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| 1 | Rho/Rock signal transduction pathway is required for MSC tenogenic differentiation显示文摘Mesenchymal stem cell(MSC)-based treatments have shown promise for improving tendon healing and repair.MSCs have the potential to differentiate into multiple lineages in response to select chemical and physical stimuli, including into tenocytes. Cell elongation and cytoskeletal tension have been shown to be instrumental to the process of MSC differentiation. Previous studies have shown that inhibition of stress fiber formation leads MSCs to default toward an adipogenic lineage, which suggests that stress fibers are required for MSCs to sense the environmental factors that can induce differentiation into tenocytes. As the Rho/ROCK signal transduction pathway plays a critical role in both stress fiber formation and in cell sensation, we examined whether the activation of this pathway was required when inducing MSC tendon differentiation using rope-like silk scaffolds. To accomplish this, we employed a loss-of-function approach by knocking out ROCK,actin and myosin(two other components of the pathway) using the specific inhibitors Y-27632, Latrunculin A and blebbistatin, respectively. We demonstrated that independently disrupting the cytoskeleton and the Rho/ROCK pathway abolished the expression of tendon differentiation markers and led to a loss of spindle morphology. Together, these studies suggest that the tension that is generated by MSC elongation is essential for MSC teno-differentiation and that the Rho/ROCK pathway is a critical mediator of tendon differentiation on rope-like silk scaffolds. | Edward Maharam Miguel Yaport Nathaniel L Villanueva Takintope Akinyibi Damien Laudier Zhiyong He Daniel J Leong Hui B Sun | 2015 | Bone Research2015，3，3： | 4 |
| 2 | Appropriateness of systemic treatments in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors显示文摘AIM:To evaluate systemic treatment choices in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors(PNETs)and provide consensus treatment recommendations.METHODS:Systemic treatment options for pancreatic neuroendocrine tumors have expanded in recent years to include somatostatin analogs,angiogenesis inhibitors,inhibitors of mammalian target of rapamycinand cytotoxic agents.At this time,there is little data to guide treatment selection and sequence.We therefore assembled a panel of expert physicians to evaluate systemic treatment choices and provide consensus treatment recommendations.Treatment appropriateness ratings were collected using the RAND/UCLA modified Delphi process.After studying the literature,a multidisciplinary panel of 10 physicians assessed the appropriateness of various medical treatment scenarios on a 1-9 scale.Ratings were done both before and after an extended discussion of the evidence.Quantitative measurements of agreement were made and consensus statements developed from the second round ratings.RESULTS:Specialties represented were medical and surgical oncology,interventional radiology,and gastroenterology.Panelists had practiced for a mean of15.5 years(range:6-33).Among 202 rated scenarios,disagreement decreased from 13.2%(26 scenarios)before the face-to-face discussion of evidence to 1%(2)after.In the final ratings,46.5%(94 scenarios)were rated inappropriate,21.8%(44)were uncertain,and30.7%(62)were appropriate.Consensus statements from the scenarios included:(1)it is appropriate to use somatostatin analogs as first line therapy in patients with hormonally functional tumors and may be appropriate in patients who are asymptomatic;(2)it is appropriate to use everolimus,sunitinib,or cytotoxic chemotherapy therapy as first line therapy in patients with symptomatic or progressive tumors;and(3)beyond first line,these same agents can be used.In patients with uncontrolled secretory symptoms,octreotide LAR doses can be titrated up to 60 mg every4 wk or up to 40 mg every 3 or 4 wk.CONCLUSION:Using the Delphi process allowed physician experts to systematically obtain a consensus on the appropriateness of a variety of medical therapies in patients with PNETs. | Jonathan R Strosberg George A Fisher Al B Benson Lowell B Anthony Bulent Arslan John F Gibbs Edward Greeno Renuka V Iyer Michelle K Kim William J Maples Philip A Philip Edward M Wolin Dasha Cherepanov Michael S Broder | 2015 | World Journal of Gastroenterology2015，21，8： | 2 |
