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https://www.readbyqxmd.com/read/27936393/suppression-of-protein-tyrosine-phosphatase-ptpn22-gene-induces-apoptosis-in-t-cell-leukemia-cell-line-jurkat-through-the-akt-and-erk-pathways
#1
Elham Baghbani, Behzad Baradaran, Fatemeh Pak, Leila Mohammadnejad, Daryoush Shanehbandi, Behzad Mansoori, Vahid Khaze, Noushin Montazami, Ali Mohammadi, Parviz Kokhaei
The aim of this study was to investigate the effect of specific PTPN22 small interfering RNAs (siRNAs) on the viability and induction of apoptosis in Jurkat cells and to evaluate apoptosis signaling pathways. In this study, Jurkat cells were transfected with specific PTPN22 siRNA. Relative PTPN22 mRNA expression was measured by Quantitative Real-time PCR. Western blotting was performed to determine the protein levels of PTPN22, AKT, P-AKT, ERK, and P-ERK. The cytotoxic effects of PTPN22 siRNA were determined using the MTT assay...
December 6, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27935917/safety-and-efficacy-of-azathioprine-as-a-second-line-therapy-for-primary-immune-thrombocytopenic-purpura
#2
B S Poudyal, B Sapkota, G S Shrestha, S Thapalia, B Gyawali, S Tuladhar
INTRODUCTION: Immune thrombocytopenic purpura remains common blood disease in Nepal. Azathioprine is an oral immunosupressive medicine which has been used widely in various autoimmune disease and solid organ transplant patients. It is inexpensive, easily available and well tolerated medicine. This study was carried out to evaluate efficacy and safety of azathioprine as a second line medicine for primary ITP patients who were refractory to steroid therapy. METHODS: The observational, pre-post study was conducted at Government of Nepal Civil Service Hospital, Kathmandu from January to October 2014...
July 2016: JNMA; Journal of the Nepal Medical Association
https://www.readbyqxmd.com/read/27935867/the-bromodomain-inhibitor-otx015-mk-8628-exerts-anti-tumor-activity-in-triple-negative-breast-cancer-models-as-single-agent-and-in-combination-with-everolimus
#3
Ramiro Vázquez, María E Riveiro, Lucile Astorgues-Xerri, Elodie Odore, Keyvan Rezai, Eugenio Erba, Nicolò Panini, Andrea Rinaldi, Ivo Kwee, Luca Beltrame, Mohamed Bekradda, Esteban Cvitkovic, Francesco Bertoni, Roberta Frapolli, Maurizio D'Incalci
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subgroup of breast tumors clinically defined by the lack of estrogen, progesterone and HER2 receptors, limiting the use of the targeted therapies employed in other breast malignancies. Recent evidence indicates that c-MYC is a key driver of TNBC. The BET-bromodomain inhibitor OTX015 (MK-8628) has potent antiproliferative activity accompanied by c-MYC down-regulation in several tumor types, and has demonstrated synergism with the mTOR inhibitor everolimus in different models...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27935770/from-breast-cancer-to-antimicrobial-combating-extremely-resistant-gram-negative-superbugs-using-novel-combinations-of-polymyxin-b-with-selective-estrogen-receptor-modulators
#4
Maytham H Hussein, Elena K Schneider, Alysha G Elliott, Meiling Han, Felisa Reyes-Ortega, Faye Morris, Mark A T Blastovich, Raad Jasim, Bart Currie, Mark Mayo, Mark Baker, Matthew A Cooper, Jian Li, Tony Velkov
Novel therapeutic approaches are urgently needed to combat nosocomial infections caused by extremely drug-resistant (XDR) "superbugs." This study aimed to investigate the synergistic antibacterial activity of polymyxin B in combination with selective estrogen receptor modulators (SERMs) against problematic Gram-negative pathogens. In vitro synergistic antibacterial activity of polymyxin B and the SERMs tamoxifen, raloxifene, and toremifene was assessed using the microdilution checkerboard and static time-kill assays against a panel of Gram-negative isolates...
December 9, 2016: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/27935576/acute-lymphoblastic-leukemia-relapsing-after-first-line-pediatric-inspired-therapy-a-retrospective-graall-study
#5
A Desjonquères, P Chevallier, X Thomas, F Huguet, T Leguay, M Bernard, J-O Bay, E Tavernier, A Charbonnier, F Isnard, M Hunault, P Turlure, M Renaud, J-N Bastié, C Himberlin, S Lepretre, B Lioure, V Lhéritier, V Asnafi, K Beldjord, M Lafage-Pochitaloff, M C Béné, N Ifrah, H Dombret
The outcome of adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL) relapsing after pediatric-inspired front-line therapy is ill known. Here 229 relapsing Ph- ALL younger adults (18-63 years) treated within the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/-2005 trials were considered. Salvage regimens consisted of potentially curative therapies in 194 cases, low-intensity therapies in 21, allogeneic stem cell transplant (allo-SCT) in 6 and best supportive care in 8...
