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https://www.readbyqxmd.com/read/27912061/tumor-interferon-signaling-regulates-a-multigenic-resistance-program-to-immune-checkpoint-blockade
#1
Joseph L Benci, Bihui Xu, Yu Qiu, Tony J Wu, Hannah Dada, Christina Twyman-Saint Victor, Lisa Cucolo, David S M Lee, Kristen E Pauken, Alexander C Huang, Tara C Gangadhar, Ravi K Amaravadi, Lynn M Schuchter, Michael D Feldman, Hemant Ishwaran, Robert H Vonderheide, Amit Maity, E John Wherry, Andy J Minn
Therapeutic blocking of the PD1 pathway results in significant tumor responses, but resistance is common. We demonstrate that prolonged interferon signaling orchestrates PDL1-dependent and PDL1-independent resistance to immune checkpoint blockade (ICB) and to combinations such as radiation plus anti-CTLA4. Persistent type II interferon signaling allows tumors to acquire STAT1-related epigenomic changes and augments expression of interferon-stimulated genes and ligands for multiple T cell inhibitory receptors...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27910041/efficient-genome-editing-in-induced-pluripotent-stem-cells-with-engineered-nucleases-in-vitro
#2
Vittavat Termglinchan, Timon Seeger, Caressa Chen, Joseph C Wu, Ioannis Karakikes
Precision genome engineering is rapidly advancing the application of the induced pluripotent stem cells (iPSCs) technology for in vitro disease modeling of cardiovascular diseases. Targeted genome editing using engineered nucleases is a powerful tool that allows for reverse genetics, genome engineering, and targeted transgene integration experiments to be performed in a precise and predictable manner. However, nuclease-mediated homologous recombination is an inefficient process. Herein, we describe the development of an optimized method combining site-specific nucleases and the piggyBac transposon system for "seamless" genome editing in pluripotent stem cells with high efficiency and fidelity in vitro...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27903535/magnetic-resonance-imaging-of-cardiac-strain-pattern-following-transplantation-of-human-tissue-engineered-heart-muscles
#3
Xulei Qin, Johannes Riegler, Malte Tiburcy, Xin Zhao, Tony Chour, Babacar Ndoye, Michael Nguyen, Jackson Adams, Mohamed Ameen, Thomas S Denney, Phillip C Yang, Patricia Nguyen, Wolfram H Zimmermann, Joseph C Wu
BACKGROUND: The use of tissue engineering approaches in combination with exogenously produced cardiomyocytes offers the potential to restore contractile function after myocardial injury. However, current techniques assessing changes in global cardiac performance after such treatments are plagued by relatively low detection ability. Since the treatment is locally performed, this detection could be improved by myocardial strain imaging that measures regional contractility. METHODS AND RESULTS: Tissue engineered heart muscles (EHMs) were generated by casting human embryonic stem cell-derived cardiomyocytes with collagen in preformed molds...
November 2016: Circulation. Cardiovascular Imaging
https://www.readbyqxmd.com/read/27898195/cost-effectiveness-of-microsurgical-reconstruction-for-head-and-neck-defects-after-oncologic-resection
#4
Lin Lin Gao, Marten Basta, Suhail K Kanchwala, Joseph M Serletti, David W Low, Liza C Wu
BACKGROUND: Microvascular free tissue transfer has become the main technique used for head and neck reconstruction. We assessed the cost-effectiveness of free flap reconstruction for head and neck defects after oncologic resection for squamous cell carcinoma (SCC). METHODS: We developed a Markov model of the cost, quality of life, survival, and incremental cost-effectiveness of reconstruction with free tissue transfer compared with locoregional flaps. Health state probabilities and quality of life scores were determined from literature...
November 29, 2016: Head & Neck
https://www.readbyqxmd.com/read/27894155/increased-lower-extremity-venous-stasis-may-contribute-to-deep-venous-thrombosis-formation-after-microsurgical-breast-reconstruction-an-ultrasonographic-study
#5
Arash Momeni, Michael G Tecce, Michael A Lanni, Shagun Aggarwal, Christopher Pannucci, Stephen J Kovach, Suhail K Kanchwala, Liza C Wu, Joseph M Serletti
Background Despite guideline-compliant prophylaxis, an increased rate of deep venous thrombosis (DVT) formation has been reported following autologous versus implant-based breast reconstruction. We hypothesized that tight abdominal fascia closure might decrease lower extremity venous return and promote venous stasis. Methods An observational crossover study of patients who underwent autologous breast reconstruction using transverse rectus abdominis musculocutaneous/deep inferior epigastric artery perforator flaps was conducted...
