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https://www.readbyqxmd.com/read/28800720/jc-virus-related-progressive-multifocal-leukoencephalopathy-after-living-donor-liver-transplant-a-rare-case
#1
Archana Rastogi, Natasha Gulati, Chhagan Bihari, Ashok Chaudhary, Kalpana Bansal, Shridhar Sasturkar, Shalini Thapar, Viniyendra Pamecha
Progressive multifocal leukoencephalopathy caused by polyoma JC virus is a rare and severe demyelinating disease of the central nervous system. It occurs in immunocompromised patients and is scarcely reported in liver transplant recipients. Brain biopsy demonstrating demyelination with presence of foamy macrophages, relative preservation of axons, astrogliosis, and typical polyomavirus inclusions in the enlarged oligodendroglial nuclei is essential for diagnosis. Here, we report a case of JC virus-associated progressive multifocal leukoencephalopathy in a living-donor liver transplant recipient who was transplanted for hepatitis C virus-related decompensated cirrhosis...
August 12, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28702160/bk-virus-associated-hemorrhagic-cystitis-in-patients-with-allogeneic-hematopoietic-cell-transplantation-report-of-three-cases
#2
Duygu Mert, Hikmetullah Batgi, Alparslan Merdin, Sabahat Çeken, Mehmet Sinan Dal, Emre Tekgündüz, Fevzi Altuntaş, Mustafa Ertek
BK viras is a human polyoma viras. It is acquired in early childhood and remains life-long latent in the genitourinary system. BK virus replication is more common in receiving immunosuppressive therapy receiving patients and transplant patients. BK virus could cause hemorrhagic cystitis in patients with allogeneic stem cell transplantation. Hemorrhagic cystitis is a serious complication of hematopoietic stem cell transplantation. Hemorrhagic cystitis could cause morbidity and long stay in the hospital. Diagnosis is more frequently determined by the presence of BK virus DNA detected with quantitative or real-time PCR testing in serum or plasma and less often in urine...
June 1, 2017: Hematology Reports
https://www.readbyqxmd.com/read/28686294/nfat-regulated-cytokine-gene-expression-during-tacrolimus-therapy-early-after-renal-transplantation
#3
Sara Bremer, Nils T Vethe, Morten Skauby, Margrete Kasbo, Elisabet D Johansson, Karsten Midtvedt, Stein Bergan
AIMS: Despite pharmacokinetic monitoring of calcineurin inhibitors, the long-term outcome after transplantation (Tx) is still hampered by the side effects of these drugs. The aim of this study was to characterize the nuclear factor of activated T cells (NFAT)-regulated gene expression as a potential pharmacodynamic biomarker for further individualization of tacrolimus (Tac) therapy. METHODS: In 29 renal allograft recipients samples were drawn once pre-Tx, and before and 1...
July 7, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28624801/bromodomain-inhibition-shows-antitumoral-activity-in-mice-and-human-luminal-breast-cancer
#4
Montserrat Pérez-Salvia, Laia Simó-Riudalbas, Pere Llinàs-Arias, Laura Roa, Fernando Setien, Marta Soler, Manuel Castro de Moura, James E Bradner, Eva Gonzalez-Suarez, Catia Moutinho, Manel Esteller
BET bromodomain inhibitors, which have an antitumoral effect against various solid cancer tumor types, have not been studied in detail in luminal breast cancer, despite the prevalence of this subtype of mammary malignancy. Here we demonstrate that the BET bromodomain inhibitor JQ1 exerts growth-inhibitory activity in human luminal breast cancer cell lines associated with a depletion of the C-MYC oncogene, but does not alter the expression levels of the BRD4 bromodomain protein. Interestingly, expression microarray analyses indicate that, upon JQ1 administration, the antitumoral phenotype also involves downregulation of relevant breast cancer oncogenes such as the Breast Carcinoma-Amplified Sequence 1 (BCAS1) and the PDZ Domain-Containing 1 (PDZK1)...
May 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611083/inhibition-of-ciliogenesis-promotes-hedgehog-signaling-tumorigenesis-and-metastasis-in-breast-cancer
#5
Nadia B Hassounah, Martha Nunez, Colleen A Fordyce, Denise J Roe, Raymond B Nagle, Thomas Allen Bunch, Kimberly Marie McDermott
Primary cilia are chemosensors that play a dual role to either activate or repress Hedgehog signaling, depending on presence or absence of ligand respectively. While inhibition of ciliogenesis has been shown to be characteristic of breast cancers, the functional consequence is unknown. Here, for the first time, inhibition of ciliogenesis led to earlier tumor formation, faster tumor growth rate, higher-grade tumor formation and increased metastasis in the polyoma middle T (PyMT) mouse model of breast cancer...
