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| 1 | Golgi protein-73:A biomarker for assessing cirrhosis and prognosis of liver disease patients显示文摘BACKGROUND Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are missing.In this context,Golgi protein-73(GP73)also called Golgi phosphoprotein-2,was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial cells.As a result,GP73 expression was found primarily in biliary epithelial cells,with only slight detection in hepatocytes.However,in patients with acute or chronic liver diseases and especially in HCC,the expression of GP73 is significantly up-regulated in hepatocytes.So far,few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression.AIM To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression.METHODS GP73 serum levels were retrospectively determined by a novel GP73 ELISA(QUANTA Lite®GP73,Inova Diagnostics,Inc.,Research Use Only)in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa,Greece(n=366)and Debrecen,Hungary(n=266).Aspartate aminotransferase(AST)/Platelets(PLT)ratio index(APRI)was also calculated at the relevant time points in all patients.Two hundred and three patients had chronic hepatitis B,183 chronic hepatitis C,198 alcoholic liver disease,28 autoimmune cholestatic liver diseases,15 autoimmune hepatitis,and 5 with other liver-related disorders.The duration of follow-up was 50(57)mo[median(interquartile range)].The development of cirrhosis,liver decompensation and/or HCC during follow-up were assessed according to internationally accepted guidelines.In particular,the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein(AFP)determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic patients.RESULTS Increased serum levels of GP73(>20 units)were detected at initial evaluation in 277 out of 632 patients(43.8%).GP73-seropositivity correlated at baseline with the presence of cirrhosis(96.4%vs 51.5%,P<0.001),decompensation of cirrhosis(60.3%vs 35.5%,P<0.001),presence of HCC(18.4%vs 7.9%,P<0.001)and advanced HCC stage(52.9%vs 14.8%,P=0.002).GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score[Area under the curve(AUC)(95%CI):0.909(0.885-0.934)vs 0.849(0.813-0.886),P=0.003].Combination of GP73 with APRI improved further the accuracy(AUC:0.925)compared to GP73(AUC:0.909,P=0.005)or APRI alone(AUC:0.849,P<0.001).GP73 levels were significantly higher in HCC patients compared to non-HCC[22.5(29.2)vs 16(20.3)units,P<0.001)and positively associated with BCLC stage[stage 0:13.9(10.8);stage A:17.1(16.8);stage B:19.6(22.3);stage C:32.2(30.8);stage D:45.3(86.6)units,P<0.001]and tumor dimensions[very early:13.9(10.8);intermediate:19.6(18.4);advanced:29.1(33.6)units,P=0.004].However,the discriminative ability for HCC diagnosis was relatively low[AUC(95%CI):0.623(0.570-0.675)].Kaplan-Meier analysis showed that the detection of GP73 in patients with compensated cirrhosis at baseline,was prognostic of higher rates of decompensation(P=0.036),HCC development(P=0.08),and liver-related deaths(P<0.001)during follow-up.CONCLUSION GP73 alone appears efficient for detecting cirrhosis and superior to APRI determination.In combination with APRI,its diagnostic performance can be further improved.Most importantly,the simple GP73 measurement proved promising for predicting a worse outcome of patients with both viral and nonviral chronic liver diseases. | Nikolaos K Gatselis Tamás Tornai Zakera Shums Kalliopi Zachou Asterios Saitis Stella Gabeta Roger Albesa Gary L Norman Mária Papp George N Dalekos | 2020 | World Journal of Gastroenterology2020，26，34： | 21 |
