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Calreticulin

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https://www.readbyqxmd.com/read/28529308/assessing-the-thrombotic-risk-of-patients-with-essential-thrombocythemia-in-the-genomic-era
#1
REVIEW
L Falchi, H M Kantarjian, S Verstovsek
The molecular characterization of myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), has enabled deeper understanding of their pathogenesis. A driver lesion, namely, Janus kinase (JAK)2V617F, calreticulin (CALR) or myeloproliferative leukemia (MPL) gene mutation can be identified in the vast majority of patients. Each of these mutations is associated with distinct clinical features and may modulate the patients' clinical course, risk of complications, including vascular events, and survival...
May 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28522876/comparative-proteomic-analysis-of-the-mitochondria-associated-er-membrane-mam-in-a-long-term-type-2-diabetic-rodent-model
#2
Jacey Hongjie Ma, Shichen Shen, Joshua J Wang, Zhanwen He, Amanda Poon, Jun Li, Jun Qu, Sarah X Zhang
The mitochondria-associated ER membrane (MAM) plays a critical role in cellular energetics and calcium homeostasis; however, how MAM is affected under diabetic condition remains elusive. This study presented a comprehensive proteome profiling of isolated brain MAM from long-term type 2 diabetic mice vs. non-diabetic controls. MAM protein was extracted efficiently by a surfactant-aided precipitation/on-pellet digestion (SOD) method, and MAM proteome was quantified by an ion-current-based MS1 method combined with nanoLC-MS/MS...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28520695/calreticulin-ameliorates-hypoxia-reoxygenation-induced-human-microvascular-endothelial-cell-injury-by-inhibiting-autophagy
#3
You Wang, Tian-Qi Tao, Dan-Dan Song, Xiu-Hua Liu
BACKGROUND: Autophagy has been found to be involved in myocardial ischemia/reperfusion injury. However, the underlying mechanism and significance of autophagy in reperfusion injury remain unclear. Herein, we evaluated the effects of exogenous calreticulin (CRT) on autophagy in hypoxia/reoxygenation (H/R)-treated human microvascular endothelial cells (MECs). METHODS: Human MECs were pretreated with CRT (25 pg/mL) for 30 min, followed by exposure in an incubator filled with a gas mixture of 90% N2, 5% O2, and 5% CO2 for 8-h hypoxia...
May 17, 2017: Shock
https://www.readbyqxmd.com/read/28515303/spontaneous-and-vaccine-induced-clearance-of-mus-musculus-papillomavirus-type-1-mmupv1-muspv1-infection
#4
Rosie T Jiang, Joshua W Wang, Shiwen Peng, Tsui-Chin Huang, Chenguang Wang, Fabiana Cannella, Yung-Nien Chang, Raphael P Viscidi, Simon R A Best, Chien-Fu Hung, Richard B S Roden
Mus musculus Papillomavirus1 (MmuPV1/MusPV1) induces persistent papillomas in immunodeficient mice but not common laboratory strains. To facilitate study of immune control, we sought an outbred and immune competent laboratory mouse strain in which persistent papillomas could be established. We found that challenge of SKH1 mice (Crl:SKH1-Hrhr) by scarification on their tail with MmuPV1 resulted in three clinical outcomes: 1) persistent (>2 months) papillomas (∼20%), 2) transient papillomas that spontaneously regress typically within 2 months (∼15%), 3) no visible papillomas and viral clearance (∼65%)...
