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| 1 | Synchronous colorectal cancer: Clinical, pathological and molecular implications显示文摘Synchronous colorectal carcinoma refers to more than one primary colorectal carcinoma detected in a single patient at initial presentation.A literature review has shown that the prevalence of the disease is approximately 3.5%of all colorectal carcinomas.This disease has a male to female ratio of 1.8:1.The mean age at presentation of patients with synchronous colorectal cancer is in the early half of the seventh decade.Patients with inflammatory bowel diseases(ulcerative colitis and Crohn’s disease),hereditary non-polyposis colorectal cancer,familial adenomatous polyposis and serrated polyps/hyperplastic polyposis are known to have a higher risk of synchronous colorectal carcinoma.These predisposing factors account for slightly more than 10%of synchronous colorectal carcinomas.Synchronous colorectal carcinoma is more common in the right colon when compared to solitary colorectal cancer.On pathological examination,some synchronous colorectal carcinomas are mucinous adenocarcinomas.They are usually associated with adenomas and metachronous colorectal carcinomas.Most of the patients with synchronous colorectal cancer have two carcinomas but up to six have been reported in one patient.Patients with synchronous colorectal carcinoma havea higher proportion of microsatellite instability cancer than patients with a solitary colorectal carcinoma.Also,limited data have revealed that in many synchronous colorectal carcinomas,carcinomas in the same patient have different patterns of microsatellite instability status,p53 mutation and K-ras mutation.Overall,the prognosis of patients with synchronous colorectal carcinoma is not significantly different from that in patients with solitary colorectal carcinoma,although a marginally better prognosis has been reported in patients with synchronous colorectal carcinoma in some series.A different management approach and long-term clinical follow-up are recommended for some patients with synchronous colorectal cancer. | Alfred King-Yin Lam Sally Sze-Yan Chan Melissa Leung | 2014 | World Journal of Gastroenterology2014，20，22： | 22 |
| 2 | Adsorptive hemofiltration for sepsis management: expert recommendations based on the Asia Pacific experience显示文摘To the Editor:In sepsis,bacterial endotoxins play a central role by inducing a dysregulated and exaggerated release of inflammatory mediators and cytokines,often described as the“cytokine storm”or“cytokinemia.”[1]Both endotoxins and cytokines have been implicated in the development of organ dysfunction,including acute kidney injury(AKI).[2]Removing circulating endotoxins and excess cytokines from the circulation restores chemotactic gradients,localizing the immune response to the principal site of infection and re-establishing a regulated immune response.[1,3]Therefore,using hemofilters with enhanced endotoxin and cytokine adsorptive properties may bring about additional therapeutic benefits compared with conventional continuous renal replacement therapy(CRRT)filters. | Ling Zhang Matthew Cove Binh G.Nguyen Nuttha Lumlertgul Kartik Ganesh Alfred Chan Giang T.H.Bui Chunwen Guo Junhua Li Songqiao Liu Mian Peng Kit W.Foong Jian Zhang Minmin Wang Jacques Goldstein Kai Harenski | 2021 | Chinese Medical Journal2021，，18： | 6 |
| 3 | 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 |
| 4 | Civil and structural engineering applications,recent trends,research and developments on pultruded fiber reinforced polymer closed sections:a review显示文摘The objectives of this study are to review and evaluate the developments and applications of pultruded fiber-reinforced polymer composites in civil and structural engineering and review advances in research and developments.Several case applications are reviewed.The paper presents a state-of-the-art review of fundamental research on the behavior of pultruded fiber reinforced polymer closed sections and highlights gaps in knowledge and areas of potential further research. | Alfred Kofi GAND Tak-Ming CHAN James Toby MOTTRAM | 2013 | Frontiers of Structural and Civil Engineering2013，7，3： | 4 |
