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https://www.readbyqxmd.com/read/28817755/measuring-toxic-effects-and-time-to-treatment-failure-for-nivolumab-plus-ipilimumab-in-melanoma
#1
Alexander N Shoushtari, Claire F Friedman, Pedram Navid-Azarbaijani, Michael A Postow, Margaret K Callahan, Parisa Momtaz, Katherine S Panageas, Jedd D Wolchok, Paul B Chapman
Importance: Nivolumab plus ipilimumab (nivo + ipi) is a standard treatment of advanced melanoma. Two randomized trials describe high objective response rates by Response Evaluation Criteria in Solid Tumors. The trials assessed toxic effects using the Common Terminology Criteria for Adverse Events (CTCAE), which may underestimate incidence of clinically significant immune-related adverse events (AEs). Objective: To describe detailed toxic effects and time to treatment failure of patients with melanoma treated with nivo + ipi in a prospective cohort...
August 17, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28817445/the-safety-of-pembrolizumab-in-metastatic-melanoma-and-rheumatoid-arthritis
#2
Akshjot Puri, Jade Homsi
Immunotherapy has been in use for the treatment of melanoma since a very long time, but only recently have the cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody ipilimumab and programmed cell death-1 inhibitors such as nivolimumab and pembrolizumab been shown to induce marked improvements in survival in patients with metastatic melanoma. An important concern arises in terms of the safety of the use of these agents in patients with autoimmune diseases, solid organ transplant recipients on immunosuppression, patients with a history of previous hepatitis B or C, and patients with HIV infections as these patients were excluded from pivotal immunotherapy studies...
August 16, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28817434/everolimus-is-associated-with-less-weight-gain-than-tacrolimus-2-years-following-liver-transplantation-results-of-a-randomized-multicenter-study
#3
Michael Charlton, Mary Rinella, Dharmesh Patel, Kevin McCague, Julie Heimbach, Kymberly Watt
BACKGROUND: Weight gain early after transplant is a risk factor for posttransplant metabolic syndrome (PTMS), cardiovascular events, and renal insufficiency. The impact of mTOR inhibition on posttransplant weight gain and the development of PTMS components postliver transplantation were examined in a randomized, controlled study. METHODS: Following a run-in period, patients (N = 719) were randomized at 30±5 days posttransplant in a 1:1:1 ratio to 3 treatment groups: (i) everolimus (EVR) + reduced tacrolimus (TAC)(n=245); (ii) TAC control (n=243) or (iii) TAC elimination (n=231)...
August 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28817184/the-influence-of-cytomegalovirus-on-expression-of-hla-g-and-its-ligand-kir2dl4-by-human-peripheral-blood-leucocyte-subsets
#4
Zaid Albayati, Ahmed Alyami, Suliman Alomar, Derek Middleton, Laura Bonnett, Sobia Aleem, Brian F Flanagan, Stephen E Christmas
HLA-G is a non-classical class I HLA antigen, normally expressed in high levels only on extravillous cytotrophoblast. It has immunosuppressive properties in pregnancy and has also been found to be upregulated on leucocytes in viral infection. In this study, proportions of all leucocyte subsets expressing HLA-G were found to be low in healthy subjects positive or negative for cytomegalovirus (CMV). Significantly greater proportions of CD4+CD69+ and CD56+ T cells expressed HLA-G compared to other T cells. However, following stimulation with CMV antigens or intact CMV, proportions of CD4+, CD8+, CD69+ and CD56+ T cells, and also B cells expressing HLA-G were significantly increased in CMV+ subjects...
