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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
Ashraf Kariminik
It has been demonstrated that IL-2 plays a dual role in induction/suppression of immune responses via activation of conventional and regulatory T lymphocytes, respectively. IL-2 contacts complete IL-2 receptor (IL-2R) which contains CD25 (α chain) on the antigen specific activated T helper and cytotoxic lymphocytes and also T regulatory cells. Additionally, previous investigations revealed that polyoma BK virus (PBK) reactivation and induction of PBK associated nephropathy (PBKAN) is a main complication following renal transplantation...
October 5, 2016: Cytokine
P Kokkinos, I Kozyra, S Lazic, K Söderberg, P Vasickova, M Bouwknegt, S Rutjes, K Willems, R Moloney, A M de Roda Husman, A Kaupke, E Legaki, M D'Agostino, N Cook, C-H von Bonsdorff, A Rzeżutka, T Petrovic, L Maunula, I Pavlik, A Vantarakis
This study condenses data acquired during investigations of the virological quality of irrigation water used in production of fresh produce. One hundred and eight samples of irrigation water were collected from five berry fruit farms in Finland (1), the Czech Republic (1), Serbia (2), and Poland (1), and sixty-one samples were collected from three leafy green vegetable farms in Poland, Serbia, and Greece. Samples were analyzed for index viruses of human or animal fecal contamination (human and porcine adenoviruses, and bovine polyoma viruses), and human pathogenic viruses (hepatitis A virus, hepatitis E virus, and noroviruses GI/GII)...
October 5, 2016: Food and Environmental Virology
Stephanie Azzopardi, Sharon Pang, David S Klimstra, Yi-Chieh Nancy Du
In human studies and mouse models, the contributions of p53 and p16(Ink4a)/p19(Arf) loss are well established in pancreatic ductal adenocarcinoma (PDAC). Although loss of functional p53 pathway and loss of Ink4a/Arf in human pancreatic acinar cell carcinoma (PACC) and pancreatic neuroendocrine tumor (PanNET) are identified, their direct roles in tumorigenesis of PACC and PanNET remain to be determined. Using transgenic mouse models expressing the viral oncogene polyoma middle T antigen (PyMT), we demonstrate that p53 loss in pancreatic Pdx1+ progenitor cells results in aggressive PACC, whereas Ink4a/Arf loss results in PanNETs...
October 2016: Neoplasia: An International Journal for Oncology Research
S Kuppachi, D Holanda, M Eberlein, B Alexiev, A J Tyler, M C Wissel, S B Kleiboeker, C P Thomas
We report a lung transplant recipient who developed BK polyoma virus (BKPyV) DNAemia and BKPyV nephropathy. With careful management of his immunosuppression he achieved significant reduction in BKPyV DNAemia and stabilization of his kidney function. He later developed a high-grade bladder cancer and shortly thereafter he experienced a major upsurge in the level of BKPyV DNAemia that coincided with the discovery of hepatic metastasis. Retrospectively, the bladder cancer and the hepatic secondary tumor stained uniformly for SV40 large T antigen, and the BKPyV DNA sequences identified in plasma corresponded to BKPyV DNA within hepatic tissue, indicating that the spike in BKPyV load was likely derived from the circulating tumor cells or cell-free tumor DNA following metastases of a BKV-associated cancer...
September 20, 2016: American Journal of Transplantation
Hongbin Li, Barry M Gumbiner
The Hippo-YAP pathway mediates organ size control, contact inhibition, and tumorigenesis. It is a kinase cascade that inhibits the nuclear localization and transcriptional activities of YAP and TAZ. E-cadherin, cell junctions, polarity proteins, and the merlin/NF2 tumor suppressor activate the pathway to inhibit YAP/TAZ activity, while growth factor signaling inhibits the pathway to activate YAP/TAZ in the nucleus. We examined its role in the development of mouse mammary glands and tumor formation using gland reconstitution by transplantation of genetically modified mammary stem cells (MaSCs)...
September 6, 2016: Mammalian Genome: Official Journal of the International Mammalian Genome Society
Muhammad Rizwan, Bengt Rönnberg, Maksims Cistjakovs, Åke Lundkvist, Rudiger Pipkorn, Jonas Blomberg
BACKGROUND: Antibodies to microbes, or to autoantigens, are important markers of disease. Antibody detection (serology) can reveal both past and recent infections. There is a great need for development of rational ways of detecting and quantifying antibodies, both for humans and animals. Traditionally, serology using synthetic antigens covers linear epitopes using up to 30 amino acid peptides. METHODS: We here report that peptides of 100 amino acids or longer ("megapeptides"), designed and synthesized for optimal serological performance, can successfully be used as detection antigens in a suspension multiplex immunoassay (SMIA)...
