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https://www.readbyqxmd.com/read/27913437/surface-expression-of-tgf%C3%AE-docking-receptor-garp-promotes-oncogenesis-and-immune-tolerance-in-breast-cancer
#1
Alessandra Metelli, Bill X Wu, Caroline W Fugle, Saleh Rachidi, Shaoli Sun, Yongliang Zhang, Jennifer Wu, Stephen Tomlinson, Philip H Howe, Yi Yang, Elizabeth Garrett-Mayer, Bei Liu, Zihai Li
GARP encoded by the Lrrc32 gene is the cell surface docking receptor for latent TGFβ, which is expressed naturally by platelets and regulatory T cells (Treg). Although Lrrc32 is amplified frequently in breast cancer, the expression and relevant functions of GARP in cancer have not been explored. Here, we report that GARP exerts oncogenic effects, promoting immune tolerance by enriching and activating latent TGFβ in the tumor microenvironment. We found that human breast, lung, and colon cancers expressed GARP aberrantly...
October 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/27911218/aberrant-t-cell-immunity-triggered-by-human-respiratory-syncytial-virus-and-human-metapneumovirus-infection
#2
Andrea E González, Margarita K Lay, Evelyn L Jara, Janyra A Espinoza, Roberto S Gómez, Jorge Soto, Claudia A Rivera, Katia Abarca, Susan M Bueno, Claudia A Riedel, Alexis M Kalergis
Human Respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are the two major etiological viral agents of lower respiratory tract diseases, affecting mainly infants, young children and the elderly. Although the infection of both viruses trigger an antiviral immune response that mediate viral clearance and disease resolution in immunocompetent individuals, the promotion of long-term immunity appears to be deficient and reinfection are common throughout life. A possible explanation for this phenomenon is that hRSV and hMPV, can induce aberrant T cell responses, which leads to exacerbated lung inflammation and poor T and B cell memory immunity...
December 2, 2016: Virulence
https://www.readbyqxmd.com/read/27906865/management-of-post-transplant-lymphoproliferative-disorders
#3
Gabriela Llaurador, Lauren McLaughlin, Birte Wistinghausen
PURPOSE OF REVIEW: Post-transplant lymphoproliferative disease (PTLD) is a major complication of hematopoietic stem cell and solid organ transplantation. The incidence of transplantation in childhood has been steadily rising, making PTLD the most common form of lymphoproliferation in childhood. The purpose of this review is to summarize the role of the Epstein-Barr virus (EBV) in the pathophysiology and discuss the management of PTLD. RECENT FINDINGS: More than 90% of pediatric PTLD is EBV-positive...
November 30, 2016: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/27906132/the-distinct-fate-of-smooth-and-rough-mycobacterium-abscessus-variants-inside-macrophages
#4
Anne-Laure Roux, Albertus Viljoen, Aïcha Bah, Roxane Simeone, Audrey Bernut, Laura Laencina, Therese Deramaudt, Martin Rottman, Jean-Louis Gaillard, Laleh Majlessi, Roland Brosch, Fabienne Girard-Misguich, Isabelle Vergne, Chantal de Chastellier, Laurent Kremer, Jean-Louis Herrmann
Mycobacterium abscessus is a pathogenic, rapidly growing mycobacterium responsible for pulmonary and cutaneous infections in immunocompetent patients and in patients with Mendelian disorders, such as cystic fibrosis (CF). Mycobacterium abscessus is known to transition from a smooth (S) morphotype with cell surface-associated glycopeptidolipids (GPL) to a rough (R) morphotype lacking GPL. Herein, we show that M. abscessus S and R variants are able to grow inside macrophages and are present in morphologically distinct phagosomes...
November 2016: Open Biology
https://www.readbyqxmd.com/read/27902353/corrigendum-to-follicular-helper-t-cells-and-virus-specific-antibody-response-in-primary-and-reactivated-human-cytomegalovirus-infections-of-the-immunocompetent-and-immunocompromised-transplant-patients
#5
Francesca Bruno, Chiara Fornara, Paola Zelini, Milena Furione, Elena Carrara, Lucia Scaramuzzi, Ilaria Cane, Federico Mele, Federica Sallusto, Daniele Lilleri, Giuseppe Gerna
No abstract text is available yet for this article.