| 5 | 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 |
| 6 | Growth arrest-specific gene 2 suppresses hepatocarcinogenesis by intervention of cell cycle and p53-dependent apoptosis显示文摘BACKGROUND Growth arrest-specific gene 2(GAS2)plays a role in modulating in reversible growth arrest cell cycle,apoptosis,and cell survival.GAS2 protein is universally expressed in most normal tissues,particularly in the liver,but is depleted in some tumor tissues.However,the functional mechanisms of GAS2 in hepatocellular carcinoma(HCC)are not fully defined.AIM To investigate the function and mechanism of GAS2 in HCC.METHODS GAS2 expression in clinic liver and HCC specimens was analyzed by real-time PCR and western blotting.Cell proliferation was analyzed by counting,MTS,and colony formation assays.Cell cycle analysis was performed by flow cytometry.Cell apoptosis was investigated by Annexin V apoptosis assay and western blotting.RESULTS GAS2 protein expression was lower in HCC than in normal tissues.Overexpression of GAS2 inhibited the proliferation of HCC cells with wide-type p53,while knockdown of GAS2 promoted the proliferation of hepatocytes(P<0.05).Furthermore,GAS2 overexpression impeded the G1-to-S cell cycle transition and arrested more G1 cells,particularly the elevation of sub G1(P<0.01).Apoptosis induced by GAS2 was dependent on p53,which was increased by etoposide addition.The expression of p53 and apoptosis markers was further enhanced when GAS2 was upregulated,but became diminished upon downregulation of GAS2.In the clinic specimen,GAS2 was downregulated in more than 60%of HCCs.The average fold changes of GAS2 expression in tumor tissues were significantly lower than those in paired non-tumor tissues(P<0.05).CONCLUSION GAS2 plays a vital role in HCC cell proliferation and apoptosis,possibly by regulating the cell cycle and p53-dependent apoptosis pathway. | Ran-Xu Zhu Alfred Sze Lok Cheng Henry Lik Yuen Chan Dong-Ye Yang Wai-Kay Seto | 2019 | World Journal of Gastroenterology2019，25，32： | 2 |
| 7 | Oncogene GAEC1 regulates CAPN10 expression which predicts survival in esophageal squamous cell carcinoma显示文摘AIM: To identify the downstream regulated genes of GAEC1 oncogene in esophageal squamous cell carcinoma and their clinicopathological significance. METHODS: The anti-proliferative effect of knocking down the expression of GAEC1 oncogene was stud-ied by using the RNA interference (RNAi) approach through transfecting the GAEC1 -overexpressed esophageal carcinoma cell line KYSE150 with the pSilencer vector cloned with a GAEC1 -targeted sequence, followed by MTS cell proliferation assay and cell cycle analysis using flow cytometry. RNA was then extracted from the parental, pSilencer-GAEC1 -targeted sequence transfected and pSilencer negative control vector transfected KYSE150 cells for further analysis of different patterns in gene expression. Genes differentially expressed with suppressed GAEC1 expression were then determined using Human Genome U133 Plus 2.0 cDNA microarray analysis by comparing with the parental cells and normalized with the pSilencer negative control vector transfected cells. The most prominently regulated genes were then studied by immunohistochemical staining using tissue microarrays to determine their clinicopathological correlations in esophageal squamous cell carcinoma by statistical analyses. RESULTS: The RNAi approach of knocking down gene expression showed the effective suppression of GAEC1 expression in esophageal squamous cell carcinoma cell line KYSE150 