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https://www.readbyqxmd.com/read/29342180/increased-prevalence-of-pregnancy-and-comparative-risk-of-program-attrition-among-individuals-starting-hiv-treatment-in-east-africa
#1
Charles B Holmes, Constantin T Yiannoutsos, Batya Elul, Elizabeth Bukusi, John Ssali, Andrew Kambugu, Beverly S Musick, Craig Cohen, Carolyn Williams, Lameck Diero, Nancy Padian, Kara K Wools-Kaloustian
BACKGROUND: The World Health Organization now recommends initiating all pregnant women on life-long antiretroviral therapy (ART), yet there is limited information about the characteristics and program outcomes of pregnant women already on ART in Africa. Our hypothesis was that pregnant women comprised an increasing proportion of those starting ART, and that sub-groups of these women were at higher risk for program attrition. METHODS AND FINDINGS: We used the International Epidemiology Databases to Evaluate AIDS- East Africa (IeDEA-EA) to conduct a retrospective cohort study including HIV care and treatment programs in Kenya, Uganda, and Tanzania...
2018: PloS One
https://www.readbyqxmd.com/read/29341936/rheumatic-manifestations-among-cancer-patients-treated-with-immune-checkpoint-inhibitors
#2
REVIEW
Merav Lidar, Eitan Giat, Daniela Garelick, Yuval Horowitz, Howard Amital, Yael Steinberg-Silman, Jacob Shachter, Ronnie Shapira-Frommer, Gal Markel
BACKGROUND: The use of immune checkpoint inhibitors (ICI) has grown incessantly since they were first approved in 2014. These monoclonal antibodies inhibit T cell activation, yielding a dramatic tumor response with improved survival. However, immunotherapy is frequently hampered by immune adverse events (iAE) such as hypophysitis, colitis, hepatitis, pneumonitis and rash. Until recently, rheumatic side effects were only infrequently reported. Aim To describe the rheumatic manifestations encountered among patients treated with ICIs in a large tertiary cancer center in Israel METHODS: The cancer center's patient registry was screened for patients who had ever been treated with ipilimumab, pembrolizumab and/or nivolumab with relevant data gathered from clinical charts...
January 13, 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29341328/histiocytosis-cutaneous-manifestations-of-hematopoietic-neoplasm-and-non-neoplastic-histiocytic-proliferations
#3
REVIEW
C M Luder, T M Nordmann, E Ramelyte, B Mühleisen, K Kerl, O Boyman, E Guenova, R Dummer
Histiocytoses are rare disorders characterized by the accumulation of cells derived from macrophages, dendritic cells, or monocytes in various tissues. There is a broad spectrum of disease manifestations with some subtypes commonly showing skin lesions while in others the skin is rarely involved. Here we describe cutaneous manifestations of histiocytoses belonging to the Langerhans group (L group), the group of cutaneous and mucocutaneous histiocytoses (C group) and the group of Rosai-Dorfman disease and related histiocytoses (R group) according to the current classification...
January 16, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29341283/mogamulizumab-induced-phosensitivity-in-patients-with-mycosis-fungoides-and-other-t-cell-neoplasms
#4
Y Masuda, K Tatsuno, S Kitano, H Miyazawa, J Ishibe, M Aoshima, T Shimauchi, T Fujiyama, T Ito, Y Tokura
BACKGROUND: Mogamulizumab (Mog) is a defucosylated, therapeutic monoclonal antibody, targeting CCR4, and was first approved in Japan for the treatment of adult T cell leukaemia/lymphoma (ATLL), followed by cutaneous T cell lymphoma and peripheral T cell lymphoma. OBJECTIVE: To retrospectively investigate development of photosensitivity in patients with mycosis fungoides and other T cell neoplasms after treatment with Mog. METHODS: We treated 7 cutaneous lymphoma patients with Mog...