October 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27900012/ubenimex-enhances-the-radiosensitivity-of-renal-cell-carcinoma-cells-by-inducing-autophagic-cell-death
#6
Shuai Liu, Xiaoqing Wang, Jiaju Lu, Liping Han, Yongfei Zhang, Zheng Liu, Sentai Ding, Zhao Liu, Dongbin Bi, Zhihong Niu
Renal cell carcinoma (RCC) is resistant to standard radiotherapy. Ubenimex, an aminopeptidase N inhibitor, is widely used as an adjunct therapy after surgery to enhance the function of immunocompetent cells and confer antitumor effects. Our previous study demonstrated that ubenimex induces autophagic cell death in RCC cells. Recently, the molecular mechanism of autophagy induction has been associated with radiosensitivity in RCC cells. In the present study, the ability of ubenimex to enhance RCC cell sensitivity to radiation via the induction of autophagic cell death was determined, and the mechanism of action of this effect was investigated...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27894616/histopathological-lesions-in-encephalon-and-heart-of-mice-infected-with-toxoplasma-gondii-increase-after-lycopodium-clavatum-200dh-treatment
#7
Andréia Vieira Pereira, Marcelo Biondaro Góis, Katiucha Rebeca Jennifer Lopes Lera, Gislane Janaina Falkowski-Temporini, Paula Fernanda Massini, Ricardo Nascimento Drozino, Denise Lessa Aleixo, Milena Menegazzo Miranda, Paulo da Silva Watanabe, Ivete Conchon-Costa, Idessania Nazareth da Costa, Mário Dos Anjos Neto Filho, Silvana Marques de Araújo, Wander Rogério Pavanelli
In many cases, symptoms of toxoplasmosis are mistaken for the ones of other infectious diseases. Clinical signs are rare in immunocompetent people. However, when they arise, in the acute phase of infection, several organs are affected due to the rapid spread of tachyzoites through the bloodstream. In the present study, the reduction of tachyzoites in peripheral blood of mice of G72 (infected 72h after treatment) and G48 (infected 48h after treatment and treated three more times), when compared with IC (infected and non-treated), suggests protective effect exerted by Lycopodium clavatum...
November 18, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27886201/cryptococcal-meningitis-epidemiology-immunology-diagnosis-and-therapy
#8
REVIEW
Peter R Williamson, Joseph N Jarvis, Anil A Panackal, Matthew C Fisher, Síle F Molloy, Angela Loyse, Thomas S Harrison
HIV-associated cryptococcal meningitis is by far the most common cause of adult meningitis in many areas of the world that have high HIV seroprevalence. In most areas in Sub-Saharan Africa, the incidence of cryptococcal meningitis is not decreasing despite availability of antiretroviral therapy, because of issues of adherence and retention in HIV care. In addition, cryptococcal meningitis in HIV-seronegative individuals is a substantial problem: the risk of cryptococcal infection is increased in transplant recipients and other individuals with defects in cell-mediated immunity, and cryptococcosis is also reported in the apparently immunocompetent...
November 25, 2016: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/27884882/lymphomatosis-cerebri-diagnostic-challenges-and-review-of-the-literature
#9
Paul J Lee, Idanis Berrios, Carolina Ionete, Thomas Smith
Lymphomatosis cerebri (LC) is a rare variant of a primary central nervous system non-Hodgkin's lymphoma (PCNSL) characterised by diffuse infiltration of tumour cells throughout the brain parenchyma. We present a 68-year-old immunocompetent woman with headaches, dizziness, blurred vision, localised right leg weakness and rapidly progressive dementia. A brain MRI demonstrated diffuse T2 hyperintense white matter lesions that did not enhance with contrast. The clinical differential diagnosis of these lesions included metastatic disease, infectious or inflammatory process such as sarcoidosis, lymphoma, demyelinating disease and less likely vascular aetiology, such as vasculitis or ischaemic stroke...
November 24, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27877217/pregnancy-specific-%C3%AE-1-glycoprotein-1-is-expressed-in-pancreatic-ductal-adenocarcinoma-and-its-subcellular-localization-correlates-with-overall-survival
#10
Jasmin H Shahinian, Hannah Fuellgraf, Stefan Tholen, Justin Mastroianni, Julia Daniela Knopf, Markus Kuehs, Bettina Mayer, Manuel Schlimpert, Birte Kulemann, Simon Kuesters, Jens Hoeppner, Ulrich F Wellner, Martin Werner, Ulrich T Hopt, Robert Zeiser, Peter Bronsert, Oliver Schilling
Proteins of the pregnancy specific β-1 glycoprotein (PSG) family are renowned for their elevated expression during pregnancy. Only few reports have investigated their expression in adenocarcinomas. We studied the expression of PSG1 in pancreatic adenocarcinoma (PDAC). In a cohort of 104 patient samples, immunohistochemical analysis determined PSG1 expression in every specimen. PSG1 was found at apical and cytoplasmic localization or solely at cytoplasmic localization, with the latter case being correlated to shortened median survival (25 vs 11 months, logrank p-value < 0...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27877000/psychiatric-aspects-of-toxoplasmosis-an-indian-perspective
#11
Ajish G Mangot
Toxoplasma gondii is one of the well-studied parasites because of its medical and veterinary importance, and its suitability as a model for cell biology and molecular studies. Latent toxoplasmosis in an immunocompetent host was considered benign until recently. The importance of this parasite has been steadily rising in the field of psychiatry and neurology as it has been implicated in numerous neuropsychiatric disorders. Researchers in India have unfortunately restricted themselves to finding the prevalence of toxoplasma antibodies in special populations and animals...
