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https://www.readbyqxmd.com/read/28544604/thymic-peripheral-crosstalk-in-lymphodepletion-therapy
#1
EDITORIAL
M E Snyder, D L Farber
T cell depletion is widely used as induction therapy in solid organ transplants and particularly in kidney transplantation, to reduce the episodes of acute cellular rejection. The resultant reduction in T cell numbers is usually temporary, as T cells are actively replenished due to thymic output and/or lymphopenia-induced proliferation of remaining, depletion-resistant T cells. However, the extent of T cell replenishment and the persistence of lymphopenia varies between individuals, with potential impacts on protective or pathogenic immune responses...
May 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28544595/severe-cytokine-release-syndrome-in-a-patient-receiving-pd-1-directed-therapy
#2
Seth J Rotz, Daniel Leino, Sara Szabo, Jennifer L Mangino, Brian K Turpin, Joseph G Pressey
Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of cellular and bispecific T-cell engaging immunotherapy. Checkpoint blockade using anti-programmed cell death 1 (anti-PD-1) inhibitors is an approach to antitumor immune system stimulation. A 29-year-old female with alveolar soft part sarcoma developed severe CRS after treatment with anti-PD-1 therapy. CRS was characterized by high fevers, encephalopathy, hypotension, hypoxia, hepatic dysfunction, and evidence of coagulopathy, and resolved after infusion of the interleukin-6 inhibitor tocilizumab and corticosteroids...
May 24, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28544545/cytoprotective-encapsulation-of-individual-jurkat-t-cells-within-durable-tio2-shells-for-t-cell-therapy
#3
Wongu Youn, Eun Hyea Ko, Mi-Hee Kim, Matthew Park, Daewha Hong, Gulaim A Seisenbaeva, Vadim G Kessler, Insung S Choi
Lymphocytes, such as T cells and natural killer (NK) cells, have therapeutic promises in adoptive cell transfer (ACT) therapy, where the cells are activated and expanded in vitro, and then infused into a patient. However, the in vitro preservation of labile lymphocytes during transfer, manipulation, and storage has been one of the bottlenecks in the development and commercialization of therapeutic lymphocytes. Herein, we suggest a "cell-in-shell" (a.k.a. artificial spore) strategy to enhance the cell viability in the practical settings, while maintaining biological activities for therapeutic efficacy...
May 25, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28544264/ampk-%C3%AE-1-reduces-tumor-progression-and-improves-survival-in-p53-null-mice
#4
Vanessa P Houde, Sara Donzelli, Andrea Sacconi, Sandra Galic, Joanne A Hammill, Jonathan L Bramson, Robert A Foster, Theodoros Tsakiridis, Bruce E Kemp, Giuseppe Grasso, Giovanni Blandino, Paola Muti, Gregory R Steinberg
The AMP-activated protein kinase (AMPK) is a heterotrimeric protein complex that is an important sensor of cellular energy status. Reduced expression of the AMPK β1 isoform has been linked to reduced survival in different cancers but whether this accelerates tumor progression and the potential mechanism mediating these effects is not known. Further, it is unknown whether AMPK β1 is implicated in tumorigenesis and if so what tissues may be most sensitive. In the current study we find that in the absence of the tumor suppressor p53, germline genetic deletion of AMPK β1 accelerates the appearance of a T cell lymphoma that reduces lifespan compared to p53 deficiency alone...
May 24, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28544152/a-risk-adapted-approach-to-treating-respiratory-syncytial-virus-and-human-parainfluenza-virus-in-allogeneic-stem-cell-transplantation-recipients-with-oral-ribavirin-therapy-a-pilot-study
#5
José Luis Piñana, Juan Carlos Hernández-Boluda, Marisa Calabuig, Isabel Ballester, Manuela Marín, Silvia Madrid, Anabel Teruel, María-José Terol, David Navarro, Carlos Solano
Here we report the applicability of a protocol based on clinical conditions and risk factors (RFs) for managing 35 allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients who developed a total of 52 episodes of respiratory viral infections (RVIs) caused by respiratory syncytial virus (RSV; n=19), human parainfluenza virus (HPIV; n=29), or both (n=4) over a 2-year study period. Risk categories were classified as high risk (cat-1) when the immunodeficiency scoring index) was ≥ 3 and/or ≥ 3 RFs and/or ≥ 1 co-infective virus(es) were present; the remaining cases were classified as low risk (cat-0)...