August 17, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28817117/increased-tumor-infiltrating-cd45ra-ccr7-regulatory-t-cell-subset-with-immunosuppressive-properties-foster-gastric-cancer-progress
#5
Fang-Yuan Mao, Hui Kong, Yong-Liang Zhao, Liu-Sheng Peng, Weisan Chen, Jin-Yu Zhang, Ping Cheng, Ting-Ting Wang, Yi-Pin Lv, Yong-Sheng Teng, Xiao-Long Fu, Yu-Gang Liu, Xiao-Long Wu, Chuan-Jie Hao, Nan You, Ping Luo, Pei-Wu Yu, Quan-Ming Zou, Gang Guo, Yuan Zhuang
Regulatory T cells (Tregs) are major components of tumor-infiltrating immune cells with potent immunosuppressive properties in gastric cancer (GC) microenvironment. However, different subsets of the Tregs and their relevance to GC are unknown. Here, we found that patients with GC showed a significantly higher Tregs infiltration in tumors, and CD45RA(-)CCR7(-) Treg subset constituted most tumor-infiltrating Tregs. Tumor-infiltrating CD45RA(-)CCR7(-) Treg subset with an effector/memory phenotype accumulated in tumors and expressed low level of HLA-DR...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28816948/medial-medullary-infarction-caused-by-antineutrophil-cytoplasmic-antibody-related-vasculitis-case-report-and-review-of-the-literature
#6
Kumi Yanagiha, Kazuhiro Ishii, Tomoyuki Ueno, Aiki Marushima, Akira Tamaoka
RATIONALE: Medial medullary infarction accounts for less than 1% of brain infarctions, and medial medullary infarctions is very rarely caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. PATIENT CONCERNS: We report the case of a 76-year-old man at low risk of arteriosclerosis who presented with disorders on the left side including gaze-evoked nystagmus, paralysis of the extremities, pyramidal signs, sensory disturbance, and dysesthesia. Brain magnetic resonance imaging also showed right medial medullary infarction...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28816394/a-review-of-inflammatory-idiopathic-myopathy-focusing-on-polymyositis
#7
REVIEW
K E N Clark, D A Isenberg
Inflammatory idiopathic myopathies are a group of autoimmune diseases affecting predominantly the proximal skeletal muscles, with raised muscle enzymes, with or without skin involvement and extramuscular organ involvement. Autoantibodies help to characterize patients into different clinical phenotypes. Successful treatment necessitates controlling inflammation early with corticosteroids and invariably requires additional immunosuppressive therapy. This review focuses on the aetiology, pathogenesis, clinical presentation, investigations and management of patients presenting with inflammatory idiopathic myopathies, predominantly focusing on polymyositis and antisynthetase syndrome...
August 17, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28816141/combined-radiation-therapy-and-immune-checkpoint-blockade-therapy-for-breast-cancer
#8
REVIEW
Zishuo I Hu, Alice Y Ho, Heather L McArthur
PURPOSE: Treatment with checkpoint inhibitors has shown durable responses in a number of solid tumors, including melanoma, lung, and renal cell carcinoma. However, most breast cancers are resistant to monotherapy with checkpoint inhibitors. Radiation therapy (RT) has been shown to have a number of immunostimulatory effects, including priming the immune system, recruiting immune cells to the tumor environment, and altering the immunosuppressive effects of the tumor microenvironment. RT therefore represents a promising adjuvant therapy to checkpoint blockade in breast cancer...
September 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28815551/atypical-fibroxanthoma-management-recurrence-metastasis-and-disease-specific-death
#9
REVIEW
Margit Marisa Polcz, Deshan Frank Sebaratnam, Pablo Fernández-Peñas
Atypical fibroxanthoma (AFX) is a rare spindle cell neoplasm predominantly found on the head and neck of elderly individuals with sun-damaged skin, with no evidence-based guidelines for their management. A systematic retrospective review of the literature focusing on treatment modality found a recurrence and metastasis rate of 8.0% (5.6% when adjusted for incomplete excisions) and 0.5% for local excision and 4.6% and 3.2% for Mohs micrographic surgery, respectively. Our results suggest that with clear surgical margins, AFX is unlikely to recur and metastases are rare, with significantly higher rates in the immunosuppressed population...
August 17, 2017: Australasian Journal of Dermatology
https://www.readbyqxmd.com/read/28815356/dent-disease-in-poland-what-we-have-learned-so-far
#10
Marcin Zaniew, Małgorzata Mizerska-Wasiak, Iga Załuska-Leśniewska, Piotr Adamczyk, Katarzyna Kiliś-Pstrusińska, Adam Haliński, Jan Zawadzki, Beata S Lipska-Ziętkiewicz, Krzysztof Pawlaczyk, Przemysław Sikora, Michael Ludwig, Maria Szczepańska
PURPOSE: Dent disease (DD) is a rare tubulopathy characterized by proximal tubular dysfunction leading to chronic kidney disease (CKD). The aim of the study was to characterize patients with DD in Poland. METHODS: A retrospective analysis of a national cohort with genetically confirmed diagnosis. RESULTS: Of 24 males, all patients except one carried mutations in the CLCN5 gene; in one patient a mutation in the OCRL gene was disclosed. Molecular diagnosis was delayed 1 year on average (range 0-21 years)...