August 10, 2016: Microarrays
Laura Jeffords Moore, Lopamudra Das Roy, Ru Zhou, Priyanka Grover, Shu-Ta Wu, Jennifer M Curry, Lloye M Dillon, Priya M Puri, Mahboubeh Yazdanifar, Rahul Puri, Pinku Mukherjee, Didier Dréau
BACKGROUND: Earlier detection of transformed cells using target-specific imaging techniques holds great promise. We have developed TAB 004, a monoclonal antibody highly specific to a protein sequence accessible in the tumor form of MUC1 (tMUC1). We present data assessing both the specificity and sensitivity of TAB 004 in vitro and in genetically engineered mice in vivo. METHODS: Polyoma Middle T Antigen mice were crossed to the human MUC1.Tg mice to generate MMT mice...
August 2016: Translational Oncology
Ismini Lasithiotaki, Eliza Tsitoura, Anastasios Koutsopoulos, Eleni Lagoudaki, Chara Koutoulaki, George Pitsidianakis, Demetrios A Spandidos, Nikolaos M Siafakas, George Sourvinos, Katerina M Antoniou
Merkel Cell Polyoma Virus (MCPyV) infection has been associated with non-small cell lung cancer (NSCLC). Viruses can manipulate cellular miRNAs or have a profound impact on cellular miRNA expression to control host regulatory pathways. In this study, we evaluated the expression profiles of cancer-associated and virally affected host microRNAs miR-21, miR-145, miR-146a, miR-155, miR-302c, miR-367 and miR-376c in a series of NSCLC tissue samples as well as in samples from "healthy" sites, distant from the tumour region that were either positive or negative for MCPyV DNA...
August 11, 2016: Oncotarget
Luciano Moscarelli, Giulia Antognoli, Elisa Buti, Egrina Dervishi, Filippo Fani, Leonardo Caroti, Aris Tsalouchos, Elena Romoli, Giulia Ghiandai, Enrico Minetti
Observation that 1,25-Dihydroxyvitamin-D3 has an immunomodulatory effect on innate and adaptive immunity raises the possible effect on clinical graft outcome. Aim of this study was to evaluate the correlation of biopsy-proven acute rejection, CMV infection, BKV infection, with 1,25-Dihydroxyvitamin-D3 deficiency and the benefit of calcitriol supplementation before and during the transplantation. Risk factors and kidney graft function were also evaluated. All RTRs received induction therapy with basiliximab, cyclosporine, mycophenolic acid, and steroids...
October 2016: Clinical Transplantation
Thomas Welte, Frederic Arnold, Kristin Technau-Hafsi, Elke Neumann-Haefelin, Rika Wobser, Stefan Zschiedrich, Gerd Walz, Albrecht Kramer-Zucker
UNLABELLED: Calciphylaxis is a rare and often fatal condition mostly associated with end-stage renal disease. The pathophysiology remains elusive and treatment options are scarce. We present a rare case of severe calciphylaxis after kidney transplantation in a patient with persistent hyperparathyroidism. CASE DESCRIPTION: A 78-year-old man with a history of end-stage renal disease developed edema and ulcerations on both lower limbs 14 months after kidney transplantation while receiving an mammalian target of rapamycin inhibitor to manage polyoma virus-associated nephropathy...
April 2016: Transplantation Direct
Jennifer Schmitz, Julian Schwab, Johannes Schwenck, Qian Chen, Leticia Quintanilla-Martinez, Markus Hahn, Beate Wietek, Nina Schwenzer, Annette Staebler, Ursula Kohlhofer, Olulanu H Aina, Neil E Hubbard, Gerald Reischl, Alexander D Borowsky, Sara Brucker, Konstantin Nikolaou, Christian la Fougère, Robert D Cardiff, Bernd J Pichler, Andreas M Schmid
Differential diagnosis and therapy of heterogeneous breast tumors poses a major clinical challenge. To address the need for a comprehensive, noninvasive strategy to define the molecular and functional profiles of tumors in vivo, we investigated a novel combination of metabolic PET and diffusion-weighted (DW)-MRI in the polyoma virus middle T antigen transgenic mouse model of breast cancer. The implementation of a voxelwise analysis for the clustering of intra- and intertumoral heterogeneity in this model resulted in a multiparametric profile based on [(18)F]Fluorodeoxyglucose ([(18)F]FDG)-PET and DW-MRI, which identified three distinct tumor phenotypes in vivo, including solid acinar, and solid nodular malignancies as well as cystic hyperplasia...
September 15, 2016: Cancer Research
Ruben Nogales-Cadenas, Ying Cai, Jhih-Rong Lin, Quanwei Zhang, Wen Zhang, Cristina Montagna, Zhengdong D Zhang
BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNA molecules of about 22 nucleotides which function to silence the expression of their target genes. Numerous studies have shown that miRNAs are not only key regulators in important cellular processes but are also drivers in the development of many diseases, especially cancer. Estrogen receptor positive luminal B is the second most common but the least studied subtype of breast cancer. Only a few studies have examined the expression profiles of miRNAs in luminal B breast cancer, and their regulatory roles in cancer progression have yet to be investigated...
