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Calreticulin

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https://www.readbyqxmd.com/read/29147614/exploiting-a-new-strategy-to-induce-immunogenic-cell-death-to-improve-dendritic-cell-based-vaccines-for-lymphoma-immunotherapy
#1
B Montico, C Lapenta, M Ravo, D Martorelli, E Muraro, B Zeng, E Comaro, M Spada, S Donati, S M Santini, R Tarallo, G Giurato, F Rizzo, A Weisz, F Belardelli, R Dolcetti, J Dal Col
Although promising, the clinical benefit provided by dendritic cell (DC)-based vaccines is still limited and the choice of the optimal antigen formulation is still an unresolved issue. We have developed a new DC-based vaccination protocol for aggressive and/or refractory lymphomas which combines the unique features of interferon-conditioned DC (IFN-DC) with highly immunogenic tumor cell lysates (TCL) obtained from lymphoma cells undergoing immunogenic cell death. We show that treatment of mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) cell lines with 9-cis-retinoic acid and IFNα (RA/IFNα) induces early membrane exposure of Calreticulin, HSP70 and 90 together with CD47 down-regulation and enhanced HMGB1 secretion...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29138861/immunogenic-tumor-cell-death-induced-by-chemotherapy-in-patients-with-breast-cancer-and-esophageal-squamous-cell-carcinoma
#2
Keita Aoto, Kousaku Mimura, Hirokazu Okayama, Motonobu Saito, Shun Chida, Masaru Noda, Takahiro Nakajima, Katsuharu Saito, Noriko Abe, Shinji Ohki, Tohru Ohtake, Seiichi Takenoshita, Koji Kono
It has been reported that chemo-radiotherapy can induce immunogenic tumor cell death (ICD), which triggers T-cell immunity mainly mediated by high-mobility group box 1 protein (HMGB1) and calreticulin. However, there is still limited information to support this theory relating to chemotherapy alone. In the present study, the expression of HMGB1 and calreticulin was evaluated by immunohistochemistry in pre-treatment biopsy specimens and surgically resected specimens, which were obtained from patients with breast cancer (n=52) and esophageal squamous cell carcinoma (ESCC) (n=8) who had been treated with neoadjuvant chemotherapy (NAC)...
November 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29134817/the-bcr-abl1-negative-myeloproliferative-neoplasms-a-review-of-jak-inhibitors-in-the-therapeutic-armamentarium
#3
Martin Griesshammer, Parvis Sadjadian
The classical BCR-ABL1-negative myeloproliferative neoplasms (MPN) include primary myelofibrosis (PMF), polycythaemia vera (PV) and essential thrombocythaemia (ET). They are characterized by stem cell-derived clonal proliferation, harbour Janus kinase 2 (JAK2), or calreticulin (CALR), or myeloproliferative leukaemia virus oncogene (MPL) driver mutations and exert an over activated JAK-signal transducer and activator of transcription (STAT) pathway. Therefore JAK inhibiting strategies have been successfully investigated in MPN clinical trials...
November 14, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29134152/the-role-of-mef2-transcription-factors-in-dehydration-and-anoxia-survival-in-rana-sylvatica-skeletal-muscle
#4
Myriam P Hoyeck, Hanane Hadj-Moussa, Kenneth B Storey
The wood frog (Rana sylvatica) can endure freezing of up to 65% of total body water during winter. When frozen, wood frogs enter a dormant state characterized by a cessation of vital functions (i.e., no heartbeat, blood circulation, breathing, brain activity, or movement). Wood frogs utilize various behavioural and biochemical adaptations to survive extreme freezing and component anoxia and dehydration stresses, including a global suppression of metabolic functions and gene expression. The stress-responsive myocyte enhancer factor-2 (MEF2) transcription factor family regulates the selective expression of genes involved in glucose transport, protein quality control, and phosphagen homeostasis...