December 9, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27933513/effect-of-yiqi-tongyang-decoction-on-blood-t-cell-subsets-in-patients-with-chronic-immune-thrombocytopenia
#6
Xiu-Peng Yang, Rou Ma, Xiao-Hong Yang, Hui-Lan Zhu, Yong-Gang Xu
OBJECTIVE: To measure the proportions of blood T cell subsets, Th1, Th2, Th17, Th22, and Treg cells, and other parameters in patients with chronic immune thrombocytopenia (CITP) before and after treatment with Yiqi Tongyang Decoction (, YTD) to explore T cell status of patients with CITP, and to define the mechanism of action of YTD. METHODS: The changes in peripheral blood T lymphocyte subsets, and those of Th1, Th2, Th17, Th22, and Treg cells in 30 patients with CITP (22 females and 8 males) were analyzed using multiparametric flow cytometry before and after treatment with YTD for 6 months, and 26 healthy volunteers (14 males and 12 females) acted as a control...
December 9, 2016: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/27933352/intracochlear-drug-delivery-in%C3%A2-combination-with-cochlear-implants-current-aspects
#7
S K Plontke, G Götze, T Rahne, A Liebau
Local drug application to the inner ear offers a number of advantages over systemic delivery. Local drug therapy currently encompasses extracochlear administration (i. e., through intratympanic injection), intracochlear administration (particularly for gene and stem cell therapy), as well as various combinations with auditory neurosensory prostheses, either evaluated in preclinical or clinical studies, or off-label. To improve rehabilitation with cochlear implants (CI), one focus is the development of drug-releasing electrode carriers, e...
December 8, 2016: HNO
https://www.readbyqxmd.com/read/27933316/systemic-therapy-with-oncolytic-myxoma-virus-cures-established-residual-multiple-myeloma-in-mice
#8
Eric Bartee, Mee Y Bartee, Bjarne Bogen, Xue-Zhong Yu
Multiple myeloma is an incurable malignancy of plasma B-cells. Traditional chemotherapeutic regimes often induce initial tumor regression; however, virtually all patients eventually succumb to relapse caused by either reintroduction of disease during autologous transplant or expansion of chemotherapy resistant minimal residual disease. It has been previously demonstrated that an oncolytic virus known as myxoma can completely prevent myeloma relapse caused by reintroduction of malignant cells during autologous transplant...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27933315/immunogenicity-of-self-tumor-associated-proteins-is-enhanced-through-protein-truncation
#9
Tim Kottke, Kevin G Shim, Vanesa Alonso-Camino, Shane Zaidi, Rosa Maria Diaz, Jose Pulido, Jill Thompson, Karishma R Rajani, Laura Evgin, Elizabeth Ilett, Hardev Pandha, Kevin Harrington, Peter Selby, Alan Melcher, Richard Vile
We showed previously that therapy with Vesicular Stomatitis Virus (VSV) expressing tumor-associated proteins eradicates established tumors. We show here that when cellular cDNA were cloned into VSV which retained their own poly-A signal, viral species emerged in culture which had deleted the cellular poly-A signal and also contained a truncated form of the protein coding sequence. Typically, the truncation occurred such that a Tyrosine-encoding codon was converted into a STOP codon. We believe that the truncation of tumor-associated proteins expressed from VSV in this way occurred to preserve the ability of the virus to replicate efficiently...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27933308/tailored-transgene-expression-to-specific-cell-types-in-the-central-nervous-system-after-peripheral-injection-with-aav9
#10
Jonathan Dashkoff, Eli P Lerner, Nhi Truong, Jacob A Klickstein, Zhanyun Fan, Dakai Mu, Casey A Maguire, Bradley T Hyman, Eloise Hudry
The capacity of certain adeno-associated virus (AAV) vectors to cross the blood-brain barrier after intravenous delivery offers a unique opportunity for noninvasive brain delivery. However, without a well-tailored system, the use of a peripheral route injection may lead to undesirable transgene expression in nontarget cells or organs. To refine this approach, the present study characterizes the transduction profiles of new self-complementary AAV9 (scAAV9) expressing the green fluorescent protein (GFP) either under an astrocyte (glial fibrillary acidic (GFA) protein) or neuronal (Synapsin (Syn)) promoter, after intravenous injection of adult mice (2 × 10(13) vg/kg)...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27933058/skewed-lung-ccr4-to-ccr6-cd4-t-cell-ratio-in-idiopathic-pulmonary-fibrosis-is-associated-with-pulmonary-function
#11
