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https://www.readbyqxmd.com/read/29145505/spontaneous-development-of-epstein-barr-virus-associated-human-lymphomas-in-a-prostate-cancer-xenograft-program
#1
Alberto J Taurozzi, Ramprakash Beekharry, Michelle Wantoch, Marie-Christine Labarthe, Hannah F Walker, Robert I Seed, Matthew Simms, Greta Rodrigues, James Bradford, Geertje van der Horst, Gabri van der Pluijm, Anne T Collins
Prostate cancer research is hampered by the lack of in vivo preclinical models that accurately reflect patient tumour biology and the clinical heterogeneity of human prostate cancer. To overcome these limitations we propagated and characterised a new collection of patient-derived prostate cancer xenografts. Tumour fragments from 147 unsupervised, surgical prostate samples were implanted subcutaneously into immunodeficient Rag2-/-γC-/- mice within 24 hours of surgery. Histologic and molecular characterisation of xenografts was compared with patient characteristics, including androgen-deprivation therapy, and exome sequencing...
2017: PloS One
https://www.readbyqxmd.com/read/29145503/zinc-sulfate-contributes-to-promote-telomere-length-extension-via-increasing-telomerase-gene-expression-telomerase-activity-and-change-in-the-tert-gene-promoter-cpg-island-methylation-status-of-human-adipose-derived-mesenchymal-stem-cells
#2
Raheleh Farahzadi, Ezzatollah Fathi, Seyed Alireza Mesbah-Namin, Nosratollah Zarghami
The use of mesenchymal stem cells (MSCs) for cell therapy and regenerative medicine has received widespread attention over the past few years, but their application can be complicated by factors such as reduction in proliferation potential, the senescent tendency of the MSCs upon expansion and their age-dependent decline in number and function. It was shown that all the mentioned features were accompanied by a reduction in telomerase activity and telomere shortening. Furthermore, the role of epigenetic changes in aging, especially changes in promoter methylation, was reported...
2017: PloS One
https://www.readbyqxmd.com/read/29145481/amiloride-enhanced-gene-transfection-of-octa-arginine-functionalized-calcium-phosphate-nanoparticles
#3
Juan Ramón Vanegas Sáenz, Taichi Tenkumo, Yuya Kamano, Hiroshi Egusa, Keiichi Sasaki
Nanoparticles represent promising gene delivery systems in biomedicine to facilitate prolonged gene expression with low toxicity compared to viral vectors. Specifically, nanoparticles of calcium phosphate (nCaP), the main inorganic component of human bone, exhibit high biocompatibility and good biodegradability and have been reported to have high affinity for protein or DNA, having thus been used as gene transfer vectors. On the other hand, Octa-arginine (R8), which has a high permeability to cell membrane, has been reported to improve intracellular delivery systems...
2017: PloS One
https://www.readbyqxmd.com/read/29144842/a-novel-fiber-chimeric-conditionally-replicative-adenovirus-ad5-f35-for-tumor-therapy
#4
Ming Yang, Chun Sheng Yang, WenWen Guo, JianQin Tang, Qian Huang, ShouXin Feng, AiJun Jiang, XiFeng Xu, Guan Jiang, Yan Qun Liu
Significant progress has been made in the diagnosis and treatment of cancer; however, significant challenges remain. Conditionally replicating adenoviruses (CRAds), which not only kill cancer cells, but also serve as vectors to express therapeutic genes, are a novel and effective method to treat cancer. However, most adenoviruses are Ad5, which infect cells through the coxsackie and adenovirus receptor (CAR). The transduction efficacy of Ad5 is restricted because of the absent or low expression of CAR on several cancer cells...
November 16, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29144820/pheochromocytoma-a-genetic-and-diagnostic-update
#5
Leilani B Mercado-Asis, Katherine I Wolf, Ivana Jochmanova, David Taïeb
OBJECTIVE: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from adrenal or extra-adrenal locations, respectively. Upon suspicion of PPGL, specific metabolomic, molecular, biochemical, imaging, and histopathological studies are performed to prove, localize, treat, and monitor disease progression. Recently, improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (less than 1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29144530/liddle-s-syndrome-in-an-african-male-due-to-a-novel-frameshift-mutation-in-the-beta-subunit-of-the-epithelial-sodium-channel-gene
#6
Robert Freercks, Surita Meldau, Erika Jones, Jason Ensor, Clarise Weimers-Willard, Brian Rayner
Resistant hypertension is a common clinical problem in South Africa and is frequently associated with low renin and aldosterone levels, especially in black Africans. In South Africa, novel variants in the epithelial sodium channel (ENaC) have been described to be associated with varying degrees of hypokalaemia and hypertension due to primary sodium retention. We report here a case of Liddle's syndrome due to a novel c.1709del11 (p.Ser570Tyrfs*20) deletion in the beta-subunit of the ENaC in a young black African male...