May 19, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28544101/belatacept-combined-with-transient-calcineurin-inhibitor-therapy-prevents-rejection-and-promotes-improved-long-term-renal-allograft-function
#6
A B Adams, J Goldstein, C Garrett, R Zhang, R E Patzer, K A Newell, N A Turgeon, A S Chami, A Guasch, A D Kirk, S O Pastan, T C Pearson, C P Larsen
Belatacept, a T cell costimulation-blocker demonstrated superior renal function, lower cardiovascular risk, and improved graft/patient survival in renal transplant recipients. Despite the potential benefits, adoption of belatacept has been limited in part due to concerns regarding higher rates and grades of acute rejection in clinical trials. Since July 2011 we have utilized belatacept-based immunosuppression regimens in clinical practice. In this retrospective analysis of 745 patients undergoing renal transplantation at our center, we compared patients treated with belatacept (n=535) to a historical cohort receiving a tacrolimus-based protocol (n=205)...
May 23, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28543931/severe-asthma-in-children
#7
REVIEW
Andrew Bush, Louise Fleming, Sejal Saglani
Most children with asthma have their disease easily controlled if low-dose inhaled corticosteroids (ICSs) are regularly and correctly administered. If a child presents with asthma which is apparently resistant to therapy with high-dose ICS and other controllers, then they have problematic severe asthma. However, in light of the UK National Review of Asthma Deaths, definitions of severe asthma based solely on the levels of prescribed treatment are too narrow. A detailed assessment of all such children should be performed...
May 25, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28543699/immune-and-molecular-correlates-in-melanoma-treated-with-immune-checkpoint-blockade
#8
REVIEW
Elizabeth H Byrne, David E Fisher
Immunotherapy for metastatic melanoma has a decades-long history, and the relatively recent use of checkpoint inhibitors has revolutionized treatment. Durable and sometimes complete remission of metastatic melanoma is now achievable in some patients who receive checkpoint-blocking therapy. However, it is unclear why some patients fare better than others. This review highlights several molecular indicators of response to checkpoint inhibition in metastatic melanoma, focusing on tumor programmed death ligand 1 expression, major histocompatibility complex class I expression, mutational load in the tumor, and T-cell infiltration into the tumor...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28543698/adoptive-t-cell-therapy-an-overview-of-obstacles-and-opportunities
#9
REVIEW
Erez Nissim Baruch, Amy Lauren Berg, Michal Judith Besser, Jacob Schachter, Gal Markel
The therapeutic potential of adoptive cell therapy (ACT) in cancer patients was first acknowledged 3 decades ago, but it was an esoteric approach at the time. In recent years, technological advancements have transformed ACT into a viable therapeutic option that can be curative in some patients. In fact, current ACT response rates are 80% to 90% for hematological malignancies and 30% for metastatic melanoma refractory to multiple lines of therapy. Although these results are encouraging, there is still much to be done to fulfill ACT's potential, specifically with regard to improving clinical efficacy, expanding clinical indications, reducing toxicity, and increasing production and cost-effectiveness...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28543586/multiple-skin-cancers-in-patients-with-mycosis-fungoides-after-long-term-ultraviolet-phototherapy
#10
K Imafuku, H Hata, T Yanagi, S Kitamura, Y Inamura-Takashima, M Nishimura, S Kitamura, S Moriwaki, H Shimizu
Phototherapy is a useful noninvasive therapy, but it can induce cutaneous malignant tumours, including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). We report on a 79-year-old man who had long-standing mycosis fungoides for 40 years, which had been treated with psoralen ultraviolet A therapy for 37 years at a dose of approximately 5000 J/cm(2) . Approximately 6 years before presentation, numerous types of cutaneous malignancies, including actinic keratosis, BCC and SCC, had begun to develop all over the patient's body...
May 22, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28543181/loss-of-l-selectin-guided-cd8-but-not-cd4-cells-protects-against-ischemia-reperfusion-injury-in-a-steatotic-liver
#11
Vasantha L Kolachala, Sirish Palle, Ming Shen, Alayna Feng, Dmitry Shayakhmetov, Nitika A Gupta
BACKGROUND & AIMS: Steatotic liver responds with increased hepatocellular injury when exposed to an ischemic-reperfusion insult. Increasing evidence supports the role of immune cells as key mediators of this injury in a normal (lean) state, but data about their role in a steatotic liver are practically non-existent. The objective of the current study was to delineate contribution of specific phenotypes of T cells and adhesion molecules in exacerbated cell death in steatotic liver injury...
