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https://www.readbyqxmd.com/read/28919991/umbilical-cord-blood-cd34-progenitor-derived-nk-cells-efficiently-kill-ovarian-cancer-spheroids-and-intraperitoneal-tumors-in-nod-scid-il2rg-null-mice
#1
Janneke S Hoogstad-van Evert, Jeannette Cany, Dirk van den Brand, Manon Oudenampsen, Roland Brock, Ruurd Torensma, Ruud L Bekkers, Joop H Jansen, Leon F Massuger, Harry Dolstra
Adoptive transfer of allogeneic natural killer (NK) cells is an attractive therapy approach against ovarian carcinoma. Here, we evaluated the potency of highly active NK cells derived from human CD34+ haematopoietic stem and progenitor cells (HSPC) to infiltrate and mediate killing of human ovarian cancer spheroids using an in vivo-like model system and mouse xenograft model. These CD56+Perforin+ HSPC-NK cells were generated under stroma-free conditions in the presence of StemRegenin-1, IL-15, and IL-12, and exerted efficient cytolytic activity and IFNγ production toward ovarian cancer monolayer cultures...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28916879/a-score-combining-baseline-neutrophilia-and-primary-tumor-suvpeak-measured-from-fdg-pet-is-associated-with-outcome-in-locally-advanced-cervical-cancer
#2
Antoine Schernberg, Sylvain Reuze, Fanny Orlhac, Irène Buvat, Laurent Dercle, Roger Sun, Elaine Limkin, Alexandre Escande, Christine Haie-Meder, Eric Deutsch, Cyrus Chargari, Charlotte Robert
PURPOSE: We investigated whether a score combining baseline neutrophilia and a PET biomarker could predict outcome in patients with locally advanced cervical cancer (LACC). METHODS: Patients homogeneously treated with definitive chemoradiation plus image-guided adaptive brachytherapy (IGABT) between 2006 and 2013 were analyzed retrospectively. We divided patients into two groups depending on the PET device used: a training set (TS) and a validation set (VS). Primary tumors were semi-automatically delineated on PET images, and 11 radiomics features were calculated (LIFEx software)...
September 15, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28905173/pharmacokinetic-and-tissue-distribution-profile-of-long-acting-tenofovir-alafenamide-and-elvitegravir-loaded-nanoparticles-in-humanized-mice-model
#3
Pavan Kumar Prathipati, Subhra Mandal, Gregory Pon, Renuga Vivekanandan, Christopher J Destache
PURPOSE: Non-adherence to the antiretroviral (ARV) regimen is a critical factor in determining efficacy of ARV drugs for pre-exposure prophylaxis (PrEP). A long-acting parenteral formulation may be an effective alternative to daily oral dosing. A pharmacokinetic and tissue distribution study of drug-loaded nanoparticle (NP) was performed in female humanized CD34(+)-NSG mice. METHODS: Mice received 200 mg/kg each of tenofovir alafenamide (TAF) and elvitegravir (EVG) as free drugs (TAF + EVG solution) or as drug loaded NP (TAF + EVG NP) formulation by subcutaneous (SubQ) administration...
September 13, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28892093/rapid-generation-of-col7a1-mouse-model-of-recessive-dystrophic-epidermolysis-bullosa-and-partial-rescue-via-immunosuppressive-dermal-mesenchymal-stem-cells
#4
Beau R Webber, Kyle T O'Connor, Ron T McElmurry, Elise N Durgin, Cindy R Eide, Christopher J Lees, Megan J Riddle, Wendy E Mathews, Natasha Y Frank, Mark A Kluth, Christoph Ganss, Branden S Moriarity, Markus H Frank, Mark J Osborn, Jakub Tolar
Recessive dystrophic epidermolysis bullosa (RDEB) is a debilitating and ultimately lethal blistering disease caused by mutations to the Col7a1 gene. Development of novel cell therapies for the treatment of RDEB would be fostered by having immunodeficient mouse models able to accept human cell grafts; however, immunodeficient models of many genodermatoses such as RDEB are lacking. To overcome this limitation, we combined the clustered regularly interspaced short palindromic repeats and associated nuclease (CRISPR/Cas9) system with microinjection into NOD/SCID IL2rγc(null) (NSG) embryos to rapidly develop an immunodeficient Col7a1(-/-) mouse model of RDEB...