January 16, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29340116/t-follicular-helper-cells-a-potential-therapeutic-target-in-follicular-lymphoma
#5
REVIEW
Jordi Ochando, Mounia S Braza
Follicular lymphoma (FL), the most common indolent B-cell non-Hodgkin lymphoma (B-NHL), is a germinal center (GC)-derived lymphoma. The mechanisms underlying B-cell differentiation/maturation in GCs could be also involved in their malignant transformation. Moreover, the non-malignant cell composition and architecture of the tumor microenvironment can influence FL development and outcome. Here, we review recent research advances on CD4 helper T cells in FL that highlight the pivotal role of T follicular helper (TFH) cells in a complex multicellular system where they interact with B cells during GC dynamics...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340104/somatic-mutation-dynamics-in-mds-patients-treated-with-azacitidine-indicate-clonal-selection-in-patients-responders
#6
Kamila Polgarova, Karina Vargova, Vojtech Kulvait, Nina Dusilkova, Lubomir Minarik, Zuzana Zemanova, Michal Pesta, Anna Jonasova, Tomas Stopka
Azacitidine (AZA) for higher risk MDS patients is a standard therapy with limited durability. To monitor mutation dynamics during AZA therapy we utilized massive parallel sequencing of 54 genes previously associated with MDS/AML pathogenesis. Serial sampling before and during AZA therapy of 38 patients (reaching median overall survival 24 months (Mo) with 60% clinical responses) identified 116 somatic pathogenic variants with allele frequency (VAF) exceeding 5%. High accuracy of data was achieved via duplicate libraries from myeloid cells and T-cell controls...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340102/the-impact-of-antibiotic-usage-on-the-efficacy-of-chemoimmunotherapy-is-contingent-on-the-source-of-tumor-reactive-t-cells
#7
Michal P Kuczma, Zhi-Chun Ding, Tao Li, Tsadik Habtetsion, Tingting Chen, Zhonglin Hao, Locke Bryan, Nagendra Singh, James N Kochenderfer, Gang Zhou
In recent years the combined use of chemotherapy and immunotherapy, collectively termed chemoimmunotherapy, has emerged as a promising treatment option for patients with cancer. Antibiotics are commonly used to reduce infection-related complications in patients undergoing chemotherapy. Intriguingly, accumulating evidence has implicated gut microbiota as a critical determinant of host antitumor immune responses, raising the question as to whether the use of broad-spectrum antibiotics would invariably diminish tumor response to chemoimmunotherapies...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339738/dna-methyltransferase-inhibition-upregulates-mhc-i-to-potentiate-cytotoxic-t-lymphocyte-responses-in-breast-cancer
#8
Na Luo, Mellissa J Nixon, Paula I Gonzalez-Ericsson, Violeta Sanchez, Susan R Opalenik, Huili Li, Cynthia A Zahnow, Michael L Nickels, Fei Liu, Mohammed N Tantawy, Melinda E Sanders, H Charles Manning, Justin M Balko
Potentiating anti-tumor immunity by inducing tumor inflammation and T cell-mediated responses are a promising area of cancer therapy. Immunomodulatory agents that promote these effects function via a wide variety of mechanisms, including upregulation of antigen presentation pathways. Here, we show that major histocompatibility class-I (MHC-I) genes are methylated in human breast cancers, suppressing their expression. Treatment of breast cancer cell lines with a next-generation hypomethylating agent, guadecitabine, upregulates MHC-I expression in response to interferon-γ...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29339440/repurposing-tin-mesoporphyrin-as-an-immune-checkpoint-inhibitor-shows-therapeutic-efficacy-in-preclinical-models-of-cancer
#9
Tamara Muliaditan, James W Opzoomer, Jonathan Caron, Mary Okesola, Paris Kosti, Sharanpreet Lall, Mieke Van Hemelrijck, Francesco Dazzi, Andrew Tutt, Anita Grigoriadis, Cheryl Gillett, Stephen F Madden, Joy M Burchell, Shahram Kordasti, Sandra S Diebold, James Spicer, James N Arnold
PURPOSE: Unprecedented clinical outcomes have been achieved in a variety of cancers by targeting immune checkpoint molecules. This preclinical study investigates heme oxygenase-1 (HO-1), an immune suppressive enzyme that is expressed in a wide variety of cancers, as a potential immune checkpoint target in the context of a chemotherapy-elicited anti-tumor immune response. We evaluate repurposing tin mesoporphyrin (SnMP), which has demonstrated safety and efficacy targeting hepatic HO in the clinic for the treatment of hyperbilirubinaemia, as an immune checkpoint blockade therapy for the treatment of cancer...
January 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29339423/immune-protection-against-lethal-fungal-bacterial-intra-abdominal-infections
#10
Elizabeth A Lilly, Melanie Ikeh, Evelyn E Nash, Paul L Fidel, Mairi C Noverr
Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non-albicans Candida (NAC) species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S...
