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Calreticulin

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https://www.readbyqxmd.com/read/27913528/mutations-in-mpns-prognostic-implications-window-to-biology-and-impact-on-treatment-decisions
#1
Jamile M Shammo, Brady L Stein
The last decade has witnessed tremendous scientific advances, ushered in by the JAK2 V617F discovery, contributing to enhanced diagnostic capability and understanding of the biology of myeloproliferative neoplasms (MPNs). Discovery of the calreticulin mutations filled a diagnostic gap; more recent work sheds light on its contribution to disease pathogenesis, and prognosis. Recent studies have also identified novel JAK2 and MPL mutations in patients with essential thrombocythemia and myelofibrosis (MF). Especially in MF, the driver mutational profile has prognostic implications, with additive contributions from the acquisition of additional somatic mutations...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27910767/immunostimulatory-effects-of-melphalan-and-usefulness-in-adoptive-cell-therapy-with-antitumor-cd4-t-cells
#2
Michal Kuczma, Zhi-Chun Ding, Gang Zhou
The alkylating agent melphalan is used in the treatment of hematological malignancies, especially multiple myeloma. In the past, the usefulness of melphalan has been solely attributed to its cytotoxicity on fastgrowing cancerous cells. Although the immunomodulatory effects of melphalan were suggested many years ago, only recently has this aspect of melphalan's activity begun to be elucidated at the molecular level. Emerging evidence indicates that melphalan can foster an immunogenic microenvironment by inducing immunogenic cell death (ICD) as characterized by membrane translocation of endoplasmic reticulum protein calreticulin (CRT) and by release of chromatin-binding protein high-mobility group box 1 (HMGB1)...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27909216/molecular-determinants-of-pathogenesis-and-clinical-phenotype-in-myeloproliferative-neoplasms
#3
Jacob Grinfeld, Jyoti Nangalia, Anthony R Green
The myeloproliferative neoplasms are a heterogeneous group of clonal disorders characterised by overproduction of mature cells in the peripheral blood, together with an increased risk of thrombosis and progression to acute myeloid leukemia. The majority of patients with Philadelphia-chromosome negative myeloproliferative neoplasms harbour somatic mutations in Janus kinase 2, leading to constitutive activation. Acquired mutations in calreticulin or myeloproliferative leukemia virus oncogene are found in a significant number of patients with essential thrombocythaemia or myelofibrosis, and mutations in numerous epigenetic regulators and spliceosome components are also seen...
December 1, 2016: Haematologica
https://www.readbyqxmd.com/read/27895277/triatoma-infestans-calreticulin-gene-cloning-and-expression-of-a-main-domain-that-interacts-with-the-host-complement-system
#4
Katherine Weinberger, Norberto Collazo, Juan Carlos Aguillón, María Carmen Molina, Carlos Rosas, Jaime Peña, Javier Pizarro, Ismael Maldonado, Pedro E Cattan, Werner Apt, Arturo Ferreira
Triatoma infestans is an important hematophagous vector of Chagas disease, a neglected chronic illness affecting approximately 6 million people in Latin America. Hematophagous insects possess several molecules in their saliva that counteract host defensive responses. Calreticulin (CRT), a multifunctional protein secreted in saliva, contributes to the feeding process in some insects. Human CRT (HuCRT) and Trypanosoma cruzi CRT (TcCRT) inhibit the classical pathway of complement activation, mainly by interacting through their central S domain with complement component C1...
November 28, 2016: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27893426/sublethal-exposure-to-alpha-radiation-223ra-dichloride-enhances-various-carcinomas-sensitivity-to-lysis-by-antigen-specific-cytotoxic-t-lymphocytes-through-calreticulin-mediated-immunogenic-modulation
#5
Anthony S Malamas, Sofia R Gameiro, Karin M Knudson, James W Hodge
Radium-223 dichloride (Xofigo®; 223Ra) is an alpha-emitting radiopharmaceutical FDA-approved for the treatment of bone metastases in patients with advanced castration-resistant prostate cancer. It is also being examined clinically in patients with breast and lung carcinoma and patients with multiple myeloma. As with other forms of radiation, the aim of 223Ra is to reduce tumor burden by directly killing tumor cells. External beam (photon) and proton radiation have been shown to augment tumor sensitivity to antigen-specific CD8+ cytotoxic T lymphocytes (CTLs)...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888524/systematic-deletion-of-the-er-lectin-chaperone-genes-reveals-their-roles-in-vegetative-growth-and-male-gametophyte-development-in-arabidopsis
#6
Kien Van Vu, Ngoc Trinh Nguyen, Chan Young Jeong, Yong-Hwa Lee, Hojoung Lee, Suk-Whan Hong
Calnexin (CNX) and calreticulin (CRT) are homologous lectin chaperones in the endoplasmic reticulum (ER) that facilitate glycoprotein folding and retain folding intermediates to prevent their transit via the secretary pathway. The Arabidopsis genome has two CNX (CNX1 and CNX2) and three CRT homologs (CRT1, CRT2, and CRT3). Despite growing evidence of the biological roles of CNXs and CRTs, little is understood about their function in Arabidopsis growth and development under normal conditions. Here, we report that deletion of CNX1, but not of CNX2, in the crt1 crt2 crt3 triple mutation background had adverse effect on pollen viability and pollen tube growth, leading to significant reduction in fertility...
