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https://www.readbyqxmd.com/read/28723643/methyltransferase-g9a-promotes-cervical-cancer-angiogenesis-and-decreases-patient-survival
#1
Ruey-Jien Chen, Chia-Tung Shun, Men-Luh Yen, Chia-Hung Chou, Ming-Chieh Lin
Research suggests that the epigenetic regulator G9a, a H3K9 histone methyltransferase, is involved in cancer invasion and metastasis. Here we show that G9a is linked to cancer angiogenesis and poor patient survival. Invasive cervical cancer has a higher G9a expression than cancer precursors or normal epithelium. Pharmacological inhibition and genetic silencing of G9a suppresses H3K9 methylation, cancer cell proliferation, angiogenesis, and cancer cell invasion/migration, but not apoptosis. Microarray and quantitative reverse transcription polymerase chain reaction analyses reveal that G9a induces a cohort of angiogenic factors that include angiogenin, interleukin-8, and C-X-C motif chemokine ligand 16...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722174/astrocytes-follow-ganglion-cell-axons-to-establish-an-angiogenic-template-during-retinal-development
#2
Matthew L O'Sullivan, Vanessa M Puñal, Patrick C Kerstein, Joseph A Brzezinski, Tom Glaser, Kevin M Wright, Jeremy N Kay
Immature astrocytes and blood vessels enter the developing mammalian retina at the optic nerve head and migrate peripherally to colonize the entire retinal nerve fiber layer (RNFL). Retinal vascularization is arrested in retinopathy of prematurity (ROP), a major cause of bilateral blindness in children. Despite their importance in normal development and ROP, the factors that control vascularization of the retina remain poorly understood. Because astrocytes form a reticular network that appears to provide a substrate for migrating endothelial cells, they have long been proposed to guide angiogenesis...
July 19, 2017: Glia
https://www.readbyqxmd.com/read/28721160/genetic-disruption-of-multidrug-resistance-associated-protein-1-improves-endothelial-function-and-attenuates-atherosclerosis-in-mrp1-ldlr-double-knockout-mice
#3
Julian Jehle, Cornelius F H Müller, Adem Aksoy, Sebastian Zimmer, Georg Nickenig, Vedat Tiyerili
INTRODUCTION: Multidrug resistance-associated protein 1 (MRP1) is an anion transporter which is implicated in the efflux of the intracellular antioxidant anion glutathione as well as leukotrienes. Pharmacological inhibition of MRP1 exhibits antioxidative and anti-atherosclerotic effects both in vitro and in vivo. However, pharmacological inhibitors of MRP1 lack selectivity, which prompted us to study the in vivo impact of a genetic disruption of MRP1 on endothelial dysfunction, reactive oxygen species formation and atherogenesis in an atherosclerotic mouse model...
June 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28720880/pattern-of-retinal-morphological-and-functional-decay-in-a-light-inducible-rhodopsin-mutant-mouse
#4
Claudia Gargini, Elena Novelli, Ilaria Piano, Martina Biagioni, Enrica Strettoi
Hallmarks of Retinitis Pigmentosa (RP), a family of genetic diseases, are a typical rod-cone-degeneration with initial night blindness and loss of peripheral vision, followed by decreased daylight sight and progressive visual acuity loss up to legal blindness. Great heterogeneity in nature and function of mutated genes, variety of mutations for each of them, variability in phenotypic appearance and transmission modality contribute to make RP a still incurable disease. Translational research relies on appropriate animal models mimicking the genetic and phenotypic diversity of the human pathology...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720848/the-natural-disc1-deletion-present-in-several-inbred-mouse-strains-does-not-affect-sleep
#5
Lars Dittrich, Alessandro Petese, Walker S Jackson
The gene Disrupted in Schizophrenia-1 (DISC1) is linked to a range of psychiatric disorders. Two recent transgenic studies suggest DISC1 is also involved in homeostatic sleep regulation. Several strains of inbred mice commonly used for genome manipulation experiments, including several Swiss and likely all 129 substrains, carry a natural deletion mutation of Disc1. This constitutes a potential confound for studying sleep in genetically modified mice. Since disturbed sleep can also influence psychiatric and neurodegenerative disease models, this putative confound might affect a wide range of studies in several fields...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720571/the-integrated-stress-response-in-hypoxia-induced-diffuse-white-matter-injury
#6
Benjamin Ll Clayton, Aaron Huang, Rejani B Kunjamma, Ani Solanki, Brian Popko
Currently no treatments exist for preterm infants with diffuse white matter injury (DWMI) caused by hypoxia. Due to improved care of preterm neonates and increased recognition by advanced imaging techniques, the prevalence of DWMI is increasing. A better understanding of the pathophysiology of DWMI is therefore of critical importance. The integrated stress response (ISR), a conserved eukaryotic response to myriad stressors including hypoxia, may play a role in hypoxia-induced DWMI and may represent a novel target for much needed therapies...
