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https://www.readbyqxmd.com/read/28407697/cytosolic-hsp90%C3%AE-and-its-mitochondrial-isoform-trap1-are-differentially-required-in-a-breast-cancer-model
#1
Evangelia Vartholomaiou, Marta Madon-Simon, Stéphane Hagmann, Guillaume Mühlebach, Wolfgang Wurst, Thomas Floss, Didier Picard
The Hsp90 family of molecular chaperones includes the cytosolic isoforms Hsp90α and Hsp90β, and the mitochondrial isoform Trap1. Hsp90α/β support a large number of client proteins in the cytoplasm and the nucleus whereas Trap1 regulates oxidative phosphorylation in mitochondria. Many of the associated proteins and cellular processes are relevant to cancer, and there is ample pharmacological and genetic evidence to support the idea that Hsp90α/β and Trap1 are required for tumorigenesis. However, a direct and comparative genetic test in a mouse cancer model has not been done...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405598/clearance-of-bk-virus-nephropathy-by-combination-antiviral-therapy-with-intravenous-immunoglobulin
#2
Kathy Kable, Carmen D Davies, Philip J O'connell, Jeremy R Chapman, Brian John Nankivell
BACKGROUND: Reactivation of BK polyoma virus causes a destructive virus allograft nephropathy (BKVAN) with graft loss in 46%. Treatment options are limited to reduced immunosuppression and largely ineffective antiviral agents. Some studies suggest benefit from intravenous immunoglobulin (IVIG). METHODS: We evaluated effectiveness of adjuvant IVIG to eliminate virus from blood and tissue, in a retrospective, single-center cohort study, against standard-of-care controls...
April 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28404866/combined-antiangiogenic-and-anti-pd-l1-therapy-stimulates-tumor-immunity-through-hev-formation
#3
Elizabeth Allen, Arnaud Jabouille, Lee B Rivera, Inge Lodewijckx, Rindert Missiaen, Veronica Steri, Kevin Feyen, Jaime Tawney, Douglas Hanahan, Iacovos P Michael, Gabriele Bergers
Inhibitors of VEGF (vascular endothelial growth factor)/VEGFR2 (vascular endothelial growth factor receptor 2) are commonly used in the clinic, but their beneficial effects are only observed in a subset of patients and limited by induction of diverse relapse mechanisms. We describe the up-regulation of an adaptive immunosuppressive pathway during antiangiogenic therapy, by which PD-L1 (programmed cell death ligand 1), the ligand of the negative immune checkpoint regulator PD-1 (programmed cell death protein 1), is enhanced by interferon-γ-expressing T cells in distinct intratumoral cell types in refractory pancreatic, breast, and brain tumor mouse models...
April 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28399927/bk-viruria-and-viremia-in-children-with-systemic-lupus-erythematosus
#4
Nirupama Gupta, Cuong Q Nguyen, Renee F Modica, Melissa E Elder, Eduardo H Garin
BACKGROUND: BK virus (BKV) is a ubiquitous polyoma virus that lies dormant in the genitourinary tract once acquired in early childhood. In states of cellular immunodeficiency, the virus can reactivate to cause hemorrhagic cystitis and nephritis. Children with systemic lupus erythematosus (SLE) have an increased risk of developing infectious complications secondary to their immunocompromised state from the administration of several immuno-modulatory drugs. Currently, there are no data regarding the prevalence of BK viruria or viremia in children with SLE...