November 26, 2016: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/27876711/calreticulin-promotes-proliferation-and-migration-but-inhibits-apoptosis-in-schwann-cells
#7
Gui Huang, Zhulei Sun, Jiang Wu, Shaofeng Shui, Xinwei Han, Dong Guo, Tengfei Li
BACKGROUND Previous studies indicated that calreticulin (CRT) regulated various biological processes. This study was aimed to investigate the function of CRT in Schwann cells (SCs). MATERIAL AND METHODS SCs were separated from sciatic nerves of mice and were transfected with pcDNA3.1-CRT (pc-CRT), small interfering RNA targets CRT (siCRT), or their corresponding negative controls. The expression of CRT was determined by quantitative reverse transcription PCR (qRT-PCR) and Western blot analysis. Then, cell proliferation, migration, and apoptosis were measured by 3-(4, 5-dimethylhiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, modified 2-chamber migration assay, and flow cytometry, respectively...
November 23, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27872147/primary-human-and-rat-beta-cells-release-the-intracellular-autoantigens-gad65-ia-2-and-proinsulin-in-exosomes-together-with-cytokine-induced-enhancers-of-immunity
#8
Chiara Cianciaruso, Edward A Phelps, Miriella Pasquier, Romain Hamelin, Davide Demurtas, Mohamed Alibashe Ahmed, Lorenzo Piemonti, Sachiko Hirosue, Melody A Swartz, Michele De Palma, Jeffrey A Hubbell, Steinunn Baekkeskov
The target autoantigens in several organ-specific autoimmune diseases, including type 1 diabetes (T1D), are intracellular membrane proteins, whose initial encounter with the immune system is poorly understood. Here we propose a new model for how these proteins can initiate autoimmunity. We found that rat and human pancreatic islets release the intracellular β-cell autoantigens in human T1D, GAD65, IA-2 and proinsulin, in exosomes, which are taken up by and activate dendritic cells. Accordingly, anchoring of GAD65 to exosome-mimetic liposomes strongly boosted antigen presentation and T cell activation in the context of the human type 1 diabetes susceptibility haplotype HLA-DR4...
November 21, 2016: Diabetes
https://www.readbyqxmd.com/read/27852125/standardized-extract-from-caesalpinia-spinosa-is-cytotoxic-over-cancer-stem-cells-and-enhance-anticancer-activity-of-doxorubicin
#9
Tito A Sandoval, Claudia P Urueña, Mónica Llano, Alejandra Gómez-Cadena, John F Hernández, Luis Gonzalo Sequeda, Alix E Loaiza, Alfonso Barreto, Shaoping Li, Susana Fiorentino
Cancer stem cells (CSC) are the primary cell type responsible for metastasis and relapse. ABC-transporters are integral membrane proteins involved in the translocation of substrates across membranes protecting CSC from chemotherapeutic agents. A plant extract derived from C. spinosa (P2Et) previously investigated for its antitumor activity has been shown to reduce lung and spleen metastasis in mice that have been transplanted with breast cancer cells, suggesting that P2Et has a significant activity against cancer stem cells (CSC)...
November 16, 2016: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/27848175/glucocorticoids-prevent-enterovirus-71-capsid-protein-vp1-induced-calreticulin-surface-exposure-by-alleviating-neuronal-er-stress
#10
Dan-Dan Hu, Jian-Ning Mai, Li-Ya He, Pei-Qing Li, Wen-Xiong Chen, Jian-Jiang Yan, Wei-Dong Zhu, Li Deng, Dan Wei, Di-Hui Liu, Si-Da Yang, Zhi-Bin Yao
Severe hand-foot-and-mouth disease (HFMD) caused by Enterovirus 71 (EV71) always accompanies with inflammation and neuronal damage in the central nervous system (CNS). During neuronal injuries, cell surface-exposed calreticulin (Ecto-CRT) is an important mediator for primary phagocytosis of viable neurons by microglia. Our data confirmed that brainstem neurons underwent neuronophagia by glia in EV71-induced death cases of HFMD. EV71 capsid proteins VP1, VP2, VP3, or VP4 did not induce apoptosis of brainstem neurons...
