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https://www.readbyqxmd.com/read/29331939/volumetric-muscle-loss-injury-repair-using-in-situ-fibrin-gel-cast-seeded-with-muscle-derived-stem-cells-mdscs
#1
Nadine Matthias, Samuel D Hunt, Jianbo Wu, Jonathan Lo, Laura A Smith Callahan, Yong Li, Johnny Huard, Radbod Darabi
Volumetric muscle defect, caused by trauma or combat injuries, is a major health concern leading to severe morbidity. It is characterized by partial or full thickness loss of muscle and its bio-scaffold, resulting in extensive fibrosis and scar formation. Therefore, the ideal therapeutic option is to use stem cells combined with bio-scaffolds to restore muscle. For this purpose, muscle-derived stem cells (MDSCs) are a great candidate due to their unique multi-lineage differentiation potential. In this study, we evaluated the regeneration potential of MDSCs for muscle loss repair using a novel in situ fibrin gel casting...
January 9, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29330552/dosimetry-prediction-for-clinical-translation-of-64cu-pembrolizumab-immunopet-targeting-human-pd-1-expression
#2
Arutselvan Natarajan, Chirag B Patel, Frezghi Habte, Sanjiv S Gambhir
The immune checkpoint programmed death 1 receptor (PD-1) expressed on some tumor-infiltrating lymphocytes, and its ligand (PD-L1) expressed on tumor cells, enable cancers to evade the immune system. Blocking PD-1 with the monoclonal antibody pembrolizumab is a promising immunotherapy strategy. Thus, noninvasively quantifying the presence of PD-1 expression in the tumor microenvironment prior to initiation of immune checkpoint blockade may identify the patients likely to respond to therapy. We have developed a 64Cu-pembrolizumab radiotracer and evaluated human dosimetry...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321436/necrotizing-sarcoid-granulomatosis-with-natural-resolution-after-a-surgical-lung-biopsy
#3
Takayuki Shibata, Koichiro Takahashi, Masaru Uchida, Fumio Yamasaki, Michihiro Kawashima, Naoko Sueoka-Aragane
Necrotizing sarcoid granulomatosis (NSG) is a rare disease that is diagnosed based on pathological findings. We herein report the case of a 27-year-old man who had multiple nodular shadows in bilateral lung fields on chest radiography and elevated levels of C-reactive protein (CRP). The pathological evaluation of a lung biopsy specimen showed the infiltration of lymphocytes, granulomas with necrosis and granulomatous angiitis. He was therefore diagnosed with NSG. He has been followed without treatment, as his fever and CRP levels decreased immediately after the surgical lung biopsy...
January 11, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29312564/azacitidine-combined-with-the-selective-flt3-kinase-inhibitor-crenolanib-disrupts-stromal-protection-and-inhibits-expansion-of-residual-leukemia-initiating-cells-in-flt3-itd-aml-with-concurrent-epigenetic-mutations
#4
Anne-Kathrin Garz, Saskia Wolf, Sonja Grath, Verena Gaidzik, Stefan Habringer, Binje Vick, Martina Rudelius, Christoph Ziegenhain, Sylvia Herold, Marie-Theresa Weickert, Martha Smets, Christian Peschel, Robert A J Oostendorp, Sebastian Bultmann, Irmela Jeremias, Christian Thiede, Konstanze Döhner, Ulrich Keller, Katharina S Götze
Effectively targeting leukemia-initiating cells (LIC) in FLT3-ITD-mutated acute myeloid leukemia (AML) is crucial for cure. Tyrosine kinase inhibitors (TKI) have limited impact as single agents, failing to eradicate LIC in the bone marrow. Using primary AML samples and a patient-derived xenograft model, we investigated whether combining the FLT3-selective TKI crenolanib with the hypomethylating agent azacitidine (AZA) eliminates FLT3-ITD LIC and whether efficacy of this combination depends on co-existing mutations...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29305793/coadministration-of-polymeric-conjugates-of-docetaxel-and-cyclopamine-synergistically-inhibits-orthotopic-pancreatic-cancer-growth-and-metastasis
#5
Saud A Almawash, Goutam Mondal, Ram I Mahato
PURPOSE: The aim of this study was to determine whether co-administration of hedgehog (Hh) pathway inhibitor cyclopamine (CYP) and microtubule stabilizer docetaxel (DTX) as polymer-drug conjugates, methoxy poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylenecarbonate-graft-dodecanol-graft-cyclopamine) (P-CYP) and methoxy poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate-graft-dodecanol-graft-docetaxel) (P-DTX) could synergistically inhibit orthotopic pancreatic tumor growth in NSG mice...
