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| 1 | High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes显示文摘Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening(HTS) data for 3 762 distinct global gene knockout(KO) mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type(WT) cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging,ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass: 23 previously reported genes(Calcr, Cebpb, Crtap, Dcstamp, Dkk1, Duoxa2, Enpp1, Fgf23, Kiss1/Kiss1 r, Kl(Klotho),Lrp5, Mstn, Neo1, Npr2, Ostm1, Postn, Sfrp4, Slc30a5, Slc39a13, Sost, Sumf1, Src, Wnt10b), five novel genes extensively characterized(Cldn18, Fam20 c, Lrrk1, Sgpl1, Wnt16), five novel genes with preliminary characterization(Agpat2, Rassf5, Slc10a7, Slc26a7, Slc30a10) and three novel undisclosed genes coding for potential osteoporosis drug targets. | Robert Brommage Jeff Liu Gwenn M Hansen Laura L Kirkpatrick David G Potter Arthur T Ss Brian Zambrowicz David R Powell Peter Vogel | 2014 | Bone Research2014，2，3： | 7 |
| 2 | Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach: Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)显示文摘 | Inzucchi Silvio E Bergenstal Richard M Buse John B Diamant Michaela Ferrannini Ele Nauck Michael Peters Anne L Tsapas Apostolos Wender Richard Matthews David R | 2012 | EN2012，，3： | 6 |
| 3 | Cryopreservation for delayed circulating tumor cell isolation is a valid strategy for prognostic association of circulating tumor cells in gastroesophageal cancer显示文摘AIM To demonstrate the feasibility of cryopreservation of peripheral blood mononuclear cells(PBMCs) for prognostic circulating tumor cell(CTC) detection in gastroesophageal cancer.METHODS Using 7.5 m L blood samples collected in EDTA tubes from patients with gastroesopheagal adenocarcinoma, CTCs were isolated by epithelial cell adhesion molecule based immunomagnetic capture using the Iso Flux platform. Paired specimens taken during the same blood draw(n = 15) were used to compare number of CTCs isolated from fresh and cryopreserved PBMCs. Blood samples were processed within 24 h to recover the PBMC fraction, with PBMCs used for fresh analysis immediately processed for CTC isolation. Cryopreservation of PBMCs lasted from 2 wk to 25.2 mo(median 14.6 mo). CTCs isolated from pre-treatment cryopreserved PBMCs(n = 43) were examined for associations with clinicopathological variables and survival outcomes.RESULTS While there was a significant trend to a decrease in CTC numbers associated with cryopreserved specimens(mean number of CTCs 34.4 vs 51.5, P = 0.04), this was predominately in samples with a total CTC count of > 50, with low CTC count samples less affected(P = 0.06). There was no significant association between the duration of cryopreservation and number of CTCs. In cryopreserved PBMCs from patient samples prior to treatment, a high CTC count(> 17) was associated with poorer overall survival(OS)(n = 43, HR = 4.4, 95%CI: 1.7-11.7, P = 0.0013). In multivariate analysis, after controlling for sex, age, stage, ECOG performance status, and primary tumor location, a high CTC count remained significantly associated with a poorer OS(HR = 3.7, 95%CI: 1.2-12.4, P = 0.03). CONCLUSION PBMC cryopreservation for delayed CTC isolation is a valid strategy to assist with sample collection, transporting and processing. | Daniel Brungs David Lynch Alison WS Luk Elahe Minaei Marie Ranson Morteza Aghmesheh Kara L Vine Martin Carolan Mouhannad Jaber Paul de Souza Therese M Becker | 2018 | World Journal of Gastroenterology2018，24，7： | 5 |
| 4 | 针对患者利益的机器学习和人工智能研究:在透明性、可重复性、伦理和有效性等方面的20个关键问题显示文摘机器学习(ML)、人工智能(AI)和其他现代统计方法正为利用先前尚未开发且极速增长的数据资源提供新的机会,以期让患者获益。尽管目前正在进行许多有前景的研究,特别是在图像方面,但就文献整体而言还缺乏透明度、对可重复性清晰的阐述、对潜在伦理问题的探究,以及对有效性的明确验证。这些问题的存在有许多原因,其中最重要的一点(为此我们提供了初步解决方案)就是当前缺乏针对ML和AI的最佳实践指南。我们认为从事研究的跨学科团队和应用ML/AI影响健康的项目,将因解决有关透明度、可重复性、伦理和有效性(TREE)的一系列问题而受益。这里提出的20个关键问题为研究团队提供了一个研究设计、实施和报告框架;帮助编辑和同行评审专家评估文献的贡献;让患者、临床医生和政策制定者评估新发现可能会给患者带来的获益。 | Sebastian Vollmer Bilal A Mateen Gergo Bohner Franz J Kirdly Rayid Ghani Pall Jonsson Sarah Cumbers Adrian Jonas Katherine S L McAllister Puja Myles David Granger Mark Birse Richard Branson Karel G M Moons Gary S Collins John P A Chris Holmes Harry Hemingwayp 李峰(译) 徐磊(校) 赵邑(校) | 2020 | 英国医学杂志中文版2020，23，9： | 5 |
