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Robert Langer

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https://www.readbyqxmd.com/read/28228258/clonal-expansion-of-lgr5-positive-cells-from-mammalian-cochlea-and-high-purity-generation-of-sensory-hair-cells
#1
Will J McLean, Xiaolei Yin, Lin Lu, Danielle R Lenz, Dalton McLean, Robert Langer, Jeffrey M Karp, Albert S B Edge
Death of cochlear hair cells, which do not regenerate, is a cause of hearing loss in a high percentage of the population. Currently, no approach exists to obtain large numbers of cochlear hair cells. Here, using a small-molecule approach, we show significant expansion (>2,000-fold) of cochlear supporting cells expressing and maintaining Lgr5, an epithelial stem cell marker, in response to stimulation of Wnt signaling by a GSK3β inhibitor and transcriptional activation by a histone deacetylase inhibitor...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28167778/barcoded-nanoparticles-for-high-throughput-in-vivo-discovery-of-targeted-therapeutics
#2
James E Dahlman, Kevin J Kauffman, Yiping Xing, Taylor E Shaw, Faryal F Mir, Chloe C Dlott, Robert Langer, Daniel G Anderson, Eric T Wang
Nucleic acid therapeutics are limited by inefficient delivery to target tissues and cells and by an incomplete understanding of how nanoparticle structure affects biodistribution to off-target organs. Although thousands of nanoparticle formulations have been designed to deliver nucleic acids, most nanoparticles have been tested in cell culture contexts that do not recapitulate systemic in vivo delivery. To increase the number of nanoparticles that could be tested in vivo, we developed a method to simultaneously measure the biodistribution of many chemically distinct nanoparticles...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28167393/biodegradable-scaffolds-promote-tissue-remodeling-and-functional-improvement-in-non-human-primates-with-acute-spinal-cord-injury
#3
Jonathan R Slotkin, Christopher D Pritchard, Brian Luque, Janice Ye, Richard T Layer, Mathew S Lawrence, Timothy M O'Shea, Roland R Roy, Hui Zhong, Isabel Vollenweider, V Reggie Edgerton, Grégoire Courtine, Eric J Woodard, Robert Langer
Tissue loss significantly reduces the potential for functional recovery after spinal cord injury. We previously showed that implantation of porous scaffolds composed of a biodegradable and biocompatible block copolymer of Poly-lactic-co-glycolic acid and Poly-l-lysine improves functional recovery and reduces spinal cord tissue injury after spinal cord hemisection injury in rats. Here, we evaluated the safety and efficacy of porous scaffolds in non-human Old-World primates (Chlorocebus sabaeus) after a partial and complete lateral hemisection of the thoracic spinal cord...
January 25, 2017: Biomaterials
https://www.readbyqxmd.com/read/28154902/guidelines-for-the-diagnosis-and-management-of-hirschsprung-associated-enterocolitis
#4
REVIEW
Ankush Gosain, Philip K Frykman, Robert A Cowles, John Horton, Marc Levitt, David H Rothstein, Jacob C Langer, Allan M Goldstein
BACKGROUND: Patients with Hirschsprung disease are at risk for Hirschsprung-associated enterocolitis (HAEC), an inflammatory disorder of the bowel that represents the leading cause of serious morbidity and death in these patients. The diagnosis of HAEC is made based on clinical signs and symptoms which are often non-specific, making it difficult to establish a definitive diagnosis in many patients. The purpose of this guideline is to present a rational, expert-based approach to the diagnosis and management of HAEC...