| 2 | Cartilage oligomeric matrix protein: A novel non-invasive marker for assessing cirrhosis and risk of hepatocellular carcinoma显示文摘AIM: To assess serum cartilage oligomeric matrix protein(COMP) as a marker of cirrhosis and risk of progression to hepatocellular carcinoma(HCC). METHODS: A COMP enzyme-linked immunosorbentassay was used to test 187 patients with chronic liver diseases at the time point of first evaluation. The selected patients included 72 with chronic hepatitis B infection, 75 with chronic hepatitis C infection, 22 with primary biliary cirrhosis, 7 with autoimmune hepatitis type 1, and 11 with alcoholic liver disease. Demographic, biochemical, histological and clinical characteristics of the patients were recorded at the first evaluation. One hundred and forty-seven patients were followed for a median [interquartile range(IQR)] duration of 96.5(102) mo. The clinical, biochemical and histological data, as well as the development of cirrhosis, HCC according to internationally accepted criteria and in case of death, a liver-related cause during the follow-up period, were recorded at the electronic database of our clinic. COMP determination was also performed in 43 healthy individuals who served as the control study group.RESULTS: COMP positivity(> 15 U/L) was detected in 22%-36% among chronic liver disease groups. Strikingly, almost 83% of COMP-positive patients were cirrhotic at baseline, independently of cause of liver disease. Among the patients who developed HCC during follow-up, 73.7%(14/19) were COMP positive at baseline. COMP positivity was significantly associated with older age(P < 0.001), advanced fibrosis(P = 0.001) and necroinflammatory activity(P = 0.001), higher aspartate aminotransferase(P < 0.001), alanine aminotransferase(P < 0.02), γ-glutamyl transpeptidase(P = 0.003), alkaline phosphatase(P = 0.001), bilirubin(P < 0.05), international normalized ratio(P = 0.002) and alpha-fetoprotein levels(P < 0.02), and lower albumin(P < 0.001), and platelet count(P = 0.008). COMP levels [median(IQR)] were significantly higher in cirrhotics compared to non-cirrhotics [13.8(7.9) U/L vs 9.8(4.6) U/L, respectively; P < 0.001]. On multivariate logistic regression analysis, COMP-positivity was independently associated only with cirrhosis(OR = 4.40, 95%CI: 1.33-14.69, P = 0.015). Kaplan-Meier analysis showed that COMP positivity was significantly associated with HCC development(P = 0.007) and higher incidence of liver-related death(P < 0.001). CONCLUSION: Elevated COMP levels are strongly associated with cirrhosis and HCC progression. Serum COMP is a new promising non-invasive biomarker for HCC risk assessment in surveillance programs. | Gary L Norman Nikolaos K Gatselis Zakera Shums Christos Liaskos Dimitrios P Bogdanos George K Koukoulis George N Dalekos | 2015 | World Journal of Hepatology2015，7，14： | 7 |
| 3 | Cancer Genome Scanning in Plasma: Detection of Tumor-Associated Copy Number Aberrations, Single-Nucleotide Variants, and Tumoral Heterogeneity by Massively Parallel Sequencing显示文摘 | Chan K C Allen Jiang Peiyong Zheng Yama W L Liao Gary J W Sun Hao Wong John Siu Shing Shun N Chan Wing C Chan Stephen L Chan Anthony T C Lai Paul B S Chiu Rossa W K Lo Y M D | 2013 | Clinical Chemistry2013，，1： | 2 |
| 4 | Using QuickTime Virtual Reality Objects in Computer-assisted Instruction of Gross Anatomy:Yorick-the VR Skull显示文摘 | Gary L Nieder Jane N Scott | 2000 | Clinical Anatomy2000，13，4： | 1 |