May 17, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28507789/calreticulin-promotes-immunity-and-type-i-interferon-dependent-survival-in-mice-with-acute-myeloid-leukemia
#5
Xiufen Chen, Dominick Fosco, Douglas E Kline, Justin Kline
Exposure of cancer cells to particular chemotherapeutic agents or γ-irradiation induces a form of cell death that stimulates an immune response in mice. This "immunogenic cell death" requires calreticulin (CRT) translocation to the plasma membrane, which has been shown to promote cancer cell phagocytosis. However, it remains unclear whether the effect of CRT on cancer cell phagocytosis is alone sufficient to affect tumor immunity. Acute myeloid leukemia (AML) cells expressing cell-surface CRT were generated in order to characterize the mechanism(s) through which CRT activates tumor immune responses...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28504081/dissecting-physical-structure-of-calreticulin-an-intrinsically-disordered-ca-2-buffering-chaperone-from-endoplasmic-reticulum
#6
Anna Rita Migliaccio, Vladimir N Uversky
Calreticulin (CALR) is a Ca(2+) binding multifunctional protein that mostly resides in the endoplasmic reticulum (ER) and plays a number of important roles in various physiological and pathological processes. Although the major functions ascribed to CALR are controlling the Ca(2+) homeostasis in ER and acting as a lectin-like ER chaperon for many glycoproteins, this moonlighting protein can be found in various cellular compartments where it has many non-ER functions. To shed more light on the mechanisms underlying polyfunctionality of this moonlighting protein that can be found in different cellular compartments and that possesses a wide spectrum of unrelated biological activities, being able to interact with Ca(2+) (and potentially other metal ions), RNA, oligosaccharides, and numerous proteins, we used a set of experimental and computational tools to evaluate the intrinsic disorder status of CALR and the role of calcium binding on structural properties and conformational stability of the full-length CALR and its isolated P- and C-domains...
May 13, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28503969/essential-thrombocythemia-a-review-of-the-clinical-features-diagnostic-challenges-and-treatment-modalities-in-the-era-of-molecular-discovery
#7
Sarah Chuzi, Brady L Stein
Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm that is associated with diminished quality of life, thrombohemorrhagic complications, and transformation to myelofibrosis (MF) and acute leukemia (AML). The important recent discoveries of driver mutations, including the calreticulin gene in addition to JAK2 and MPL, have led to a greater understanding of disease pathogenesis and set the stage for the advent of more sophisticated prognostic, diagnostic, and therapeutic strategies. In this paper we summarize recent studies describing the molecular basis of ET...
May 15, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28500851/calreticulin-modulates-the-intracellular-survival-of-mycobacteria-by-regulating-er-stress-mediated-apoptosis
#8
Sung Hee Jo, Ji-Ae Choi, Yun-Ji Lim, Junghwan Lee, Soo-Na Cho, Sung-Man Oh, Dam Go, Seon-Hwa Kim, Chang-Hwa Song
Endoplasmic reticulum (ER)-stress-mediated apoptosis is a host defense mechanism against Mycobacterium tuberculosis (Mtb) infection. Calreticulin (CRT) is the major calcium-binding chaperone protein. Previous reports have suggested a close relationship between the cell-surface expression of CRT and apoptosis. In this study, the role of CRT during Mtb infection was examined. The results showed that Mtb infection induces CRT production by macrophages and that CRT levels are correlated with the degree of apoptotic cell death...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28498357/adiponectin-is-involved-in-connective-tissue-growth-factor-induced-proliferation-migration-and-overproduction-of-the-extracellular-matrix-in-keloid-fibroblasts
#9
Limin Luo, Jun Li, Han Liu, Xiaoqing Jian, Qianlei Zou, Qing Zhao, Qu Le, Hongdou Chen, Xinghua Gao, Chundi He
Adiponectin, an adipocyte-derived hormone, exerts pleiotropic biological effects on metabolism, inflammation, vascular homeostasis, apoptosis and immunity. Recently, adiponectin has been suggested to attenuate the progression of human dermal fibrosis. Connective tissue growth factor (CTGF) is induced in keloids and is thought to be participated in the formation of keloid fibrosis. However, the roles played by adiponectin in keloids remain unclear. In this study, we explored the effects of adiponectin on CTGF-induced cell proliferation, migration and the deposition of extracellular matrix (ECM) and their associated intracellular signalling pathways in keloid fibroblasts (KFs)...
May 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28497265/proteomics-analysis-of-pleomorphic-adenoma-of-the-human-parotid-gland
#10
Ahmet Mutlu, Murat Ozturk, Gurler Akpinar, Murat Kasap, Aylin Kanli
The objective of this study is to perform proteomic analysis of pleomorphic adenoma (PA) in the human parotid gland (PG) with comparison of normal PG. This is an individual prospective randomized controlled trial. This study was performed in a tertiary referral center. Tissue samples of PG and PA were taken after surgical excision of PG from 13 patients. Protein extracts were prepared and protein pools created from the soluble extracts were subjected to 2D-DIGE analysis. Proteins displaying regulation in their abundance were determined and identified using MALDIT-OF/TOF analysis...