January 5, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29299824/the-value-of-synchro-cystourethrometry-for-evaluating-the-relationship-between-urethral-instability-and-overactive-bladder
#6
Chaoyang Hua, Yibo Wen, Yan Zhang, Quande Feng, Xiangfei He, Yunlong Li, Junwei Wu, Jinjin Feng, Stuart B Bauer, Jianguo Wen
PURPOSE: To investigate the correlation between urethral instability (URI) and overactive bladder (OAB) in children. METHODS: We retrospectively investigated 126 children with OAB and 36 children without OAB using synchro-cystourethrometry. The prevalence of detrusor overactivity (DO) and URI, and the diagnostic sensitivity of DO alone and DO combined with URI, was compared. The OAB children with URI voluntarily received transcutaneous electrical pudendal nerve stimulation with anisodamine (stimulation group, SG) or anisodamine alone (non-stimulation group, NSG)...
January 3, 2018: International Urology and Nephrology
https://www.readbyqxmd.com/read/29299131/strong-fascin-expression-promotes-metastasis-independent-of-its-f-actin-bundling-activity
#7
Lisa S Heinz, Stefanie Muhs, Johanna Schiewek, Saskia Grüb, Marcus Nalaskowski, Yuan-Na Lin, Harriet Wikman, Leticia Oliveira-Ferrer, Tobias Lange, Jasmin Wellbrock, Anja Konietzny, Marina Mikhaylova, Sabine Windhorst
High expression of the actin bundling protein Fascin increases the malignancy of tumor cells. Here we show that fascin expression is up-regulated in more malignant sub-cell lines of MDA-MB-231 cells as compared to parental cells. Since also parental MDA-MB-231 cells exhibit high fascin levels, increased fascin expression was termed as "hyperexpression". To examine the effect of fascin hyperexpression, fascin was hyperexpressed in parental MDA-MB-231 cells and metastasis was analyzed in NOD scid gamma (NSG) mice...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29298841/galectin-8-induces-partial-epithelial-mesenchymal-transition-with-invasive-tumorigenic-capabilities-involving-a-fak-egfr-proteasome-pathway-in-mdck-cells
#8
Claudia Oyanadel, Christopher Holmes, Evelyn Pardo, Claudio Retamal, Ronan Shaughnessy, Patricio Smith, Priscilla Cortes, Marcela Bravo-Zehnder, Claudia Metz, Teo Feuerhake, Diego Romero, Juan Carlos Roa, Viviana Montecinos, Andrea Soza, Alfonso González
Epithelial cells can acquire invasive and tumorigenic capabilities through epithelial-mesenchymal-transition (EMT). The glycan-binding protein Galectin-8 (Gal-8) is over-expressed by certain carcinomas and activates selective β1-integrins involved in EMT. Here we show that Gal-8 over-expression or exogenous addition promotes proliferation, migration and invasion in non-tumoral MDCK cells, involving focal-adhesion kinase (FAK)-mediated transactivation of the EGFR, likely triggered by α5β1integrin binding...
January 3, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29296856/measles-virus-envelope-pseudotyped-lentiviral-vectors-transduce-quiescent-human-hscs-at-an-efficiency-without-precedent
#9
Camille Lévy, Fouzia Amirache, Anais Girard-Gagnepain, Cecilia Frecha, Francisco J Roman-Rodríguez, Ornellie Bernadin, Caroline Costa, Didier Nègre, Alejandra Gutierrez-Guerrero, Lenard S Vranckx, Isabelle Clerc, Naomi Taylor, Lars Thielecke, Kerstin Cornils, Juan A Bueren, Paula Rio, Rik Gijsbers, François-Loïc Cosset, Els Verhoeyen
Hematopoietic stem cell (HSC)-based gene therapy trials are now moving toward the use of lentiviral vectors (LVs) with success. However, one challenge in the field remains: efficient transduction of HSCs without compromising their stem cell potential. Here we showed that measles virus glycoprotein-displaying LVs (hemagglutinin and fusion protein LVs [H/F-LVs]) were capable of transducing 100% of early-acting cytokine-stimulated human CD34+ (hCD34+) progenitor cells upon a single application. Strikingly, these H/F-LVs also allowed transduction of up to 70% of nonstimulated quiescent hCD34+ cells, whereas conventional vesicular stomatitis virus G (VSV-G)-LVs reached 5% at the most with H/F-LV entry occurring exclusively through the CD46 complement receptor...
October 24, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296739/engraftment-of-chronic-myelomonocytic-leukemia-cells-in-immunocompromised-mice-supports-disease-dependency-on-cytokines
#10
Yanyan Zhang, Liang He, Dorothée Selimoglu-Buet, Chloe Jego, Margot Morabito, Christophe Willekens, M'boyba Khadija Diop, Patrick Gonin, Valérie Lapierre, Nathalie Droin, Eric Solary, Fawzia Louache
Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder that typically associates with mutations in epigenetic, splicing, and signaling genes. Genetically modified mouse models only partially recapitulate the disease phenotype, whereas xenotransplantation of CMML cells in immunocompromised mice has been rarely successful so far. Here, CMML CD34+ cells sorted from patient bone marrow (BM) or peripheral blood (PB) were injected intravenously into NSG (NOD/LtSz-scid IL2rγnull) mice and NSG mice engineered to express human granulo-monocyte colony-stimulating factor, stem cell factor, and interleukin-3 (NSGS mice)...