February 2, 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/28152774/quality-of-life-qol-in-patients-pts-with-squamous-scc-nsclc-treated-with-nab-paclitaxel-with-carboplatin-nab-p-c-induction-therapy-interim-analysis-of-the-phase-iii-abound-sqm-study
#5
Corey J Langer, Robert M Jotte, Edward S Kim, Amy Ko, Teng Jin Ong, Mark A Socinski, Peter Staib, Nataliya Trunova, David R Spigel
: 64 Background: Recent data on QoL in pts with advanced NSCLC treated with platinum-doublets are limited. This interim analysis evaluated QoL in pts with SCC NSCLC treated with nab-P/C during the induction part of the ABOUND.sqm study. METHODS: In the ongoing phase III ABOUND.sqm study, pts with advanced SCC NSCLC are treated with first-line nab-P 100 mg/m(2) d 1, 8, 15 and C AUC 6 mg•min/mL d 1 (21-d cycles) for 4 cycles (induction). Pts not progressing after 4 cycles are randomized 2:1 to maintenance nab-P 100 mg/m(2)d 1 and 8 of each 21-d cycle + best supportive care (BSC) or BSC alone until progression...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28107282/early-posthepatoportoenterostomy-predictors-of-native-liver-survival-in-biliary-atresia
#6
Scott Nightingale, Michael O Stormon, Edward V O'Loughlin, Albert Shun, Gordon Thomas, Eric I Benchimol, Andrew S Day, Susan Adams, Edward Shi, Chee Y Ooi, Binita M Kamath, Annie Fecteau, Jacob C Langer, Eve A Roberts, Simon C Ling, Vicky L Ng
OBJECTIVES: Most infants with biliary atresia (BA) require liver transplantation (LT) after hepatoportoenterostomy (HPE), including those who initially clear jaundice. The aim of the present study was to identify clinical and routine laboratory factors in infants with BA post-HPE that predict native liver survival at 2 years. METHODS: A retrospective cohort study was conducted in 217 patients with BA undergoing HPE in Sydney, Australia and Toronto, Canada between January 1986 and July 2009...
February 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28088460/ultrasound-mediated-delivery-of-rna-to-colonic-mucosa-of-live-mice
#7
Carl M Schoellhammer, Gregory Y Lauwers, Jeremy A Goettel, Matthias A Oberli, Cody Cleveland, June Y Park, Daniel Minahan, Yiyun Chen, Daniel G Anderson, Ana Jaklenec, Scott B Snapper, Robert Langer, Giovanni Traverso
BACKGROUND & AIMS: It is a challenge to deliver nucleic acids to gastrointestinal (GI) tissues due to their size and need for intracellular delivery. They are also extremely susceptible to degradation by nucleases, which are ubiquitous in the GI tract. We investigated whether ultrasound, which can permeabilize tissue through a phenomenon known as transient cavitation, can be used to deliver RNA to the colonic mucosa of living mice. METHODS: We investigated delivery of fluorescently labeled permeants to colon tissues of Yorkshire pigs ex vivo and mice in vivo...
January 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28057890/in-vitro-3d-model-and-mirna-drug-delivery-to-target-calcific-aortic-valve-disease
#8
REVIEW
Casper F T van der Ven, Pin-Jou Wu, Mark W Tibbitt, Alain van Mil, Joost P G Sluijter, Robert Langer, Elena Aikawa
Calcific aortic valve disease (CAVD) is the most prevalent valvular heart disease in the Western population, claiming 17000 deaths per year in the United States and affecting 25% of people older than 65 years of age. Contrary to traditional belief, CAVD is not a passive, degenerative disease but rather a dynamic disease, where initial cellular changes in the valve leaflets progress into fibrotic lesions that induce valve thickening and calcification. Advanced thickening and calcification impair valve function and lead to aortic stenosis (AS)...
February 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28024083/direct-evidence-for-cancer-cell-autonomous-extracellular-protein-catabolism-in-pancreatic-tumors
#9
Shawn M Davidson, Oliver Jonas, Mark A Keibler, Han Wei Hou, Alba Luengo, Jared R Mayers, Jeffrey Wyckoff, Amanda M Del Rosario, Matthew Whitman, Christopher R Chin, Kendall J Condon, Alex Lammers, Katherine A Kellersberger, Brian K Stall, Gregory Stephanopoulos, Dafna Bar-Sagi, Jongyoon Han, Joshua D Rabinowitz, Michael J Cima, Robert Langer, Matthew G Vander Heiden
Mammalian tissues rely on a variety of nutrients to support their physiological functions. It is known that altered metabolism is involved in the pathogenesis of cancer, but which nutrients support the inappropriate growth of intact malignant tumors is incompletely understood. Amino acids are essential nutrients for many cancer cells that can be obtained through the scavenging and catabolism of extracellular protein via macropinocytosis. In particular, macropinocytosis can be a nutrient source for pancreatic cancer cells, but it is not fully understood how the tumor environment influences metabolic phenotypes and whether macropinocytosis supports the maintenance of amino acid levels within pancreatic tumors...
