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https://www.readbyqxmd.com/read/28332262/haploidentical-peripheral-blood-stem-cell-transplantation-without-irradiation-or-busulfan-after-reduced-intensity-conditioning-for-kmt2a-mll-rearranged-infant-b-cell-precursor-acute-lymphoblastic-leukemia-report-of-two-cases
#1
Ai Yoshimi, Keisuke Kato, Sho Hosaka, Ryoko Suzuki, Hiroko Fukushima, Tomohei Nakao, Chie Kobayashi, Takashi Fukushima, Kazutoshi Koike, Ryo Sumazaki, Masahiro Tsuchida
We present two infants with KMT2A(MLL)-gene-R-associated BCP-ALL, who received HLA haploidentical PBSCT after RIC. The patients developed ALL at age 6 months and 3 months, respectively. Case 1 underwent PBSCT at the second CR with detectable KMT2A-AFF1(MLL-AF4) fusion gene transcript at 11 months of age, and Case 2 at the first CR without KMT2A-MLLT1(MLL-ENL) fusion gene transcript at 8 months of age. Both patients received G-CSF-mobilized unmanipulated peripheral blood mononuclear cells from their HLA haploidentical mothers after administration of FLU, MEL, and ATG...
March 22, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28332231/development-of-humanized-mice-in-the-age-of-genome-editing
#2
Vishnu Hosur, Benjamin E Low, Cindy Avery, Leonard D Shultz, Michael V Wiles
Mice are the most commonly used model organisms to study human disease. Many genetic human diseases can be recapitulated by modifying the mouse genome, which permits testing of existing and novel therapeutics, including combinatorial therapeutics, without putting humans at risk. Specifically, the development of "humanized" mice, i.e., severely immunodeficient mice engrafted with functional human hematopoietic and immune cells and tissues, has revolutionized our ability to study and model human diseases in preclinical in vivo systems...
March 22, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28331226/the-histone-deacetylase-inhibitor-givinostat-itf2357-exhibits-potent-anti-tumor-activity-against-crlf2-rearranged-bcp-all
#3
A M Savino, J Sarno, L Trentin, M Vieri, G Fazio, M Bardini, C Bugarin, G Fossati, K Davis, G Gaipa, S Izraeli, L H Meyer, G P Nolan, A Biondi, G Te Kronnie, C Palmi, G Cazzaniga
Leukemias bearing CRLF2 and JAK2 gene alterations are characterized by aberrant JAK/STAT signaling and poor prognosis. The HDAC inhibitor givinostat/ITF2357 has been shown to exert antineoplastic activity against both systemic juvenile idiopathic arthritis and myeloproliferative neoplasms through inhibition of the JAK/STAT pathway. These findings led us to hypothesize that givinostat might also act against CRLF2-rearranged BCP-ALL, which lack effective therapies. Here, we found that givinostat inhibited proliferation and induced apoptosis of BCP-ALL CRLF2-rearranged cell lines, positive for exon 16 JAK2 mutations...
March 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28331055/reticular-dysgenesis-international-survey-on-clinical-presentation-transplantation-and-outcome
#4
Manfred Hoenig, Chantal Lagresle-Peyrou, Ulrich Pannicke, Luigi D Notarangelo, Fulvio Porta, Andrew R Gennery, Mary Slatter, Morton J Cowan, Polina Stepensky, Hamoud Al-Mousa, Daifulah Al-Zahrani, Sung-Yun Pai, Waleed Al Herz, Hubert B Gaspar, Paul Veys, Koichi Oshima, Kohsuke Imai, Hiromasa Yabe, Lenora M Noroski, Nico M Wulffraat, Karl-Walter Sykora, Pere Soler-Palacin, Hideki Muramatsu, Mariam Al Hilali, Despina Moshous, Klaus-Michael Debatin, Catharina Schuetz, Eva-Maria Jacobsen, Ansgar S Schulz, Klaus Schwarz, Alain Fischer, Wilhelm Friedrich, Marina Cavazzana
Reticular Dysgenesis (RD) is a rare congenital disorder defined clinically by the combination of severe combined immunodeficiency (SCID), agranulocytosis and sensorineural deafness. Mutations in the gene encoding Adenylate Kinase 2 (AK2) were identified to cause the disorder. Hematopoietic stem cell transplantation (HSCT) is the only option to cure this otherwise fatal disease. Retrospective data on clinical presentation, genetics and outcome of HSCT were collected from centers in Europe, Asia and North America for a total of 32 patients born between 1982 and 2011...