June 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28576905/cmv-and-bkpyv-infections-in-renal-transplant-recipients-receiving-an-mtor-inhibitor-based-regimen-versus-a-cni-based-regimen-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#6
Samir G Mallat, Bassem Y Tanios, Houssam S Itani, Tamara Lotfi, Ciaran McMullan, Steven Gabardi, Elie A Akl, Jamil R Azzi
BACKGROUND AND OBJECTIVES: The objective of this meta-analysis is to compare the incidences of cytomegalovirus and BK polyoma virus infections in renal transplant recipients receiving a mammalian target of rapamycin inhibitor (mTOR)-based regimen compared with a calcineurin inhibitor-based regimen. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a comprehensive search for randomized, controlled trials up to January of 2016 addressing our objective. Other outcomes included acute rejection, graft loss, serious adverse events, proteinuria, wound-healing complications, and eGFR...
June 2, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28557306/sk4-channels-modulate-ca-2-signalling-and-cell-cycle-progression-in-murine-breast-cancer
#7
Friederike A Steudel, Corinna J Mohr, Benjamin Stegen, Hoang Y Nguyen, Andrea Barnert, Marc Steinle, Sandra Beer-Hammer, Pierre Koch, Wing-Yee Lo, Werner Schroth, Reiner Hoppe, Hiltrud Brauch, Peter Ruth, Stephan M Huber, Robert Lukowski
Oncogenic signalling via Ca(2+) -activated K(+) channels of intermediate conductance (SK4, also known as KCa 3.1 or IK) has been implicated in different cancer entities including breast cancer. Yet, the role of endogenous SK4 channels for tumourigenesis is unclear. Herein, we generated SK4-negative tumours by crossing SK4-deficient (SK4 KO) mice to the polyoma middle T-antigen (PyMT) and epidermal growth factor receptor 2 (cNeu) breast cancer models in which oncogene expression is driven by the retroviral promotor MMTV...
May 30, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28500840/cystatin-c-deficiency-suppresses-tumor-growth-in-a-breast-cancer-model-through-decreased-proliferation-of-tumor-cells
#8
Janja Završnik, Miha Butinar, Mojca Trstenjak Prebanda, Aleksander Krajnc, Robert Vidmar, Marko FonoviÄ, Anders Grubb, Vito Turk, Boris Turk, Olga Vasiljeva
Cysteine cathepsins are proteases that, in addition to their important physiological functions, have been associated with multiple pathologies, including cancer. Cystatin C (CstC) is a major endogenous inhibitor that regulates the extracellular activity of cysteine cathepsins. We investigated the role of cystatin C in mammary cancer using CstC knockout mice and a mouse model of breast cancer induced by expression of the polyoma middle T oncoprotein (PyMT) in the mammary epithelium. We showed that the ablation of CstC reduced the rate of mammary tumor growth...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28462542/clinical-profile-and-outcome-of-progressive-multifocal-leukoencephalopathy-in-hiv-infected-indian-patients
#9
Vipul Shah, Harsh Toshniwal, Manoj Shevkani
BACKGROUND AND OBJECTIVE: Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the Central nervous system (CNS) caused by the human polyoma virus JC (JCV). Human Immunodeficiency Virus (HIV) infection predisposes to PML. Very sparse data is available regarding the effect of Highly Active Anti Retroviral Therapy (HAART) on clinical outcome of PML in Indian settings. This study was carried out to look into clinical profile, survival and neurological outcome of HIV infected PML patients in HAART era...
March 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28460546/an-update-on-chemical-pharmacotherapy-options-for-the-prevention-of-kidney-transplant-rejection-with-a-focus-on-costimulation-blockade
#10
Florian Kälble, Matthias Schaier, Sebastian Schäfer, Caner Süsal, Martin Zeier, Claudia Sommerer, Christian Morath
The introduction of calcineurin inhibitors (CNI) has greatly improved graft survival in the past three decades. However, long-term graft survival is still limited due to chronic allograft injury and side-effects of immunosuppressive medication. Areas covered: The present overview gives an update on pharmacotherapeutic strategies after kidney transplantation. The main focus is on CNI-sparing regimens using co-stimulatory blockade and on new substances on the horizone. Expert opinion: CNI sparing regimens are well-established...
June 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28407697/cytosolic-hsp90%C3%AE-and-its-mitochondrial-isoform-trap1-are-differentially-required-in-a-breast-cancer-model
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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 showed polyoma virus large T-antigen expression in tubular epithelium using 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
#17
Pascale Coric, A Sami Saribas, Magid Abou-Gharbia, Wayne Childers, Jon H 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 region was found to adopt a major alpha-helix conformation spanning amino acids 23-39...
October 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28281550/reduced-h3k27me3-expression-in-merkel-cell-polyoma-virus-positive-tumors
#18
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)...
June 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
#19
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...
June 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
#20
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
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