April 11, 2017: Pediatric Rheumatology Online Journal
https://www.readbyqxmd.com/read/28340807/prevalence-of-human-herpesvirus-8-and-bk-polyoma-virus-infections-in-end-stage-renal-disease-and-the-influence-of-renal-transplantation
#5
A Turkmen, O Guven, S Mese, A Agacfidan, B Yelken, M Onel, Y Caliskan, G Celik, S Turkoglu, B Kocak
Viral infections lead to significant morbidity and mortality in kidney transplant recipients. We evaluated 49 kidney transplant recipients for human herpesvirus 8 (HHV-8) and BK polyomavirus infections in conjunction with data obtained from 43 donors. The seroprevalence of HHV-8 was 6.9% in donors and 12.2% in recipients. HHV-8 DNA was detected below the limit of quantification (<5000 copies/mL) in a recipient with HHV-8 seropositivity at the pretransplant period and was undetectable at month 3 after transplantation...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28295760/variability-in-assessing-for-bk-viremia-whole-blood-is-not-reliable-and-plasma-is-not-above-reproach-a-retrospective-analysis
#6
Neerja Agrawal, Ignacio A Echenique, Shane M Meehan, Ajit P Limaye, Linda Cook, Anthony Chang, Robert C Harland, Basit Javaid, Pradeep V Kadambi, Scott Matushek, James Williams, Michelle A Josephson
Polyomavirus nephropathy (PVN) is a major complication of kidney transplantation. Most reports describe polyomavirus viremia either precedes or is detectable at the time of diagnosis of PVN. This association is the basis of current screening recommendations. We retrospectively reviewed the PCR results of blood and urine samples from 29 kidney transplant recipients with biopsy proven PVN. Biopsies were performed for a rise in serum creatinine or persistent high-level BK viruria. All biopsies had polyoma virus large T-antigen expression in tubular epithelium by immunohistochemistry...
March 14, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28295503/nuclear-magnetic-resonance-structure-of-the-human-polyoma-jc-virus-agnoprotein
#7
Pascale Coric, A Sami Saribas, Magid Abou-Gharbia, Wayne Childers, Jon Condra, Martyn K White, Mahmut Safak, Serge Bouaziz
Agnoprotein is an important regulatory protein of the human polyoma JC virus (JCV) and plays critical roles during the viral replication cycle. It forms highly stable dimers and oligomers through its Leu/Ile/Phe-rich domain, which is important for the stability and function of the protein. We recently resolved the partial 3D structure of this protein by NMR using a synthetic peptide encompassing amino acids Thr17 to Gln52, where the Leu/Ile/Phe- rich domain was found to adopt a major alpha-helix conformation spanning amino acids 23 to 39...
March 10, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28281550/reduced-h3k27me3-expression-in-merkel-cell-polyoma-virus-positive-tumors
#8
Klaus J Busam, Melissa P Pulitzer, Daniel C Coit, Maria Arcila, Danielle Leng, Achim A Jungbluth, Thomas Wiesner
Merkel cell carcinoma is a primary cutaneous neuroendocrine carcinoma, which once metastatic is difficult to treat. Recent mutation analyses of Merkel cell carcinoma revealed a low number of mutations in Merkel cell polyomavirus-associated tumors, and a high number of mutations in virus-negative combined squamous cell and neuroendocrine carcinomas of chronically sun-damaged skin. We speculated that the paucity of mutations in virus-positive Merkel cell carcinoma may reflect a pathomechanism that depends on derangements of chromatin without alterations in the DNA sequence (epigenetic dysregulation)...
March 10, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28245526/progressive-multi-focal-leucoencephalopathy%C3%A2-%C3%A2-driven-from-rarity-to-clinical-mainstream-by-iatrogenic-immunodeficiency
#9
REVIEW
S A Misbah
Advances in immune-mediated targeted therapies have proved to be a double-edged sword for patients by highlighting the risk of iatrogenic infective complications. This has been exemplified by progressive multi-focal leucoencephalopathy (PML), a hitherto rare devastating viral infection of the brain caused by the neurotrophic JC polyoma virus. While PML achieved prominence during the first two decades of the HIV epidemic, effective anti-retroviral treatment and restitution of T cell function has led to PML being less prominent in this population...
February 28, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28237875/tumor-growth-factor-%C3%AE-is-an-important-factor-for-immunosuppression-and-tumorgenesis-in-polyoma-bk-virus-infection-a-systematic-review-article
#10
REVIEW
Ashraf Kariminik, Babak Kheirkhah
Polyoma BK virus (PBK) is a prevalent human specific virus and the cause of several malignancies in human. The main mechanisms used by PBK to induce/stimulate human cancers are yet to be clarified but it has been proposed that PBK may use several mechanisms to induce/stimulate cancers in human including attenuation of immune responses via up-regulation of immunosuppressor molecules. Transforming growth factor beta (TGF-β) is a key multifunctional factor from modulation of immunosurveillance to angiogenesis...