November 28, 2016: Journal of Reconstructive Microsurgery
https://www.readbyqxmd.com/read/27864127/no-difference-between-latiglutenase-and-placebo-in-reducing-villous-atrophy-or-improving-symptoms-in-patients-with-symptomatic-celiac-disease
#6
Joseph A Murray, Ciarán P Kelly, Peter H R Green, Annette Marcantonio, Tsung-Teh Wu, Markku Mäki, Daniel C Adelman
BACKGROUND & AIMS: Gluten ingestion leads to symptoms and small intestinal mucosal injury in patients with celiac disease. The only option is the strict lifelong exclusion of dietary gluten, which is difficult to accomplish. Many patients following a gluten-free diet continue to have symptoms and have small intestinal mucosal injury. Non-dietary therapies are needed. We performed a phase 2 study of the ability of latiglutenase, an orally administered mixture of 2 recombinant gluten-targeting proteases, to reduce mucosal morphometric measures in biopsies from patients with celiac disease...
November 15, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27859893/psychosocial-effects-of-a-skin-camouflage-program-in-female-survivors-with-head-and-neck-cancer-a-randomized-controlled-trial
#7
Shu-Ching Chen, Bing-Shen Huang, Chien-Yu Lin, Kang-Hsing Fan, Joseph Tung-Chien Chang, Shu-Chen Wu, Yeur-Hur Lai
OBJECTIVE: The purpose of this study was to evaluate the effects of a skin camouflage program on disfigurement, self-esteem, social interaction, and body image in female head and neck cancer (HNC) survivors. METHODS: A prospective, repeated-measures, randomized controlled therapeutic intervention design was used. A total of 66 participants were randomly assigned to each group, with 32 in the experimental group and 34 in the control group. The experimental group received a 4-session skin camouflage program, and the control group received routine care...
November 15, 2016: Psycho-oncology
https://www.readbyqxmd.com/read/27827824/plasma-biomarkers-of-risk-for-death-in-a-multicenter-phase-3-trial-with-uniform-transplant-characteristics-post-allogeneic-hct
#8
Mohammad Abu Zaid, Juan Wu, Cindy Wu, Brent R Logan, Jeffrey Yu, Corey Cutler, Joseph H Antin, Sophie Paczesny, Sung Won Choi
A phase 3 clinical trial (BMT CTN 0402) comparing tacrolimus/sirolimus (Tac/Sir) versus tacrolimus/methotrexate (Tac/Mtx) as graft-versus-host disease (GVHD) prophylaxis after matched-related allogeneic hematopoietic cell transplantation (HCT) recently showed no difference between study arms in acute GVHD-free survival. Within this setting of a prospective, multicenter study with uniform GVHD prophylaxis, conditioning regimen, and donor source, we explored the correlation of 10 previously identified biomarkers with clinical outcomes after allogeneic HCT...
November 8, 2016: Blood
https://www.readbyqxmd.com/read/27825554/development-of-a-novel-series-of-non-natural-triaryl-agonists-and-antagonists-of-the-pseudomonas-aeruginosa-lasr-quorum-sensing-receptor
#9
Joseph N Capilato, Shane V Philippi, Thomas Reardon, Ashleigh McConnell, Dylan C Oliver, Amy Warren, Jill S Adams, Chun Wu, Lark J Perez
Bacterial chemical communication, through a process called quorum sensing (QS), plays a central role in infection in numerous bacterial pathogens. Quorum sensing in Pseudomonas aeruginosa employs a series of small molecule receptors including the master QS regulator, LasR. In this study we investigate a non-natural triaryl series of LasR ligands using a combination of structure activity relationship studies and computational modeling. These studies have enabled the identification of key structural requirements for ligand binding and have revealed a new strategy for inducing the therapeutically relevant antagonism of LasR...