May 11, 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/28496337/immunogenicity-of-oncolytic-vaccinia-viruses-jx-gfp-and-tg6002-in-a-human-melanoma-in-vitro-model-studying-immunogenic-cell-death-dendritic-cell-maturation-and-interaction-with-cytotoxic-t-lymphocytes
#11
B Heinrich, J Klein, M Delic, K Goepfert, V Engel, L Geberzahn, M Lusky, P Erbs, X Preville, M Moehler
Oncolytic virotherapy is an emerging immunotherapeutic modality for cancer treatment. Oncolytic viruses with genetic modifications can further enhance the oncolytic effects on tumor cells and stimulate antitumor immunity. The oncolytic vaccinia viruses JX-594-GFP+/hGM-CSF (JX-GFP) and TG6002 are genetically modified by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF) or transforming 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU). We compared their properties to kill tumor cells and induce an immunogenic type of cell death in a human melanoma cell model using SK29-MEL melanoma cells...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28492521/coinjection-of-il2-dna-enhances-e7-specific-antitumor-immunity-elicited-by-intravaginal-therapeutic-hpv-dna-vaccination-with-electroporation
#12
Y Sun, S Peng, A Yang, E Farmer, T-C Wu, Chien-Fu Hung
The generation and use of therapeutic human papillomavirus (HPV) DNA vaccines represent an appealing treatment method against HPV-associated cervical cancer due to their safety and durability. Previously, we created a therapeutic HPV DNA vaccine candidate by linking the HPV16-E7 DNA sequence to calreticulin (CRT/E7), which we showed could generate significant E7-specific cytotoxic T lymphocyte (CTL)-mediated anti-tumor immune responses against HPV16 oncogenes expressing murine tumor model TC-1. Here we assess the therapeutic efficacy of intravaginal immunization with pcDNA3-CRT/E7 followed by electroporation...
May 11, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28483676/selective-testing-for-calreticulin-gene-mutations-in-patients-with-splanchnic-vein-thrombosis-a-prospective-cohort-study
#13
Johanne Poisson, Aurélie Plessier, Jean-Jacques Kiladjian, Fanny Turon, Bruno Cassinat, Annalisa Andreoli, Emmanuelle De Raucourt, Odile Goria, Kamal Zekrini, Christophe Bureau, Florence Lorre, Francisco Cervantes, Dolors Colomer, François Durand, Juan-Carlos Garcia-Pagan, Nicole Casadevall, Dominique-Charles Valla, Pierre-Emmanuel Rautou, Christophe Marzac
BACKGROUND AND AIMS: Myeloproliferative neoplasms (MPN) are the leading cause of splanchnic vein thrombosis (SVT). JAK2(V617F) mutation is found in 80-90% of patients with SVT and MPN. Mutations of the calreticulin (CALR) gene have also been reported. However, as their prevalence ranges from 0 to 2%, the utility of routine testing can be questioned. This study aimed at identifying a group of patients with SVT at high risk of harboring CALR mutations and thus requiring this genetic testing...
May 5, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28482023/understanding-the-genomic-basis-of-adaptive-response-to-variable-osmotic-niches-in-freshwater-prawns-a-comparative-intraspecific-rna-seq-analysis-of-macrobrachium-australiense
#14
Azam Moshtaghi, Md Lifat Rahi, Peter B Mather, David A Hurwood
Understanding the molecular basis of adaptive response to variable environmental conditions is a central goal of evolutionary biology. Here we sought to identify potential outlier SNPs (single nucleotide polymorphisms) in three wild populations of a freshwater prawn (Macrobrachium australiense) that are exposed to differing osmotic niches by using a comparative transcriptomics approach. De novo assembly of approximately 542 million (75 nt) pair end reads collected from 10 individuals revealed 123,396 longer contigs/transcripts of variable length, that showed 97...
May 6, 2017: Journal of Heredity
https://www.readbyqxmd.com/read/28478799/role-of-microrna-124-in-cardiomyocyte-hypertrophy-inducedby-angiotensin-ii
#15
Q Bao, L Chen, J Li, M Zhao, S Wu, W Wu, X Liu
Cardiac hypertrophy is a crucial predictor of heart failure and is regulated by microRNAs. MicroRNA-124 (miR-124) is regarded as a prognostic indicator for outcomes after cardiac arrest. However, whether miR-124 participates in cardiac hypertrophy remains unclear. Therefore, our study aimed to determine the role of miR-124 in angiotensin II(AngII)-induced myocardial hypertrophy and the possible mechanism. Primary cultured rat neonatal cardiomyocytes(NCMs) were transfected with miR-124 mimics or inhibitor, followed by AngII stimulation...