June 13, 2017: Blood Advances
https://www.readbyqxmd.com/read/29290798/ultrasound-molecular-imaging-of-vegfr-2-in-clear-cell-renal-cell-carcinoma-tracks-disease-response-to-antiangiogenic-and-notch-inhibition-therapy
#11
Juan D Rojas, Fanglue Lin, Yun-Chen Chiang, Anna Chytil, Diana C Chong, Victoria L Bautch, W Kimryn Rathmell, Paul A Dayton
Metastatic clear-cell renal cell carcinoma (ccRCC) affects thousands of patients worldwide each year. Antiangiogenic therapy has been shown to have beneficial effects initially, but resistance is eventually developed. Therefore, it is important to accurately track the response of cancer to different therapeutics in order to appropriately adjust the therapy to maximize efficacy. Change in tumor volume is the current gold standard for determining efficacy of treatment. However, functional variations can occur much earlier than measurable volume changes...
2018: Theranostics
https://www.readbyqxmd.com/read/29284644/cox-2-seh-dual-inhibitor-ptupb-potentiates-the-anti-tumor-efficacy-of-cisplatin
#12
Fuli Wang, Hongyong Zhang, Ai-Hong Ma, Weimin Yu, Maike Zimmermann, Jun Yang, Sung Hee Hwang, Daniel Zhu, Tzu-Yin Lin, Michael Malfatti, Kenneth W Turteltaub, Paul T Henderson, Susan Airhart, Bruce D Hammock, Jianlin Yuan, Ralph W de Vere White, Chong-Xian Pan
Cisplatin-based therapy is highly toxic, but moderately effective in most cancers. Concurrent inhibition of cyclooxygenase-2 (COX-2) and soluble epoxide hydrolase (sEH) results in anti-tumor activity, and has organ protective effects. The goal of this study was to determine the anti-tumor activity of PTUPB, an orally bioavailable COX-2/sEH dual inhibitor, in combination with cisplatin and gemcitabine (GC) therapy. NSG mice bearing bladder cancer patient-derived xenografts were treated with vehicle, PTUPB, cisplatin, GC or combinations thereof...
December 28, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29282132/design-and-validation-of-a-disease-network-of-inflammatory-processes-in-the-nsg-uc-mouse-model
#13
Henrika Jodeleit, Pia Palamides, Florian Beigel, Thomas Mueller, Eckhard Wolf, Matthias Siebeck, Roswitha Gropp
BACKGROUND: Ulcerative colitis (UC) is a highly progressive inflammatory disease that requires the interaction of epithelial, immune, endothelial and muscle cells and fibroblasts. Previous studies suggested two inflammatory conditions in UC-patients: 'acute' and 'remodeling' and that the design of a disease network might improve the understanding of the inflammatory processes. The objective of the study was to design and validate a disease network in the NOD-SCID IL2rγnull (NSG)-UC mouse model to get a better understanding of the inflammatory processes...
December 28, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29261129/lym-1-chimeric-antigen-receptor-t-cells-exhibit-potent-anti-tumor-effects-against-b-cell-lymphoma
#14
Long Zheng, Peisheng Hu, Brandon Wolfe, Caryn Gonsalves, Luqing Ren, Leslie A Khawli, Harvey R Kaslow, Alan L Epstein
T cells expressing chimeric antigen receptors (CARs) recognizing CD19 epitopes have produced remarkable anti-tumor effects in patients with B-cell malignancies. However, cancer cells lacking recognized epitopes can emerge, leading to relapse and death. Thus, CAR T cells targeting different epitopes on different antigens could improve immunotherapy. The Lym-1 antibody targets a conformational epitope of Human Leukocyte Antigen-antigen D Related (HLA-DR) on the surface of human B-cell lymphomas. Lym-1 CAR T cells were thus generated for evaluation of cytotoxic activity towards lymphoma cells in vitro and in vivo...