February 23, 2017: Cytokine
https://www.readbyqxmd.com/read/28221173/new-developments-in-transplant-proteomics
#11
Julie Ho, Patricia Hirt-Minkowski, John A Wilkins
PURPOSE OF REVIEW: Despite modern immunosuppression, renal allograft rejection remains a major contributor to graft loss. Novel biomarkers may help improve posttransplant outcomes through the early detection and treatment of rejection. Our objective is to provide an overview of proteomics, review recent discovery-based rejection studies, and explore innovative approaches in biomarker development. RECENT FINDINGS: Urine MMP7 was identified as a biomarker of subclinical and clinical rejection using two-dimensional liquid chromatography tandem-mass spectrometry (LC-MS/MS) and improved the overall diagnostic discrimination of urine CXCL10 : Cr alone for renal allograft inflammation...
May 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28194662/mmtv-pymt-and-derived-met-1-mouse-mammary-tumor-cells-as-models-for-studying-the-role-of-the-androgen-receptor-in-triple-negative-breast-cancer-progression
#12
Jessica L Christenson, Kiel T Butterfield, Nicole S Spoelstra, John D Norris, Jatinder S Josan, Julie A Pollock, Donald P McDonnell, Benita S Katzenellenbogen, John A Katzenellenbogen, Jennifer K Richer
Triple-negative breast cancer (TNBC) has a faster rate of metastasis compared to other breast cancer subtypes, and no effective targeted therapies are currently FDA-approved. Recent data indicate that the androgen receptor (AR) promotes tumor survival and may serve as a potential therapeutic target in TNBC. Studies of AR in disease progression and the systemic effects of anti-androgens have been hindered by the lack of an AR-positive (AR+) immunocompetent preclinical model. In this study, we identified the transgenic MMTV-PyMT (mouse mammary tumor virus-polyoma middle tumor-antigen) mouse mammary gland carcinoma model of breast cancer and Met-1 cells derived from this model as tools to study the role of AR in breast cancer progression...
April 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28183770/genome-sequence-of-a-marbled-eel-polyoma-like-virus-in-taiwan
#13
Chiu-Ming Wen, Ping-Chung Liu, Fan-Hua Nan
We report here the complete genome sequence of a virus isolated from a diseased marbled eel (Anguilla marmorata) in Taiwan. The virus has been characterized as being related to Japanese eel endothelial cell-infecting virus (JEECV), with a large T-antigen-like protein. The sequence of the marbled eel virus displays low homology to the JEECV.
February 9, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28152548/high-folic-acid-diet-enhances-tumour-growth-in-pymt-induced-breast-cancer
#14
Mariann Fagernæs Hansen, Sarah Østrup Jensen, Ernst-Martin Füchtbauer, Pia M Martensen
BACKGROUND: The B-vitamin folate is among the most studied bioactive food compound, and a dietary intake meeting the daily requirements has been found to reduce the risk of cancer and cardiovascular diseases as well as preventing neural tube defects during fetal development. Several countries have therefore introduced dietary fortification with folic acid. However, clinical and animal studies suggest that folic acid has a dual role in cancer development. METHODS: During the period of initial tumour progression, MMTV-PyMT (MMTV-polyoma virus middle T) transgenic mice were fed with normal diet and high folic acid diet...
March 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28137206/biopsy-proven-bk-virus-associated-nephropathy-clinico-pathologic-correlations
#15
Sarah Jahdali, Noura Al Oudah, Khaled O Alsaad, Hala Kfoury, Salem Qurashi, Abdulla Al Sayyari
OBJECTIVES: Our objective was to study the clinico-pathologic correlations in BK virus nephropathy. MATERIALS AND METHODS: We conducted a retrospective study of all patients with biopsy-proven polyoma (BK) virus infection. We compared their survival and renal outcomes versus BK virus-negative patients with biopsy-proven graft rejection. Histopathologic characterization by a blinded nephropathologist was performed. RESULTS: BK nephropathy was found in 10 patients biopsied for graft dysfunction...