November 15, 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27846717/-endoplasmic-reticulum-chaperones-at-the-tumor-cell-surface-and-in-the-extracellular-space
#11
V Brychtová, B Vojtěšek
BACKGROUND: Endoplasmic reticulum chaperones are stress induced proteins capable of translocation into cytosol, cell membrane or extracellular space. The chaperones are transported from the endoplasmic reticulum particularly under endoplasmic reticulum stress conditions, while their constitutive extracellular expression was found in many cancers. Cell surface or extracellular endoplasmic reticulum chaperones take up distinct functions compared to their endoplasmic reticulum resident variants because they act like multifunctional receptors and thus affect cell signaling and proliferation...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27836573/human-mesenchymal-stromal-cells-undergo-apoptosis-and-fragmentation-after-intravenous-application-in-immune-competent-mice
#12
Johannes Leibacher, Katrin Dauber, Sabrina Ehser, Veronika Brixner, Katarina Kollar, Anja Vogel, Gabi Spohn, Richard Schäfer, Erhard Seifried, Reinhard Henschler
BACKGROUND AIMS: The biodistribution of human MSCs after systemic delivery is incompletely understood. We investigated the changes in cell size and cell surface markers of human MSCs after intravenous (IV) injection in immune competent mice. METHODS: Male human MSCs were labeled with fluorescent vital dye PKH67 and tracked after IV administration in C57/BL6 mice. MSCs were tracked in blood and different murine tissues by human SRY gene quantitative polymerase chain reaction (qPCR) analysis, flow cytometry and fluorescence microscopy...
November 8, 2016: Cytotherapy
https://www.readbyqxmd.com/read/27825129/late-stage-inhibition-of-autophagy-enhances-calreticulin-surface-exposure
#13
Dan-Dan Li, Bo Xie, Xiao-Jun Wu, Jing-Jing Li, Ya Ding, Xi-Zhi Wen, Xing Zhang, Shu-Guang Zhu, Wei Liu, Xiao-Shi Zhang, Rui-Qing Peng
Calreticulin (CRT) exposure on the cell surface is essential for inducing immunogenic cell death by chemotherapy. Recent studies have shown conflicting effects of chemotherapy-induced autophagy on CRT exposure in cancer cells. Our data revealed that surface-exposed CRT (Ecto-CRT) emission was attenuated by inhibition of autophagy at early stages; however, inhibition of autophagy at late stages resulted in increased Ecto-CRT. Furthermore, neither autophagy activation nor endoplasmic reticulum (ER) stress induction alone was sufficient for CRT surface exposure...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27815895/image-cytofluorometry-for-the-quantification-of-ploidy-and-endoplasmic-reticulum-stress-in-cancer-cells
#14
Laura Senovilla, Yohann Demont, Juliette Humeau, Norma Bloy, Guido Kroemer
One of the mechanisms of cancer-associated genomic instability involves a transient phase of polyploidization, in most cases tetraploidization, followed by asymmetric divisions and chromosome loss. Increases in ploidy are consistently accompanied by the activation of an endoplasmic reticulum (ER) stress response, resulting in the translocation of calreticulin to the outer surface of the plasma membrane where it stimulates anticancer immune responses. Conversely, immunoselection leads to a coordinated reduction in ploidy, ER stress, and calreticulin exposure...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27815707/calreticulin-attenuated-microwave-radiation-induced-human-microvascular-endothelial-cell-injury-through-promoting-actin-acetylation-and-polymerization
#15
Feifei Xu, You Wang, Tianqi Tao, Dandan Song, Xiuhua Liu
Recent work reveals that actin acetylation modification has been linked to different normal and disease processes and the effects associated with metabolic and environmental stressors. Herein, we highlight the effects of calreticulin on actin acetylation and cell injury induced by microwave radiation in human microvascular endothelial cell (HMEC). HMEC injury was induced by high-power microwave of different power density (10, 30, 60, 100 mW/cm(2), for 6 min) with or without exogenous recombinant calreticulin...
