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https://www.readbyqxmd.com/read/28818731/association-between-severities-of-striae-gravidarum-and-obstetric-anal-sphincter-injuries-oasis
#1
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...
August 1, 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
#2
A L Oh, D Mahmud, B Nicolini, N Mahmud, V Senyuk, P R Patel, E Bonetti, M Arpinati, Jlm Ferrara, D 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) (NSG) mice. T cells caused graft failure when transplanted at any CD34:CD3 ratio between 1:50 to 1:0.1. Kinetics experiments showed that two weeks after transplantation CD34+ cells engrafted the marrow and T cells expanded in the spleen. Then at four 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), or 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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.<br /><br />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
#9
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
#10
(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
#11
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
https://www.readbyqxmd.com/read/28733324/nadph-oxidase-2-derived-superoxide-drives-mitochondrial-transfer-from-bone-marrow-stromal-cells-to-leukemic-blasts
#12
Christopher R Marlein, Lyubov Zaitseva, Rachel E Piddock, Stephen Robinson, Dylan Edwards, Manar S Shafat, Zhigang Zhou, Matthew Lawes, Kristian M Bowles, Stuart A Rushworth
Improvements in the understanding of the metabolic cross-talk between cancer and its micro-environment are expected to lead to novel therapeutic approaches. Acute myeloid leukemia (AML) cells have increased mitochondria compared to non-malignant CD34+ hematopoietic progenitor cells. Furthermore, contrary to the Warburg hypothesis, (AML) relies on oxidative phosphorylation to generate ATP. Here we report that in human AML, NOX2 generates superoxide which stimulates bone marrow stromal cells (BMSC) to AML blast transfer of mitochondria through AML derived tunnelling nanotubes...
July 21, 2017: Blood
https://www.readbyqxmd.com/read/28729148/clinical-grade-expanded-regulatory-t-cells-prevent-graft-versus-host-disease-while-allowing-a-powerful-t-cell-dependent-graft-versus-leukemia-effect-in-murine-models
#13
Beatrice Del Papa, Loredana Ruggeri, Elena Urbani, Stefano Baldoni, Debora Cecchini, Tiziana Zei, Roberta Iacucci Ostini, Barbara Crescenzi, Alessandra Carotti, Antonio Pierini, Paolo Sportoletti, Paolo Di Bartolomeo, Franca Falzetti, Cristina Mecucci, Andrea Velardi, Massimo F Martelli, Mauro Di Ianni
We developed a good manufacturing practices-compatible expansion protocol to improve number and purity of regulatory T cells (Tregs) available for clinical trials. Six clinical-grade separation procedures were performed, followed by expansion with high-dose interleukin (IL)-2, anti-CD3/anti-CD28 TCR stimulation, and rapamycin for 19 days achieving a median of 8.5-fold (range, 6.25 to 13.7) expansion. FOXP3 expression was stably maintained over the culture period, while the percentage of CD127 was significantly reduced...
July 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28726547/three-dimensional-bio-printing-of-hepatic-structures-with-direct-converted-hepatocyte-like-cells
#14
Kyojin Kang, Yohan Kim, Seung Bum Lee, Ji Sook Kim, Sua Park, Wan-Doo Kim, Heung-Mo Yang, Sung-Joo Kim, Jaemin Jeong, Dongho Choi
Three-dimensional (3D) bio-printing technology is a promising new technology in the field of bio-artificial organ generation with regard to overcoming the limitations of organ supply. The cell source for bio-printing is very important. Here, we generated 3D hepatic scaffold with mouse induced hepatocyte-like cells (miHeps), and investigated whether their function was improved after transplantation in vivo. To generate miHeps, mouse embryonic fibroblasts were transformed with pMX retroviruses individually expressing hepatic transcription factors Hnf4a and Foxa3...
July 20, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28726516/targeting-nsg-mice-engrafting-cells-with-a-clinically-applicable-lentiviral-vector-corrects-osteoclasts-in-infantile-malignant-osteopetrosis
#15
Ilana Moscatelli, Henrik Löfvall, Christian Schneider Thudium, Michael Rothe, Carmen Montano, Zsuzsanna Kertész, Mehtap Sirin, Ansgar Schulz, Axel Schambach, Kim Henriksen, Johan Richter
Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by nonfunctional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to develop a clinically applicable lentiviral vector expressing TCIRG1 to correct osteoclast function in IMO. We compared two mammalian promoters: elongation factor 1α short promoter (EFS) and chimeric myeloid promoter (ChimP). EFS was chosen for continued experiments as it performed better...