July 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28718445/mouse-versus-human-neutrophils-in-cancer-a-major-knowledge-gap
#7
REVIEW
Evgeniy B Eruslanov, Sunil Singhal, Steven M Albelda
Many types of cancer recruit neutrophils that could have protumor or antitumor effects on tumor development. Numerous findings in murine models suggest a predominantly protumoral role for neutrophils in cancer development. However, there are fundamental differences between mouse and human tumors in the evolution of tumors, genetic diversity, immune response, and also in the intrinsic biology of neutrophils that might have a profound impact on tumor development and the function of these cells. A crucial difference is that the majority of mouse tumor models lack the prolonged initial phases of multistage tumor evolution present in humans when antitumoral mechanisms are activated...
February 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28717969/decreasing-the-expression-of-gabaa-%C3%AE-5-subunit-containing-receptors-partially-improves-cognitive-electrophysiological-and-morphological-hippocampal-defects-in-the-ts65dn-model-of-down-syndrome
#8
Verónica Vidal, Susana García-Cerro, Paula Martínez, Andrea Corrales, Sara Lantigua, Rebeca Vidal, Noemí Rueda, Laurence Ozmen, Maria-Clemencia Hernández, Carmen Martínez-Cué
Trisomy 21 or Down syndrome (DS) is the most common cause of intellectual disability of a genetic origin. The Ts65Dn (TS) mouse, which is the most commonly used and best-characterized mouse model of DS, displays many of the cognitive, neuromorphological, and biochemical anomalies that are found in the human condition. One of the mechanisms that have been proposed to be responsible for the cognitive deficits in this mouse model is impaired GABA-mediated inhibition. Because of the well-known modulatory role of GABAA α5 subunit-containing receptors in cognitive processes, these receptors are considered to be potential targets for improving the intellectual disability in DS...
July 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28717940/alopecia-areata-a-comprehensive-review-of-pathogenesis-and-management
#9
REVIEW
Ralph M Trüeb, Maria Fernanda Reis Gavazzoni Dias
Alopecia areata is a common hair loss condition that is characterized by acute onset of non-scarring hair loss in usually sharply defined areas ranging from small patches to extensive or less frequently diffuse involvement. Depending on its acuity and extent, hair loss is an important cause of anxiety and disability. The current understanding is that the condition represents an organ-specific autoimmune disease of the hair follicle with a genetic background. Genome-wide association studies provide evidence for the involvement of both innate and acquired immunity in the pathogenesis, and mechanistic studies in mouse models of alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFNγ, IFNγ-induced chemokines and cytotoxic CD8 T cells as the main drivers of disease pathogenesis...
July 17, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28716119/stat1-dependent-and-independent-pulmonary-allergic-and-fibrogenic-responses-in-mice-after-exposure-to-tangled-versus-rod-like-multi-walled-carbon-nanotubes
#10
Katherine S Duke, Alexia J Taylor-Just, Mark D Ihrie, Kelly A Shipkowski, Elizabeth A Thompson, Erinn C Dandley, Gregory N Parsons, James C Bonner
BACKGROUND: Pulmonary toxicity of multi-walled carbon nanotubes (MWCNTs) is influenced by physicochemical characteristics and genetic susceptibility. We hypothesized that contrasting rigidities of tangled (t) versus rod-like (r) MWCNTs would result in differing immunologic or fibrogenic responses in mice and that these responses would be exaggerated in transgenic mice lacking the signal transducer and activator of transcription-1 (STAT1), a susceptible mouse model of pulmonary fibrosis...
July 17, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28715967/hyperthermia-enhanced-targeted-drug-delivery-using-magnetic-resonance-guided-focussed-ultrasound-a-pre-clinical-study-in-a-genetic-model-of-pancreatic-cancer
#11
Navid Farr, Yak-Nam Wang, Samantha D'Andrea, Frank Starr, Ari Partanen, Kayla M Gravelle, Jeannine S McCune, Linda J Risler, Stella G Whang, Amy Chang, Sunil R Hingorani, Donghoon Lee, Joo Ha Hwang
PURPOSE: The lack of effective treatment options for pancreatic cancer has led to a 5-year survival rate of just 8%. Here, we evaluate the ability to enhance targeted drug delivery using mild hyperthermia in combination with the systemic administration of a low-temperature sensitive liposomal formulation of doxorubicin (LTSL-Dox) using a relevant model for pancreas cancer. MATERIALS AND METHODS: Experiments were performed in a genetically engineered mouse model of pancreatic cancer (KPC mice: LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre)...