| 3 | Metabolic response of sheep skin to a chronic infusion of a variant of insulin-like growth factor Ⅰ显示文摘 | Hocking Edwards J E Khalaf S K Sinclaire B R | 1995 | Biochem J1995，308，2： | 1 |
| 4 | An iterative growing and pruning algorithm for classification tree design显示文摘 | Saul B Gelfand C S Ravishankar Edward J Delp | 1991 | IEEE Transaction on Pattern Analysis and Machine Intelligence1991，13，2： | 1 |
| 5 | The allocation of risk in PPP/PFI construction projects in the UK 显示文摘 | LI B AKINTOVE A EDWARDS P J | 2005 | International Journal of Project Management2005，，23： | 1 |
| 6 | Minimizing communication costs in hierarchically-clustered networks of wireless sensors显示文摘 | Edward J C | 2004 | Computer Networks2004，44，1： | 1 |
| 7 | Use of FlowCAM for semi automated recognition and enumeration of red tide cells (Karenia brevis) in natural plankton samples显示文摘 | EDWARD J B CAMMIE J H | 2006 | Harmful Algae2006，5，： | 1 |
| 8 | Weather-related road accidents in England and Wales: A spatial analysis 显示文摘 | Edwards J B | 1996 | Journal of Transport Geography1996，4，3： | 1 |
| 9 | Determining the fluxes of Tl^+ and K^+ at the root surface of wheat and canola using Tl( I ) and K ion-selective microelectrodes显示文摘 | JAMES G H MICHAEL J O EDWARD B | 2010 | Plant Soil2010，335，1： | 1 |
| 10 | Development and verification of a one-dimensional ablation code including pyrolysis gas flow 显示文摘 | Amar A J Blackwell B F Edwards J R | 2009 | Journal of Thermophysics and Heat Transfer2009，23，1： | 1 |
| 11 | Development of a laser Raman spectrometer for deep-ocean science显示文摘 | Peter G Brewer George Malby Jill D Pasteris Sheri N White Edward T Peltzer B Wopenka J Freeman Mark O Brown | 2004 | Deep-Sea Research Part I2004，，5： | 1 |
| 12 | In silicon predictions of Escherichia coli metabolic capabilities are consistent with experimental data显示文摘 | Edwards J S Ibarra R U Palsson B O | 2001 | Nat Biotechnol2001，19，： | 1 |
| 13 | Consumption of watermelon juice increases plasma concentrations of lycopene and beta- carotene in humans显示文摘 | EDWARDS A J VINYARD B T WILEY E R | 2003 | The Journal of Nutrition2003，133，4： | 1 |
| 14 | Control of a desert-grassland transition by a keystone rodent guild显示文摘 | James H B Edward J H | 1990 | Science1990，250，： | 1 |
| 15 | Correlation between sensitivity and approximated heats of detonation of several nitroamines using quantum mechanical methods显示文摘 | Edwards J Eybl C Johnson B | 2004 | Inter J quantum Chem2004，100，： | 1 |
| 16 | Effi- cacy of pyropheophorbide-α-hexyl ether for photody- namic therapy of rat 9L gliosareoma显示文摘 | AUTRY S A EDWARDS B F BOGGAN J E | 1993 | Optical Methods for Tumor Treatment and Detection1993，，： | 1 |
| 17 | Membrane ther- mostability and heat tolerance of spring wheat 显示文摘 | Shanahan J F Edwards I B Quick J S | 1990 | Crop Sci- ence1990，30，2： | 1 |
| 18 | OMEGA EP high-energy petawatt laser: progress and prospects显示文摘 | D N Maywar J H Kelly L J Waxer S F B Morse I A Begishev J Bromage C Dorrer J L Edwards L Folnsbee M J Guardalben S D Jacobs R Jungquist T J Kessler R W Kidder B E Kruschwitz S J Loucks J R Marciante R L McCrory D D Meyerhofer A V Okishev J B Oliver G Pien | 2008 | Journal of Physics: Conference Series2008，，3： | 1 |
| 19 | Effects of music tempo upon submaximal cycling performance 显示文摘 | Waterhouse J Hudson P Edwards B | 2010 | Scand J Med Sci Sports2010，20，4： | 1 |
| 20 | Structure and biosynthesis of the jamaicamides,new mixed polyketidepeptide neurotoxins from the marine cyanobacterium Lyngbya majuscula显示文摘 | Edwards D J Marquez B L Nogle L M | | 0，，06： | 1 |
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