January 16, 2018: MBio
https://www.readbyqxmd.com/read/29339377/robust-antitumor-responses-result-from-local-chemotherapy-and-ctla-4-blockade
#11
Charlotte E Ariyan, Mary Sue Brady, Robert H Siegelbaum, Jian Hu, Danielle M Bello, Jamie Green, Charles Fisher, Robert A Lefkowitz, Katherine S Panageas, Melissa Pulitzer, Marissa Vignali, Ryan Emerson, Christopher Tipton, Harlan Robins, Taha Merghoub, Jianda Yuan, Achim Jungbluth, Jorge Blando, Padmanee Sharma, Alexander Y Rudensky, Jedd D Wolchok, James P Allison
Clinical responses to immunotherapy have been associated with augmentation of preexisting immune responses, manifested by heightened inflammation in the tumor microenvironment. However, many tumors have a non-inflamed microenvironment, and response rates to immunotherapy in melanoma have been <50%. We approached this problem by utilizing immunotherapy (CTLA-4 blockade) combined with chemotherapy to induce local inflammation. In murine models of melanoma and prostate cancer, the combination of chemotherapy and CTLA-4 blockade induced a shift in the cellular composition of the tumor microenvironment, with infiltrating CD8+ and CD4+ T cells increasing the CD8/Foxp3 T-cell ratio...
January 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29339375/tusc2-immunogene-synergizes-with-anti-pd1-through-enhanced-proliferation-and-infiltration-of-natural-killer-cells-in-syngeneic-kras-mutant-mouse-lung-cancer-models
#12
Ismail M Meraz, Mourad Majidi, Xiaobo Cao, Heather Lin, Lerong Li, Jing Wang, Veerabhadran Baladandayuthapani, David Rice, Boris Sepesi, Lin Ji, Jack A Roth
Expression of the multikinase inhibitor encoded by tumor suppressor gene TUSC2 (also known as FUS1) is lost or decreased in non-small cell lung carcinoma (NSCLC). TUSC2 delivered systemically by nanovesicles has mediated tumor regression in clinical trials. Because of the role of TUSC2 in regulating immune cells, we assessed TUSC2 efficacy on antitumor immune responses alone and in combination with anti-PD-1 in two Kras-mutant syngeneic mouse lung cancer models. TUSC2 alone significantly reduced tumor growth and prolonged survival compared with anti-PD-1...
January 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29339270/proceedings-from-the-fourth-haploidentical-stem-cell-transplantation-symposium-haplo2016-san-diego-california-december-1-2016
#13
REVIEW
Monzr Al Malki, Richard Jones, Qing Ma, Dean Lee, Yair Reisner, Jeffrey S Miller, Peter Lang, Suradej Hongeng, Parameswaran Hari, Samuel Strober, Jianhua Yu, Richard Maziarz, Domenico Mavilio, Denis-Claude Roy, Chiara Bonini, Richard E Champlin, Ephraim J Fuchs, Stefan O Ciurea
The resurgence of haploidentical stem cell transplantation (HaploSCT) over the last decade is one of the most important advances in the field of hematopoietic stem cell transplantation (HSCT). The modified platforms of T cell depletion either ex vivo (CD34+ selection, 'mega-dose' of purified CD34+ cells, or selective depletion of T-cells) or newer platforms of in vivo depletion of T cells, with either post-transplant high-dose cyclophosphamide (PTCy) or intensified immune suppression, have contributed to better outcomes, with survival that is similar to HLA-match donor transplantation...
January 12, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29339209/extratumoral-pd-1-blockade-does-not-perpetuate-obesity-associated-inflammation-in-esophageal-adenocarcinoma
#14
Karen C Galvin, Melissa J Conroy, Suzanne L Doyle, Margaret R Dunne, Ronan Fahey, Emma Foley, Katie E O'Sullivan, Derek G Doherty, Justin G Geoghegan, Narayanasamy Ravi, Cliona O'Farrelly, John V Reynolds, Joanne Lysaght
Checkpoint inhibitors, such as anti-PD-1 (Programmed death-1), are transforming cancer treatment for inoperable or advanced disease. As the incidence of obesity-associated malignancies, including esophageal adenocarcinoma (EAC) continue to increase and treatment with checkpoint inhibitors are being FDA approved for a broader range of cancers, it is important to assess how anti-PD-1 treatment might exacerbate pre-existing inflammatory processes at other sites. Outside the EAC tumor, the omentum and liver were found to be enriched with substantial populations of PD-1 expressing T cells...
January 12, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29338938/distinct-met-protein-localization-associated-with-met-exon-14-mutation-types-in-patients-with-non-small-cell-lung-cancer
#15
Tian Qiu, Weihua Li, Tongtong Zhang, Puyuan Xing, Wenting Huang, Bingning Wang, Lixia Chu, Lei Guo, Xiuyun Liu, Yan Li, Jianming Ying, Junling Li
BACKGROUND: The MET gene has been recognized as a potential important therapeutic target in non-small-cell lung cancer (NSCLC). We sought to investigate the MET exon 14 mutations in a cohort of Chinese patients with NSCLC. METHODS: We tested 461 NSCLCs for MET exon 14 mutations by sequencing whole exon 14 and its flanking introns. The protein expression was determined by immunohistochemical analysis. RESULTS: In this study, we identified MET exon 14 mutations in 9 (2...
