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https://www.readbyqxmd.com/read/28926402/reversing-hiv-latency-via-sphingosine-1-phosphate-receptor-1-signaling
#1
Charline Duquenne, Sandrine Gimenez, Adeline Guigues, Benjamin Viala, Caroline Boulouis, Clément Mettling, Damien Maurel, Noëlie Campos, Etienne Doumazane, Laetitia Comps-Agrar, Jamal Tazi, Laurent Prézeau, Pierre Corbeau, Vincent François
OBJECTIVE: In this study, we looked for a new family of latency reversing agents. DESIGN: We searched for G protein-coupled receptors (GPCR) coexpressed with CCR5 in primary CD4+ T cells that activate infected cells and boost HIV production. METHODS: GPCR coexpression was unveiled by RT-PCR. We used FRET to analyze the dimerization with CCR5 of the expressed GPCR. Viral entry was measured by flow cytometry, reverse transcription by quantitative PCR, NFkB translocation by immunofluorescence, LTR activation using a gene reporter assay, and viral production by p24 quantification...
September 18, 2017: AIDS
https://www.readbyqxmd.com/read/28924876/inhibitory-effects-of-antagonists-of-growth-hormone-releasing-hormone-ghrh-in-thyroid-cancer
#2
Helena Pópulo, Bruno Nunes, Cristina Sampaio, Rui Batista, Marta Teixeira Pinto, Tiago B Gaspar, Leandro Miranda-Alves, Ren-Zhi Cai, Xian Yang Zhang, Andrew V Schally, Manuel Sobrinho-Simões, Paula Soares
Growth hormone-releasing hormone (GHRH) is a peptide hormone secreted by the hypothalamus that regulates the synthesis and secretion of growth hormone (GH) in the pituitary. The extra-hypothalamic GHRH and its cognate receptors (GHRHR and splice variants) play a mitogenic role by stimulating cell proliferation and preventing apoptotic cell death. It is well established that GHRH antagonists inhibit the growth, tumorigenicity, and metastasis of various human malignancies. In this work, we studied the effect of two new GHRH antagonists, MIA602 and MIA690, on thyroid cancer...
September 18, 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28923647/is-cytomegalovirus-surveillance-necessary-for-patients-with-low-reactivation-risk-in-an-autologous-hematopoietic-cell-transplantation-setting
#3
A H Kaya, E Tekgunduz, S Akpinar, H Batgi, F Bekdemir, O Kayikci, S Namdaroglu, B U Ulu, M S Dal, M K Cakar, S Korkmaz, F Altuntas
BACKGROUND: In an autologous hematopoietic cell transplantation (AHCT) setting, routine cytomegalovirus (CMV) surveillance is not indicated except in high-risk situations. On the other hand, some studies reported increased CMV reactivation in AHCT setting as a result of incorporation of novel agents into treatment algorithms, such as bortezomib and rituximab. We retrospectively analyzed CMV reactivation and infection rates in patients with no high-risk features, who were treated with AHCT...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28922324/biological-properties-and-therapeutic-value-of-cryopreserved-fat-tissue
#4
Takanobu Mashiko, Szu-Hsien Wu, Koji Kanayama, Rintaro Asahi, Takako Shirado, Masanori Mori, Ataru Sunaga, Shunji Sarukawa, Hirokazu Uda, Kotaro Yoshimura
BACKGROUND: Fat grafting frequently requires multiple treatments and thus repeated liposuction to achieve treatment goals. The purpose of this study is to evaluate whether cryopreservation of adipose tissue may facilitate future fat grafting. METHODS: Lipoaspirates were harvested from six adult females and preserved using two cryopreservation methods: 1) simple cooling to -80˚C (cryo-1); or 2) programmed cooling to -190˚C (cryo-2). Fresh fat, cryo-1 fat, and cryo-2 fat were analyzed both in vitro and in vivo...
September 14, 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28920919/age-dependent-human-%C3%AE-cell-proliferation-induced-by-glucagon-like-peptide-1-and-calcineurin-signaling
#5
Chunhua Dai, Yan Hang, Alena Shostak, Greg Poffenberger, Nathaniel Hart, Nripesh Prasad, Neil Phillips, Shawn E Levy, Dale L Greiner, Leonard D Shultz, Rita Bottino, Seung K Kim, Alvin C Powers
Inadequate pancreatic β cell function underlies type 1 and type 2 diabetes mellitus. Strategies to expand functional cells have focused on discovering and controlling mechanisms that limit the proliferation of human β cells. Here, we developed an engraftment strategy to examine age-associated human islet cell replication competence and reveal mechanisms underlying age-dependent decline of β cell proliferation in human islets. We found that exendin-4 (Ex-4), an agonist of the glucagon-like peptide 1 receptor (GLP-1R), stimulates human β cell proliferation in juvenile but not adult islets...