| 5 | Crisis management, Booz & Company CEO succession survey 显示文摘 | Karlsson P O Gary L N | 2009 | Strategy Business2009，35，11： | 1 |
| 6 | Neural control mechanisms wi thin airways: disruption by respiratory syncytial virus显示文摘 | Gary L Larsen Giuseppe N Colasurdo | 1999 | J Pediatr1999，，： | 1 |
| 7 | Superoxide Dismutase Evolution and Life Span Regulation显示文摘 | Gary N L John T | 2005 | Mech Ageing Dev2005，126，： | 1 |
| 8 | The definition and classification of Dry Eye Disease:Report of the Definition and classification subcommittee of the international Dry Eye Work shop(2007)显示文摘 | Mechael A L Baudouin C Gary N F | 2007 | Ocular surface2007，5，2： | 1 |
| 9 | Unhairing with proteolytie enzymes derived from StreptoCnyees griseus显示文摘 | Andrew G Gehring Gary L Dimaio William N Marmer | 2002 | JALCA2002，97，： | 1 |
| 10 | Liquid-phase sintering of alumina coated with magnesium aluminosilicate glass显示文摘 | AKIRA N GARY L M | 1998 | J Am Ceram Soc1998，81，5： | 1 |
| 11 | 早期乳腺癌最佳辅助化疗方案与人类表皮生长因子受体2阳性乳腺癌辅助靶向治疗选择:依据 ASCO 对 CCO临床实践指南的改编显示文摘目的研究加拿大安大略癌症治疗中心(CCO)关于早期乳腺癌最佳辅助化疗方案,包括人类表皮生长因子受体2(HER2)阳性乳腺癌辅助靶向治疗方案,并对其进行改编。方法按照美国临床肿瘤协会(ASCO)对其他组织临床实践指南改编的策略和程序,对CCO临床实践指南的严谨性与内容适用性进行回顾。结果基于对CCO临床实践指南内容的回顾,ASCO小组认为,CCO临床实践指南在整体上清晰全面,以最确切的科学证据为基础,为患者提供可接受的治疗选项。推荐关于辅助化疗方案的决定,应考虑到基线复发风险、毒性、利益可能性和宿主因素(如合并症)。对于高风险HER2阴性的身体状况良好的人群,蒽环类和紫杉烷治疗方案是标准治疗方案。4个周期的多西他赛和环磷酰胺治疗方案是可接受的非蒽环类治疗方案。对于高风险HER2阳性患者,推荐蒽环类与紫杉烷序贯疗法联合曲妥单抗或多西他赛、卡铂、曲妥单抗进行6个周期的治疗。对于低风险、非淋巴结转移、HER2阳性人群,推荐每周一次的紫杉醇和曲妥单抗连续进行12个周期的替代治疗。曲妥单抗应持续使用1年。不应采用铂复合盐对三阴性人群进行常规的辅助管理,除非出现有效的生存数据加以支持。 | Neelima Denduluri Mark R Somerfield Andrea Eisen Jamie N Holloway Arti Hurria Tari A King Gary H Lyman Ann H Partridge Melinda L Telli Maureen E Trudeau Antonio C Wolff 本刊编辑部 | 2016 | 中国全科医学2016，19，18： | 1 |
| 12 | Liquid - phase sintering of alumina coated with magnesium aluminosilicated glass 显示文摘 | Akira N Gary L M | 1998 | J AmCeram Soc1998，81，5： | 1 |
| 13 | Individual particle analysis of indoor,outdoor and community samples from the 1998 Baltimore particulate matter study显示文摘 | Teri L C Gary A N Mattew S L | 2001 | Atmospheric Environment2001，35，： | 1 |
| 14 | Individualism, collectivism and delinquency in Asian American adolescents显示文摘 | Thao N L Gary 0 S | 2005 | 1 Clin Child Adolesc Psychol2005，34，4： | 1 |
| 15 | Interactions among dietary minerals, arginine and lysine in rainbow trout (Saimo gairdneri )显示文摘 | Chiu Y N Richard E A Gary L R | 1987 | Fish Physiology and Biochemistry1987，4，： | 1 |
| 16 | Powder metal pastes for brazing and soldering applications 显示文摘 | Anil V N Gary L C Aida V G | 2001 | The International Journal of Powder Metallurgy2001，37，7： | 1 |
| 17 | Experimental investigation of PCCI-DI combustion on emissions in a light-duty diesel engine 显示文摘 | Gary D N Shizuo S Jeffrey A L | 2004 | SAE ransaction2004，113，4： | 1 |
| 18 | Clinical validation studies of Neoral C2 monitoring: a review显示文摘 | Bjom N Edward C Gary L | 2002 | Transplantation2002，73，9： | 1 |
| 19 | Slopping resulting from gas injection in a Peirce-Smith converter:Water modeling显示文摘 | LIOW J L GARY N B | 1990 | Metallurgical and Materials Transactions B1990，21，12： | 1 |
| 20 | Molecular typing of Borrelia burgdorferi from Lyme disease patients by PCR-re striction fragment length polymorphism analysis 显示文摘 | Diongsios L Gary PW John N | 1996 | J Clin Microbiol1996，34，5： | 1 |
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