September 23, 2017: Cardiovascular Journal of Africa
https://www.readbyqxmd.com/read/29144448/regeneration-of-the-entire-human-epidermis-using-transgenic-stem-cells
#7
Tobias Hirsch, Tobias Rothoeft, Norbert Teig, Johann W Bauer, Graziella Pellegrini, Laura De Rosa, Davide Scaglione, Julia Reichelt, Alfred Klausegger, Daniela Kneisz, Oriana Romano, Alessia Secone Seconetti, Roberta Contin, Elena Enzo, Irena Jurman, Sonia Carulli, Frank Jacobsen, Thomas Luecke, Marcus Lehnhardt, Meike Fischer, Maximilian Kueckelhaus, Daniela Quaglino, Michele Morgante, Silvio Bicciato, Sergio Bondanza, Michele De Luca
Junctional epidermolysis bullosa (JEB) is a severe and often lethal genetic disease caused by mutations in genes encoding the basement membrane component laminin-332. Surviving patients with JEB develop chronic wounds to the skin and mucosa, which impair their quality of life and lead to skin cancer. Here we show that autologous transgenic keratinocyte cultures regenerated an entire, fully functional epidermis on a seven-year-old child suffering from a devastating, life-threatening form of JEB. The proviral integration pattern was maintained in vivo and epidermal renewal did not cause any clonal selection...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29144447/bcat1-restricts-%C3%AE-kg-levels-in-aml-stem-cells-leading-to-idhmut-like-dna-hypermethylation
#8
Simon Raffel, Mattia Falcone, Niclas Kneisel, Jenny Hansson, Wei Wang, Christoph Lutz, Lars Bullinger, Gernot Poschet, Yannic Nonnenmacher, Andrea Barnert, Carsten Bahr, Petra Zeisberger, Adriana Przybylla, Markus Sohn, Martje Tönjes, Ayelet Erez, Lital Adler, Patrizia Jensen, Claudia Scholl, Stefan Fröhling, Sibylle Cocciardi, Patrick Wuchter, Christian Thiede, Anne Flörcken, Jörg Westermann, Gerhard Ehninger, Peter Lichter, Karsten Hiller, Rüdiger Hell, Carl Herrmann, Anthony D Ho, Jeroen Krijgsveld, Bernhard Radlwimmer, Andreas Trumpp
The branched-chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities. However, the mechanistic role of BCAT1 in this process remains largely uncertain. Here, by performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem-cell and non-stem-cell populations, we find the BCAA pathway enriched and BCAT1 protein and transcripts overexpressed in leukaemia stem cells. We show that BCAT1, which transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), is a critical regulator of intracellular αKG homeostasis...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29144216/the-truth-about-in-vitro-culture-of-cryptosporidium-species
#9
Panagiotis Karanis
Cryptosporidium research has focused on the development of infection control, and effective therapy that has thus far been hampered by the inability to culture Cryptosporidium in vitro. Other limitations include inadequate animal models, cumbersome screening procedures for chemotherapeutic approaches and a lack of tools for genetic manipulation. These limitations can, however, be eased by the improvement and focused development of in vitro cultivation. The ability to culture relevant Cryptosporidium isolates in vitro and to propagate the life cycle stages that are responsible for causing disease in an infected host is still a critical link...
November 16, 2017: Parasitology
https://www.readbyqxmd.com/read/29144165/gene-therapy-evidence-value-and-affordability-in-the-us-health-care-system
#10
Grace Hampson, Adrian Towse, Steven D Pearson, William B Dreitlein, Chris Henshall
AIMS: To explore the challenges presented by gene therapies, discuss potential solutions, and present policy recommendations. METHODS: A review of the literature and series of expert interviews were conducted and discussed at a Policy Forum convened by The Institute for Clinical and Economic Review (ICER). The Policy Forum was attended by independent experts and senior representatives from 20 payer organizations and life sciences companies. RESULTS: Three categories of challenges are identified: evidence generation, assessing value and affordability...