September 18, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28918304/haploidentical-transplantation-for-older-patients-with-acute-myeloid-leukemia-and-myelodysplastic-syndrome
#6
Stefan O Ciurea, Mithun V Shah, Rima M Saliba, Sameh Gaballa, Piyanuch Kongtim, Gabriela Rondon, Julianne Chen, Whitney Wallis, Kai Cao, Marina Konopleva, Naval Daver, Jorge Cortes, Farhad Ravandi, Amin Alousi, Sairah Ahmed, Uday Popat, Simrit Parmar, Qaiser Bashir, Oran Betul, Chitra Hosing, Elizabeth J Shpall, Katayoun Rezvani, Issa F Khouri, Partow Kebriaei, Richard E Champlin
Allogeneic stem cell transplant (ASCT) with HLA matched donors is increasingly used for older patients with AML/MDS. It remains unclear if haploidentical transplantation (haploSCT) is a suitable option for older patients with this disease. We analyzed 43 patients with AML/MDS (median age 61 years) who underwent a haploSCT at our institution. All the patients received a fludarabine-melphalan-based reduced-intensity conditioning regimen and post-transplant cyclophosphamide-based GVHD prophylaxis. Except one patient who had early death, the remaining 42 patients (98%) engrafted donor cells...
September 13, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28915623/inhibition-of-the-pi3k-akt-mtor-pathway-activates-autophagy-and-compensatory-ras-raf-mek-erk-signalling-in-prostate-cancer
#7
Dominika E Butler, Christopher Marlein, Hannah F Walker, Fiona M Frame, Vincent M Mann, Matthew S Simms, Barry R Davies, Anne T Collins, Norman J Maitland
The PI3K/AKT/mTOR pathway is frequently activated in advanced prostate cancer, due to loss of the tumour suppressor PTEN, and is an important axis for drug development. We have assessed the molecular and functional consequences of pathway blockade by inhibiting AKT and mTOR kinases either in combination or as individual drug treatments. In established prostate cancer cell lines, a decrease in cell viability and in phospho-biomarker expression was observed. Although apoptosis was not induced, a G1 growth arrest was observed in PTEN null LNCaP cells, but not in BPH1 or PC3 cells...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912374/collagen-embedded-tumor-transplantations-in-xenopus-laevis-tadpoles
#8
Maureen Banach, Jacques Robert
The Xenopus laevis tadpole provides a valuable model for studying tumorigenesis and tumor immunity by intravital real-time microscopy. Using well-characterized thymic lymphoid tumor lines (15/0 and ff-2) that are transplantable into their compatible hosts (LG-15 isogenic clones and the F inbred strain, respectively), a system of semisolid tumor engraftment has been designed. Because these lymphoid tumor cell lines are not adherent and grow in suspension, they are first immobilized in a matrix of type I rat tail collagen before transplantation as a semisolid tumor graft under the transparent dorsal skin in the head region of a tadpole...
September 14, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28911908/enhancement-of-mouse-hematopoietic-stem-progenitor-cell-function-via-transient-gene-delivery-using-integration-deficient-lentiviral-vectors
#9
Maria E Alonso-Ferrero, Niek P van Til, Kerol Bartolovic, Márcia F Mata, Gerard Wagemaker, Dale Moulding, David A Williams, Christine Kinnon, Simon N Waddington, Michael D Milsom, Steven J Howe
Integration-deficient lentiviruses (IdLV) effectively deliver genes to tissues but are rapidly lost from dividing cells. This property can be harnessed to transiently express transgenes to manipulate cell biology. Here, we demonstrate the utility of short-term gene expression to improve functional potency of Hematopoietic Stem/Progenitor Cells (HSPC) during transplantation by delivering HOXB4 and Angptl3 using IdLV to enhance the engraftment of HSPC. Constitutive overexpression of either of these genes is likely to be undesirable, but the transient nature of IdLVs reduces this risk and those associated with unsolicited gene expression in daughter cells...