| 5 | Antenna-assisted picosecond control of nanoscale phase transition in vanadium dioxide显示文摘Nanoscale devices in which the interaction with light can be configured using external control signals hold great interest for next-generation optoelectronic circuits.Materials exhibiting a structural or electronic phase transition offer a large modulation contrast with multi-level optical switching and memory functionalities.In addition,plasmonic nanoantennas can provide an efficient enhancement mechanism for both the optically induced excitation and the readout of materials strategically positioned in their local environment.Here,we demonstrate picosecond all-optical switching of the local phase transition in plasmonic antenna-vanadium dioxide(VO_(2))hybrids,exploiting strong resonant field enhancement and selective optical pumping in plasmonic hotspots.Polarization-and wavelength-dependent pump–probe spectroscopy of multifrequency crossed antenna arrays shows that nanoscale optical switching in plasmonic hotspots does not affect neighboring antennas placed within 100 nm of the excited antennas.The antenna-assisted pumping mechanism is confirmed by numerical model calculations of the resonant,antenna-mediated local heating on a picosecond time scale.The hybrid,nanoscale excitation mechanism results in 20 times reduced switching energies and 5 times faster recovery times than a VO_(2) film without antennas,enabling fully reversible switching at over two million cycles per second and at local switching energies in the picojoule range.The hybrid solution of antennas and VO_(2) provides a conceptual framework to merge the field localization and phase-transition response,enabling precise,nanoscale optical memory functionalities. | Otto L Muskens Luca Bergamini Yudong Wang Jeffrey M Gaskell Nerea Zabala CH de Groot David W Sheel Javier Aizpurua | 2016 | Light(Science & Applications)2016，5，1： | 5 |
| 6 | Fecal immunochemical test accuracy in average-risk colorectal cancer screening显示文摘AIM:To assess the fecal immunochemical test(FIT)accuracy for colorectal cancer(CRC)and advanced neoplasia(AN)detection in CRC screening.METHODS:We performed a multicentric,prospective,double blind study of diagnostic tests on asymptomatic average-risk individuals submitted to screening colonoscopy.Two stool samples were collected and the fecal hemoglobin concentration was determined in the first sample(FIT1)and the highest level of both samples(FITmax)using the OC-sensor.Areas under the curve(AUC)for CRC and AN were calculated.The best FIT1and FITmax cut-off values for CRC were determined.At this threshold,number needed to scope(NNS)to detect a CRC and an AN and the cost per lesion detected were calculated.RESULTS:About 779 individuals were included.An AN was found in 97(12.5%)individuals:a CRC in 5(0.6%)and an advanced adenoma(≥10 mm,villous histology or high grade dysplasia)in 92(11.9%)subjects.For CRC diagnosis,FIT1 AUC was 0.96(95%CI:0.95-0.98)and FITmax AUC was 0.95(95%CI:0.93-0.97).For AN,FIT1 and FITmax AUC were similar(0.72,95%CI:0.66-0.78 vs 0.73,95%CI:0.68-0.79,respectively,P=0.34).Depending on the number of determinations and the positivity threshold cut-off used sensitivity for AN detection ranged between 28%and 42%and specificity between 91%and 97%.At the best cut-off point for CRC detection(115 ng/mL),the NNS to detect a CRC were 10.2 and 15.8;and the cost per CRC was 1814€and 2985€on FIT1 and FITmax strategies respectively.At this threshold the sensitivity,NNS and cost per AN detected were 30%,1.76,and 306€,in FIT1 strategy,and 36%,2.26€and 426€,in FITmax strategy,respectively.CONCLUSION:Performing two tests does not improve diagnostic accuracy,but increases cost and NNS to detect a lesion. | Vicent Hernandez Joaquin Cubiella M Carmen Gonzalez-Mao Felipe Iglesias Concepción Rivera M Begoa Iglesias Lucía Cid Ines Castro Luisa de Castro Pablo Vega Jose Antonio Hermo Ramiro Macenlle Alfonso Martínez-Turnes David Martínez-Ares Pamela Estevez Estela Cid M Carmen Vidal Angeles López-Martínez Elisabeth Hijona Marta Herreros-Villanueva Luis Bujanda Jose Ignacio Rodriguez-Prada the COLONPREV study investigators | 2014 | World Journal of Gastroenterology2014，20，4： | 4 |