November 16, 2017: Journal of Comparative Effectiveness Research
https://www.readbyqxmd.com/read/29143979/analysis-of-anti-tnf-induced-skin-lesions-reveals-strong-th1-activation-with-some-distinct-immunological-characteristics
#11
E Stoffel, H Maier, E Riedl, M-C Brüggen, B Reininger, M Schaschinger, C Bangert, E Guenova, G Stingl, P M Brunner
BACKGROUND: Psoriasiform and eczematous eruptions are the most common dermatological adverse reaction linked to anti-TNF-α therapy. Yet, a detailed characterization of their immune phenotype is lacking. OBJECTIVES: We sought to characterize anti-TNF-α induced inflammatory skin lesions on a histopathologic, cellular and molecular level, compared to psoriasis, eczema (atopic dermatitis), and healthy control skin. METHODS: Histopathologic evaluation, gene expression (quantitative RT-PCR) and computer-assisted immunohistologic studies (TissueFAXS) were performed on 19 skin biopsies from IBD (n=17) and rheumatoid arthritis (n=2) patients with new-onset inflammatory skin lesions during anti-TNF-α-therapy...
November 16, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29143976/stat3-atg5-signal-axis-inducing-autophagy-to-alleviate-hepatic-ischemia-reperfusion-injury
#12
Yu-Fang Han, Yan-Bing Zhao, Jun Li, Li Li, Yong-Gan Li, Shi-Peng Li, Zhong-Dong Li
In performing our experiment, impaired autophagy increased hepatocellular damage during the reperfusion period. It was demonstrated by the effect of blocking autophagy using bafilomycin A1 or knocking Atg5 gene out reduces the anti-apoptotic effect of Stat3. Here we focus on the role of signal transducer and activator of transcription 3 (Stat3) in regulating autophagy to alleviate hepatic IRI. We found that Stat3 was up-regulated during hepatic IRI and was associated with an activation of the autophagic signaling pathway...
November 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29143897/anaplastic-lymphoma-kinase-testing-ihc-vs-fish-vs-ngs
#13
REVIEW
Xiaomin Niu, Jody C Chuang, Gerald J Berry, Heather A Wakelee
Personalized targeted therapy has emerged as a promising strategy in lung cancer treatment, with current attention focused on elucidation and detection of oncogenic drivers responsible for tumor initiation and maintenance and development of drug resistance. In lung cancer, several oncogenic drivers have been reported, triggering the application of tyrosine kinase inhibitors (TKIs) to target these dysfunctional genes. The anaplastic lymphoma kinase (ALK) rearrangement is responsible for about 4-7% of all non-small cell lung cancers (NSCLCs) and perhaps as high as a third in specific patient populations such as younger, male, non-smokers with advanced stage, epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) wild type, and signet ring cell adenocarcinoma with abundant intracytoplasmic mucin...
November 16, 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29143824/pd-1-is-a-haploinsufficient-suppressor-of-t-cell-lymphomagenesis
#14
Tim Wartewig, Zsuzsanna Kurgyis, Selina Keppler, Konstanze Pechloff, Erik Hameister, Rupert Öllinger, Roman Maresch, Thorsten Buch, Katja Steiger, Christof Winter, Roland Rad, Jürgen Ruland
T cell non-Hodgkin lymphomas are a heterogeneous group of highly aggressive malignancies with poor clinical outcomes. T cell lymphomas originate from peripheral T cells and are frequently characterized by genetic gain-of-function variants in T cell receptor (TCR) signalling molecules. Although these oncogenic alterations are thought to drive TCR pathways to induce chronic proliferation and cell survival programmes, it remains unclear whether T cells contain tumour suppressors that can counteract these events...
November 15, 2017: Nature
https://www.readbyqxmd.com/read/29143813/ship1-but-not-an-aml-derived-ship1-mutant-suppresses-myeloid-leukemia-growth-in-a-xenotransplantation-mouse-model
#15
M Täger, S Horn, E Latuske, P Ehm, M Schaks, M Nalaskowski, B Fehse, W Fiedler, C Stocking, J Wellbrock, M Jücker
Constitutive activation of the PI3K/AKT signaling pathway is found in ~50-70% of AML patients. The SH2-containing inositol 5-phosphatase 1 (SHIP1) is a negative regulator of PI3K/AKT signaling in hematopoietic cells. SHIP1 knockout mice develop a myeloproliferative syndrome and concomitant deletion of SHIP1 and the tumor suppressor PTEN leads to the development of lethal B-cell lymphomas. In the study presented here, we investigated the role of SHIP1 as a tumor suppressor in myeloid leukemia cells in an in vivo xenograft transplantation model...