October 20, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27812494/proteome-response-of-phaeodactylum-tricornutum-during-lipid-accumulation-induced-by-nitrogen-depletion
#10
Joseph Longworth, Danying Wu, María Huete-Ortega, Phillip C Wright, Seetharaman Vaidyanathan
Nitrogen stress is a common strategy employed to stimulate lipid accumulation in microalgae, a biofuel feedstock of topical interest. Although widely investigated, the underlying mechanism of this strategy is still poorly understood. We examined the proteome response of lipid accumulation in the model diatom, Phaeodactylum tricornutum (CCAP 1055/1), at an earlier stage of exposure to selective nitrogen exclusion than previously investigated, and at a time point when changes would reflect lipid accumulation more than carbohydrate accumulation...
September 2016: Algal research
https://www.readbyqxmd.com/read/27810048/patient-specific-and-genome-edited-induced-pluripotent-stem-cell-derived-cardiomyocytes-elucidate-single-cell-phenotype-of-brugada-syndrome
#11
Ping Liang, Karim Sallam, Haodi Wu, Yingxin Li, Ilanit Itzhaki, Priyanka Garg, Ying Zhang, Vittavat Vermglinchan, Feng Lan, Mingxia Gu, Tingyu Gong, Yan Zhuge, Chunjiang He, Antje D Ebert, Veronica Sanchez-Freire, Jared Churko, Shijun Hu, Arun Sharma, Chi Keung Lam, Melvin M Scheinman, Donald M Bers, Joseph C Wu
BACKGROUND: Brugada syndrome (BrS), a disorder associated with characteristic electrocardiogram precordial ST-segment elevation, predisposes afflicted patients to ventricular fibrillation and sudden cardiac death. Despite marked achievements in outlining the organ level pathophysiology of the disorder, the understanding of human cellular phenotype has lagged due to a lack of adequate human cellular models of the disorder. OBJECTIVES: The objective of this study was to examine single cell mechanism of Brugada syndrome using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs)...
November 8, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27799523/telomere-shortening-and-metabolic-compromise-underlie-dystrophic-cardiomyopathy
#12
Alex Chia Yu Chang, Sang-Ging Ong, Edward L LaGory, Peggy E Kraft, Amato J Giaccia, Joseph C Wu, Helen M Blau
Duchenne muscular dystrophy (DMD) is an incurable X-linked genetic disease that is caused by a mutation in the dystrophin gene and affects one in every 3,600 boys. We previously showed that long telomeres protect mice from the lethal cardiac disease seen in humans with the same genetic defect, dystrophin deficiency. By generating the mdx(4cv)/mTR(G2) mouse model with "humanized" telomere lengths, the devastating dilated cardiomyopathy phenotype seen in patients with DMD was recapitulated. Here, we analyze the degenerative sequelae that culminate in heart failure and death in this mouse model...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27797940/quantitation-of-faecal-fusobacterium-improves-faecal-immunochemical-test-in-detecting-advanced-colorectal-neoplasia
#13
Sunny H Wong, Thomas N Y Kwong, Tai-Cheong Chow, Arthur K C Luk, Rudin Z W Dai, Geicho Nakatsu, Thomas Y T Lam, Lin Zhang, Justin C Y Wu, Francis K L Chan, Simon S M Ng, Martin C S Wong, Siew C Ng, William K K Wu, Jun Yu, Joseph J Y Sung
OBJECTIVE: There is a need for an improved biomarker for colorectal cancer (CRC) and advanced adenoma. We evaluated faecal microbial markers for clinical use in detecting CRC and advanced adenoma. DESIGN: We measured relative abundance of Fusobacterium nucleatum (Fn), Peptostreptococcus anaerobius (Pa) and Parvimonas micra (Pm) by quantitative PCR in 309 subjects, including 104 patients with CRC, 103 patients with advanced adenoma and 102 controls. We evaluated the diagnostic performance of these biomarkers with respect to faecal immunochemical test (FIT), and validated the results in an independent cohort of 181 subjects...