| 7 | MicroRNA-let-7a promotes E2F-mediated cell proliferation and NFKB activation in vitro显示文摘Epigenetic 因素,包括的改变的 microRNA (miRNA ) 表示,可以在全身的豺狼座 erythematosus (SLE ) 贡献异常有免疫力的房间功能。MiRNA-let-7a (let-7a ) 被显示了直接改变房间周期前进和 proinflammatory cytokine 生产。由于在房间分割和发炎的 let-7a 的关键角色,我们调查了 let-7a-mediated 增长和 NFκ在 J774A.1 巨噬细胞和 MES 的 B translocation 在 vitro 的 13 个 mesangial 房间。在有 let-7a 的刺激免疫者的房间 transfected,房间增长显著地随着时间的过去被增加。在 S 和 G 2 阶段的刺激免疫者的房间的数字有重要增加。刺激免疫者的房间 overexpressing let-7a 增加了 NFκ 的原子 translocation; B。Bioinformatical 分析表明 E2F 家庭, G 1-S 转变的批评管理者,在他们的 mRNA 抄本为 let-7a 有潜在的有约束力的地点。Let-7a overexpression 显著地增加了房间周期使活跃之物 E2F2 的表示并且在刺激免疫者的房间增加了 retinoblastoma 蛋白质(Rb ) phosphorylation。房间周期禁止者 E2F5 显著地在刺激免疫者的 let-7a-transfected 房间被减少。Bioinformatical 分析揭示了 E2F2 和 NFκ B 是预言调整 let-7a 倡导者的抄写因素。我们与 E2F2 和 NFκ 用染色质 immunoprecipitation 由即时 RT-PCR 分析了 let-7a 的 transcriptional 规定; B 抗体。E2F2 和 NFκ 有增加;在在刺激免疫者的房间为 let-7a 倡导者充实的 DNA 的 B 绑定。Silencing E2F2 或 NFκ B 显著地减少了在刺激免疫者的房间的 let-7a 表示和 IL-6 生产。一起拿,我们的结果建议 let-7a 的 overexpression 可以在 SLE 贡献增生和 proinflammatory 反应。 | Cristen B Chafin Nicole L Regna David L Caudell Christopher M Reilly | 2014 | Cellular & Molecular Immunology2014，11，1： | 3 |
| 8 | Analysis of a Successful Immune Response against Hepatitis C Virus显示文摘 | Stewart Cooper Ann L Erickson Erin J Adams Joe Kansopon Amy J Weiner David Y Chien Michael Houghton Peter Parham Christopher M Walker | 1999 | Immunity1999，，4： | 3 |
| 9 | Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial显示文摘 | David N Krag Stewart J Anderson Thomas B Julian Ann M Brown Seth P Harlow Joseph P Costantino Takamaru Ashikaga Donald L Weaver Eleftherios P Mamounas Lynne M Jalovec Thomas G Frazier R Dirk Noyes André Robidoux Hugh MC Scarth Norman Wolmark | 2010 | Lancet Oncology2010，，10： | 3 |
| 10 | Outcomes and patients' perspectives of transition from paediatric to adult care in inflammatory bowel disease显示文摘AIM: To describe the disease and psychosocialoutcomes of an inflammatory bowel disease(IBD) transition cohort and their perspectives.METHODS: Patients with IBD, aged > 18 years, who had moved from paediatric to adult care within 10 years were identified through IBD databases at three tertiary hospitals. Participants were surveyed regarding demographic and disease specific data and their perspectives on the transition process. Survey response data were compared to contemporaneously recorded information in paediatric service case notes. Data were compared to a similar age cohort who had never received paediatric IBD care and therefore who had not undergone a transition process. RESULTS: There were 81 returned surveys from 46 transition and 35 non-transition patients. No statistically significant differences were found in disease burden, disease outcomes or adult roles and responsibilities between cohorts. Despite a high prevalence of mood disturbance(35%), there was a very low usage(5%) of psychological services in both cohorts. In the transition cohort, knowledge of their transition plan was reported by only 25/46 patients and the majority(54%) felt they were not strongly prepared. A high rate(78%) of discussion about work/study plans was recorded prior to transition, but a near complete absence of discussion regarding sex(8%), and other adult issues was recorded. Both cohorts agreed that their preferred method of future transition practices(of the options offered) was a shared clinic appointment with all key stakeholders. CONCLUSION: Transition did not appear to adversely affect disease or psychosocial outcomes. Current transition care processes could be optimised, with better psychosocial preparation and agreed transition plans. | Alice L Bennett David Moore Peter A Bampton Robert V Bryant Jane M Andrews | 2016 | World Journal of Gastroenterology2016，22，8： | 3 |