July 20, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28725894/quantifying-spontaneous-metastasis-in-a-syngeneic-mouse-melanoma-model-using-real-time-pcr
#16
Wentao Deng, Sarah L McLaughlin, David J Klinke
Modeling metastasis in vivo with animals is a priority for both revealing mechanisms of tumor dissemination and developing therapeutic methods. While conventional intravenous injection of tumor cells provides an efficient and consistent system for studying tumor cell extravasation and colonization, studying spontaneous metastasis derived from orthotopic tumor sites has the advantage of modeling more aspects of the metastatic cascade, but is challenging as it is difficult to detect small numbers of metastatic cells...
August 7, 2017: Analyst
https://www.readbyqxmd.com/read/28719220/egfr-targeted-cationic-polymeric-mixed-micelles-for-codelivery-of-gemcitabine-and-mir-205-for-treating-advanced-pancreatic-cancer
#17
Goutam Mondal, Saud Almawash, Amit Kumar Chaudhary, Ram I Mahato
Gemcitabine (GEM), a first-line chemotherapy for pancreatic cancer undergoes rapid metabolism and develops chemoresistance after repeated administration. We previously demonstrated that the combination of GEM and miR-205 provides an effective therapeutic strategy to sensitize GEM-resistant pancreatic cancer cells. Since epidermal growth factor receptor (EGFR) is overexpressed in pancreatic cancer cells, in this study, we aimed to deliver mixed micelles containing GEM and miR-205 decorated with EGFR-targeting cetuximab (C225) monoclonal antibody for targeted therapy...
July 31, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28713380/targeting-the-human-t-cell-inducible-costimulator-molecule-with-a-monoclonal-antibody-prevents-graft-vs-host-disease-and-preserves-graft-vs-leukemia-in-a-xenograft-murine-model
#18
Aude Burlion, Simon Brunel, Nicolas Y Petit, Daniel Olive, Gilles Marodon
BACKGROUND: Graft-vs-host disease (GVHD) is a major complication of allogenic bone marrow transplantation (BMT). Targeting costimulatory molecules with antagonist antibodies could dampen the excessive immune response that occurs, while preserving the beneficial graft vs leukemia (GVL) of the allogeneic response. Previous studies using a mouse model of GVHD have shown that targeting the T-cell Inducible COStimulator (ICOS, CD278) molecule is beneficial, but it is unclear whether the same applies to human cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28703806/inhibition-of-autophagy-as-a-treatment-strategy-for-p53-wild-type-acute-myeloid-leukemia
#19
Hendrik Folkerts, Susan Hilgendorf, Albertus T J Wierenga, Jennifer Jaques, André B Mulder, Paul J Coffer, Jan Jacob Schuringa, Edo Vellenga
Here we have explored whether inhibition of autophagy can be used as a treatment strategy for acute myeloid leukemia (AML). Steady-state autophagy was measured in leukemic cell lines and primary human CD34(+) AML cells with a large variability in basal autophagy between AMLs observed. The autophagy flux was higher in AMLs classified as poor risk, which are frequently associated with TP53 mutations (TP53(mut)), compared with favorable- and intermediate-risk AMLs. In addition, the higher flux was associated with a higher expression level of several autophagy genes, but was not affected by alterations in p53 expression by knocking down p53 or overexpression of wild-type p53 or p53(R273H)...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28698205/an-fc-engineered-cd19-antibody-eradicates-mrd-in-patient-derived-mll-rearranged-acute-lymphoblastic-leukemia-xenografts
#20
Denis M Schewe, Ameera Alsadeq, Cornelia Sattler, Lennart Lenk, Fotini Vogiatzi, Gunnar Cario, Simon Vieth, Thomas Valerius, Sophia Rosskopf, Fabian Meyersieck, Julia Alten, Martin Schrappe, Martin Gramatzki, Matthias Peipp, Christian Kellner
Antibody therapy constitutes a major advance in the treatment of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). To evaluate the efficacy and the mechanisms of action of CD19 monoclonal antibody therapy in pediatric BCP-ALL, an Fc engineered CD19 antibody carrying the S239D/I332E mutation for improved effector cell recruitment (CD19-DE) was tested. Patient derived xenografts (PDX) of pediatric MLL-rearranged ALL were established in NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ (NSG) mice. Antibody CD19-DE was efficient in prolonging the survival of NSG mice in a minimal residual disease (MRD) model...
July 11, 2017: Blood
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