May 20, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28543072/obstructive-sleep-apnea-in-the-irradiated-head-and-neck-cancer-patient
#12
Phillip Huyett, Seungwon Kim, Jonas T Johnson, Ryan J Soose
OBJECTIVES/HYPOTHESIS: To assess the prevalence of obstructive sleep apnea (OSA) in head and neck cancer (HNSCC) patients treated with radiation therapy. STUDY DESIGN: Prospective case series without comparison group. METHODS: Patients who underwent radiation therapy for oropharyngeal or laryngeal squamous cell carcinoma completed a 3-night home sleep test (HST), Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and University of Washington Quality of Life questionnaire...
May 23, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28542715/hyperleucocytosis-in-paediatric-acute-myeloid-leukaemia-the-challenge-of-white-blood-cell-counts-above-200%C3%A2-%C3%A3-%C3%A2-10-9-l-the-nopho-experience-1984-2014
#13
Bernward Zeller, Heidi Glosli, Erik Forestier, Shau-Yin Ha, Kirsi Jahnukainen, Ólafur G Jónsson, Birgitte Lausen, Josefine Palle, Henrik Hasle, Jonas Abrahamsson
Hyperleucocytosis in paediatric acute myeloid leukaemia (AML) is associated with increased morbidity and mortality. We studied hyperleucocytosis in 890 patients with AML aged 0-18 years registered in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) registry, with special focus on very high white blood cell counts (WBC >200 × 10/l). Eighty-six patients (10%) had WBC 100-199 × 10(9) /l and 57 (6%) had WBC ≥200 × 10(9) /l. Patients with WBC ≥200 × 10(9) /l had a high frequency of t(9;11) and a paucity of trisomy 8...
May 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28542701/two-separate-effects-contribute-to-regulatory-t-cell-defect-in-sle-patients-and-their-unaffected-relatives
#14
Nuno Costa, Oriana Marques, Sandra I Godinho, Cláudia Carvalho, Barbara Leal, Ana M Figueiredo, Carlos Vasconcelos, António Marinho, Maria F Moraes-Fontes, António Gomes da Costa, Cristina Ponte, Raquel Campanilho-Marques, Telma Cóias, Ana R Martins, João F Viana, Margarida Lima, Berta Martins, Constantin Fesel
FOXP3(+) regulatory T-cells (Tregs) are functionally deficient in Systemic Lupus Erythematosus (SLE), characterized by reduced surface CD25 (the IL-2 receptor alpha chain). Low-dose IL-2 therapy is a promising current approach to correct this defect. To elucidate the origins of the SLE Treg phenotype, we studied its role through developmentally defined Treg subsets in 45 SLE patients, 103 SLE-unaffected first-degree relatives and 61 unrelated healthy control subjects, and genetic association with the CD25-encoding IL2RA locus...
May 24, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28542679/patterns-of-treatment-failure-and-postrecurrence-outcomes-among-patients-with-locally-advanced-head-and-neck-squamous-cell-carcinoma-after-chemoradiotherapy-using-modern-radiation-techniques
#15
Jonathan E Leeman, Jin-Gao Li, Xin Pei, Praveen Venigalla, Zachary S Zumsteg, Evangelia Katsoulakis, Eitan Lupovitch, Sean M McBride, Chiaojung J Tsai, Jay O Boyle, Benjamin R Roman, Luc G T Morris, Lara A Dunn, Eric J Sherman, Nancy Y Lee, Nadeem Riaz
Importance: Even though 15% to 50% of patients with head and neck squamous cell carcinoma (HNSCC) experience recurrence, relatively little is known regarding patterns of treatment failure and postrecurrence outcomes after chemoradiotherapy using modern radiation techniques (intensity-modulated radiotherapy [IMRT]). Recurrence patterns are significantly affected by variations in the quality of radiotherapy, which may confound findings from multicenter trials. Objective: To assess patterns of treatment failure and postrecurrence outcomes for patients with HNSCC treated with contemporary radiotherapy techniques...