February 2017: Nature Medicine
https://www.readbyqxmd.com/read/27976536/a-facile-and-versatile-method-to-endow-biomaterial-devices-with-zwitterionic-surface-coatings
#10
Volkan Yesilyurt, Omid Veiseh, Joshua C Doloff, Jie Li, Suman Bose, Xi Xie, Andrew R Bader, Michael Chen, Matthew J Webber, Arturo J Vegas, Robert Langer, Daniel G Anderson
The surface modification of implantable biomaterials with zwitterionic phosphorylcholine polymer is demonstrated through mussel-mimetic catecholamine polymer thin films. Using this method, the surfaces of alginate hydrogel microspheres and polystyrene microbeads, a model material known to produce robust foreign body responses and fibrosis, are successfully modified to reduce the tissue reaction by reducing the fibrosis in immunocompetent C57BL/6J mice.
February 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/27942257/multi-material-tissue-engineering-scaffold-with-hierarchical-pore-architecture
#11
Kathy Ye Morgan, Demetra Sklaviadis, Zachary L Tochka, Kristin M Fischer, Keith Hearon, Thomas D Morgan, Robert Langer, Lisa E Freed
Multi-material polymer scaffolds with multiscale pore architectures were characterized and tested with vascular and heart cells as part of a platform for replacing damaged heart muscle. Vascular and muscle scaffolds were constructed from a new material, poly(limonene thioether) (PLT32i), which met the design criteria of slow biodegradability, elastomeric mechanical properties, and facile processing. The vascular-parenchymal interface was a poly(glycerol sebacate) (PGS) porous membrane that met different criteria of rapid biodegradability, high oxygen permeance, and high porosity...
August 23, 2016: Advanced Functional Materials
https://www.readbyqxmd.com/read/27938692/special-issue-polylactide-pla-based-biopolymers
#12
EDITORIAL
Robert Langer, Arijit Basu, Abraham J Domb
No abstract text is available yet for this article.
December 15, 2016: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/27923550/treatment-design-and-rationale-for-a-randomized-trial-of-cisplatin-and-etoposide-plus-thoracic-radiotherapy-followed-by-nivolumab-or-placebo-for-locally-advanced-non-small-cell-lung-cancer-rtog-3505
#13
David E Gerber, James J Urbanic, Corey Langer, Chen Hu, I-Fen Chang, Bo Lu, Benjamin Movsas, Robert Jeraj, Walter J Curran, Jeffrey D Bradley
Radiation Therapy Oncology Group (RTOG) 3505 is a randomized phase 3 study of concurrent chemoradiation followed by immune checkpoint inhibitor therapy or placebo in patients with locally advanced non-small-cell lung cancer (NSCLC). Patients with surgically unresectable stage 3 NSCLC will receive thoracic radiotherapy to 60 Gy with concurrent cisplatin 50 mg/m(2) intravenously (I.V.) on days 1, 8, 29, and 36, and etoposide 50 mg/m(2) I.V. on days 1 to 5 and days 29 to 33. Between 4 and 12 weeks after completion of concurrent chemoradiation, eligible patients will be randomized to the anti-programmed death 1 (PD-1) monoclonal antibody nivolumab 240 mg I...
October 26, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27911849/scalable-manufacturing-of-biomimetic-moldable-hydrogels-for-industrial-applications
#14
Anthony C Yu, Haoxuan Chen, Doreen Chan, Gillie Agmon, Lyndsay M Stapleton, Alex M Sevit, Mark W Tibbitt, Jesse D Acosta, Tony Zhang, Paul W Franzia, Robert Langer, Eric A Appel
Hydrogels are a class of soft material that is exploited in many, often completely disparate, industrial applications, on account of their unique and tunable properties. Advances in soft material design are yielding next-generation moldable hydrogels that address engineering criteria in several industrial settings such as complex viscosity modifiers, hydraulic or injection fluids, and sprayable carriers. Industrial implementation of these viscoelastic materials requires extreme volumes of material, upwards of several hundred million gallons per year...
December 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911829/supramolecular-pegylation-of-biopharmaceuticals
#15
Matthew J Webber, Eric A Appel, Brittany Vinciguerra, Abel B Cortinas, Lavanya S Thapa, Siddharth Jhunjhunwala, Lyle Isaacs, Robert Langer, Daniel G Anderson
The covalent modification of therapeutic biomolecules has been broadly explored, leading to a number of clinically approved modified protein drugs. These modifications are typically intended to address challenges arising in biopharmaceutical practice by promoting improved stability and shelf life of therapeutic proteins in formulation, or modifying pharmacokinetics in the body. Toward these objectives, covalent modification with poly(ethylene glycol) (PEG) has been a common direction. Here, a platform approach to biopharmaceutical modification is described that relies on noncovalent, supramolecular host-guest interactions to endow proteins with prosthetic functionality...