September 11, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28835380/single-dose-of-the-cxcr4-antagonist-bl-8040-induces-rapid-mobilization-for-the-collection-of-human-cd34-cells-in-healthy-volunteers
#5
Michal Abraham, Yaron Pereg, Baruch Bulvik, Shiri Klein, Inbal Mishalian, Hanna Wald, Orly Eizenberg, Katia Beider, Arnon Nagler, Rottem Golan, Abi Vainstein, Arnon Aharon, Eithan Galun, Yoseph Caraco, Reuven Or, Amnon Peled
PURPOSE: The potential of the high affinity CXCR4 antagonist BL-8040 as a monotherapy mobilizing agent and its derived graft composition and quality were evaluated in a phase I clinical study in healthy volunteers (NCT02073019). EXPERIMENTAL DESIGN: The first part of the study was a randomized, double-blind, placebo-controlled dose escalation phase. The second part of the study was an open label phase, in which 8 subjects received a single injection of BL-8040 (1mg/kg) and approximately 4hrs later underwent a standard leukapheresis procedure...
August 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28829785/dendrimer-doxorubicin-conjugates-exhibit-improved-anticancer-activity-and-reduce-doxorubicin-induced-cardiotoxicity-in-a-murine-hepatocellular-carcinoma-model
#6
Sibu P Kuruvilla, Gopinath Tiruchinapally, A Colleen Crouch, Mohamed E H ElSayed, Joan M Greve
Hepatocellular carcinoma (HCC) is the 2nd leading cause of cancer-related deaths every year globally. The most common form of treatment, hepatic arterial infusion (HAI), involves the direct injection of doxorubicin (DOX) into the hepatic artery. It is plagued with limited therapeutic efficacy and the occurrence of severe toxicities (e.g. cardiotoxicity). We aim to improve the therapeutic index of DOX delivered via HAI by loading the drug onto generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers targeted to hepatic cancer cells via N-acetylgalactosamine (NAcGal) ligands...
2017: PloS One
https://www.readbyqxmd.com/read/28828964/clinical-nutrition-and-gastrointestinal-dysfunction-in-critically-ill-stroke-patients
#7
Robert Patejdl, Matthias Kästner, Stephan Kolbaske, Matthias Wittstock
Background Data on the epidemiology and risk factors of altered gastrointestinal motility (AGIM) is virtually lacking for patients suffering from non-traumatic neurologic diseases and stroke. This study investigated whether patterns of AGIM differ between patients with stroke and other severe acute brain diseases. Methods Clinical records of stroke and non-stroke patients treated at a neurological intensive care unit (ICU) were reviewed at day 1-5 and at day 10 after admission. The data was analyzed for the course of enteral/parenteral nutrition and for and for signs and symptoms of gastrointestinal dysfunction...
August 22, 2017: Neurological Research
https://www.readbyqxmd.com/read/28827518/activated-protein-c-protects-from-gvhd-via-par2-par3-signalling-in-regulatory-t-cells
#8
Satish Ranjan, Alexander Goihl, Shrey Kohli, Ihsan Gadi, Mandy Pierau, Khurrum Shahzad, Dheerendra Gupta, Fabian Bock, Hongjie Wang, Haroon Shaikh, Thilo Kähne, Dirk Reinhold, Ute Bank, Ana C Zenclussen, Jana Niemz, Tina M Schnöder, Monika Brunner-Weinzierl, Thomas Fischer, Thomas Kalinski, Burkhart Schraven, Thomas Luft, Jochen Huehn, Michael Naumann, Florian H Heidel, Berend Isermann
Graft-vs.-host disease (GvHD) is a major complication of allogenic hematopoietic stem-cell(HSC) transplantation. GvHD is associated with loss of endothelial thrombomodulin, but the relevance of this for the adaptive immune response to transplanted HSCs remains unknown. Here we show that the protease-activated protein C (aPC), which is generated by thrombomodulin, ameliorates GvHD aPC restricts allogenic T-cell activation via the protease activated receptor (PAR)2/PAR3 heterodimer on regulatory T-cells (Tregs, CD4(+)FOXP3(+))...
August 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28826231/gene-therapy-with-an-aav-vector-expressing-human-il-2-alters-immune-system-homeostasis-in-humanized-mice
#9
Philip Durost, Ken-Edwin Aryee, Fatima Manzoor, Roland Tisch, Christian Mueller, Agata Jurczyk, Leonard Shultz, Michael Brehm
Recombinant adeno associated viruses (rAAV) serve as vectors for in vivo gene delivery in both mice and humans, and have broad applicability for the treatment of genetic diseases. Clinical trials with AAV vectors have demonstrated promise and safety in several human diseases. However, the in vivo validation of novel AAV constructs expressing products that act specifically on human cells and tissues is limited by a paucity of effective translatable models. Humanized mice that are engrafted with human cells, tissues, and immune systems offer strong potential to test the biological effectiveness of AAV vectors on human cells and tissues...