March 22, 2017: Blood
https://www.readbyqxmd.com/read/28330618/latexin-inactivation-enhances-survival-and-long-term-engraftment-of%C3%A2-hematopoietic-stem-cells-and-expands-the-entire-hematopoietic-system-in-mice
#5
Yi Liu, Cuiping Zhang, Zhenyu Li, Chi Wang, Jianhang Jia, Tianyan Gao, Gerhard Hildebrandt, Daohong Zhou, Subbarao Bondada, Peng Ji, Daret St Clair, Jinze Liu, Changguo Zhan, Hartmut Geiger, Shuxia Wang, Ying Liang
Natural genetic diversity offers an important yet largely untapped resource to decipher the molecular mechanisms regulating hematopoietic stem cell (HSC) function. Latexin (Lxn) is a negative stem cell regulatory gene identified on the basis of genetic diversity. By using an Lxn knockout mouse model, we found that Lxn inactivation in vivo led to the physiological expansion of the entire hematopoietic hierarchy. Loss of Lxn enhanced the competitive repopulation capacity and survival of HSCs in a cell-intrinsic manner...
March 7, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28330501/intraarterial-transplantation-of-human-umbilical-cord-blood-mononuclear-cells-in-hyperacute-stroke-improves-vascular-function
#6
Lei Huang, Yichu Liu, Jianfei Lu, Bianca Cerqueira, Vivek Misra, Timothy Q Duong
BACKGROUND: Human umbilical cord blood (hUCB) cell therapy is a promising treatment for ischemic stroke. The effects of hyperacute stem cell transplantation on cerebrovascular function in ischemic stroke are, however, not well understood. This study evaluated the effects of hyperacute intraarterial transplantation of hUCB mononuclear cells (MNCs) on cerebrovascular function in stroke rats using serial magnetic resonance imaging (MRI). METHODS: HUCB MNCs or vehicle were administered to stroke rats via the internal carotid artery immediately after reperfusion at 60 min following ischemia onset...
March 22, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28330488/cigarette-smoke-challenges-bone-marrow-mesenchymal-stem-cell-capacities-in-guinea-pig
#7
Olga Tura-Ceide, Borja Lobo, Tanja Paul, Raquel Puig-Pey, Núria Coll-Bonfill, Jéssica García-Lucio, Valérie Smolders, Isabel Blanco, Joan A Barberà, Víctor I Peinado
BACKGROUND: Cigarette smoke (CS) is associated with lower numbers of circulating stem cells and might severely affect their mobilization, trafficking and homing. Our study was designed to demonstrate in an animal model of CS exposure whether CS affects the homing and functional capabilities of bone marrow-derived mesenchymal stem cells (BM-MSCs). METHODS: Guinea pigs (GP), exposed or sham-exposed to CS, were administered via tracheal instillation or by vascular administration with 2...
March 23, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28329030/protective-factors-in-the-intestinal-microbiome-against-clostridium-difficile-infection-in-recipients-of-allogeneic-hematopoietic-stem-cell-transplantation
#8
Yeon Joo Lee, Esther P Arguello, Robert R Jenq, Eric Littmann, Grace J Kim, Liza C Miller, Lilan Ling, Cesar Figueroa, Elizabeth Robilotti, Miguel-Angel Perales, Juliet N Barker, Sergio Giralt, Marcel R M van den Brink, Eric G Pamer, Ying Taur
Background.: Clostridium difficile infection (CDI) is a frequent complication in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT), who receive intensive treatments that significantly disrupt the intestinal microbiota. In this study, we examined the microbiota composition of allo-HSCT recipients to identify bacterial colonizers that confer protection against CDI following engraftment. Methods.: Feces collected from adult recipients allo-HSCT at engraftment were analyzed; 16S rRNA genes were sequenced and analyzed from each sample...
January 30, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28328168/intrastriatal-transplantation-of-human-neural-stem-cells-restores-the-impaired-subventricular-zone-in-parkinsonian-mice
#9
Fuxing Zuo, Feng Xiong, Xia Wang, Xueyuan Li, Renzhi Wang, Wei Ge, Xinjie Bao
Cell replacement therapy using neural stem cells (NSCs) transplantation has recently emerged as a promising method of Parkinson's disease (PD) treatment; however, the underlying mechanisms are not fully understood. To gain new insights into the mechanisms of 6-hydroxydopamine (6-OHDA)-induced lesioning and therapeutic efficacy of human NSCs (hNSCs) transplantation, the striatum (ST) of intrastriatal 6-OHDA-injected parkinsonian mice were unilaterally engrafted with undifferentiated hNSCs. A high-throughput quantitative proteomic approach was used to characterize the proteome profiles of PD-related brain regions such as the SN, ST, olfactory bulb (OB), and subventricular zone (SVZ) in these mice...