December 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27856796/oral-ultra-long-lasting-drug-delivery-application-toward-malaria-elimination-goals
#16
Andrew M Bellinger, Mousa Jafari, Tyler M Grant, Shiyi Zhang, Hannah C Slater, Edward A Wenger, Stacy Mo, Young-Ah Lucy Lee, Hormoz Mazdiyasni, Lawrence Kogan, Ross Barman, Cody Cleveland, Lucas Booth, Taylor Bensel, Daniel Minahan, Haley M Hurowitz, Tammy Tai, Johanna Daily, Boris Nikolic, Lowell Wood, Philip A Eckhoff, Robert Langer, Giovanni Traverso
Efforts at elimination of scourges, such as malaria, are limited by the logistic challenges of reaching large rural populations and ensuring patient adherence to adequate pharmacologic treatment. We have developed an oral, ultra-long-acting capsule that dissolves in the stomach and deploys a star-shaped dosage form that releases drug while assuming a geometry that prevents passage through the pylorus yet allows passage of food, enabling prolonged gastric residence. This gastric-resident, drug delivery dosage form releases small-molecule drugs for days to weeks and potentially longer...
November 16, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27771050/progress-in-formulation-based-approaches-for-antiretrovirals
#17
Ameya R Kirtane, Robert Langer, Giovanni Traverso
The human immunodeficiency virus has infected millions of people and the epidemic continues to grow rapidly in some parts of the world. Antiretroviral (ARV) therapy has provided improved treatment and prolonged the life expectancy of patients. Moreover, there is growing interest in using ARVs to protect against new infections. Hence, ARVs have emerged as our primary strategy in combating the virus. Unfortunately, several challenges limit the optimal performance of these drugs. First, ARVs often require life-long use and complex dosing regimens...
October 19, 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27754567/adhere-randomized-controlled-trial-comparing-renal-function-in-de-novo-kidney-transplant-recipients-receiving-prolonged-release-tacrolimus-plus-mycophenolate-mofetil-or-sirolimus
#18
Oleg O Rummo, Mario Carmellini, Lionel Rostaing, Rainer Oberbauer, Maarten H L Christiaans, Christiane Mousson, Robert M Langer, Franco Citterio, Bernard Charpentier, Malcolm Brown, Gbenga Kazeem, Frank Lehner
ADHERE was a randomized, open-label, Phase IV study comparing renal function at Week 52 postkidney transplant, in patients who received prolonged-release tacrolimus-based immunosuppressive regimens. On Days 0-27, patients received prolonged-release tacrolimus (initially 0.2 mg/kg/day), corticosteroids, and mycophenolate mofetil (MMF). Patients were randomized on Day 28 to receive either prolonged-release tacrolimus plus MMF (Arm 1) or prolonged-release tacrolimus (≥25% dose reduction on Day 42) plus sirolimus (Arm 2)...
January 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27739624/phosphine-stabilized-borylenes-and-boryl-anions-as-ligands-redox-reactivity-in-boron-based-pincer-complexes
#19
Lisa Vondung, Nicolas Frank, Maximilian Fritz, Lukas Alig, Robert Langer
Stabilized borylenes (L2 BH:) with weakly π-accepting substituents L, such as phosphines, were previously believed to be unstable. In the current manuscript, we describe a series of complexes formally containing a phosphine-stabilized borylene or boryl anion. In contrast to common trivalent boron compounds, the boron-based ligands in this study act as electron-donating ligands. The reported iron hydride complexes exhibit a unique reactivity pattern, undergoing a reversible B-H reductive elimination concomitant with oxidation of the boron(I) center...
October 14, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27734871/in-vitro-and-ex-vivo-strategies-for-intracellular-delivery
#20
REVIEW
Martin P Stewart, Armon Sharei, Xiaoyun Ding, Gaurav Sahay, Robert Langer, Klavs F Jensen
Intracellular delivery of materials has become a critical component of genome-editing approaches, ex vivo cell-based therapies, and a diversity of fundamental research applications. Limitations of current technologies motivate development of next-generation systems that can deliver a broad variety of cargo to diverse cell types. Here we review in vitro and ex vivo intracellular delivery approaches with a focus on mechanisms, challenges and opportunities. In particular, we emphasize membrane-disruption-based delivery methods and the transformative role of nanotechnology, microfluidics and laboratory-on-chip technology in advancing the field...
13, 2016: Nature
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