December 2016: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
https://www.readbyqxmd.com/read/27876058/a-novel-non-hodgkin-lymphoma-murine-model-closer-to-the-standard-clinical-scenario
#12
Thais Bascuas, María Moreno, Amy Mónaco, Laura Reyes, Andrea Paolino, Patricia Oliver, María G Kramer, Henry Engler, José P Pacheco, Sofía Grille, José A Chabalgoity
BACKGROUND: Non-Hodgkin lymphomas (NHL) are the most frequent hemato-oncological malignancies. Despite recent major advances in treatment, a substantial proportion of patients relapses highlighting the need for new therapeutic modalities. Promissory results obtained in pre-clinical studies are usually not translated when moving into clinical trials. Pre-clinical studies are mainly conducted in animals with high tumor burden; instead patients undergo chemotherapy as first line of treatment and most likely are under remission when immunotherapies are applied...
November 22, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27872096/polyi-c-and-cpg-synergize-with-anti-erbb2-mab-for-treatment-of-breast-tumors-resistant-to-immune-checkpoint-inhibitors
#13
Roxanne Charlebois, Bertrand Allard, David Allard, Laurence Buisseret, Martin Turcotte, Sandra Pommey, Pavel Chrobak, John Stagg
Innate and adaptive immune cells play an important role in the therapeutic activity of anti-ErbB2 mAbs such as trastuzumab. In the clinic, breast tumors poorly infiltrated with immune cells are more resistant to trastuzumab and patients have a worse prognosis. Because type I and II interferons (IFNs) are critical to the immune-mediated activity of anti-ErbB2 mAb, we investigated the effect of combining polyI:C and CpG with trastuzumab-like therapy in immunocompetent mouse models of ErbB2+ breast cancer. We demonstrated that in situ delivery of polyI:C and CpG combined to systemic anti-ErbB2 mAb triggered a potent inflammatory response in breast tumors able to induce long lasting CD8+ T cell-dependent anti-tumor immunity...
November 21, 2016: Cancer Research
https://www.readbyqxmd.com/read/27870450/the-immune-system-as-a-novel-regulator-of-sex-differences-in-brain-and-behavioral-development
#14
REVIEW
Lars H Nelson, Kathryn M Lenz
Sexual differentiation of the brain occurs early in life as a result of sex-typical hormone action and sex chromosome effects. Immunocompetent cells are being recognized as underappreciated regulators of sex differences in brain and behavioral development, including microglia, astrocytes, and possibly other less well studied cell types, including T cells and mast cells. Immunocompetent cells in the brain are responsive to steroid hormones, but their role in sex-specific brain development is an emerging field of interest...
January 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27869820/tet-proteins-regulate-the-lineage-specification-and-tcr-mediated-expansion-of-inkt-cells
#15
Ageliki Tsagaratou, Edahí González-Avalos, Sini Rautio, James P Scott-Browne, Susan Togher, William A Pastor, Ellen V Rothenberg, Lukas Chavez, Harri Lähdesmäki, Anjana Rao
TET proteins oxidize 5-methylcytosine in DNA to 5-hydroxymethylcytosine and other oxidation products. We found that simultaneous deletion of Tet2 and Tet3 in mouse CD4(+)CD8(+) double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T cells (iNKT cells). Tet2-Tet3 double-knockout (DKO) iNKT cells displayed pronounced skewing toward the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK...