2016: Breast Cancer Research: BCR
Peter Boan, Christopher Hewison, Ramyasuda Swaminathan, Ashley Irish, Kevin Warr, Rajalingam Sinniah, Todd M Pryce, James Flexman
BACKGROUND: BK virus is a polyoma virus causing renal allograft nephropathy. Reduction of immunosuppression with the early recognition of significant BK viral loads in urine and plasma can effectively prevent BKV associated nephropathy (BKVN), however the optimal compartment and frequency of BK viral load measurement post renal transplantation are undetermined. Our purpose was to examine time to detection and viral loads in urine compared to plasma, and establish viral load cut-offs associated with histological BKVN...
2016: BMC Infectious Diseases
Alberto López-Bueno, Carla Mavian, Alejandro M Labella, Dolores Castro, Juan J Borrego, Antonio Alcami, Alí Alejo
UNLABELLED: Lymphocystis disease is a geographically widespread disease affecting more than 150 different species of marine and freshwater fish. The disease, provoked by the iridovirus lymphocystis disease virus (LCDV), is characterized by the appearance of papillomalike lesions on the skin of affected animals that usually self-resolve over time. Development of the disease is usually associated with several environmental factors and, more frequently, with stress conditions provoked by the intensive culture conditions present in fish farms...
October 1, 2016: Journal of Virology
Armine Darbinyan, Eugene O Major, Susan Morgello, Steven Holland, Caroline Ryschkewitsch, Maria Chiara Monaco, Thomas P Naidich, Joshua Bederson, Joanna Malaczynska, Fei Ye, Ronald Gordon, Charlotte Cunningham-Rundles, Mary Fowkes, Nadejda M Tsankova
Human BK polyomavirus (BKV) is reactivated under conditions of immunosuppression leading most commonly to nephropathy or cystitis; its tropism for the brain is rare and poorly understood. We present a unique case of BKV-associated encephalopathy in a man with hypohidrotic ectodermal dysplasia and immunodeficiency (HED-ID) due to IKK-gamma (NEMO) mutation, who developed progressive neurological symptoms. Brain biopsy demonstrated polyomavirus infection of gray and white matter, with predominant involvement of cortex and distinct neuronal tropism, in addition to limited demyelination and oligodendroglial inclusions...
2016: Acta Neuropathologica Communications
Kamal Kant Sahu, Gaurav Prakash, Alka Khadwal, Subhash Chander Varma, Pankaj Malhotra
Post bone marrow transplant patients are susceptible to atypical infections, especially viral pathogens. The risk increases many folds in cases of allogeneic transplantation, which also receive GVHD prophylaxis. Viral pathogens like cytomegalovirus and herpes are the common ones encountered during follow-up period. However, in recent times there have been reports of a variety of disease manifestations of rare viruses like polyoma virus and adenovirus. These viral infections may play a crucial role in morbidity and mortality in immunocompromised patients...
June 2016: Indian Journal of Hematology & Blood Transfusion
Emily J Gallagher, Zara Zelenko, Aviva Tobin-Hess, Ulrich Werner, Norbert Tennagels, Derek LeRoith
AIMS/HYPOTHESIS: Previous epidemiological studies have reported a potential link between insulin analogues and breast cancer; however, a prospective randomised controlled trial showed neutral effects of insulin glargine on cancer risk. Insulin glargine is metabolised in vivo to an M1 metabolite. A question remains whether a subset of individuals with slower rates of glargine metabolism or who are on high doses could, theoretically, have an increased risk of cancer progression if a tumour is already present...
September 2016: Diabetologia
M El Ansary, S Abd Elhamid, G Saadi, W Ismail, N Ibrahim, N Bahaa El-Din, S Alhsyek
BACKGROUND: Polyomavirus nephropathy (PVN) mainly caused by BK polyomavirus (BKPyV) remains the most common productive viral infection of the kidney in immunosuppressed patients. The diagnosis of PVN is based on the detection of BK viruria and BK viremia in conjunction with histological findings in the graft biopsy. METHODS: Our study was aimed to estimate the prevalence of productive BKPyV infection among renal transplant patients within the first year post-transplant and identify those at risk of developing PVN...
August 2016: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Donald J Tipper, Eva Szomolanyi-Tsuda
Background. U65, a self-aggregating peptide scaffold, traps fused protein antigens in yeast cells. Conversion to Yeast Cell Particle (YCP) vaccines by partial removal of surface mannoproteins exposes β-glucan, mediating efficient uptake by antigen-presenting cells (APCs). YCP vaccines are inexpensive, capable of rapid large-scale production and have potential for both parenteral and oral use. Results. YCP processing by alkaline hydrolysis exposes up to 20% of the glucan but converts scaffolded antigen and internal yeast proteins into a common aggregate, preventing selective yeast protein removal...
2016: Journal of Immunology Research
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