| 11 | Heat shock protein 90 inhibition by 17-DMAG lessens disease in the MRL/Ipr mouse model of systemic lupus erythematosus显示文摘热吃惊蛋白质 90 的提高的表示(HSP90 ) 在全身的豺狼座 erythematosus (SLE ) 的肾和浆液被发现了病人和 MRL/Mp-Fas lpr /Fas lpr (MRL/lpr ) 自体免疫的老鼠。如果 HSP90 的抑制将在 MRL/lpr 老鼠减少疾病,我们调查了。在在 vivo 的 vitro,有在 IL-6 的有免疫力刺激的显示出的减少的表示以前的 HSP90 禁止者 Geldanamycin 的 mesangial 房间的预告的处理, IL-12 和号码,我们发现当与 C57BL/6 相比鼠标和 MRL/lpr 鼠标与 HSP90 禁止者 17-DMAG 对待时, HSP90 表示在 MRL/lpr 肾被提高。与 17-DMAG 对待的 MRL/lpr 老鼠显示出减少的 proteinuria 并且减少了浆液 anti-dsDNA 抗体生产。Glomerulonephritis 和 glomerular IgG 和 C3 没被 17-DMAG 的管理显著地在 MRL/lpr 影响。17-DMAG 增加了 CD8 + T 房间,减少的双 negative T 房间,减少 CD4/CD8 比率和减少的小囊的 B 房间。这些研究建议 HSP90 可以在调整 T 房间区别和激活起一个作用并且 HSP90 抑制可以在豺狼座减少发炎。 | Samuel K Shimp III Cristen B Chafin Nicole L Regna Sarah E Hammond Molly A Read David L Caudell Marissa Nichole Rylander Christopher M Reilly | 2012 | Cellular & Molecular Immunology2012，9，3： | 3 |
| 12 | DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice显示文摘 | Meira Lisiane B Bugni James M Green Stephanie L Lee Chung-Wei Pang Bo Borenshtein Diana Rickman Barry H Rogers Arlin B Moroski-Erkul Catherine A McFaline Jose L Schauer David B Dedon Peter C Fox James G Samson Leona D | 2008 | Journal of Clinical Investigation2008，，7： | 2 |
| 13 | Outcomes after arthroscopic repair of rotator cuff tears in the setting of mild to moderate glenohumeral osteoarthritis显示文摘BACKGROUND Rotator cuff pathology is a very common source of shoulder pain.Similarly,osteoarthritis of the glenohumeral joint can cause shoulder pain and produce similar symptoms.Surgical management can be indicated for both pathologies,however,outcomes data is limited when examining rotator cuff repair(RCR) in the setting of glenohumeral arthritis(GHOA).Thus,this study sought to determine outcomes for patients who undergo RCR in the setting of GHOA.AIM To evaluate if a relationship exists between outcomes of RCR in the setting of GHOA.METHODS This was a retrospective analysis of patients who underwent arthroscopic rotator cuff repair with concurrent glenohumeral osteoarthritis between 2010-2017.Patients were stratified based on rotator cuff tear size and glenohumeral osteoarthritis severity.Cohorts were paired 1:1 with patients without glenohumeral osteoarthritis.Patients included had a minimum two year follow-up.Rate of conversion to total shoulder arthroplasty,complication rates following initial surgery,and patient-reported outcome measures were collected.RESULTS A total of 142 patients were included.The number of patients that required total shoulder arthroplasty within two years after index surgery was low.2/71(2.8%) patients with GHOA,and 1/71(1.4%) without GHOA.Following rotator cuff repair,both groups showed favorable patientreported outcomes.CONCLUSION Patients with glenohumeral osteoarthritis who underwent arthroscopic rotator cuff repair showed comparable outcomes to patients without glenohumeral osteoarthritis. | Ian S Hong Allison J Rao Tyler L CarlLee Joshua D Meade Daniel J Hurwit Gregory Scarola David P Trofa Shadley C Schiffern Nady Hamid Patrick M Connor James E Fleischli Bryan Michael Saltzman | 2022 | World Journal of Orthopedics2022，13，7： | 2 |
| 14 | Evaluation and treatment of internal impingement of the shoulder in overhead athletes显示文摘One of the most common pathologic processes seen in overhead throwing athletes is posterior shoulderpain resulting from internal impingement. 