May 25, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28542574/combination-therapy-of-cancer-with-cancer-vaccine-and-immune-checkpoint-inhibitors-a-mathematical-model
#16
Xiulan Lai, Avner Friedman
In this paper we consider a combination therapy of cancer. One drug is a vaccine which activates dendritic cells so that they induce more T cells to infiltrate the tumor. The other drug is a checkpoint inhibitor, which enables the T cells to remain active against the cancer cells. The two drugs are positively correlated in the sense that an increase in the amount of each drug results in a reduction in the tumor volume. We consider the question whether a treatment with combination of the two drugs at certain levels is preferable to a treatment by one of the drugs alone at 'roughly' twice the dosage level; if that is the case, then we say that there is a positive 'synergy' for this combination of dosages...
2017: PloS One
https://www.readbyqxmd.com/read/28542546/albendazole-increases-the-inflammatory-response-and-the-amount-of-em2-positive-small-particles-of-echinococcus-multilocularis-spems-in-human-hepatic-alveolar-echinococcosis-lesions
#17
Franz J Ricken, Juliane Nell, Beate Grüner, Julian Schmidberger, Tanja Kaltenbach, Wolfgang Kratzer, Andreas Hillenbrand, Doris Henne-Bruns, Peter Deplazes, Peter Möller, Peter Kern, Thomas F E Barth
BACKGROUND: Alveolar echinococcosis (AE) is caused by the metacestode stage of Echinococcus multilocularis. The inflammatory response to this infection is influenced by the interaction of the parasite with the host. We aimed to analyze human liver lesions infected with Echinococcus multilocularis and the changes of the cellular infiltrates during albendazole (ABZ) treatment. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed liver tissue samples from 8 untreated patients, 5 patients treated with two daily doses of 400 mg ABZ for up to two months and 7 patients treated for more than two months with the same ABZ therapy...
May 25, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28542329/novel-agoshrna-molecules-for-silencing-of-the-ccr5-co-receptor-for-hiv-1-infection
#18
Elena Herrera-Carrillo, Ben Berkhout
Allogeneic transplantation of blood stem cells from a CCR5-Δ32 homozygous donor to an HIV-infected individual, the "Berlin patient", led to a cure. Since then there has been a search for approaches that mimic this intervention in a gene therapy setting. RNA interference (RNAi) has evolved as a powerful tool to regulate gene expression in a sequence-specific manner and can be used to inactivate the CCR5 mRNA. Short hairpin RNA (shRNA) molecules can impair CCR5 expression, but these molecules may cause unintended side effects and they will not be processed in cells that lack Dicer, such as monocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28542260/hookworm-infection-is-associated-with-decreased-cd4-t-cell-counts-in-hiv-infected-adult-ugandans
#19
Bozena M Morawski, Miya Yunus, Emmanuel Kerukadho, Grace Turyasingura, Logose Barbra, Andrew Mijumbi Ojok, Andrew DiNardo, Stefanie Sowinski, David R Boulware, Rojelio Mejia
Most studies evaluating epidemiologic relationships between helminths and HIV have been conducted in the pre-ART era, and evidence of the impact of helminth infections on HIV disease progression remains conflicting. Less is known about helminth infection and clinical outcomes in HIV-infected adults receiving antiretroviral therapy (ART). We sampled HIV-infected adults for eight gastrointestinal parasites and correlated parasitic infection with demographic predictors, and clinical and immunologic outcomes. Contrasting with previous studies, we measured parasitic infection with a quantitative, highly sensitive and specific polymerase chain reaction (PCR) method...
May 25, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28541773/induction-of-salivary-gland-like-cells-from-dental-follicle-epithelial-cells
#20
Q L Xu, A Furuhashi, Q Z Zhang, C M Jiang, T-H Chang, A D Le
The dental follicle (DF), most often associated with unerupted teeth, is a condensation of ectomesenchymal cells that surrounds the tooth germ in early stages of tooth development. In the present study, we aim to isolate epithelial stem-like cells from the human DF and explore their potential differentiation into salivary gland (SG) cells. We demonstrated the expression of stem cell-related genes in the epithelial components of human DF tissues, and these epithelial progenitor cells could be isolated and ex vivo expanded in a reproducible manner...
May 1, 2017: Journal of Dental Research
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