August 16, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28815305/predictors-of-early-mortality-after-rabbit-antithymocyte-globulin-as-first-line-treatment-in-severe-aplastic-anemia
#11
Elias H Atta, Carlos B L Lima, Danielle S P Dias, Diego V Clé, Mariana M Bonduel, Gabriela B Sciuccati, Larissa A Medeiros, Michel M Oliveira, Marco A Salvino, Marlene P Garanito, Patricia B Blum Fonseca, Sara Teresinha O Saad, Rodrigo T Calado, Phillip Scheinberg
Despite being recommended as first-line immunosuppressive therapy in severe aplastic anemia (SAA), horse antithymocyte globulin (ATG) is still unavailable in many countries outside the USA. Rabbit ATG is more lymphocytoxic than horse ATG, and this might result in a higher incidence of severe infections and early mortality. This study was designed to identify the risk factors for early mortality and overall survival (OS) after rabbit ATG in patients with SAA. We retrospectively reviewed 185 patients with SAA who underwent rabbit ATG and cyclosporine...
August 16, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28815213/identification-of-rab18-as-an-essential-host-factor-for-bk-polyomavirus-infection-using-a-whole-genome-rna-interference-screen
#12
Linbo Zhao, Michael J Imperiale
BK polyomavirus (BKPyV) is a human pathogen first isolated in 1971. BKPyV infection is ubiquitous in the human population, with over 80% of adults worldwide being seropositive for BKPyV. BKPyV infection is usually asymptomatic; however, BKPyV reactivation in immunosuppressed transplant patients causes two diseases, polyomavirus-associated nephropathy and hemorrhagic cystitis. To establish a successful infection in host cells, BKPyV must travel in retrograde transport vesicles to reach the nucleus. To make this happen, BKPyV requires the cooperation of host cell proteins...
July 2017: MSphere
https://www.readbyqxmd.com/read/28815045/tumor-derived-exosomes-induce-cd8-t-cell-suppressors
#13
Brian T Maybruck, Lukas W Pfannenstiel, Marcela Diaz-Montero, Brian R Gastman
BACKGROUND: The suppressive nature of immune cells in the tumor microenvironment plays a major role in regulating anti-tumor immune responses. Our previous work demonstrated that a soluble factor from tumor cells is able to induce a suppressor phenotype (SP) in human CD8(+) T cells typified by loss of CD27/CD28 expression and acquisition of a potent suppressor function. The present study hypothesized that the soluble mechanism that is inducing the SP in CD8(+) T cells are tumor-derived exosomes (TDEs)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28815043/the-mek-inhibitor-selumetinib-complements-ctla-4-blockade-by-reprogramming-the-tumor-immune-microenvironment
#14
Edmund Poon, Stefanie Mullins, Amanda Watkins, Geoffrey S Williams, Jens-Oliver Koopmann, Gianfranco Di Genova, Marie Cumberbatch, Margaret Veldman-Jones, Shaun E Grosskurth, Vasu Sah, Alwin Schuller, Corrine Reimer, Simon J Dovedi, Paul D Smith, Ross Stewart, Robert W Wilkinson
BACKGROUND: T-cell checkpoint blockade and MEK inhibitor combinations are under clinical investigation. Despite progress elucidating the immuno-modulatory effects of MEK inhibitors as standalone therapies, the impact of MEK inhibition on the activity of T-cell checkpoint inhibitors remains incompletely understood. Here we sought to characterize the combined effects of MEK inhibition and anti-CTLA-4 mAb (anti-CTLA-4) therapy, examining effects on both T-cells and tumor microenvironment (TME)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28815025/oesophageal-candidiasis-and-squamous-cell-cancer-in-patients-with-gain-of-function-stat1-gene-mutation
#15
Sara Koo, Deepak Kejariwal, Tariq Al-Shehri, Anjan Dhar, Desa Lilic
BACKGROUND: Oesophageal candidiasis is a common, usually self-limiting opportunistic infection, but long-term infection with Candida is known to predispose to oral and oesophageal squamous cell cancer (SCC). Permissive factors that lead to immune deficiencies can underlie persistent or recurring candidiasis, called chronic mucocutaneous candidiasis (CMC). Secondary immune deficiencies are most often due to human immunodeficiency virus (HIV) infection, antibiotic use and immunosuppressive treatment (steroids, chemotherapy)...