November 16, 2017: Gene Therapy
https://www.readbyqxmd.com/read/29143810/next-generation-pacemakers-from-small-devices-to-biological-pacemakers
#16
REVIEW
Eugenio Cingolani, Joshua I Goldhaber, Eduardo Marbán
Electrogenesis in the heart begins in the sinoatrial node and proceeds down the conduction system to originate the heartbeat. Conduction system disorders lead to slow heart rates that are insufficient to support the circulation, necessitating implantation of electronic pacemakers. The typical electronic pacemaker consists of a subcutaneous generator and battery module attached to one or more endocardial leads. New leadless pacemakers can be implanted directly into the right ventricular apex, providing single-chamber pacing without a subcutaneous generator...
November 16, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/29143804/telomeres-and-telomerase-in-hematopoietic-dysfunction-prognostic-implications-and-pharmacological-interventions
#17
REVIEW
Theresa Vasko, Andrea Kaifie, Matthias B Stope, Thomas Kraus, Patrick Ziegler
Leukocyte telomere length (TL) has been suggested as a marker of biological age in healthy individuals, but can also reflect inherited and acquired hematopoietic dysfunctions or indicate an increased turnover of the hematopoietic stem and progenitor cell compartment. In addition, TL is able to predict the response rate of tyrosine kinase inhibitor therapy in chronic myeloid leukemia (CML), indicates clinical outcomes in chronic lymphocytic leukemia (CLL), and can be used as screening tool for genetic sequencing of selected genes in patients with inherited bone marrow failure syndromes (BMFS)...
October 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29143727/characterization-of-clinically-isolated-thymidine-dependent-small-colony-variants-of-escherichia-coli-producing-extended-spectrum-%C3%AE-lactamase
#18
Tatsuya Negishi, Takehisa Matsumoto, Kazuki Horiuchi, Eriko Kasuga, Tatsuya Natori, Mina Matsuoka, Naoko Ogiwara, Mitsutoshi Sugano, Takeshi Uehara, Noriyuki Nagano, Takayuki Honda
PURPOSE: Thymidine-dependent small-colony variants (TD-SCVs) are difficult to detect or test for antimicrobial susceptibility. We investigated the characteristics of clonal TD-SCVs of Escherichia coli, both with and without blaCTX-M-3, isolated from a patient. METHODOLOGY: Mutation in the thyA gene was analysed by sequencing, and morphological abnormalities in the colonies and cells of the isolates were examined. Additionally, conjugational transfer experiments were performed to prove the horizontal transferability of plasmids harbouring resistance genes...
November 16, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/29143560/induced-pluripotent-stem-cells-derived-from-human-amnion-in-chemically-defined-conditions
#19
Jaroslav Slamecka, Steven McClellan, Anna Wilk, Javier Laurini, Elizabeth Manci, Simon P Hoerstrup, Benedikt Weber, Laurie Owen
Fetal stem cells are a unique type of adult stem cells that have been suggested to be broadly multipotent with some features of pluripotency. Their clinical potential has been documented but their upgrade to full pluripotency could open up a wide range of cell-based therapies particularly suited for pediatric tissue engineering, longitudinal studies or disease modeling. Here we describe episomal reprogramming of mesenchymal stem cells from the human amnion to pluripotency (AM-iPSC) in chemically defined conditions...
November 16, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29143488/isolation-and-characterization-of-novel-goose-parvovirus-related-virus-reveal-the-evolution-of-waterfowl-parvovirus
#20
P Li, S Lin, R Zhang, J Chen, D Sun, J Lan, S Song, Z Xie, S Jiang
Short beak and dwarfism syndrome (SBDS) has been constantly breaking out in China since 2015. It is caused by a novel goose parvovirus-related virus (NGPV) and can severely restrict the growth of ducks. In this study, seven NGPV stains were isolated from different regions in China between 2015 and 2016. To better understand the correlation between NGPV and goose parvovirus (GPV), we conducted complete genome sequencing and a comprehensive analysis of the NGPV genome. The phylogenetic and alignment analysis showed that NGPV is a branch of GPV, sharing 92...
November 16, 2017: Transboundary and Emerging Diseases
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