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https://www.readbyqxmd.com/read/28231431/enhancing-adoptive-cell-therapy-of-cancer-through-targeted-delivery-of-small-molecule-immunomodulators-to-internalizing-or-non-internalizing-receptors
#1
Yiran Zheng, Li Tang, Llian Mabardi, Sudha Kumari, Darrell J Irvine
Adoptive cell therapy (ACT) has achieved striking efficacy in B-cell leukemias, but less success treating other cancers, in part due to the rapid loss of ACT T-cell effector function in vivo due to immunosuppression in solid tumors. Transforming growth factor-β (TGF-β) signaling is an important mechanism of immune suppression in the tumor microenvironment, but systemic inhibition of TGF-β is toxic. Here we evaluated the potential of targeting a small molecule inhibitor of TGF-β to ACT T-cells using PEGylated immunoliposomes...
February 23, 2017: ACS Nano
https://www.readbyqxmd.com/read/28228214/inhibition-of-protein-tyrosine-phosphatase-non-receptor-type-2-by-ptp-inhibitor-xix-its-role-as-a-multiphosphatase-inhibitor
#2
Hien Thi Thu Le, Young-Chang Cho, Sayeon Cho
Protein tyrosine phosphatases (PTPs) play crucial roles in signal transduction and their functional alteration has been detected in many diseases. PTP inhibitors have been developed as therapeutic drugs for diseases that are related to the activity of PTPs. In this study, PTP inhibitor XIX, an inhibitor of CD45 and PTEN, was investigated whether it inhibits other PTPs. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) was selectively inhibited by the inhibitor in a competitive manner. Drug affinity responsive target stability (DARTS) analysis showed that the inhibitor induces conformational changes in PTPN2...
February 23, 2017: BMB Reports
https://www.readbyqxmd.com/read/28225836/analysis-of-immune-cell-populations-in-atrial-myocardium-of-patients-with-atrial-fibrillation-or-sinus-rhythm
#3
Natalia Smorodinova, Martin Bláha, Vojtěch Melenovský, Karolína Rozsívalová, Jaromír Přidal, Mária Ďurišová, Jan Pirk, Josef Kautzner, Tomáš Kučera
BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia and despite obvious clinical importance remains its pathogenesis only partially explained. A relation between inflammation and AF has been suggested by findings of increased inflammatory markers in AF patients. OBJECTIVE: The goal of this study was to characterize morphologically and functionally CD45-positive inflammatory cell populations in atrial myocardium of patients with AF as compared to sinus rhythm (SR)...
2017: PloS One
https://www.readbyqxmd.com/read/28218774/osteoblast-differentiation-of-rabbit-adipose-derived-stem-cells-by-polyethylenimine-mediated-bmp-2-gene-transfection-in-vitro
#4
Q F Wang, Y Huang, G C He, H S Wang, Z H Chen, X H Cai, Y H Xie, Q Liu
The aim of this study was to examine the efficiency of polyethylenimine-mediated transfection of the human bone morphogenetic protein-2 (BMP-2) gene into rabbit adipose-derived stem cells (ADSCs), and its effect on osteoblast differentiation. Adipose tissue was isolated from the necks of adult Japanese white rabbits and cultured in vitro to obtain ADSCs. Gene delivery of BMP-2 was mediated by polyethylenimine and stable transformants were selected by G-418. The expression of BMP-2 mRNA was confirmed by reverse transcription-polymerase chain reaction, and of the BMP-2 protein by ELISA...
February 16, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28218384/clinical-significance-of-circulating-tumor-cells-in-patients-with-small-cell-lung-cancer
#5
Yu-Li Wang, Chun-Hua Liu, Jing Li, Xiao-Ping Ma, Ping Gong
BACKGROUND: This study investigated the correlation of the presence of circulating tumor cells (CTCs) with clinical characteristics, and the predictive value of CTCs for progression-free survival (PFS) in patients with small-cell lung cancer (SCLC). METHODS: Samples were obtained from 42 patients with SCLC before and after the first cycle of chemotherapy. CTCs were quantitated by negative immunomagnetic enrichment and immunocytochemistry using anti-CD45 and anti-pancytokeratin antibodies...