August 2017: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/28814905/conjunctival-flora-of-human-immunodeficiency-virus-patients-on-antiretroviral-treatment
#16
Kagmeni Giles, Yannick Bilong, Andin Viola Dohvoma, Steve Robert Ebana, Hortance Gonsu
OBJECTIVES: To determine the conjunctival flora of human immunodeficiency virus (HIV) patients on antiretroviral treatment (ART). METHODOLOGY: A total of 104 conjunctival swabs from 104 HIV patients on ART underwent microbiological evaluation to describe the flora. RESULT: There were 71 (68.26%) women and 33 (31.74%) men. The mean age was 42.9 ± 9.77 (range: 22-70) years. Negative cultures were found in 39 (37.50%) cases. Bacterial growth occurred in 65 (62...
2017: Ophthalmology and Eye Diseases
https://www.readbyqxmd.com/read/28814524/mutation-of-the-putative-immunosuppressive-domain-of-the-retroviral-envelope-glycoprotein-compromises-infectivity
#17
Urszula Eksmond, Bryony Jenkins, Julia Merkenschlager, Walther Mothes, Jonathan P Stoye, George Kassiotis
The envelope glycoprotein of diverse endogenous and exogenous retroviruses is considered inherently immunosuppressive. Extensive work mapped the immunosuppressive activity to a highly conserved domain, termed the immunosuppressive domain (ISD), in the transmembrane (TM) subunit of the envelope glycoprotein and identified two naturally polymorphic key residues that afford immunosuppressive activity to distinct envelope glycoproteins. Concurrent mutation of these two key residues (E14R and A20F) in the envelope glycoprotein of Friend murine leukemia virus (F-MLV) ISD has been reported to abolish its immunosuppressive activity, without affecting its fusogenicity, and to weaken the ability of the virus to replicate specifically in immunocompetent hosts...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28814193/sirolimus-and-mirabegron-interaction-in-a-hematopoietic-cell-transplant-patient
#18
Jeff A Engle, Christina Fair
Purpose Hematopoietic cell transplant patients are exposed to numerous classes of medications. Transplant practitioners must vigilantly monitor for drug interactions especially involving immunosuppressants. We report a hematopoietic cell transplant patient receiving sirolimus who developed supratherapeutic serum concentrations after initiating mirabegron. Summary A 31-year-old, 98 kg female received a second umbilical cord blood transplant four years after the first transplant for relapsed acute myeloid leukemia...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28813676/pharmacologic-or-genetic-targeting-of-glutamine-synthetase-skews-macrophages-toward-an-m1-like-phenotype-and-inhibits-tumor-metastasis
#19
Erika M Palmieri, Alessio Menga, Rosa Martín-Pérez, Annamaria Quinto, Carla Riera-Domingo, Giacoma De Tullio, Douglas C Hooper, Wouter H Lamers, Bart Ghesquière, Daniel W McVicar, Attilio Guarini, Massimiliano Mazzone, Alessandra Castegna
Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813659/the-dna-methylcytosine-dioxygenase-tet2-sustains-immunosuppressive-function-of-tumor-infiltrating-myeloid-cells-to-promote-melanoma-progression
#20
Wen Pan, Shu Zhu, Kun Qu, Katrina Meeth, Jijun Cheng, Kaixin He, Hongdi Ma, Yan Liao, Xizhi Wen, Christine Roden, Zuzana Tobiasova, Zheng Wei, Jun Zhao, Jun Liu, Ji Zheng, Bo Guo, Sajid A Khan, Marcus Bosenberg, Richard A Flavell, Jun Lu
Ten-Eleven-Translocation-2 (Tet2) is a DNA methylcytosine dioxygenase that functions as a tumor suppressor in hematopoietic malignancies. We examined the role of Tet2 in tumor-tissue myeloid cells and found that Tet2 sustains the immunosuppressive function of these cells. We found that Tet2 expression is increased in intratumoral myeloid cells both in mouse models of melanoma and in melanoma patients and that this increased expression is dependent on an IL-1R-MyD88 pathway. Ablation of Tet2 in myeloid cells suppressed melanoma growth in vivo and shifted the immunosuppressive gene expression program in tumor-associated macrophages to a proinflammatory one, with a concomitant reduction of the immunosuppressive function...
August 15, 2017: Immunity
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