September 11, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28910431/hla-mismatched-microtransplant-in-older-patients-newly-diagnosed-with-acute-myeloid-leukemia-results-from-the-microtransplantation-interest-group
#10
Mei Guo, Nelson J Chao, Jian-Yong Li, David A Rizzieri, Qi-Yun Sun, Ann Mohrbacher, Elizabeth F Krakow, Wan-Jun Sun, Xu-Liang Shen, Xin-Rong Zhan, De-Pei Wu, Li Liu, Juan Wang, Min Zhou, Lin-Hua Yang, Yang-Yi Bao, Zheng Dong, Bo Cai, Kai-Xun Hu, Chang-Lin Yu, Jian-Hui Qiao, Hong-Li Zuo, Ya-Jing Huang, Anthony D Sung, Jun-Xiao Qiao, Zhi-Qing Liu, Tie-Qiang Liu, Bo Yao, Hong-Xia Zhao, Si-Xuan Qian, Wei-Wei Liu, Rafael Forés, Rafael F Duarte, Hui-Sheng Ai
Importance: The outcome of older patients with acute myeloid leukemia (AML) remains unsatisfactory. Recent studies have shown that HLA-mismatched microtransplant could improve outcomes in such patients. Objective: To evaluate outcomes in different age groups among older patients with newly diagnosed AML who receive HLA-mismatched microtransplant. Design, Setting, and Participants: This multicenter clinical study included 185 patients with de novo AML at 12 centers in China, the United States, and Spain in the Microtransplantation Interest Group...
September 14, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28902579/effect-of-liver-histopathology-on-islet-cell-engraftment-in-the-model-mimicking-autologous-islet-cell-transplantation
#11
Chirag S Desai, Khalid M Khan, Xiaobo Ma, Henghong Li, Juan Wang, Lijuan Fan, Guoling Chen, Jill P Smith, Wanxing Cui
BACKGROUND: The inflammatory milieu in the liver as determined by histopathology is different in individual patients undergoing autologous islet cell transplantation. We hypothesized that inflammation related to fatty-liver adversely impacts islet survival. To test this hypothesis, we used a mouse model of fatty-liver to determine the outcome of syngeneic islet transplantation after chemical pancreatectomy. METHODS: Mice (C57BL/6) were fed a high-fat-diet from 6 weeks of age until attaining a weight of ≥28 grams (6-8 weeks) to produce a fatty liver (histologically > 30% fat);steatosis was confirmed with lipidomic profile of liver tissue...
September 13, 2017: Islets
https://www.readbyqxmd.com/read/28902069/antiinflammatory-strategies-in-intrahepatic-islet-transplantation-a-comparative-study-in-preclinical-models
#12
A Citro, E Cantarelli, S Pellegrini, E Dugnani, L Piemonti
BACKGROUND: The identification of pathway(s) playing a pivotal role in peritransplant detrimental inflammatory events represents the crucial step towards a better management and outcome of pancreatic islet transplanted patients. Recently, we candidate the CXCR1/2 inhibition as a relevant strategy in enhancing pancreatic islet survival after transplantation. METHODS: Here, the most clinically used antiinflammatory compounds (IL1-receptor antagonist, steroids and TNF-α inhibitor) alone or in combination with a CXCR1/2 inhibitor were evaluated in their ability to improve engraftment or delay graft rejection...
September 8, 2017: Transplantation
https://www.readbyqxmd.com/read/28901186/recipient-adipose-derived-stem-cells-enhance-recipient-cell-engraftment-and-prolong-allotransplant-survival-in-a-miniature-swine-hind-limb-model
#13
Yur-Ren Kuo, Chien-Chang Chen, Yen-Chou Chen, Ching-Ming Chien
Donor mesenchymal stem cells (MSCs) could prolong vascularized composite allotransplantation (VCA) survival in our previous studies. However, recipient adipose tissue is easier to harvest than donor tissue for preconditioning modulation. Hence, this study investigated the efficacy of recipient autologous adipose-derived stem cells (rADSCs) for VCA survival. The heterotopic hind-limb transplantation from female donor to male recipient was performed in outbred miniature swine. Group I ( n = 6) was untreated controls...
August 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28901184/ex-vivo-pretreatment-of-islets-with-mitomycin-c-reduction-in-immunogenic-potential-of-islets-by-suppressing-secretion-of-multiple-chemotactic-factors
#14
Naoya Sato, Junichiro Haga, Takayuki Anazawa, Akira Kenjo, Takashi Kimura, Ikuo Wada, Tsutomu Mori, Shigeru Marubashi, Mitsukazu Gotoh
Strategies to reduce the immunogenicity of pancreatic islets and to prevent the activation of proinflammatory events are essential for successful islet engraftment. Pretransplant islet culture presents an opportunity for preconditioning to improve outcomes of islet transplantation. We previously demonstrated that ex vivo mitomycin C (MMC) pretreatment and subsequent culture significantly prolonged graft survival. Fully understanding the biological process of pretreatment could result in the development of a protocol to improve the survival of islet grafts...