February 15, 2017: Tumori
https://www.readbyqxmd.com/read/28216546/bach2-controls-homeostasis-of-eosinophils-by-restricting-the-type-2-helper-function-of-t-cells
#6
Yuki Sato, Hiroki Kato, Risa Ebina-Shibuya, Ari Itoh-Nakadai, Ryuhei Okuyama, Kazuhiko Igarashi
Bach2 is a transcription factor which represses its target genes and plays important roles in the differentiation of B and T lymphoid cells. Bach2-deficient (KO) mice develop severe pulmonary alveolar proteinosis, which is associated with increased numbers of granulocytes and T cells. Bach2 is essential for the regulation of T cells, but its role in the regulation of granulocytes is not clear. Here, we observed increased numbers of eosinophils but not neutrophils in the bone marrow, spleen, peripheral blood, and bronchoalveolar lavage fluids of Bach2 KO mice compared with those of wild-type (WT) mice...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28213979/mmp-2-and-mmp-14-silencing-inhibits-vegfr2-cleavage-and-induces-the-differentiation-of-porcine-adipose-derived-mesenchymal-stem-cells-to-endothelial-cells
#7
Sami G Almalki, Yovani Llamas Valle, Devendra K Agrawal
The molecular mechanisms that control the ability of adipose-derived mesenchymal stem cells (AMSCs) to remodel three-dimensional extracellular matrix barriers during differentiation are not clearly understood. Herein, we studied the expression of matrix metalloproteinases (MMPs) during the differentiation of AMSCs to endothelial cells (ECs) in vitro. MSCs were isolated from porcine abdominal adipose tissue, and characterized by immunopositivity to CD44, CD90, CD105, and immunonegativity to CD14 and CD45. Plasticity of AMSCs was confirmed by multilineage differentiation...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28212995/heterogeneity-of-circulating-tumor-cells-ctcs-in-patients-with-recurrent-small-cell-lung-cancer-sclc-treated-with-pazopanib
#8
I Messaritakis, E Politaki, M Plataki, V Karavassilis, N Kentepozidis, F Koinis, E Samantas, V Georgoulias, A Kotsakis
OBJECTIVES: To investigate the effect of pazopanib on different CTCs subpopulations in patients with recurrent SCLC and evaluate their clinical relevance. METHODS: Peripheral blood was obtained before the administration of pazopanib (n=56 patients), after the first cycle (n=35 patients) and at disease progression (n=45 patients). CTCs were detected by CellSearch and double immunofluorescent staining using antibodies against the cytokeratins (CK), TTF-1, CD56 and VEGFR2...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28212663/isolation-of-primary-microglia-from-the-human-post-mortem-brain-effects-of-ante-and-post-mortem-variables
#9
Mark R Mizee, Suzanne S M Miedema, Marlijn van der Poel, Adelia, Karianne G Schuurman, Miriam E van Strien, Jeroen Melief, Joost Smolders, Debbie A Hendrickx, Kirstin M Heutinck, Jörg Hamann, Inge Huitinga
Microglia are key players in the central nervous system in health and disease. Much pioneering research on microglia function has been carried out in vivo with the use of genetic animal models. However, to fully understand the role of microglia in neurological and psychiatric disorders, it is crucial to study primary human microglia from brain donors. We have developed a rapid procedure for the isolation of pure human microglia from autopsy tissue using density gradient centrifugation followed by CD11b-specific cell selection...
February 17, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28210430/growth-kinetics-and-characterization-of-human-dental-pulp-stem-cells-comparison-between-third-molar-and-first-premolar-teeth
#10
Davood Mehrabani, Parisa Mahdiyar, Kianoosh Torabi, Reza Robati, Shahrokh Zare, Mehdi Dianatpour, Amin Tamadon
BACKGROUND: Dental pulp stem cells (DPSCs) play an important role in tissue regeneration. This study compares the growth kinetics and characterization of third molar and first premolar human DPSCs. MATERIAL AND METHODS: Dental pulp tissues were isolated from human first premolar and third molar teeth and were digested by treating them with collagenase type I. Single-cell suspensions from each dental pulp were seeded in T25 culture flasks and the media were replaced every 3 days until 70% confluence...
February 2017: Journal of Clinical and Experimental Dentistry
https://www.readbyqxmd.com/read/28209483/a-new-size-based-platform-for-circulating-tumor-cell-detection-in-colorectal-cancer-patients
#11
Bo Young Oh, Jhingook Kim, Woo Yong Lee, Hee Cheol Kim
BACKGROUND: Circulating tumor cells (CTCs) might play a significant role in cancer progression and metastasis. However, the ability to detect CTCs is limited, especially in cells undergoing epithelial-mesenchymal transition. In this study, we evaluated a new size-based CTC detection platform and its clinical efficacy in colorectal cancer. PATIENTS AND METHODS: Blood samples were obtained from 76 patients with colorectal cancer and 20 healthy control subjects for CTC analysis...