Ayodeji Adegunsoye, Cara L Hrusch, Catherine A Bonham, Mohammad R Jaffery, Kelly M Blaine, Meghan Sullivan, Matthew M Churpek, Mary E Strek, Imre Noth, Anne I Sperling
RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease. While it has been suggested that T cells may contribute to IPF pathogenesis, these studies have focused primarily on T cells outside of the pulmonary interstitium. Thus, the role of T cells in the diseased lung tissue remains unclear. OBJECTIVE: To identify whether specific CD4(+) T cell subsets are differentially represented in lung tissue from patients with IPF. METHODS: CD4(+) T cell subsets were measured in lung tissue obtained from patients with IPF at the time of lung transplantation, and from age- and gender-matched organ donors with no known lung disease...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27932443/pd-l1-blockade-enhances-response-of-pancreatic-ductal-adenocarcinoma-to-radiotherapy
#12
Abul Azad, Su Yin Lim, Zenobia D'Costa, Keaton Jones, Angela Diana, Owen J Sansom, Philipp Kruger, Stanley Liu, W Gillies McKenna, Omer Dushek, Ruth J Muschel, Emmanouil Fokas
Pancreatic ductal adenocarcinoma (PDAC) is considered a non-immunogenic tumor, and immune checkpoint inhibitor monotherapy lacks efficacy in this disease. Radiotherapy (RT) can stimulate the immune system. Here, we show that treatment of KPC and Pan02 murine PDAC cells with RT and gemcitabine upregulated PD-L1 expression in a JAK/Stat1-dependent manner. In vitro, PD-L1 inhibition did not alter radio- and chemosensitivity. In vivo, addition of anti-PD-L1 to high (12, 5 × 3, 20 Gy) but not low (6, 5 × 2 Gy) RT doses significantly improved tumor response in KPC and Pan02 allografts...
December 8, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27932160/successful-short-term-intravenous-treatment-of-disseminated-nocardia-farcinica-infection-with-severe-hyponatremia-after-kidney-transplantation-a-case-report
#13
A L Herzog, C Wanner, K Lopau
BACKGROUND: Nocardia is a genus of gram-positive Actinomycetes that are ubiquitous in decaying organic material, soil, and water. Some Nocardia species can infect humans, mainly by airborne transmission. Several reports describe disseminated infections, which are rare and mostly affect strongly immunocompromised patients because intact T-cell-mediated immunity is the major protective mechanism. CASE REPORT: We report a case of disseminated pulmonary, cerebral, and cutaneous infection with Nocardia farcinica in a 66-year-old kidney transplant recipient treated with low-dose triple immunosuppression...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27932157/belatacept-and-eculizumab-for-treatment-of-calcineurin-inhibitor-induced-thrombotic-microangiopathy-after-kidney-transplantation-case-report
#14
J Merola, P S Yoo, J Schaub, J D Smith, M I Rodriguez-Davalos, E Tichy, D C Mulligan, W Asch, R Formica, M Kashgarian, S Kulkarni
Thrombotic microangiopathy (TMA) after kidney transplantation is an uncommon and challenging cause of graft dysfunction and is associated with early graft loss. An idiosyncratic endothelial reaction to calcineurin inhibitors (CNIs) has been implicated as a frequent cause of TMA. This reaction is marked by uncontrolled activation of complement and subsequent cellular destruction. Usual therapy consists of withdrawal of the inciting drug and plasmapheresis to minimize levels of circulating complement. Recently, eculizumab, a monoclonal antibody to complement component C5, has been used for the treatment of atypical hemolytic uremic syndrome...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27931835/management-of-patients-with-recurrent-advanced-cervical-cancer-beyond-first-line-platinum-regimens-where-do-we-stand-a-literature-review
#15
REVIEW
Stergios Boussios, Esmeralda Seraj, George Zarkavelis, Dimitrios Petrakis, Aristomenes Kollas, Aikaterini Kafantari, Abraam Assi, Konstantina Tatsi, Nicholas Pavlidis, George Pentheroudakis
BACKGROUND: Cervical cancer is the fourth most common cancer affecting women worldwide. Despite advances in screening and human papillomavirus (HPV) vaccination, a significant number of women present with or develop advanced disease. Palliative platinum-based chemotherapy (CT) is the standard first-line treatment for metastatic/recurrent cervical cancer. The prognosis remains poor and effective second line options are urgently needed. METHODS: We searched the English-language medical literature as well as relevant guideline databases, published from January 1981 to December 2015 and identified publications related to cervical cancer and its therapies...