March 22, 2017: Stem Cells
https://www.readbyqxmd.com/read/28327189/microrna-27a-contributes-to-the-malignant-behavior-of-gastric-cancer-cells-by-directly-targeting-ph-domain-and-leucine-rich-repeat-protein-phosphatase-2
#10
Lei Ding, Shanyong Zhang, Mu Xu, Renwen Zhang, Pengcheng Sui, Qing Yang
BACKGROUND: Accumulating evidence indicates that microRNA-27a (miR-27a) is involved in carcinogenesis and tumor progression. However, the exact function and molecular mechanism of miR-27a in gastric cancer remain unclear. METHODS: Quantitative real-time PCR (qRT-PCR) was used to quantify the expression of miR-27a and its target gene. The function of miR-27a in gastric cancer was investigated through in vitro and in vivo assays (MTT assay, colony formation assay, flow cytometry assay, wound healing assay, migration and invasion assay, immunohistochemistry (IHC), immunofluorescence (IF) and Western blot)...
March 21, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28326106/in-vivo-assessment-of-stem-cells-for-treating-neurodegenerative-disease-current-approaches-and-future-prospects
#11
REVIEW
Byeong-Wook Song
In recent years, stem cell-related therapies have been widely applied for treating neurodegenerative disease. Despite their potential, stem cell tracking and imaging techniques for the evaluation of in vivo proof-of-concept (PoC) therapies have not been sufficiently represented in the research area. This review summarizes the recent approaches that have been used for tracking and imaging engrafted stem cells in vivo. Furthermore, we introduce tissue clearing technology that can be applied to develop three-dimensional in vivo experiments...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28325666/development-of-novel-patient-derived-preclinical-models-from-malignant-effusions-in-patients-with-tyrosine-kinase-inhibitor-resistant-clear-cell-renal-cell-carcinoma
#12
Jiryeon Jang, Oliver Rath, Julia Schueler, Hyun Hwan Sung, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Han-Yong Choi, Ghee-Young Kwon, Woong Yang Park, Jeeyun Lee, Se Hoon Park
PURPOSE: Although targeting angiogenesis with tyrosine kinase inhibitors (TKIs) has become standard of care in the treatment of clear cell renal cell carcinoma (RCC), resistance mechanism are not fully understood, and there is a need to develop new therapeutic options overcoming them. METHODS AND MATERIALS: To develop a preclinical model that predicts clinical activity of novel agents in 19 RCC patients, we established patient-derived cell (PDC) and xenograft (PDX) models derived from malignant effusions or surgical specimen...
March 15, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28325054/-the-use-of-negative-pressure-wound-therapy-in-the-fixation-of-split-thickness-skin-grafts
#13
J Ulianko, J Janek, Ľ Laca
INTRODUCTION: Negative pressure wound therapy is one of the latest methods of dealing with complicated healing wounds. It promotes granulation, mechanically attracts the edges of the wound, removes secretions, reduces the number of bacteria in the wound and reduces swelling. In addition to its use to start and enhance the healing process, this method is also important in the fixation of split-thickness skin grafts in non-ideal conditions. The goal of this article is to establish basic indications for negative pressure fixation of meshed split-thickness skin grafts in non-ideal conditions in the wound and to assess the impact of contamination of wounds on engraftment using vacuum therapy...
2017: Rozhledy V Chirurgii: Měsíčník Československé Chirurgické Společnosti
https://www.readbyqxmd.com/read/28324008/vessel-network-architecture-of-adult-human-islets-promotes-distinct-cell-cell-interactions-in-situ-and-is-altered-after-transplantation
#14
Christian M Cohrs, Chunguang Chen, Stephan R Jahn, Julia Stertmann, Helena Chmelova, Jürgen Weitz, Andrea Bähr, Nikolai Klymiuk, Anja Steffen, Barbara Ludwig, Virginia Kamvissi, Eckhard Wolf, Stefan R Bornstein, Michele Solimena, Stephan Speier
Islet cell hormone release is modulated by signals from endothelial and endocrine cells within the islet. However, models of intra-islet vascularization and paracrine cell signaling are mostly based on rodent pancreas. We here assessed for the first time the architecture and endocrine cell interaction of the vascular network in unperturbed human islets in situ and their potential to re-establish their endogenous vascular network after transplantation in vivo. We prepared pancreas tissue slices of fresh tissue obtained from non-diabetic patients undergoing partial pancreatectomy...
January 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323411/engineering-an-injectable-muscle-specific-microenvironment-for-improved-cell-delivery-using-a-nanofibrous-extracellular-matrix-hydrogel
#15
Nikhil Rao, Gillie Agmon, Matthew T Tierney, Jessica L Ungerleider, Rebecca L Braden, Alessandra Sacco, Karen L Christman
Injection of skeletal muscle progenitors has the potential to be a minimally invasive treatment for a number of diseases that negatively affect vasculature and skeletal muscle, including peripheral artery disease (PAD). However, success with this approach has been limited because of poor transplant cell survival. This is primarily attributed to cell death due to extensional flow through the needle, the harsh ischemic environment of the host tissue, a deleterious immune cell response, and a lack of biophysical cues supporting exogenous cell viability...