December 21, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29338744/new-insights-in-the-relative-radiobiological-effectiveness-of-proton-irradiation
#16
REVIEW
K Ilicic, S E Combs, T E Schmid
BACKGROUND: Proton radiotherapy is a form of charged particle therapy that is preferentially applied for the treatment of tumors positioned near to critical structures due to their physical characteristics, showing an inverted depth-dose profile. The sparing of normal tissue has additional advantages in the treatment of pediatric patients, in whom the risk of secondary cancers and late morbidity is significantly higher. Up to date, a fixed relative biological effectiveness (RBE) of 1...
January 16, 2018: Radiation Oncology
https://www.readbyqxmd.com/read/29338718/a-live-cell-assay-of-gpcr-coupling-allows-identification-of-optogenetic-tools-for-controlling-go-and-gi-signaling
#17
Edward R Ballister, Jessica Rodgers, Franck Martial, Robert J Lucas
BACKGROUND: Animal opsins are light-sensitive G-protein-coupled receptors (GPCRs) that enable optogenetic control over the major heterotrimeric G-protein signaling pathways in animal cells. As such, opsins have potential applications in both biomedical research and therapy. Selecting the opsin with the best balance of activity and selectivity for a given application requires knowing their ability to couple to a full range of relevant Gα subunits. We present the GsX assay, a set of tools based on chimeric Gs subunits that transduce coupling of opsins to diverse G proteins into increases in cAMP levels,  measured with a real-time reporter in living cells...
January 16, 2018: BMC Biology
https://www.readbyqxmd.com/read/29338679/therapeutic-role-of-methotrexate-in-pediatric-crohn-s-disease
#18
REVIEW
Zlatko Djurić, Ljiljana Šaranac, Ivana Budić, Voja Pavlović, Jelena Djordjević
The main role of therapy in Crohn's disease is to achieve long-term clinical remission, and to allow for normal growth and development of children. The immunomodulatory drugs used for the maintenance of remission in Crohn's disease include thiopurines (azathioprine and 6-mercaptopurine) and methotrexate. Development of hepatosplenic T-cell lymphoma in some patients with inflammatory bowel disease, treated with thiopurines independently or in combination with anti-tumor necrosis factor agents, resulted in a growing interest in the therapeutic application of methotrexate in children suffering from Crohn's disease...
January 16, 2018: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29338452/an-update-on-diagnostic-and-prognostic-biomarkers-for-traumatic-brain-injury
#19
Kevin K Wang, Zhihui Yang, Tian Zhu, Yuan Shi, Richard Rubenstein, J Adrian Tyndall, Geoff T Manley
Traumatic brain injury (TBI) is a major worldwide neurological disorder of epidemic proportions. To date, there are still no FDA-approved therapies to treat any forms of TBI. Encouragingly, there are emerging data showing that biofluid-based TBI biomarker tests have the potential to diagnose the presence of TBI of different severities including concussion, and to predict outcome. Area covered: The authors provide an update on the current knowledge of TBI biomarkers, including protein biomarkers for neuronal cell body injury (UCH-L1, NSE), astroglial injury (GFAP, S100B), neuronal cell death (αII-spectrin breakdown products), axonal injury (NF proteins), white matter injury (MBP), post-injury neurodegeneration (total Tau and phospho-Tau), post-injury autoimmune response (brain antigen-targeting autoantibodies), and other emerging non-protein biomarkers...
January 17, 2018: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29338160/higher-activities-of-hepatic-versus-splenic-cd8-t-cells-in-responses-to-adoptive-t-cell-therapy-and-vaccination-of-b6-mice-with-mhc-class-1-binding-antigen
#20
Mohamed Labib Salem, Randa E El Naggar, Sabry A El Naggar, Maysa A Mobasher, Mohamed H Mahmoud, Gamal Badr
The liver has unique microenvironment which is known to induce tolerance of cytolytic CD8+ T cells to hepatic and extra hepatic antigens, resulting in persistence of infection of the liver by the hepatitis B and C viruses. However, under some conditions, functional immune responses can be elicited in the liver in particular to show preferential retention of activated CD8+ T cells. It is not clear whether this retention depends on the type of the exogenous immunostimulatory or the endogenous innate immune cells...
December 2017: Iranian Journal of Allergy, Asthma, and Immunology
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