patients, and to investigate their prognostic significance.METHODS: Preoperative sera,paired tumorous and non-tumorous tissues were collected from 19 consecutive patients who had undergone surgical resection of HCC.ST6Gal T activities in the tissues were measured by an in vitro microsomal enzyme activity assay. The percentages of tumor-specific msAFP in the sera were also estimated by an isoelectric focusing-immunoblotting assay.RESULTS: The tumor ST6Gal I activity was negatively correlated with serum msAFP percentage (r = -0.53,P = 0.019). Both decreased tumor ST6Gal I activity andincreased serum msAFP percentage were associatedwith poor tumor cell differentiation. Univariate analyses showed that both decreased tumor ST6Gal T activity (P = 0.028), increased serum msAFP percentage (P = 0.034) and poor tumor cell differentiation (P = 0.031)were associated with shorter overall survival. Multivariate analysis using the Cox regression model showed that the preoperative serum msAFP percentage (P = 0.022)and tumor cell differentiation status (P = 0.048) were independent prognostic indicators for patient overall survival.CONCLUSION: Our results indicate that the presence of msAFP in blood circulation is associated with a decreased activity of ST6Gal I activity in HCC. Both tissue ST6Gal I and serum msAFP are potential prognostic markers for patients with operable HCC. | Terence CW Poon Clarissa HS Chiu Paul BS Lai Tony SK Mok Benny Zee Anthony TC Chan Joseph JY Sung Philip J Johnson | 2005 | World Journal of Gastroenterology2005，11，42： | 4 |
| 3 | Use of the Over-The-Scope Clip for treatment of refractory upper gastrointestinal bleeding: a case series显示文摘 | Shannon Chan Philip Chiu Anthony Teoh James Lau | 2014 | Endoscopy2014，，： | 2 |
| 4 | The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase显示文摘 | Thomas F Franke Sung-Il Yang Tung O Chan Ketaki Datta Andrius Kazlauskas Deborah K Morrison David R Kaplan Philip N Tsichlis | 1995 | Cell1995，，5： | 2 |
| 5 | Outcome and prognostic factors in 110 consecutive patients with primary uterine leiomyosarcoma:A Rare Cancer Network study显示文摘Objective: Primary uterine leiomyosarcomas(ULMS) are rare,and the optimal treatment is controversial.We aimed to assess the outcome and prognostic factors in a multicenter population of women treated for primary ULMS.Methods: We retrospectively collected data of 110 women treated in 19 institutions of the Rare Cancer Network(RCN).Inclusion criteria consisted of a pathology report confirming the diagnosis of ULMS,aged 18–80 years,complete International Federation of Gynecology and Obstetrics(FIGO) stage information,complete information on treatment,and a minimum follow-up of 6 months.Local control(LC) and locoregional control(LRC),overall survival(OS) and disease-free survival(DFS) rates were computed using the Kaplan-Meier method.Univariate analysis was implemented using the log rank test,and multivariate analysis using the Cox model.Results: All patients underwent surgery.Seventy-five patients(68%) received adjuvant radiotherapy(RT),including brachytherapy in 18(16%).Seventeen patients(15%) received adjuvant chemotherapy.Median follow-up was 58(range,6–240) months.Five-year OS and DFS rates were 50% and 34%,and LC and LRC rates were 88%and 72%,respectively.On multivariate analysis,independent favorable prognostic factors were younger age,FIGO stage I,small tumor size,previous uterine disease,and no vascular invasion for OS and DFS.FIGO stage was the only favorable factor influencing LRC.Adjuvant local or systemic treatments did not improve the outcomes.Eight patients treated with RT presented a grade 3 acute toxicity,and only one patient with grade 3 late toxicity.Conclusions: In this large population of primary ULMS patients,we found good results in terms of LC and LRC.Nevertheless,OS remains poor,mainly due to the occurrence of distant metastases.An early diagnosis seemed to improve the prognosis of the patients.Adjuvant local or systemic treatments,or more aggressive surgicalprocedures such as the Wertheim procedure,did not seem to impact the outcome. | Alessandra Franzetti Pellanda Berardino De Bari Elisabeth Deniaud-Alexandre MarcoKrengli Paul Van Houtte Antonella Riehetti Salvador Villa Hadassah Goldberg EwaSzutowiez-Zielifiska Michel Bolla Heidi Rutten Marc Van Eijkeren Philip Poortmans Guido Henke Yavuz Anaeak Steve Chan Christine Landmann Carine Kirkove LueianoScandolaro Jacques Bernier Rene-Olivier Mirimanof Mahmut Ozsahin | 2017 | Chinese Journal of Cancer Research2017，29，6： | 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 | Cancer stem cell markers are associated with adverse biomarker profiles and molecular subtypes of breast cancer显示文摘 | Julia Y. S. Tsang Yu-Hua Huang Ming-Hua Luo Yun-Bi Ni Siu-Ki Chan Philip C. W. Lui Alex M. C. Yu Puay Hoon Tan Gary M. Tse | 2012 | Breast Cancer Research and Treatment2012，，2： | 1 |