April 29, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28470469/somatic-mutations-of-calreticulin-in-myeloproliferative-neoplasms
#16
REVIEW
Misa Imai, Marito Araki, Norio Komatsu
Recurrent somatic mutations in calreticulin (CALR) gene that encodes a molecular chaperone residing in the endoplasmic reticulum were identified in 2013 in a subset of patients with myeloproliferative neoplasms (MPNs). All of these mutations found in patients were either small insertion or deletion in a narrow region on exon 9 of CALR gene, and caused +1 frameshift in the reading frame for the translation of the carboxyl-terminus of CALR. Because of this unique feature, the CALR mutation is believed to be a gain-of-function mutation...
June 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28467380/nanosecond-pulsed-dbd-plasma-generated-reactive-oxygen-species-trigger-immunogenic-cell-death-in-a549-lung-carcinoma-cells-through-intracellular-oxidative-stress
#17
Abraham Lin, Billy Truong, Sohil Patel, Nagendra Kaushik, Eun Ha Choi, Gregory Fridman, Alexander Fridman, Vandana Miller
A novel application for non-thermal plasma is the induction of immunogenic cancer cell death for cancer immunotherapy. Cells undergoing immunogenic death emit danger signals which facilitate anti-tumor immune responses. Although pathways leading to immunogenic cell death are not fully understood; oxidative stress is considered to be part of the underlying mechanism. Here; we studied the interaction between dielectric barrier discharge plasma and cancer cells for oxidative stress-mediated immunogenic cell death...
May 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28460421/calreticulin-inhibits-inflammation-induced-osteoclastogenesis-and-bone-resorption
#18
Charla R Fischer, Maya Mikami, Hiroshi Minematsu, Saqib Nizami, Heon Goo Lee, Danielle Stamer, Neel Patel, Do Yu Soung, Jung-Ho Back, Lee Song, Hicham Drissi, Francis Y Lee
Osteoclasts play key roles in bone remodeling and pathologic osteolytic disorders such as inflammation, infection, bone implant loosening, rheumatoid arthritis, metastatic bone cancers, and pathological fractures. Osteoclasts are formed by the fusion of monocytes in response to receptor activators of NF-ĸB-ligand (RANKL) and macrophage colony stimulating factor 1 (M-CSF). Calreticulin (CRT), a commonly known intracellular protein as a calcium-binding chaperone, has an unexpectedly robust anti-osteoclastogenic effect when its recombinant form is applied to osteoclast precursors in vitro or at the site of bone inflammation externally in vivo...
April 29, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28459470/multivalent-bi-specific-nanobioconjugate-engager-for-targeted-cancer-immunotherapy
#19
Hengfeng Yuan, Wen Jiang, Christina A von Roemeling, Yaqing Qie, Xiujie Liu, Yuanxin Chen, Yifan Wang, Robert E Wharen, Kyuson Yun, Guojun Bu, Keith L Knutson, Betty Y S Kim
Tumour-targeted immunotherapy offers the unique advantage of specific tumouricidal effects with reduced immune-associated toxicity. However, existing platforms suffer from low potency, inability to generate long-term immune memory and decreased activities against tumour-cell subpopulations with low targeting receptor levels. Here we adopted a modular design approach that uses colloidal nanoparticles as substrates to create a multivalent bi-specific nanobioconjugate engager (mBiNE) to promote selective, immune-mediated eradication of cancer cells...
May 1, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28456374/pdi-family-protein-erp29-recognizes-p-domain-of-molecular-chaperone-calnexin
#20
Hitomi Nakao, Akira Seko, Yukishige Ito, Masafumi Sakono
Endoplasmic reticulum (ER) resident lectin chaperone calnexin (CNX) and calreticulin (CRT) assist folding of nascent glycoproteins. Their association with ERp57, a member of PDI family proteins (PDIs) which promote disulfide bond formation of unfolded proteins, has been well documented. Recent studies have provided evidence that other PDIs may also interact with CNX and CRT. Accordingly, it seems possible that the ER provides a repertoire of CNX/CRT-PDI complexes, in order to facilitate refolding of various glycoproteins...
April 26, 2017: Biochemical and Biophysical Research Communications
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