August 21, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28818731/association-between-severities-of-striae-gravidarum-and-obstetric-anal-sphincter-injuries-oasis
#10
Ofra Halperin, Anita Noble, Shosh Balachsan, Ester Klug, Michal Liebergall-Wischnitzer
OBJECTIVES: to examine the association between the severities of Striae Gravidarum (SG) and Obstetric Anal Sphincter Injuries (OASIS) and to measure the symptoms regarding urinary incontinence, fecal/flatus incontinence, and dyspareunia, at 6 and 12 months postpartum. DESIGN: this is a cohort study. SETTING: four university teaching medical centers in Israel, two in the north and two in the center of the country. PARTICIPANTS: women with OASIS were interviewed and assessed for SG...
November 2017: Midwifery
https://www.readbyqxmd.com/read/28818684/t-cell-mediated-rejection-of-human-cd34-cells-is-prevented-by-costimulatory-blockade-in-a-xenograft-model
#11
Annie L Oh, Dolores Mahmud, Benedetta Nicolini, Nadim Mahmud, Vitalyi Senyuk, Pritesh R Patel, Elisa Bonetti, Mario Arpinati, James L M Ferrara, Damiano Rondelli
A xenograft model of stem cell rejection was developed by co-transplantating human CD34(+) and allogeneic CD3(+) T cells into NOD-scid ɣ-chain(null) mice. T cells caused graft failure when transplanted at any CD34/CD3 ratio between 1:50 and 1:.1. Kinetics experiments showed that 2 weeks after transplantation CD34(+) cells engrafted the marrow and T cells expanded in the spleen. Then, at 4 weeks only memory T cells populated both sites and rejected CD34(+) cells. Blockade of T cell costimulation was tested by injecting the mice with abatacept (CTLA4-IgG1) from day -1 to +27 (group A), from day -1 to +13 (group B), or from day +14 to +28 (group C)...
August 14, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28817720/targeting-of-cdk9-with-indirubin-3-monoxime-safely-and-durably-reduces-hiv-viremia-in-chronically-infected-humanized-mice
#12
Sandra Medina-Moreno, Thomas C Dowling, Juan C Zapata, Nhut M Le, Edward Sausville, Joseph Bryant, Robert R Redfield, Alonso Heredia
Successful propagation of HIV in the human host requires entry into a permissive cell, reverse transcription of viral RNA, integration into the human genome, transcription of the integrated provirus, and assembly/release of new virus particles. Currently, there are antiretrovirals against each of these viral steps, except for provirus transcription. An inhibitor of HIV transcription could both increase potency of treatment and suppress drug-resistant strains. Cellular cyclin-dependent kinase 9 (CDK9) serves as a cofactor for the HIV Tat protein and is required for effective transcription of the provirus...
2017: PloS One
https://www.readbyqxmd.com/read/28801972/brief-report-a-differential-transcriptomic-profile-of-ex-vivo-expanded-adult-human-hematopoietic-stem-cells-empowers-them-for-engraftment-better-than-their-surface-phenotype
#13
Nikoletta Psatha, Grigorios Georgolopoulos, Susan Phelps, Thalia Papayannopoulou
Transplantation of small cord blood (CB) units, or of autologous ex vivo-genetically modified adult hematopoietic stem cells (HSC), face the common challenge of suboptimal HSC doses for infusion and impaired engraftment of the transplanted cells. Ex vivo expansion of HSCs, using either cell-based coculture approaches or especially small molecules have been successfully tested mainly in CB and in prolonged cultures. Here, we explored whether innovative combinations of small molecules can sufficiently, after short culture, expand adult HSCs while retaining their functionality in vivo...
August 11, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28800593/in-vivo-functional-and-morphological-characterization-of-bone-and-striated-muscle-microcirculation-in-nsg-mice
#14
Haider Mussawy, Lennart Viezens, Gerrit Hauenherm, Malte Schroeder, Christian Schaefer
Organ-specific microcirculation plays a central role in tumor growth, tumor cell homing, tissue engineering, and wound healing. Mouse models are widely used to study these processes; however, these mouse strains often possess unique microhemodynamic parameters, making it difficult to directly compare experiments. The full functional characterization of bone and striated muscle microcirculatory parameters in non-obese diabetic-severe combined immunodeficiency/y-chain; NOD-Prkds IL2rg (NSG) mice has not yet been reported...