March 21, 2017: ACS Nano
https://www.readbyqxmd.com/read/28321824/therapeutic-hypothesis-testing-with-rodent-brain-tumor-models
#16
REVIEW
Derek A Wainwright, Craig M Horbinski, Rintaro Hashizume, C David James
The development and application of rodent models for preclinical testing of novel therapeutics and approaches for treating brain tumors has been a mainstay of neuro-oncology preclinical research for decades, and is likely to remain so into the foreseeable future. These models serve as an important point of entry for analyzing the potential efficacy of experimental therapies that are being considered for clinical trial evaluation. Although rodent brain tumor models have seen substantial change, particularly since the introduction of genetically engineered mouse models, certain principles associated with the use of these models for therapeutic testing are enduring, and form the basis for this review...
March 20, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28321124/combined-inhibition-of-%C3%AE-catenin-and-bcr-abl-synergistically-targets-tyrosine-kinase-inhibitor-resistant-blast-crisis-chronic-myeloid-leukemia-blasts-and-progenitors-in-vitro-and-in-vivo
#17
H Zhou, P Y Mak, H Mu, D H Mak, Z Zeng, J Cortes, Q Liu, M Andreeff, B Z Carter
Tyrosine kinase inhibitor (TKI) resistance and progression to blast crisis (BC), both related to persistent β-catenin activation remain formidable challenges for chronic myeloid leukemia (CML). We observed overexpression of β-catenin in BC-CML stem/progenitor cells, particularly in GMP progenitors, and highest among a novel CD34(+)CD38(+)CD123(hi)Tim-3(hi) subset as determined by CyTOF analysis. Co-culture with mesenchymal stromal cells (MSCs) induced the expression of β-catenin and its target CD44 in CML cells...
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28321091/azacitidine-therapy-for-low-risk-myelodysplastic-syndrome-developing-after-solid-organ-transplantation
#18
Hiroaki Inoue, Yasuyoshi Morita, Shinya Rai, Hiroaki Kakutani, Yasuyo Ohyama, Yasuhiro Taniguchi, Hirokazu Tanaka, Takahiro Shimada, Yoichi Tatsumi, Takashi Ashida, Itaru Matsumura
Immunosuppressive therapy after solid organ transplantation is known to be a risk factor for the development of myelodysplastic syndromes (MDS). Herein, we report 2 patients, both of whom developed low-risk MDS after solid organ transplantation and were successfully treated with azacitidine (AZA). The 1st case was a 74-year-old man who had received liver transplantation. The initial immunosuppressive therapy consisted of cyclosporine and prednisolone. Nine years after transplantation, he was diagnosed as having MDS (RCMD)...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28320463/hyaluronan-coating-improves-liver-engraftment-of-transplanted-human-biliary-tree-stem-progenitor-cells
#19
Lorenzo Nevi, Guido Carpino, Daniele Costantini, Vincenzo Cardinale, Olga Riccioni, Sabina Di Matteo, Fabio Melandro, Pasquale Bartolomeo Berloco, Lola Reid, Eugenio Gaudio, Domenico Alvaro
BACKGROUND: Cell therapy of liver diseases with human biliary tree stem cells (hBTSCs) is biased by low engraftment efficiency. Coating the hBTSCs with hyaluronans (HAs), the primary constituents of all stem cell niches, could facilitate cell survival, proliferation, and, specifically, liver engraftment given that HAs are cleared selectively by the liver. METHODS: We developed a fast and easy method to coat hBTSCs with HA and assessed the effects of HA-coating on cell properties in vitro and in vivo...
March 20, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28319446/good-laboratory-practice-preclinical-safety-studies-for-gsk2696273-mlv-vector-based-ex-vivo-gene-therapy-for-adenosine-deaminase-deficiency-severe-combined-immunodeficiency-in-nsg-mice
#20
Nicola Carriglio, Jan Klapwijk, Raisa Jofra Hernandez, Michela Vezzoli, Franck Chanut, Rhiannon Lowe, Draghici Elena, Melanie Nord, Paola Albertini, Patrizia Cristofori, Jane Richards, Hazel Staton, Jonathan Appleby, Alessandro Aiuti, Aisha V Sauer
GSK2696273 (autologous CD34+ cells transduced with retroviral vector that encodes for the human adenosine deaminase [ADA] enzyme) is a gamma-retroviral ex vivo gene therapy of bone marrow-derived CD34+ cells for the treatment of adenosine deaminase deficiency severe combined immunodeficiency (ADA-SCID). ADA-SCID is a severe monogenic disease characterized by immunologic and nonimmunologic symptoms. Bone-marrow transplant from a matched related donor is the treatment of choice, but it is available for only a small proportion of patients...
March 2017: Human Gene Therapy. Clinical Development
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