October 24, 2016: Gut
https://www.readbyqxmd.com/read/27784746/crlx101-a-nanoparticle-drug-conjugate-containing-camptothecin-improves-rectal-cancer-chemoradiotherapy-by-inhibiting-dna-repair-and-hif-1%C3%AE
#14
Xi Tian, Minh Nguyen, Henry Putnam Foote, Joseph M Caster, Kyle C Roche, Christian G Peters, Pauline Wu, Lata Jayaraman, Edward G Garmey, Joel E Tepper, Scott Eliasof, Andrew Z Wang
Novel agents are needed to improve chemoradiotherapy for locally advanced rectal cancer. In this study, we assessed the ability of CRLX101, an investigational nanoparticle-drug conjugate containing the payload camptothecin (CPT), to improve therapeutic responses as compared to standard chemotherapy. CRLX101 was evaluated as a radiosensitizer in colorectal cancer cell lines and murine xenograft models. CRLX101 was as potent as CPT in vitro in its ability to radiosensitize cancer cells. Evaluations in vivo demonstrated that the addition of CRLX101 to standard chemoradiotherapy significantly increased therapeutic efficacy by inhibiting DNA repair and HIF-1α pathway activation in tumor cells...
October 26, 2016: Cancer Research
https://www.readbyqxmd.com/read/27779452/ipsc-model-of-pulmonary-arterial-hypertension-reveals-novel-gene-expression-and-patient-specificity
#15
Silin Sa, Mingxia Gu, James Chappell, Ning-Yi Shao, Mohamed Ameen, Kathryn A T Elliott, Dan Li, Fabian Grubert, Caiyun G Li, Shalina Taylor, Aiqin Cao, Yu Ma, Ryan Fong, Long Nguyen, Joseph C Wu, Michael P Snyder, Marlene Rabinovitch
RATIONALE: Idiopathic or heritable pulmonary arterial hypertension is characterized by loss and obliteration of lung vasculature. Endothelial cell dysfunction is pivotal to the pathophysiology but different causal mechanisms may reflect a need for patient-tailored therapies. OBJECTIVES: Endothelial cells differentiated from induced pluripotent stem cells were compared to pulmonary arterial endothelial cells from the same patients with idiopathic or heritable pulmonary arterial hypertension, to determine whether they shared functional abnormalities and altered gene expression patterns, that differed from those in unused donor cells...
October 25, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27765019/impact-of-rna-degradation-on-fusion-detection-by-rna-seq
#16
Jaime I Davila, Numrah M Fadra, Xiaoke Wang, Amber M McDonald, Asha A Nair, Barbara R Crusan, Xianglin Wu, Joseph H Blommel, Jin Jen, Kandelaria M Rumilla, Robert B Jenkins, Umut Aypar, Eric W Klee, Benjamin R Kipp, Kevin C Halling
BACKGROUND: RNA-seq is a well-established method for studying the transcriptome. Popular methods for library preparation in RNA-seq such as Illumina TruSeq® RNA v2 kit use a poly-A pulldown strategy. Such methods can cause loss of coverage at the 5' end of genes, impacting the ability to detect fusions when used on degraded samples. The goal of this study was to quantify the effects RNA degradation has on fusion detection when using poly-A selected mRNA and to identify the variables involved in this process...
October 20, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27746093/defective-signaling-in-the-jak-stat-pathway-tracks-with-chronic-inflammation-and-cardiovascular-risk-in-aging-humans
#17
Shai S Shen-Orr, David Furman, Brian A Kidd, Francois Hadad, Patricia Lovelace, Ying-Wen Huang, Yael Rosenberg-Hasson, Sally Mackey, Fatemeh A Gomari Grisar, Yishai Pickman, Holden T Maecker, Yueh-Hsiu Chien, Cornelia L Dekker, Joseph C Wu, Atul J Butte, Mark M Davis
Chronic inflammation, a decline in immune responsiveness, and reduced cardiovascular function are all associated with aging, but the relationships among these phenomena remain unclear. Here, we longitudinally profiled a total of 84 signaling conditions in 91 young and older adults and observed an age-related reduction in cytokine responsiveness within four immune cell lineages, most prominently T cells. The phenotype can be partially explained by elevated baseline levels of phosphorylated STAT (pSTAT) proteins and a different response capacity of naive versus memory T cell subsets to interleukin 6 (IL-6), interferon α (IFN-α), and, to a lesser extent, IL-21 and IFN-γ...