'Internal impingement' is a term used to describe a constellation of symptoms which result from the greater tuberosity of the humerus and the articular surface of the rotator cuff abutting the posterosuperior glenoid when the shoulder is in an abducted and externally rotated position. The pathophysiology in symptomatic internal impingement is multifactorial,involving physiologic shoulder remodeling,posterior capsular contracture,and scapular dyskinesis. Throwers with internal impingement may complain of shoulder stiffness or the need for a prolonged warm-up,decline in performance,or posterior shoulder pain. On physical examination,patients will demonstrate limited internal rotation and posterior shoulder pain with a posterior impingement test. Common imaging findings include the classic 'Bennett lesion' on radiographs,as well as articular-sided partial rotator cuff tears and concomitant SLAP lesions. Mainstays of treatment include intense non-operative management focusing on rest and stretching protocols focusing on the posterior capsule. Operative management is variable depending on the exact pathology,but largely consists of rotator cuff debridement. Outcomes of operative treatment have been mixed,therefore intense non-operative treatment should remain the focus of treatment. | Keith T Corpus Christopher L Camp David M Dines David W Altchek Joshua S Dines | 2016 | World Journal of Orthopedics2016，7，12： | 2 |
| 15 | Age at diagnosis of type 2 diabetes and cardiovascular risk factor profile:A pooled analysis显示文摘BACKGROUND The diagnosis of type 2 diabetes(T2D)in younger adults,an increasingly common public health issue,is associated with a higher risk of cardiovascular complications and mortality,which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger age.AIM To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with T2D.METHODS A pooled dataset was used,comprised of data from five previous studies of adults with T2D,including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 years.Anthropometric and blood biomarker measurements included body weight,body mass index(BMI),waist circumference,body fat percentage,glycaemic control(HbA1c),lipid profile and blood pressure.Univariable and multivariable linear regression models,adjusted for diabetes duration,sex,ethnicity and smoking status,were used to investigate the association between age at diagnosis and each cardiovascular risk factor.RESULTS A higher proportion of participants diagnosed with T2D under the age of 40 were female,current smokers and treated with glucose-lowering medications,compared to participants diagnosed later in life.Participants diagnosed with T2D under the age of 40 also had higher body weight,BMI,waist circumference and body fat percentage,in addition to a more adverse lipid profile,compared to participants diagnosed at an older age.Modelling results showed that each one year reduction in age at diagnosis was significantly associated with 0.67 kg higher body weight[95%confidence interval(CI):0.52-0.82 kg],0.18 kg/m^(2) higher BMI(95%CI:0.10-0.25)and 0.32 cm higher waist circumference(95%CI:0.14-0.49),after adjustment for duration of diabetes and other confounders.Younger age at diagnosis was also significantly associated with higher HbA1c,total cholesterol,low-density lipoprotein cholesterol and triglycerides.CONCLUSION The diagnosis of T2D earlier in life is associated with a worse cardiovascular risk factor profile,compared to those diagnosed later in life. | Mary M Barker Francesco Zaccardi Emer M Brady Gaurav S Gulsin Andrew P Hall Joseph Henson Zin ZinHtike Kamlesh Khunti Gerald P McCann Emma L Redman David R Webb Emma G Wilmot Tom Yates Jian Yeo Melanie J Davies Jack A Sargeant | 2022 | World Journal of Diabetes2022，13，3： | 2 |
| 16 | Where is the global in global mental health?A call for inclusive multicultural collaboration显示文摘To the editor:Common mental health disorders,like depression and anxiety,account for 45%of the global disease burden on youths aged 15-29.1 This challenge is particularly significant in low and middle-income countries(LMICs)where risk factors such as poverty,limited treatment options and stigma restrict access to care and exacerbate the burden and magnify the impact of mental disorders.23 Given these barriers,there is an urgent need for research dedicated to expanding mental healthcare for young people in LMICs. | Tom L Osborn Akash R Wasil John R Weisz Arthur Kleinman David M Ndetei | 2020 | General Psychiatry2020，33，6： | 2 |