November 21, 2016: Nature Immunology
https://www.readbyqxmd.com/read/27856486/myocardial-immunocompetent-cells-and-macrophage-phenotypes-as%C3%A2-histopathological-surrogates-for-diagnosis-of-cardiac-sarcoidosis-in-japanese
#16
Yasuyuki Honda, Toshiyuki Nagai, Yoshihiko Ikeda, Mamoru Sakakibara, Naoya Asakawa, Nobutaka Nagano, Michikazu Nakai, Kunihiro Nishimura, Yasuo Sugano, Keiko Ohta-Ogo, Yasuhide Asaumi, Takeshi Aiba, Hideaki Kanzaki, Kengo Kusano, Teruo Noguchi, Satoshi Yasuda, Hiroyuki Tsutsui, Hatsue Ishibashi-Ueda, Toshihisa Anzai
BACKGROUND: The histological diagnosis of cardiac sarcoidosis (CS) is based on the presence of myocardial granulomas; however, the sensitivity of endomyocardial biopsy is relatively low. We investigated whether immunocompetent cells including dendritic cells (DC) and macrophages in nongranuloma sections of endomyocardial biopsy samples could be histopathological surrogates for CS diagnosis. METHODS AND RESULTS: The numbers of DC and macrophages were investigated in 95 consecutive CS patients and 50 patients with nonischemic cardiomyopathy as controls...
November 17, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27856263/rational-design-of-protamine-nanocapsules-as-antigen-delivery-carriers
#17
José Vicente González-Aramundiz, Elena Presas, Inmaculada Dalmau-Mena, Susana Martínez-Pulgarín, Covadonga Alonso, José M Escribano, María J Alonso, Noemi Stefánia Csaba
: Current challenges in global immunization indicate the demand for new delivery strategies, which could be applied to the development of new vaccines against emerging diseases, as well as to improve safety and efficacy of currently existing vaccine formulations. Here, we report a novel antigen nanocarrier consisting of an oily core and a protamine shell, further stabilized with pegylated surfactants. These nanocarriers, named protamine nanocapsules, were rationally designed to promote the intracellular delivery of antigens to immunocompetent cells and to trigger an efficient and long-lasting immune response...
November 14, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27855206/zika-prvabc59-infection-is-associated-with-t-cell-infiltration-and-neurodegeneration-in-cns-of-immunocompetent-neonatal-c57bl-6-mice
#18
Mohanraj Manangeeswaran, Derek D C Ireland, Daniela Verthelyi
The recent spread of Zika virus (ZIKV) and its association with increased rates of Guillain Barre and other neurological disorders as well as congenital defects that include microcephaly has created an urgent need to develop animal models to examine the pathogenesis of the disease and explore the efficacy of potential therapeutics and vaccines. Recently developed infection models for ZIKV utilize mice defective in interferon responses. In this study we establish and characterize a new model of peripheral ZIKV infection using immunocompetent neonatal C57BL/6 mice and compare its clinical progression, virus distribution, immune response, and neuropathology with that of C57BL/6-IFNAR KO mice...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27845732/the-complexity-of-targeting-pi3k-akt-mtor-signalling-in-human-acute-myeloid-leukaemia-the-importance-of-leukemic-cell-heterogeneity-neighbouring-mesenchymal-stem-cells-and-immunocompetent-cells
#19
REVIEW
Annette K Brenner, Tor Henrik Andersson Tvedt, Øystein Bruserud
Therapeutic targeting of PI3K-Akt-mTOR is considered a possible strategy in human acute myeloid leukaemia (AML); the most important rationale being the proapoptotic and antiproliferative effects of direct PI3K/mTOR inhibition observed in experimental studies of human AML cells. However, AML is a heterogeneous disease and these effects caused by direct pathway inhibition in the leukemic cells are observed only for a subset of patients. Furthermore, the final effect of PI3K-Akt-mTOR inhibition is modulated by indirect effects, i...
November 11, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27843579/a-prospective-clinical-trial-to-assess-lapatinib-effects-on-cutaneous-squamous-cell-carcinoma-and-actinic-keratosis
#20
D Jenni, M B Karpova, B Mühleisen, J Mangana, J Dreier, J Hafner, R Dummer
BACKGROUND: Antiepidermal growth factor receptor (EGFR)-targeted therapy is widely used in many epithelial cancer types. We investigated lapatinib effects on cutaneous squamous cell carcinoma (cSCC) scheduled for resection and in coexisting precursor lesions (actinic keratosis (AK) and Bowen's disease (BD)) in a phase 2 mode of action clinical trial including a histological workup of the cSCC. PATIENTS AND METHODS: We initiated a prospective single-centre, open-label, non-controlled clinical study with translational intentions to investigate changes in size and histopathological features in cSCC after a 14-day period of neoadjuvant lapatinib therapy at a dose of 1500 mg/day prior to surgery, to quantify the impact on AK and BD in the same patient after 56 days and to evaluate the tolerability in patients with cSCC and precursor lesions...
2016: ESMO Open
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