July 17, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28715512/mouse-models-of-deep-vein-thrombosis
#12
T Schönfelder, S Jäckel, P Wenzel
The pathogenesis of venous thromboembolism (VTE) is still not completely understood. Experimental animals in which human deep vein thrombosis can be modeled are useful tools to investigate the pathogenesis of VTE. Besides the availability of transgenic and genetically modified mice, the use of high frequency ultrasound and intravital microscopy plays an important role in identifying thrombotic processes in mouse models. In this article, an overview about the application of various new technologies and existing mouse models is provided, and the impact of venous side branches on deep vein thrombosis in the mouse model is discussed...
2017: Gefässchirurgie: Zeitschrift Für Vaskuläre und Endovaskuläre Chirurgie
https://www.readbyqxmd.com/read/28715385/a-genetically-engineered-mouse-model-of-sporadic-colorectal-cancer
#13
Alexander M Betzler, Susan Kochall, Linda Blickensdörfer, Sebastian A Garcia, May-Linn Thepkaysone, Lahiri K Nanduri, Michael H Muders, Jürgen Weitz, Christoph Reissfelder, Sebastian Schölch
Despite the advantages of easy applicability and cost-effectiveness, colorectal cancer mouse models based on tumor cell injection have severe limitations and do not accurately simulate tumor biology and tumor cell dissemination. Genetically engineered mouse models have been introduced to overcome these limitations; however, such models are technically demanding, especially in large organs such as the colon in which only a single tumor is desired. As a result, an immunocompetent, genetically engineered mouse model of colorectal cancer was developed which develops highly uniform tumors and can be used for tumor biology studies as well as therapeutic trials...
July 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28713672/bap1-a-tumor-suppressor-gene-driving-malignant-mesothelioma
#14
REVIEW
Mitchell Cheung, Joseph R Testa
Like cancer generally, malignant mesothelioma (MM) is a genetic disease at the cellular level. DNA copy number analysis of mesothelioma specimens has revealed a number of recurrent sites of chromosomal loss, including 3p21.1, 9p21.3, and 22q12.2. The key inactivated driver genes located at 9p21.1 and 22q12.2 were discovered two decades ago as being the tumor suppressor loci CDKN2A and NF2, respectively. Only relatively recently was the BAP1 gene determined to be the driver gene at 3p21.1 that is somatically inactivated...
June 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28713247/divergent-roles-of-central-serotonin-in-adult-hippocampal-neurogenesis
#15
REVIEW
Ning-Ning Song, Ying Huang, Xin Yu, Bing Lang, Yu-Qiang Ding, Lei Zhang
The central serotonin (5-HT) system is the main target of selective serotonin reuptake inhibitors (SSRIs), the first-line antidepressants widely used in current general practice. One of the prominent features of chronic SSRI treatment in rodents is the enhanced adult neurogenesis in the hippocampus, which has been proposed to contribute to antidepressant effects. Therefore, tremendous effort has been made to decipher how central 5-HT regulates adult hippocampal neurogenesis. In this paper, we review how changes in the central serotonergic system alter adult hippocampal neurogenesis...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28711224/the-radioprotector-ortho-phospho-l-tyrosine-ptyr-attenuates-the-side-effects-of-fractionated-irradiation-in-retinoblastoma-mouse-models-but-also-decreases-the-local-tumour-control
#16
Alexander V Tschulakow, Klaus Dittmann, Stephan M Huber, Dominik Klumpp, Benjamin Stegen, Ulrich Schraermeyer, H Peter Rodemann, Sylvie Julien-Schraermeyer
BACKGROUND: Radiotherapy (RT) is used to treat retinoblastoma (Rb), the most frequent ocular tumour in children. Besides eradicating the tumour, RT can cause severe side effects including secondary malignancies. This study aimed to define whether the radioprotector ortho-phospho-L-tyrosine (pTyr) prevents RT-induced side effects and affects local tumour control in a xenograft and a genetic orthotopic Rb mouse model. METHODS: B6;129-Rb1tm3Tyj/J (Rb(+/-)) and Y79-Rb cell-xenografted nude mice were fractionated external beam irradiated (15 fractions of 5Gy 6MV photons during 3weeks) with or without pTyr pre-treatment (100mg/kg BW, 16h prior to each irradiation)...