January 30, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/27932159/fulminant-clostridium-perfringens-sepsis-in-kidney-transplant-a-case-report
#16
P Mihaylov, J A Powelson, W C Goggins
BACKGROUND: Infections, particularly urinary tract infections, and cardiovascular accidents are the main causes of morbidity and mortality during the 1st year after kidney transplantation (KT). Bacteria and viruses, such as Escherichia coli, Enteroccoci, and Polyoma BK virus are common in the 1st 6 months, so they are controlled routinely. On the other hand, Clostridium perfringens infection is a rare life-threatening condition, associated with a high mortality rate especially in the transplant population, that is not controlled routinely...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27893716/hic-5-remodeling-of-the-stromal-matrix-promotes-breast-tumor-progression
#17
G J Goreczny, J L Ouderkirk-Pecone, E C Olson, M Krendel, C E Turner
The remodeling of the stromal extracellular matrix (ECM) has a crucial, but incompletely understood role during tumor progression and metastasis. Hic-5, a focal adhesion scaffold protein, has previously been implicated in tumor cell invasion, proliferation and metastasis. To investigate the role of Hic-5 in breast tumor progression in vivo, Hic-5(-/-) mice were generated and crossed with the Mouse Mammary Tumor Virus-Polyoma Middle T-Antigen mouse. Tumors from the Hic-5(-/-);PyMT mice exhibited increased latency and reduced growth, with fewer lung metastases, as compared with Hic-5(+/-);PyMT mice...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27808249/apoa-i-mimetic-administration-but-not-increased-apoa-i-containing-hdl-inhibits-tumour-growth-in-a-mouse-model-of-inherited-breast-cancer
#18
Lídia Cedó, Annabel García-León, Lucía Baila-Rueda, David Santos, Victor Grijalva, Melanie Raquel Martínez-Cignoni, José M Carbó, Jari Metso, Laura López-Vilaró, Antonio Zorzano, Annabel F Valledor, Ana Cenarro, Matti Jauhiainen, Enrique Lerma, Alan M Fogelman, Srinivasa T Reddy, Joan Carles Escolà-Gil, Francisco Blanco-Vaca
Low levels of high-density lipoprotein cholesterol (HDLc) have been associated with breast cancer risk, but several epidemiologic studies have reported contradictory results with regard to the relationship between apolipoprotein (apo) A-I and breast cancer. We aimed to determine the effects of human apoA-I overexpression and administration of specific apoA-I mimetic peptide (D-4F) on tumour progression by using mammary tumour virus-polyoma middle T-antigen transgenic (PyMT) mice as a model of inherited breast cancer...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27798510/infections-in-de-novo-kidney-transplant-recipients-treated-with-the-rankl-inhibitor-denosumab
#19
Marco Bonani, Diana Frey, Olivier de Rougemont, Nicolas J Mueller, Thomas F Mueller, Nicole Graf, Rudolf P Wüthrich
BACKGROUND: Infections are a major cause of morbidity and mortality in kidney allograft recipients. In this posthoc analysis of a randomized clinical trial which tested the effect of denosumab on bone mineral density we assessed the impact of this drug on the incidence and severity of infections in the first year after kidney transplantation. METHODS: In this clinical trial we randomized 90 de novo kidney transplant recipients shortly after transplantation to either denosumab on top of standard treatment (calcium and vitamin D) (n=46), or to standard treatment alone (n=44)...
October 28, 2016: Transplantation
https://www.readbyqxmd.com/read/27738494/adam17-in-tumor-associated-leukocytes-regulates-inflammatory-mediators-and-promotes-mammary-tumor-formation
#20
Laura R Bohrer, Thomas S Chaffee, Pavlina Chuntova, Nicholas J Brady, Patrice M Witschen, Sarah E Kemp, Andrew C Nelson, Bruce Walcheck, Kathryn L Schwertfeger
The presence of inflammatory cells within the tumor microenvironment has been tightly linked to mammary tumor formation and progression. Specifically, interactions between tumor cells and infiltrating macrophages can contribute to the generation of a pro-tumorigenic microenvironment. Understanding the complex mechanisms that drive tumor cell-macrophage cross-talk will ultimately lead to the development of approaches to prevent or treat early stage breast cancers. As described here, we demonstrate that the cell surface protease a disintegrin and metalloproteinase 17 (ADAM17) is expressed by macrophages in mammary tumors and contributes to regulating the expression of pro-inflammatory mediators, including inflammatory cytokines and the inflammatory mediator cyclooxygenase-2 (Cox-2)...
July 2016: Genes & Cancer
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