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| 1 | Metformin does not improve survival in patients with hepatocellular carcinoma显示文摘AIM:To assess whether metformin,which has a chemopreventive effect in chronic liver disease,has any chemotherapeutic effect in hepatocellular carcinoma.METHODS:This was a retrospective study of 701 patients with newly diagnosed hepatocellular carcinoma(HCC)seen between January 2005 and June 2011 at Mayo Clinic,Rochester,Minnesota.This patient cohort was a part of the global HCC BRIDGE study,which is a large longitudinal study of HCC determining the realworld experience of HCC characteristics,management and patient outcomes.We defined significant metformin exposure as continuation of this agent at least 90d beyond diagnosis of HCC,and compared survival of diabetic patients on metformin to diabetic patients not on metformin and non-diabetics.RESULTS:Our cohort was 72.9%male,with a mean±SD age of 62.6±12.3 years.The most common etiologies of liver disease were hepatitis C(34%),alcoholic liver disease(29%),fatty liver disease(15%)and hepatitis B(9%).By univariate analysis,using diabetics not on metformin as the reference group,diabetic patients with HCC on metformin had no survival advantage,with a HR(95%CI)of 1.0(0.8-1.3).Non-diabetic HCC patients also did not appear to have a survival advantage as compared to diabetic HCC patients not on metformin,as demonstrated by a HR(95%CI)of1.1(0.7-1.7).Diabetics on metformin beyond 90 d after HCC diagnosis had a longer median survival at 34.2 mo,as compared to 25.5 mo among diabetic patients who were not on metformin or had discontinued metformin within 90 d after HCC diagnosis.This finding was likely due to potential survival bias among those who lived long enough to receive metformin.CONCLUSION:Although the literature suggests a chemotherapeutic effect in other malignancies,our study demonstrates no survival benefit to the use of metformin in diabetic patients with HCC. | Mamatha Bhat Roongruedee Chaiteerakij William S Harmsen Cathy D Schleck Ju Dong Yang Nasra H Giama Terry M Therneau Gregory J Gores Lewis R Roberts | 2014 | World Journal of Gastroenterology2014，20，42： | 11 |
| 2 | Three-dimensional perfused human in vitro model of nonalcoholic fatty liver disease显示文摘AIM To develop a human in vitro model of non-alcoholic fatty liver disease(NAFLD), utilising primary hepatocytes cultured in a three-dimensional(3D) perfused platform. METHODS Fat and lean culture media were developed to directly investigate the effects of fat loading on primary hepatocytes cultured in a 3D perfused culture system. Oil Red O staining was used to measure fat loading in the hepatocytes and the consumption of free fatty acids(FFA) from culture medium was monitored. Hepatic functions, gene expression profiles and adipokine release were compared for cells cultured in fat and lean conditions. To determine if fat loading in the system could be modulated hepatocytes were treated with known anti-steatotic compounds. RESULTS Hepatocytes cultured in fat medium were found to accumulate three times more fat than lean cells and fat uptake was continuous over a 14-d culture. Fat loading of hepatocytes did not cause any hepatotoxicity and significantly increased albumin production. Numerous adipokines were expressed by fatty cells and genes associated with NAFLD and liver disease were upregulated including: Insulin-like growth factorbinding protein 1, fatty acid-binding protein 3 and CYP7A1. The metabolic activity of hepatocytes cultured in fatty conditions was found to be impaired and the activities of CYP3A4 and CYP2C9 were significantlyreduced, similar to observations made in NAFLD patients. The utility of the model for drug screening was demonstrated by measuring the effects of known antisteatotic compounds. Hepatocytes, cultured under fatty conditions and treated with metformin, had a reduced cellular fat content compared to untreated controls and consumed less FFA from cell culture medium.CONCLUSION The 3D in vitro NAFLD model recapitulates many features of clinical NAFLD and is an ideal tool for analysing the efficacy of anti-steatotic compounds. | Tomasz Kostrzewski Terri Cornforth Sophie A Snow Larissa Ouro-Gnao Cliff Rowe Emma M Large David J Hughes | 2017 | World Journal of Gastroenterology2017，23，2： | 6 |
| 3 | Model combining pre-transplant tumor biomarkers and tumor size shows more utility in predicting hepatocellular carcinoma recurrence and survival than the BALAD models显示文摘AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein(AFP), Lens culinaris agglutinin-reactive AFP(AFP-L3), and des-gammacarboxyprothrombin(DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios(HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42(1.18-5.00), 1.86(0.98-3.52), and 2.83(1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48(1.15-1.91) and 1.59(1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45(1.06-1.98) and 1.38(1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65,0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant(S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter(S-LAD). | Nicha Wongjarupong Gabriela M Negron-Ocasio Roongruedee Chaiteerakij Benyam D Addissie Essa A Mohamed Kristin C Mara William S Harmsen J Paul Theobald Brian E Peters Joseph G Balsanek Melissa M Ward Nasra H Giama Sudhakar K Venkatesh Denise M Harnois Michael R Charlton Hiroyuki Yamada Alicia Algeciras-Schimnich Melissa R Snyder Terry M Therneau Lewis R Roberts | 2018 | World Journal of Gastroenterology2018，24，12： | 5 |