| 17 | Increasing diabetes self-management education in community settings显示文摘 | Susan L Norris Phyllis J Nichols Carl J Caspersen Russell E Glasgow Michael M Engelgau Leonard Jack Susan R Snyder Vilma G Carande-Kulis George Isham Sanford Garfield Peter Briss David McCulloch | 2002 | American Journal of Preventive Medicine2002，，4： | 2 |
| 18 | Experimental Investigation of the Creep Behavior of Garnet at High Temperatures and Pressures显示文摘To provide constraints on the rheological properties of garnet, we have experimentally investigated the creep behavior of garnet at high pressures and temperatures using a deformation-DIA. Samples were cold-pressed from a garnet powder and deformed at constant displacement rates ranging from 1.1×10-5 to 2.6×10-5 s-1 at high temperatures (1 273–1 473 K) and high pressures (2.4–4.1 GPa). Differential stress and pressure were measured using X-ray diffraction techniques based on the elastic strain of various lattice planes as a function of orientation with respect to the applied stress field. The plastic strain of a deforming sample was monitored in-situ through a series of radiographs. Our results provide a measure of the dependence of creep rate of garnet on the temperature with an activation en-ergy of ~280 kJ/mol and on pressure with an activation volume of ~10×10-6 m3/mol. The flow behavior of garnet quantified by this study provides the basis for modeling geodynamic processes occurring within subducted lithosphere. | Shenghua Mei Ayako M Suzuki David L Kohlstedt 许丽丽 | 2010 | Journal of Earth Science2010，21，5： | 2 |
| 19 | Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial显示文摘 | David N Krag Stewart J Anderson Thomas B Julian Ann M Brown Seth P Harlow Takamaru Ashikaga Donald L Weaver Barbara J Miller Lynne M Jalovec Thomas G Frazier R Dirk Noyes André Robidoux Hugh MC Scarth Denise M Mammolito David R McCready Eleftherios P Mamo | 2007 | Lancet Oncology2007，，10： | 2 |
| 20 | Hepatocytes isolated from neoplastic liver-immunomagnetic purging as a new source for transplantation显示文摘AIM: To investigate whether hepatocytes isolated from macroscopically normal liver during hepatic resection for neoplasia could provide a novel source of healthy hepatocytes, including the development of reliable protocols for malignant cells removal from the hepatocyte preparation. METHODS: Hepatocytes were procured from resected liver of 18 patients with liver tumors using optimised digestion and cell-enrichment protocols. Suspensions of various known quantities of the HT-29 tumor cell line and patient hepatocytes were treated or not with Ep-CAM-antibody-coated immunomagnetic beads in order to investigate the effi cacy of tumor-purging by immunomagnetic depletion, using a semi-quantitative RT-PCR method developed to detect tumor cells. Immunomagnetic bead-treated or bead-untreated tumor cell-hepatocyte suspensions were transplanted intra-peritoneally in Balb/C nude mice to assess the rates of tumor development. RESULTS: Mean viable hepatocyte yield was 9.3 x 106 cells per gram of digested liver with mean viability of 70.5%. Immunomagnetic depletion removed tumor cells to below the RT-PCR detection-threshold of 1 tumor cell in 106 hepatocytes, representing a maximum tumor purging efficacy of greater than 400 000-fold. Transplanted, immunomagnetic bead-purged tumor cell-hepatocyte suspensions did not form peritonealtumors in Balb/C nude mice. Co-transplantation of hepatocytes with tumor cells did not increase tumorigenesis of the tumor cells. CONCLUSION: Immunomagnetic depletion appears to be an effective method of purging contaminating tumor cells to below threshold for likely tumorigenesis. Along with improved techniques for isolation of large numbers of viable hepatocytes, normal liver resected for neoplasia has potential as another clinically useful source of hepatocytes | Aravin Gunasegaram Javed Akhter Peng Yao Loreena A Johnson Stephen M Riodan David L Morris | 2008 | World Journal of Gastroenterology2008，14，32： | 2 |
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