January 25, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28205525/testicular-activin-and-follistatin-levels-are-elevated-during-the-course-of-experimental-autoimmune-epididymo-orchitis-in-mice
#12
Nour Nicolas, Vera Michel, Sudhanshu Bhushan, Eva Wahle, Susan Hayward, Helen Ludlow, David M de Kretser, Kate L Loveland, Hans-Christian Schuppe, Andreas Meinhardt, Mark P Hedger, Monika Fijak
Experimental autoimmune epididymo-orchitis (EAEO) is a model of chronic inflammation, induced by immunisation with testicular antigens, which reproduces the pathology of some types of human infertility. Activins A and B regulate spermatogenesis and steroidogenesis, but are also pro-inflammatory, pro-fibrotic cytokines. Expression of the activins and their endogenous antagonists, inhibin and follistatin, was examined in murine EAEO. Adult untreated and adjuvant-treated control mice showed no pathology. All mice immunised with testis antigens developed EAEO by 50 days, characterised by loss of germ cells, immune cell infiltration and fibrosis in the testis, similar to biopsies from human inflamed testis...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205462/atypical-chronic-myeloid-leukemia-in-a-german-shepherd-dog
#13
Christina L Marino, Jimmy N S N Tran, Tracy Stokol
A 4-y-old neutered male German Shepherd Dog was presented with a 3-d duration of lethargy, restlessness, and vomiting. Physical examination revealed generalized lymphadenopathy, pale mucous membranes, systolic heart murmur, dehydration, and fever. Hematologic abnormalities included moderate-to-marked leukocytosis, characterized by neutrophilia with a left shift to progranulocytes and 2% presumptive myeloid blasts, marked anemia that was nonregenerative, and marked thrombocytopenia. Dysplasia was evident in neutrophils and platelets...
February 1, 2017: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/28205389/growth-inhibition-of-formed-corneal-neovascularization-following-fosaprepitant-treatment
#14
Fabio Bignami, Anna Lorusso, Paolo Rama, Giulio Ferrari
PURPOSE: The aim of this study was to test the efficacy of Neurokinin-1 Receptor (NK-1R) antagonist -Fosaprepitant- in inducing regression of established corneal neovascularization (CNV). METHODS: Twenty C57BL/6 mice underwent alkali burn. Seven days later, when corneal neovessels had developed, they received Fosaprepitant 10 mg/ml, administered topically six times a day in the right eye for 10 days. In parallel, a group of 20 causticated mice was treated with normal saline, as control...
February 15, 2017: Acta Ophthalmologica
https://www.readbyqxmd.com/read/28205023/low-serum-culture-with-novel-medium-promotes-maxillary-mandibular-bone-marrow-stromal-cell-proliferation-and-osteogenic-differentiation-ability
#15
Fumio Suehiro, Masakazu Ishii, Izumi Asahina, Hiroshi Murata, Masahiro Nishimura
OBJECTIVES: The purpose of this study was to evaluate the effect of low-serum STK2 medium on the isolation and osteogenic differentiation of human maxillary/mandibular bone marrow stromal cells (MBMSCs). MATERIALS AND METHODS: Human MBMSCs were obtained from patients undergoing dental implant treatment. These cells were cultured in serum-free medium or STK2 medium containing 1  % fetal bovine serum (low-serum) or α-MEM containing 10  % fetal bovine serum (control)...
February 16, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/28202223/filtration-based-enrichment-of-circulating-tumor-cells-from-all-prostate-cancer-risk-groups
#16
Julius Adebayo Awe, Jeff Saranchuk, Darrel Drachenberg, Sabine Mai
OBJECTIVE: To combine circulating tumor cell (CTC) isolation by filtration and immunohistochemistry to investigate the presence of CTCs in low, intermediate, and high-risk prostate cancer (PCa). CTCs isolated from these risk groups stained positive for both cytokeratin and androgen receptors, but negative for CD45. PATIENTS AND METHODS: Blood samples from 41 biopsy confirmed patients with PCa at different clinical stages such as low, intermediate, and high risk were analyzed...