November 4, 2016: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/27807369/calreticulin-mutant-mice-develop-essential-thrombocythemia-that-is-ameliorated-by-the-jak-inhibitor-ruxolitinib
#16
K Shide, T Kameda, T Yamaji, M Sekine, N Inada, A Kamiunten, K Akizuki, K Nakamura, T Hidaka, Y Kubuki, H Shimoda, A Kitanaka, A Honda, A Sawaguchi, H Abe, T Miike, H Iwakiri, Y Tahara, M Sueta, S Hasuike, S Yamamoto, K Nagata, K Shimoda
Mutations of calreticulin (CALR) are detected in 25-30% of patients with essential thrombocythemia (ET) or primary myelofibrosis and cause frameshifts that result in proteins with a novel C-terminal. We demonstrate that CALR mutations activated signal transducer and activator of transcription 5 (STAT5) in 293T cells in the presence of thrombopoietin receptor (MPL). Human megakaryocytic CMK11-5 cells and erythroleukemic F-36P-MPL cells with knocked-in CALR mutations showed increased growth and acquisition of cytokine-independent growth, respectively, accompanied by STAT5 phosphorylation...
November 29, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27803995/quality-control-of-glycoprotein-folding-and-erad-the-role-of-n-glycan-handling-edem1-and-os-9
#17
REVIEW
Jürgen Roth, Christian Zuber
Protein N-glycosylation and quality control of protein folding as well as the connected ER-associated degradation of misfolded glycoproteins (ERAD) are not only evolutionary highly conserved but also functionally linked. It is now established that particular N-glycan structures which result from processing reactions by exo-glycosidases in the ER are of importance for glycoprotein folding and for ERAD. Thus, mono-glucosylated N-glycan intermediates harbor structural information which is important for promoting glycoprotein folding...
November 1, 2016: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/27802968/calreticulin-exposure-by-malignant-blasts-correlates-with-robust-anticancer-immunity-and-improved-clinical-outcome-in-aml-patients
#18
Jitka Fucikova, Iva Truxova, Michal Hensler, Etienne Becht, Lenka Kasikova, Irena Moserova, Sarka Vosahlikova, Jana Klouckova, Sarah E Church, Isabelle Cremer, Oliver Kepp, Guido Kroemer, Lorenzo Galluzzi, Cyril Salek, Radek Spisek
Cancer cell death can be perceived as immunogenic by the host only when malignant cells emit immunostimulatory signals (so-called "damage-associated molecular patterns", DAMPs), as they die in the context of failing adaptive responses to stress. Accumulating preclinical and clinical evidence indicates that the capacity of immunogenic cell death (ICD) to (re-)activate an anticancer immune response is key to the success of various chemo- and radiotherapeutic regimens. Malignant blasts from acute myeloid leukemia (AML) patients exposed multiple DAMPs including calreticulin (CRT), heat-shock protein 70 (HSP70) and HSP90 on their plasma membrane irrespective of treatment...
November 1, 2016: Blood
https://www.readbyqxmd.com/read/27766390/jak2v617f-and-calreticulin-mutations-in-recurrent-venous-thromboembolism-results-from-the-edith-prospective-cohort
#19
Jean-Christophe Ianotto, Aurélie Chauveau, Dominique Mottier, Valérie Ugo, Christian Berthou, Eric Lippert, Aurélien Delluc
Cancer incidence in patients with recurrent unprovoked venous thromboembolism (VTE) is much higher than after a first event, but the incidence of myeloproliferative neoplasms (MPN) in this situation is still unknown. We tested for JAK2V617F and calreticulin mutants, 372 DNA samples of patients treated for (VTR). Among these patients, 10 (2.7%) were carrying JAK2V617F mutation and none of them any of the calreticulin (CALR) mutations. Among the 19 patients who had VTE recurrence under vitamin K antagonists, 4 patients (21...
October 20, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27764253/differential-dynamics-of-calr-mutant-allele-burden-in-myeloproliferative-neoplasms-during-interferon-alfa-treatment
#20
Lasse Kjær, Sabrina Cordua, Morten O Holmström, Mads Thomassen, Torben A Kruse, Niels Pallisgaard, Thomas S Larsen, Karin de Stricker, Vibe Skov, Hans C Hasselbalch
Discovery of somatic mutations in the calreticulin gene (CALR) has identified a subgroup of Philadelphia-negative chronic myeloproliferative neoplasms (MPN) with separate haematological characteristics and prognosis. CALR mutations serve as novel markers both of diagnostic value and as targets for monitoring molecular responses during therapy. Interferon-α (IFN) selectively targets the malignant clone in a subset of MPN patients and can induce both haematological and molecular remissions in CALR mutated essential thrombocythemia (ET) patients...
2016: PloS One
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