2017: PloS One
https://www.readbyqxmd.com/read/28754914/memory-type-st2-cd4-t-cells-participate-in-the-steroid-resistant-pathology-of-eosinophilic-pneumonia
#15
Naoko Mato, Kiyoshi Hirahara, Tomomi Ichikawa, Jin Kumagai, Masayuki Nakayama, Hideaki Yamasawa, Masashi Bando, Koichi Hagiwara, Yukihiko Sugiyama, Toshinori Nakayama
The lung develops an unique epithelial barrier system to protect host from continuous invasion of various harmful particles. Interleukin (IL-)33 released from epithelial cells in the lung drives the type 2 immune response by activating ST2- expressed immune cells in various allergic diseases. However, the involvement of memory-type ST2(+)CD4(+) T cells in such lung inflammation remains unclear. Here we demonstrated that intratracheal administration of IL-33 resulted in the substantial increase of numbers of tissue-resident memory-type ST2(+)CD4(+) T cells in the lung...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28754817/multifaceted-role-of-btla-in-the-control-of-cd8-t-cell-fate-after-antigen-encounter
#16
Krit Ritthipichai, Cara Haymaker, Melisa Martinez-Paniagua, Andrew Aschenbrenner, Xiaohui Yi, Minying Zhang, Charuta Kale, Yared Hailemichael, Willem W Overwijk, Luis Vence, Jason Roszik, Navin Varadarajan, Roza Nurieva, Laszlo G Radvanyi, Patrick Hwu, Chantale Bernatchez
Adoptive T-cell therapy using autologous tumor-infiltrating lymphocytes (TIL) has shown an overall clinical response rate 40-50% in metastatic melanoma patients. BTLA (B-and-T lymphocyte attenuator) expression on transferred CD8(+) TIL was associated with better clinical outcome. The suppressive function of the ITIM and ITSM motifs of BTLA is well described. Here, we sought to determine the functional characteristics of the CD8(+)BTLA(+)TIL subset and define the contribution of the Grb2 motif of BTLA in T cell co-stimulation...
July 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28751450/infiltrating-t-cells-increase-ido1-expression-in-glioblastoma-and-contribute-to-decreased-patient-survival
#17
Lijie Zhai, Erik Ladomersky, Kristen L Lauing, Meijing Wu, Matthew Genet, Galina Gritsina, Balázs Győrffy, Priscilla K Brastianos, David Binder, Jeffrey A Sosman, Francis J Giles, C David James, Craig Horbinski, Roger Stupp, Derek A Wainwright
Indoleamine 2,3 dioxygenase 1 (IDO1) mediates potent immunosuppression in multiple preclinical models of cancer. However, the basis for elevated IDO1 expression in human cancer, including the most common primary malignant brain tumor in adults, glioblastoma (GBM), is poorly understood. The major objective of this study is to address this gap in our understanding of how IDO1 expression contributes to the biology of GBM, and whether its level of expression is a determinant of GBM patient outcome. Experimental Design: Patient-resected GBM, the cancer genome atlas, human T cell:GBM co-cultures, as well as nu/nu, NOD-scid and humanized (NSG-SGM3-BLT) mice engrafted human GBM, form the basis of our investigation...
July 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28751353/cmml-jmml-pdxs-as-easy-as-1-2-nsg-sgm3
#18
Rachel E Rau
No abstract text is available yet for this article.
July 27, 2017: Blood
https://www.readbyqxmd.com/read/28746332/proceeding-report-of-joint-meeting-of-nepalese-association-for-the-studies-of-the-liver-and-nepalese-society-of-gastroenterologists-on-overcoming-the-challenges-for-hepatitis-c-virus-elimination-in-nepal-by-2030
#19
(no author information available yet)
No abstract text is available yet for this article.
April 2017: JNMA; Journal of the Nepal Medical Association
https://www.readbyqxmd.com/read/28744323/in-depth-characterization-of-a-tcr-specific-tracer-for-sensitive-detection-of-tumor-directed-transgenic-t-cells-by-immuno-pet
#20
Nahid Yusufi, Sabine Mall, Henrique de Oliveira Bianchi, Katja Steiger, Sybille Reder, Richard Klar, Stefan Audehm, Mona Mustafa, Stephan Nekolla, Christian Peschel, Markus Schwaiger, Angela M Krackhardt, Calogero D'Alessandria
A number of different technologies have been developed to monitor in vivo the distribution of gene-modified T cells used in immunotherapy. Nevertheless, in-depth characterization of novel approaches with respect to sensitivity and clinical applicability are so far missing. We have previously described a novel method to track engineered human T cells in tumors using (89)Zr-Df-aTCRmu-F(ab')2 targeting the murinized part of the TCR beta domain (TCRmu) of a transgenic TCR. Here, we performed an in-depth in vitro characterization of the tracer in terms of antigen affinity, immunoreactivity, influence on T-cell functionality and stability in vitro and in vivo...
2017: Theranostics
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