July 12, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28710273/pd-l1-up-regulation-restrains-th17-cell-differentiation-in-stat3-loss-and-stat1-gain-of-function-patients
#17
Yuan Zhang, Chi A Ma, Monica G Lawrence, Timothy J Break, Michael P O'Connell, Jonathan J Lyons, Diego B López, John S Barber, Yongge Zhao, Daniel L Barber, Alexandra F Freeman, Steven M Holland, Michail S Lionakis, Joshua D Milner
Patients with hypomorphic mutations in STAT3 and patients with hypermorphic mutations in STAT1 share several clinical and cellular phenotypes suggesting overlapping pathophysiologic mechanisms. We, therefore, examined cytokine signaling and CD4(+) T cell differentiation in these cohorts to characterize common pathways. As expected, differentiation of Th17 cells was impaired in both cohorts. We found that STAT1 was hyperphosphorylated in response to cytokine stimulation in both cohorts and that STAT1-dependent PD-L1 up-regulation-known to inhibit Th17 differentiation in mouse models-was markedly enhanced as well...
July 14, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28710250/near-infrared-1064-nm-laser-modulates-migratory-dendritic-cells-to-augment-the-immune-response-to-intradermal-influenza-vaccine
#18
Kaitlyn Morse, Yoshifumi Kimizuka, Megan P K Chan, Mai Shibata, Yusuke Shimaoka, Shu Takeuchi, Benjamin Forbes, Christopher Nirschl, Binghao Li, Yang Zeng, Roderick T Bronson, Wataru Katagiri, Ayako Shigeta, Ruxandra F Sîrbulescu, Huabiao Chen, Rhea Y Y Tan, Kosuke Tsukada, Timothy Brauns, Jeffrey Gelfand, Ann Sluder, Joseph J Locascio, Mark C Poznansky, Niroshana Anandasabapathy, Satoshi Kashiwagi
Brief exposure of skin to near-infrared (NIR) laser light has been shown to augment the immune response to intradermal vaccination and thus act as an immunologic adjuvant. Although evidence indicates that the NIR laser adjuvant has the capacity to activate innate subsets including dendritic cells (DCs) in skin as conventional adjuvants do, the precise immunological mechanism by which the NIR laser adjuvant acts is largely unknown. In this study we sought to identify the cellular target of the NIR laser adjuvant by using an established mouse model of intradermal influenza vaccination and examining the alteration of responses resulting from genetic ablation of specific DC populations...
July 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28709963/animal-models-of-biliary-injury-and-altered-bile-acid-metabolism
#19
REVIEW
Valeria Mariotti, Mario Strazzabosco, Luca Fabris, Diego F Calvisi
In the last 25years, a number of animal models, mainly rodents, have been generated with the goal to mimic cholestatic liver injuries and, thus, to provide in vivo tools to investigate the mechanisms of biliary repair and, eventually, to test the efficacy of innovative treatments. Despite fundamental limitations applying to these models, such as the distinct immune system and the different metabolism regulating liver homeostasis in rodents when compared to humans, multiple approaches, such as surgery (bile duct ligation), chemical-induced (3,5-diethoxycarbonyl-1,4-dihydrocollidine, DDC, α-naphthylisothiocyanate, ANIT), viral infections (Rhesus rotavirustype A, RRV-A), and genetic manipulation (Mdr2, Cftr, Pkd1, Pkd2, Prkcsh, Sec63, Pkhd1) have been developed...
July 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28709001/ciliary-hedgehog-signaling-restricts-injury-induced-adipogenesis
#20
Daniel Kopinke, Elle C Roberson, Jeremy F Reiter
Injured skeletal muscle regenerates, but with age or in muscular dystrophies, muscle is replaced by fat. Upon injury, muscle-resident fibro/adipogenic progenitors (FAPs) proliferated and gave rise to adipocytes. These FAPs dynamically produced primary cilia, structures that transduce intercellular cues such as Hedgehog (Hh) signals. Genetically removing cilia from FAPs inhibited intramuscular adipogenesis, both after injury and in a mouse model of Duchenne muscular dystrophy. Blocking FAP ciliation also enhanced myofiber regeneration after injury and reduced myofiber size decline in the muscular dystrophy model...
July 13, 2017: Cell
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