December 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27931590/cytotoxic-t-lymphocyte-associated-protein-4-acts-on-local-draining-lymph-nodes-in-the-allogeneic-abdominal-skin-flap-of-a-rat-model-to-extend-its-survival
#16
G Ma, J Pei, Y Li, Y Han, D Liu
BACKGROUND: Early acute allograft rejection is the result of immune cells mainly composed of thymocyte (T) cells, which are activated, mature, and differentiate in lymphoid tissue. METHODS: Cytotoxic T lymphocyte-associated protein 4 immunoglobulin (CTLA4-Ig) competitively suppresses the cluster of differentiation 28/CTLA4-B7 costimulatory signaling pathway and alters the ratio of T helper 1 to T helper 2, leading to the inhibition of T cell activation. RESULTS: We used lentivirus-packed CTLA4-Ig to infect the local draining lymph nodes of the allograft skin flap in a rat model, which effectively extended the survival of the allograft...
December 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27931536/advances-in-atopic-dermatitis-in-2015
#17
REVIEW
Takashi Nomura, Kenji Kabashima
This review aims to highlight recently published articles on atopic dermatitis (AD). Updated are the insights into epidemiology, pathology, diagnostics, and therapy. Epidemiologic studies have revealed a positive correlation between AD and systemic conditions, such as rheumatoid arthritis, inflammatory bowel disease, and neonatal adiposity. Pathologic findings highlight the involvement of novel barrier factors (desmoplakin and claudin), novel immune cell subsets (pathogenic effector TH2 cells and group 2 innate lymphoid cells), and differential skewing of helper T cells (eg, TH17 dominance in Asians with AD)...
December 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27931534/advances-in-clinical-immunology-in-2015
#18
REVIEW
Javier Chinen, Luigi D Notarangelo, William T Shearer
Advances in clinical immunology in the past year included the report of practice parameters for the diagnosis and management of primary immunodeficiencies to guide the clinician in the approach to these relatively uncommon disorders. We have learned of new gene defects causing immunodeficiency and of new phenotypes expanding the spectrum of conditions caused by genetic mutations such as a specific regulator of telomere elongation (RTEL1) mutation causing isolated natural killer cell deficiency and mutations in ras-associated RAB (RAB27) resulting in immunodeficiency without albinism...
December 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27931505/phase-iii-clinical-trial-assessing-safety-and-efficacy-of-umbilical-cord-blood-mononuclear-cell-transplant-therapy-of-chronic-complete-spinal-cord-injury
#19
Hui Zhu, Waisang Poon, Yansheng Liu, Gilberto Ka-Kit Leung, Yatwa Wong, Yaping Feng, Stephanie C P Ng, Kam Sze Tsang, David T F Sun, David K Yeung, Caihong Shen, Fang Niu, Zhexi Xu, Pengju Tan, Shaofeng Tang, Hongkun Gao, Yun Cha, Kwok-Fai So, Robert Fleischaker, Dongming Sun, John Chen, Jan Lai, Wendy Cheng, Wise Young
Umbilical cord blood-derived mononuclear cell (UCB-MNC) transplants improve recovery in animal spinal cord injury (SCI) models. We transplanted UCB-MNCs into 28 patients with chronic complete SCI in Hong Kong (HK) and Kunming (KM). Stemcyte Inc. donated UCB-MNCs isolated from human leukocyte antigen (HLA 4:6)-matched UCB units. In HK, four patients received four 4-l injections (1.6 million cells) into dorsal entry zones above and below the injury site, and another four received 8-l injections (3.2 million cells)...
November 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27931306/idiopathic-cd4-lymphocytopenia
#20
Joel P Brooks, Gisoo Ghaffari
BACKGROUND: Idiopathic CD4 lymphocytopenia (ICL) is a rare disorder of unknown etiology. Diagnostic criteria include a persistent CD4 T-cell lymphopenia with no underlying primary or secondary immune deficiencies and a CD4 T-cell count of 300 cells/mL or 20% total lymphocyte on multiple occasions. OBJECTIVE: To increase awareness of ICL and to provide a review of the clinical characteristics, diagnosis, and management of this disease process. Presently, many of these patients receive prophylactic treatment similar to other T-cell deficient conditions, most notably patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome; however, the same indications may not necessarily apply to this patient population because the T cells are not affected by a virus as in HIV...
November 2016: Allergy and Asthma Proceedings:
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