December 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29260748/-necrotizing-sarcoid-granulomatosis-with-clinical-presentations-of-recurrent-acute-abdomen-case-report-and-literature-review
#15
V I Vasilyev, S G Palshina, B D Chaltsev, S G Radenska-Lopovok, T N Safonova
The authors have described the world's first case of necrotizing sarcoid granulomatosis (NSG) in a 22-year-old woman with the clinical presentations of acute abdomen, which are associated with abdominal lymph nodal infiltration and necrosis, obvious constitutional disturbances (fever, nocturnal sweats, and significant weight loss), high inflammatory activity (anemia, leukocytosis, high erythrocyte sedimentation rates and C-reactive protein levels), the gradual appearance of splenic and hepatic necrotic foci, and infiltration into the lung and lacrimal glands with the development of unilateral uveitis...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/29246292/control-of-hiv-infection-in%C3%A2-vivo-using-gene-therapy-with-a-secreted-entry-inhibitor
#16
Alexander Falkenhagen, Jastaranpreet Singh, Sabah Asad, Danila Leontyev, Stanley Read, Juan Carlos Zúñiga-Pflücker, Sadhna Joshi
HIV entry inhibitors are highly effective in controlling virus replication. We have developed a lentiviral vector that expresses a secreted entry inhibitor, soluble CD4 (sCD4), which binds to the HIV envelope glycoproteins and inactivates the virus. We have shown that sCD4 was secreted from gene-modified CD4+ T cells, as well as from human umbilical cord blood-derived CD34+ hematopoietic stem/progenitor cells (HSPCs), and protected unmodified HIV target cells from infection in vitro. To investigate the in vivo application of our approach, we injected gene-modified HSPCs into NOD/SCID/γcnull (NSG) mice...
December 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/29209043/crispr-cas9-edited-nsg-mice-as-pdx-models-of-human-leukemia-to-address-the-role-of-niche-derived-sparc
#17
I Tirado-Gonzalez, E Czlonka, A Nevmerzhitskaya, D Soetopo, E Bergonzani, A Mahmoud, A Contreras, I Jeremias, U Platzbecker, J P Bourquin, U Kloz, F Van der Hoeven, H Medyouf
Leukemia accepted article preview online, 06 December 2017. doi:10.1038/leu.2017.346.
December 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29203662/methylprednisolone-acetate-induces-and-%C3%AE-7-dafachronic-acid-suppresses-strongyloides-stercoralis-hyperinfection-in-nsg-mice
#18
John B Patton, Sandra Bonne-Année, Jessica Deckman, Jessica A Hess, April Torigian, Thomas J Nolan, Zhu Wang, Steven A Kliewer, Amy C Durham, James J Lee, Mark L Eberhard, David J Mangelsdorf, James B Lok, David Abraham
Strongyloides stercoralis hyperinfection causes high mortality rates in humans, and, while hyperinfection can be induced by immunosuppressive glucocorticoids, the pathogenesis remains unknown. Since immunocompetent mice are resistant to infection with S. stercoralis, we hypothesized that NSG mice, which have a reduced innate immune response and lack adaptive immunity, would be susceptible to the infection and develop hyperinfection. Interestingly, despite the presence of large numbers of adult and first-stage larvae in S...
December 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29199273/mir-215-5p-is-a-tumor-suppressor-in-colorectal-cancer-targeting-egfr-ligand-epiregulin-and-its-transcriptional-inducer-hoxb9
#19
Petra Vychytilova-Faltejskova, Jana Merhautova, Tana Machackova, Irene Gutierrez-Garcia, José Garcia-Solano, Lenka Radova, Dominika Brchnelova, Katerina Slaba, Marek Svoboda, Jana Halamkova, Regina Demlova, Igor Kiss, Rostislav Vyzula, Pablo Conesa-Zamora, Ondrej Slaby
Growing evidence suggests that microRNAs are involved in the development and progression of colorectal cancer (CRC). In the present study, deregulation and functioning of tumor-suppressive miR-215-5p was evaluated in CRC. In total, 448 tumor tissues and 325 paired adjacent healthy tissues collected from Czech and Spain cohorts of CRC patients have been used for miR-215-5p expression analyses. A series of in vitro experiments have been performed using transient transfection of miR-215-5p mimics into four CRC cell lines to identify specific cellular processes affected by miR-215-5p...
December 4, 2017: Oncogenesis
https://www.readbyqxmd.com/read/29196297/acetylsalicylic-acid-governs-the-effect-of-sorafenib-in-ras-mutant-cancers
#20
Heinz Hammerlindl, Dinoop Ravindran Menon, Sabrina Hammerlindl, Abdullah Al Emran, Joachim Torrano, Katrin Sproesser, Divya Thakkar, Min Xiao, Victoria G Atkinson, Brian Gabrielli, Nikolas K Haass, Meenhard Herlyn, Clemens Krepler, Helmut Schaider
PURPOSE: Identify and characterize novel combinations of sorafenib with anti-inflammatory painkillers to target difficult to treat RAS-mutant cancer. EXPERIMENTAL DESIGN: The cytotoxicity of acetylsalicylic acid (aspirin) in combination with the multikinase inhibitor sorafenib (Nexavar) was assessed in RAS-mutant cell lines in vitro. The underlying mechanism for the increased cytotoxicity was investigated using selective inhibitors and shRNA-mediated gene knockdown...
December 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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