| 8 | CNOP for Diffuse Aggressive Non-Hodgkin’s Lymphoma: The Nebraska Lymphoma Study Group Experience显示文摘 | Julie M. Vose Dennis D. Weisenburger James C. Lynch Philip J. Bierman John C. Chan Martin Bast Patricia Aoun Gregory Bociek Timothy Greiner James O. Armitage | 2002 | Leukemia & Lymphoma2002，，4： | 1 |
| 9 | Accurate analytical method for the extraction of solar cell model parameters显示文摘 | Phang J C J Chan D S H Philips J R | 1984 | Electronics Letters1984，20，10： | 1 |
| 10 | Using extreme value theory to measure value-at-risk for daily electricity spot price 显示文摘 | Kan Fong Chan Philip Gray | 2006 | International Journal of Forecasting2006，22，2： | 1 |
| 11 | 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 |
| 12 | Inhibition of Human Sperm Motility by Specific Herbs Used in Alternative Medicine显示文摘 | Richard R. Ondrizek Philip J. Chan William C. Patton Alan King | 1999 | Journal of Assisted Reproduction and Genetics1999，，2： | 1 |
| 13 | Hedgehog signa- ling antagonist promotes regression of both liver fibrosis and hepatocellular carcinoma in a murine model of primary liver cancer显示文摘 | Philips GM Chan IS Swiderska M | 2011 | PLoS One2011，6，23： | 1 |
| 14 | Clostridium Difficile Colitis: Increasing Incidence, Risk Factors, and Outcomes in Solid Organ Transplant Recipients显示文摘 | Marylise Boutros Maha Al-Shaibi Gabriel Chan Marcelo Cantarovich Elham Rahme Steven Paraskevas Marc Deschenes Peter Ghali Philip Wong Myriam Fernandez Nadia Giannetti Renzo Cecere Mazen Hassanain Prosanto Chaudhury Peter Metrakos Jean Tchervenkov Jeffrey | 2012 | Transplantation Journal2012，，10： | 1 |
| 15 | Hedgehog signaling antagonist promotes regression of both liver fibrosis and hepatocel- lular carcinoma in a murine model of primary liver cancer 显示文摘 | Philips G M Chan I S Swiderska M | 2011 | PLoS One2011，6，23： | 1 |
| 16 | Expression of microRNAs in the Urine of Patients With Bladder Cancer显示文摘 | Gang Wang Eddie Shu-Yin Chan Bonnie Ching-Ha Kwan Philip Kam-Tao Li Sidney Kam-Hung Yip Cheuk-Chun Szeto Chi-Fai Ng | 2012 | Clinical Genitourinary Cancer2012，，2： | 1 |
| 17 | Silicon-based highQ inductors incorporating electroplated copper and low-K BCB dielectric 显示文摘 | Xiao Huo Chen K J Chan Philip C H | 2002 | IEEE Electron Device Letters2002，23，9： | 1 |
| 18 | Accurate analytical method for the extraction of solar cell model parameters显示文摘 | Phang J C H Chan D S H Philips J R | 1984 | Electronics Letters1984，20，： | 1 |
| 19 | Aurone derivatives as Vps34 inhibitors that modulate autophagy显示文摘We report in this study the identification of a natural product-like antagonist(1a) of Vps34 as a potent autophagy modulator via structure-based virtual screening. Aurone derivative 1a strongly inhibited Vps34 activity in cell-free and cell-based assays. Significantly, 1a prevents autophagy in human cells induced either by starvation or by an mT OR inhibitor. In silico modeling and kinetic data revealed that 1a could function as an ATP-competitive inhibitor of Vps34. Moreover, it suppressed autophagy in vivo and without inducing heart or liver damage in mice. 1a could be utilized as a new motif for more selective and efficacious antagonists of Vps34 for the potential treatment of autophagy-related human diseases. | Guodong Li Joshua William Boyle Chung-Nga Ko Wu Zeng Vincent Kam Wai Wong Jian-Bo Wan Philip Wai Hong Chan Dik-Lung Ma Chung-Hang Leung | 2019 | Acta Pharmaceutica Sinica B2019，9，3： | 1 |
| 20 | Long waves through emergent coastal vegetation显示文摘 | CHIANG C Mei CHAN I-Chi LIU Philip L-F | 2011 | J Fluid Mech2011，687，： | 1 |
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