that resulted in the inhibition of cell proliferation and increase of apoptotic population. cDNA microarray analysis for identifying differentially expressed genes detected the greatest levels of downregulation of calpain 10 (CAPN10 ) and upregulation of trinucleotide repeat containing 6C (TNRC6C ) transcripts when GAEC1 expression was suppressed. At the tissue level, the high level expression of calpain 10 protein was significantly associated with longer patient survival (month) of esophageal squamous cell carcinoma compared to the patients with low level of calpain 10 expression (37.73 ± 16.33 vs 12.62 ± 12.44, P = 0.032). No significant correction was observed among the TNRC6C protein expression level and the clinocopathologcial features of esophageal squamous cell carcinoma. CONCLUSION: GAEC1 regulates the expression of CAPN10 and TNRC6C downstream. Calpain 10 expression is a potential prognostic marker in patients with esophageal squamous cell carcinoma. | Dessy Chan Miriam Yuen-Tung Tsoi Christina Di Liu SauHing Chan Simon Ying-Kit Law Kwok-Wah Chan Yuen-Piu Chan Vinod Gopalan Alfred King-Yin Lam Johnny Cheuk-On Tang | 2013 | World Journal of Gastroenterology2013，19，18： | 2 |
| 8 | Living status and psychological well-being: Social comparison as a moderator in later life显示文摘 | Sheung-Tak Cheng Helene H. Fung Alfred C. M. Chan | 2008 | Aging & Mental Health2008，，5： | 1 |
| 9 | 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 |
| 10 | 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 |
| 11 | Chlorpromazine-induced refractile corneal deposits and cataract显示文摘 | Alfred TS Arthur CK Wai-Man Chan | 1999 | Arch Ophthalmol1999，117，： | 1 |
| 12 | Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in hepatocellular carcinoma:the PLANET study显示文摘Intra-tumor heterogeneity(ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic(transcriptomic and immune)heterogeneity. Using one of the largest prospective surgical cohorts for hepatocellular carcinoma(HCC)with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients(331 samples). We found that while genomic ITH was rather constant across stages, phenotypic ITH had a very different trajectory and quickly diversified in stage Ⅱ patients. Most strikingly, 30% of patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types. | Weiwei Zhai Hannah Lai Neslihan Arife Kaya Jianbin Chen Hechuan Yang Bingxin Lu Jia Qi Lim Siming Ma Sin Chi Chew Khi Pin Chua Jacob Josiah Santiago Alvarez Pauline Jieqi Chen Mei Mei Chang Lingyan Wu Brian K.P.Goh Alexander Yaw-Fui Chung Chung Yip Chan Peng Chung Cheow Ser Yee Lee Juinn Huar Kam Alfred Wei-Chieh Kow Iyer Shridhar Ganpathi Rawisak Chanwat Jidapa Thammasiri Boon Koon Yoong Diana Bee-Lan Ong Vanessa H.de Villa Rouchelle D.Dela Cruz Tracy Jiezhen Loh Wei Keat Wan Zeng Zeng Anders Jacobsen Skanderup Yin Huei Pang Krishnakumar Madhavan Tony Kiat-Hon Lim Glenn Bonney Wei Qiang Leow Valerie Chew Yock Young Dan Wai Leong Tam Han Chong Toh Roger Sik-Yin Foo Pierce Kah-Hoe Chow | 2022 | National Science Review2022，9，3： | 1 |
| 13 | Preoperative chemotherapy and pelvic radiation for tethered or fixed rectal cancer: A phase II dose escalation study显示文摘 | Alexander K.P Chan Alfred O Wong James Langevin Daryl Jenken John Heine Donald Buie Douglas R.E Johnson | 2000 | International Journal of Radiation Oncology, Biology, Physics2000，，3： | 1 |
| 14 | Expression of HBx and COX -2 in chronic hepatitis B, cirrhosis and hepatocellular carcinoma: implication of HBx in upregulation of COX -2 显示文摘 | Alfred S - L Cheng Henry L - Y Chan | 2004 | Modern Pathol2004，17，： | 1 |
| 15 | CONSIDERATIONS FOR THE USE OF ADVANCE DIRECTIVES AMONG OLDER PERSONS WITH DEMENTIA IN HONG KONG显示文摘 | Alfred Cheung-ming Chan Alastair Jin-lon Chan David Dai Lok Kwan | 2016 | US-China Law Review2016，13，2： | 0 |
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