| 4 | Dysfunctional stem and progenitor cells impair fracture healing with age显示文摘Successful fracture healing requires the simultaneous regeneration of both the bone and vasculature;mesenchymal stem cells (MSCs) are directed to replace the bone tissue, while endothelial progenitor cells (EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with age are complex and multidimensional, reduced expression of growth factors, accumulation of oxidative damage from reactive oxygen species, and altered signaling of the Sirtuin-1 pathway are contributing factors to aging at the cellular level of both MSCs and EPCs. Because of these geriatric-specific issues, effective treatment for fracture repair may require new therapeutic techniques to restore cellular function. Some suggested directions for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics. Advanced age is the primary risk factor for a fracture, due to the low bone mass and inferior bone quality associated with aging;a better understanding of the dysfunctional behavior of the aging cell will provide a foundation for new treatments to decrease healing time and reduce the development of complications during the extended recovery from fracture healing in the elderly. | Diane R Wagner Sonali Karnik Zachary J Gunderson Jeffery J Nielsen Alanna Fennimore Hunter J Promer Jonathan W Lowery M Terry Loghmani Philip S Low Todd O McKinley Melissa A Kacena Matthias Clauss Jiliang Li | 2019 | World Journal of Stem Cells2019，11，6： | 3 |
| 5 | A two-stage technique for the digestion of forage crops显示文摘 | Tilley J M A Terry R A | 1963 | Br Grassl Soc1963，18，： | 1 |
| 6 | Aerodynamic interactions during laser cutting 显示文摘 | FIERET J TERRY M J WARD B A | 1986 | Proc SPIE1986，668，： | 1 |
| 7 | Diabetes and outcomes after radical prostatectomy:are results affected by obesity and race?Results from the shared equal-access regional cancer hospital database显示文摘 | Jayachandran J Aronson W Terris M | 2010 | Cancer Epidemiol Biomarkers Prev2010，1，19： | 1 |
| 8 | Random systematic versus directed ultrasound guided transrectal core biopsies of the prostate显示文摘 | Hodge K K McNeal J E Terris M K | 1989 | J Urol1989，142，1： | 1 |
| 9 | X ray spectra estimation using attenuation measurements from 25 kVp to 18 MV显示文摘 | Waggener R G Blough M B Terry J A | 1999 | Med Phys1999，26，12： | 1 |
| 10 | Changes of fermentation pathways of fecal microbial communities associated with d drug treatment that increases diatary starch in the human colon显示文摘 | MEYER J W TERRY L M YERRY S | 1999 | Appl Environ Microbiol1999，65，7： | 1 |
| 11 | Deep lamellar endothelial keratoplasty in the first United States patients: early clinical results显示文摘 | TERRY M A OUSLEY P J | 2001 | Cornea2001，20，3： | 1 |
| 12 | A two-stage technique for in vitro digestion for crops显示文摘 | Tilley J M A Terry R A | 1963 | Briish Grassland Society1963，18，： | 1 |
| 13 | Functional indices {or sciatic, peroneal, and posterior tibial nerve lesions in the mouse 显示文摘 | Inserra M M Bloch D A Terris D J | 1998 | Microsurgery1998，18，2： | 1 |
| 14 | Social identity and self-categoriza- tion processes in organizational contex-ts 显示文摘 | Hogg M A Terry D J | 2000 | Academy of Management Review2000，25，： | 1 |
| 15 | A Two-stage technique for the in vitro digestion of forage crop显示文摘 | Tilley J M A Terry R A | 1963 | J Brit Grassland Soc1963，18，： | 1 |
| 16 | A two stage technique for the in vitro digestion of forage crops显示文摘 | Tilly J M A Terry R A | 1963 | Journal of the British Grassland Society1963，18，： | 1 |
| 17 | Bioconversion of cellulose to acetate with pure cultures of ruminococcus albus and a hydrogen-using acetogen 显示文摘 | TERRY L M MEYER J W | 1995 | Applied And Environmental Microbiology1995，11，： | 1 |
| 18 | Feedback inhibition of chlorophyll synthesis in the phytochrome chromophore-deficient aurea and yellow-green-2 mutants of tomato显示文摘 | Terry M J Kendrick R E | 1999 | Plant Physiology1999，119，1： | 1 |
| 19 | Feedback inhibition of chlorophyll synthesis in the phytochrome chromophore-deficient aurea and yellow- green-2 mutants of tomato显示文摘 | Terry M J Kendrick R E | 1999 | Plant Physiology1999，119，1： | 1 |
| 20 | Social identity and self-categorization processes in organizational contexts显示文摘 | Hogg M A and Terry D J | 2000 | Academy of Management Review2000，25，1： | 1 |
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