October 12, 2016: Cell Systems
https://www.readbyqxmd.com/read/27745890/reliable-prediction-of-postmastectomy-lymphedema-the-risk-assessment-tool-evaluating-lymphedema
#18
Marten N Basta, Liza C Wu, Suhail K Kanchwala, Joseph M Serletti, Julia C Tchou, Stephen J Kovach, Joshua Fosnot, John P Fischer
BACKGROUND: Breast cancer-related lymphedema remains a significant complication post mastectomy. Identifying patients at highest risk may better inform targeted healthcare resource allocation and improve outcomes. This study aims to identify lymphedema predictors after mastectomy to develop a simple, accurate risk assessment tool. METHODS: An institutional retrospective review identified all women with breast cancer undergoing mastectomy between January 2000 and July 2013 with postmastectomy lymphedema as the primary outcome...
September 7, 2016: American Journal of Surgery
https://www.readbyqxmd.com/read/27726358/identification-of-tricyclic-agonists-of-sphingosine-1-phosphate-receptor-1-s1p1-employing-ligand-based-drug-design
#19
Hai-Yun Xiao, Scott H Watterson, Charles M Langevine, Anurag S Srivastava, Soo S Ko, Yanlei Zhang, Robert Joseph Cherney, Weiwei Guo, John L Gilmore, James E Sheppeck, Dauh-Rurng Wu, Peng Li, Duraisamy Ramasamy, Pirama Nayagam Arunachalam, Arvind Mathur, Tracy L Taylor, David J Shuster, Kim W McIntyre, Ding Ren Shen, Melissa Yarde, Mary Ellen Cvijic, Anthony M Marino, Praveen V Balimane, Zheng Yang, Dana M Banas, Georgia Cornelius, Celia J D Arienzo, Bethanne M Warrack, Lois D Lehman-McKeeman, Luisa M Salter-Cid, Jenny H Xie, Joel C Barrish, Percy H Carter, Alaric J Dyckman, T G Murali Dhar
Fingolimod (1) is the first approved oral therapy for the treatment of relapsing remitting multiple sclerosis. While the phosphorylated metabolite of fingolimod was found to be a non-selective S1P receptor agonist, agonism specifically of S1P1 is responsible for the peripheral blood lymphopenia believed to be key to its efficacy. Identification of modulators that maintain activity on S1P1 while sparing activity on other S1P receptors could offer equivalent efficacy with reduced liabilities. We disclose in this paper a ligand based drug design approach that led to the discovery of a series of potent tricyclic agonists of S1P1 with selectivity over S1P3 and were efficacious in a pharmacodynamic model of suppression of circulating lymphocytes...
October 11, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27698005/risk-prediction-for-epithelial-ovarian-cancer-in-11-united-states-based-case-control-studies-incorporation-of-epidemiologic-risk-factors-and-17-confirmed-genetic-loci
#20
Merlise A Clyde, Rachel Palmieri Weber, Edwin S Iversen, Elizabeth M Poole, Jennifer A Doherty, Marc T Goodman, Roberta B Ness, Harvey A Risch, Mary Anne Rossing, Kathryn L Terry, Nicolas Wentzensen, Alice S Whittemore, Hoda Anton-Culver, Elisa V Bandera, Andrew Berchuck, Michael E Carney, Daniel W Cramer, Julie M Cunningham, Kara L Cushing-Haugen, Robert P Edwards, Brooke L Fridley, Ellen L Goode, Galina Lurie, Valerie McGuire, Francesmary Modugno, Kirsten B Moysich, Sara H Olson, Celeste Leigh Pearce, Malcolm C Pike, Joseph H Rothstein, Thomas A Sellers, Weiva Sieh, Daniel Stram, Pamela J Thompson, Robert A Vierkant, Kristine G Wicklund, Anna H Wu, Argyrios Ziogas, Shelley S Tworoger, Joellen M Schildkraut
Previously developed models for predicting absolute risk of invasive epithelial ovarian cancer have included a limited number of risk factors and have had low discriminatory power (area under the receiver operating characteristic curve (AUC) < 0.60). Because of this, we developed and internally validated a relative risk prediction model that incorporates 17 established epidemiologic risk factors and 17 genome-wide significant single nucleotide polymorphisms (SNPs) using data from 11 case-control studies in the United States (5,793 cases; 9,512 controls) from the Ovarian Cancer Association Consortium (data accrued from 1992 to 2010)...
October 15, 2016: American Journal of Epidemiology
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