February 12, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28198402/an-integrated-microfluidic-device-for-rapid-and-high-sensitivity-analysis-of-circulating-tumor-cells
#17
Jianing Jiang, Hui Zhao, Weiliang Shu, Jing Tian, Yuqing Huang, Yongxin Song, Ruoyu Wang, Encheng Li, Dennis Slamon, Dongmei Hou, Xiaohui Du, Lichuan Zhang, Yan Chen, Qi Wang
Recently there has been a more focus on the development of an efficient technique for detection of circulating tumor cells (CTCs), due to their significance in prognosis and therapy of metastatic cancer. However, it remains a challenge because of the low count of CTCs in the blood. Herein, a rapid and high-sensitivity approach for CTCs detection using an integrated microfluidic system, consisting of a deterministic lateral displacement (DLD) isolating structure, an automatic purifying device with CD45-labeled immunomagnetic beads and a capturing platform coated with rat-tail collagen was reported...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197017/characterization-and-therapeutic-application-of-canine-adipose-mesenchymal-stem-cells-to-treat-elbow-osteoarthritis
#18
Éva Kriston-Pál, Ágnes Czibula, Zoltán Gyuris, Gyula Balka, Antal Seregi, Farkas Sükösd, Miklós Süth, Endre Kiss-Tóth, Lajos Haracska, Ferenc Uher, Éva Monostori
Visceral adipose tissue (AT) obtained from surgical waste during routine ovariectomies was used as a source for isolating canine mesenchymal stem cells (MSCs). As determined by cytofluorimetry, passage 2 cells expressed MSC markers CD44 and CD90 and were negative for lineage-specific markers CD34 and CD45. The cells differentiated toward osteogenic, adipogenic, and chondrogenic directions. With therapeutic aims, 30 dogs (39 joints) suffering from elbow dysplasia (ED) and osteoarthritis (OA) were intra-articularly transplanted with allogeneic MSCs suspended in 0...
January 2017: Canadian Journal of Veterinary Research, Revue Canadienne de Recherche Vétérinaire
https://www.readbyqxmd.com/read/28196035/perivascular-stem-cells-diminish-muscle-atrophy-following-massive-rotator-cuff-tears-in-a-small-animal-model
#19
Claire D Eliasberg, Ayelet Dar, Andrew R Jensen, Iain R Murray, Winters R Hardy, Tomasz J Kowalski, Cameron A Garagozlo, Kyle M Natsuhara, Adam Z Khan, Owen J McBride, Peter I Cha, Benjamin V Kelley, Denis Evseenko, Brian T Feeley, David R McAllister, Bruno Péault, Frank A Petrigliano
BACKGROUND: Rotator cuff tears are a common cause of shoulder pain and often necessitate operative repair. Muscle atrophy, fibrosis, and fatty infiltration can develop after rotator cuff tears, which may compromise surgical outcomes. This study investigated the regenerative potential of 2 human adipose-derived progenitor cell lineages in a murine model of massive rotator cuff tears. METHODS: Ninety immunodeficient mice were used (15 groups of 6 mice). Mice were assigned to 1 of 3 surgical procedures: sham, supraspinatus and infraspinatus tendon transection (TT), or TT and denervation via suprascapular nerve transection (TT + DN)...
February 15, 2017: Journal of Bone and Joint Surgery. American Volume
https://www.readbyqxmd.com/read/28194440/transient-antibody-targeting-of-cd45rc-induces-transplant-tolerance-and-potent-antigen-specific-regulatory-t-cells
#20
Elodie Picarda, Séverine Bézie, Laetitia Boucault, Elodie Autrusseau, Stéphanie Kilens, Dimitri Meistermann, Bernard Martinet, Véronique Daguin, Audrey Donnart, Eric Charpentier, Laurent David, Ignacio Anegon, Carole Guillonneau
Rat and human CD4(+) and CD8(+) Tregs expressing low levels of CD45RC have strong immunoregulatory properties. We describe here that human CD45 isoforms are nonredundant and identify distinct subsets of cells. We show that CD45RC is not expressed by CD4(+) and CD8(+) Foxp3(+) Tregs, while CD45RA/RB/RO are. Transient administration of a monoclonal antibody (mAb) targeting CD45RC in a rat cardiac allotransplantation model induced transplant tolerance associated with inhibition of allogeneic humoral responses but maintained primary and memory responses against cognate antigens...
February 9, 2017: JCI Insight
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