August 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28899758/chronic-global-analysis-of-vascular-permeability-and-cerebral-blood-flow-after-bone-marrow-stromal-cell-treatment-of-traumatic-brain-injury-in-the-rat-a-long-term-mri-study
#15
Lian Li, Michael Chopp, Guangliang Ding, Qingjiang Li, Asim Mahmood, Quan Jiang
Vascular permeability and hemodynamic alteration in response to the transplantation of human bone marrow stromal cells (hMSCs) after traumatic brain injury (TBI) were longitudinally investigated in non directly injured and normal-appearing cerebral tissue using magnetic resonance imaging (MRI). Male Wistar rats (300-350g, n=30) subjected to controlled cortical impact TBI were intravenously injected with 1 ml of saline (at 6-hours or 1-week post-injury, n=5/group) or with hMSCs in suspension (∼3x10(6) hMSCs, at 6-hours or 1-week post-injury, n=10/group)...
September 9, 2017: Brain Research
https://www.readbyqxmd.com/read/28898706/profiles-of-pro-inflammatory-cytokines-in-allogenic-stem-cell-transplantation-with-post-transplant-cyclophosphamide
#16
O V Pirogova, I S Moiseev, E A Surkova, S V Lapin, S N Bondarenko, A D Kulagin, B V Afanasyev
Large number of studies was published about predictive value of cytokines for graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. Recently, there has been a growing interest in GVHD prophylaxis with post-transplant cyclophosphamide (PTCy). Clinical data on the dynamics of proinflammatory cytokines with this prophylaxis is lacking. In this study, we have measured the levels of IL-17, IL-6, IL-8, IFN-γ and TNF-α in plasma on days -7, 0, +7, +14 and after engraftment in 20 patients with acute GVHD and 40 matched control patients with PTCy-based prophylaxis...
September 9, 2017: Cytokine
https://www.readbyqxmd.com/read/28898528/post-transplant-oxygen-inhalation-improves-the-outcome-of-subcutaneous-islet-transplantation-a-promising-clinical-alternative-to-the-conventional-intrahepatic-site
#17
H Komatsu, J Rawson, A Barriga, N Gonzalez, D Mendez, J Li, K Omori, F Kandeel, Y Mullen
Subcutaneous tissue is a promising site for islet transplantation, due to its large area and accessibility, which allows minimally invasive procedures for transplantation, graft monitoring, and removal of malignancies as needed. However, relative to the conventional intrahepatic transplantation site, the subcutaneous site requires a large number of islets to achieve engraftment success and diabetes reversal, due to hypoxia and low vascularity. We report that the efficiency of subcutaneous islet transplantation in a Lewis rat model is significantly improved by treating recipients with inhaled 50% oxygen, in conjunction with prevascularization of the graft bed by agarose-bFGF...
September 12, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28895851/gene-therapy-approaches-to-hemoglobinopathies
#18
REVIEW
Giuliana Ferrari, Marina Cavazzana, Fulvio Mavilio
Gene therapy for hemoglobinopathies is currently based on transplantation of autologous hematopoietic stem cells genetically modified with a lentiviral vector expressing a globin gene under the control of globin transcriptional regulatory elements. Preclinical and early clinical studies showed the safety and potential efficacy of this therapeutic approach as well as the hurdles still limiting its general application. In addition, for both beta-thalassemia and sickle cell disease, an altered bone marrow microenvironment reduces the efficiency of stem cell harvesting as well as engraftment...
October 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/28895849/opening-marrow-niches-in-patients-undergoing-autologous-hematopoietic-stem-cell-gene-therapy
#19
REVIEW
Morton J Cowan, Christopher C Dvorak, Janel Long-Boyle
Successful gene therapy for genetic disorders requires marrow niches to be opened to varying degrees to engraft gene-corrected hematopoietic stem cells (HSC). For example, in severe combined immunodeficiency, relatively limited chimerism is necessary for both T- and B-cell immune reconstitution, whereas for inborn errors of metabolism maximal donor chimerism is the goal. Currently, alkylating chemotherapy is used for this purpose. Significant pharmacokinetic variability exists in drug clearance in children less than 12 years old...
October 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/28895848/gene-editing-regulatory-and-translation-to-clinic
#20
REVIEW
Dale Ando, Kathleen Meyer
The clinical application and regulatory strategy of genome editing for ex vivo cell therapy is derived from the intersection of two fields of study: viral vector gene therapy trials; and clinical trials with ex vivo purification and engraftment of CD34(+) hematopoietic stem cells, T cells, and tumor cell vaccines. This article covers the regulatory and translational preclinical activities needed for a genome editing clinical trial modifying hematopoietic stem cells and the genesis of this current strategy based on previous clinical trials using genome-edited T cells...
October 2017: Hematology/oncology Clinics of North America
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