2017: PeerJ
https://www.readbyqxmd.com/read/29132406/sjcrt-a-recombinant-schistosoma-japonicum-calreticulin-induces-maturation-of-dendritic-cells-and-a-th1-polarized-immune-response-in-mice
#5
Lizhen Ma, Dandan Li, Chunxiu Yuan, Xiangqian Zhang, Na Ta, Xiaochao Zhao, Yumei Li, Xingang Feng
BACKGROUND: It is well known that immunization of radiation-attenuated (RA) schistosoma cercariae or schistosomula can induce high levels of protective immunity against schistosoma cercariae reinfection in many animals. Many studies have shown that the Th1 cellular immune response is crucial for the protective effect elicited by RA schistosomula. However, the molecular mechanism of this strong protective immunity remains unclear. METHODS: The expression profiles of Schistosoma japonicum calreticulin (SjCRT) in RA and normal schistosoma-derived cells were investigated by flow cytometry...
November 13, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/29125686/neurophagy-the-phagocytosis-of-live-neurons-and-synapses-by-glia-contributes-to-brain-development-and-disease
#6
REVIEW
Anna Vilalta, Guy C Brown
It was previously thought that neurons were phagocytosed only when dead or dying. However, it is increasingly clear that viable synapses, dendrites, axons and/or neurons can be phagocytosed alive (defined here as "neurophagy"), and this may contribute to a wide range of developmental, physiological and pathological processes. Phagocytosis of live synapses, dendrites and axons by glia, contribute to experience-dependent sculpting of neuronal networks during development, but excessive phagocytosis of synapses may contribute to pathology in Alzheimer's disease, schizophrenia and aging...
November 10, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29123956/mutations-in-jak2-and-calreticulin-genes-are-associated-with-specific-alterations-of-the-immune-system-in-myelofibrosis
#7
Marco Romano, Daria Sollazzo, Sara Trabanelli, Martina Barone, Nicola Polverelli, Margherita Perricone, Dorian Forte, Simona Luatti, Michele Cavo, Nicola Vianelli, Camilla Jandus, Francesca Palandri, Lucia Catani
Myelofibrosis (MF) is a clonal neoplasia associated with chronic inflammation due to aberrant cytokine production. Mutations in Janus Kinase-2 (JAK2), calreticulin (CALR) and myeloproliferative leukemia protein (MPL) genes have been recently associated to MF and they all activate the JAK/STAT signaling pathway. Since this pathway is essential in shaping the immune response, we investigated the role of circulating immune subsets and cytokines in 38 patients (20 carrying JAK2((V617F)),13 exon-9 CALR mutation and 5 triple negative)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29122814/non-endoplasmic-reticulum-based-calr-calreticulin-can-coordinate-heterocellular-calcium-signaling-and-vascular-function
#8
Lauren A Biwer, Miranda E Good, Kwangseok Hong, Rahul K Patel, Neha Agrawal, Robin Looft-Wilson, Swapnil K Sonkusare, Brant E Isakson
OBJECTIVE: In resistance arteries, endothelial cell (EC) extensions can make contact with smooth muscle cells, forming myoendothelial junction at holes in the internal elastic lamina (HIEL). At these HIEL, calcium signaling is tightly regulated. Because Calr (calreticulin) can buffer ≈50% of endoplasmic reticulum calcium and is expressed throughout IEL holes in small arteries, the only place where myoendothelial junctions form, we investigated the effect of EC-specific Calr deletion on calcium signaling and vascular function...
November 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29115545/effects-of-calcium-dependent-molecular-chaperones-and-endoplasmic-reticulum-in-the-amygdala-in-rats-under-single%C3%A2-prolonged-stress
#9
Bing Xiao, Jian-Gang Wang, Fang Han, Yu-Xiu Shi
The purpose of the present study was to investigate the role of endoplasmic reticulum (ER)‑resident molecular chaperone proteins to identify whether these proteins were involved in post‑traumatic stress disorder (PTSD). The present study detected changes of calreticulin (CRT), calnexin (CNX) and ERp57 in the amygdala of rats, which may with aim of providing a novel insight into the modulation effect of amygdala in PTSD. Single‑prolonged stress (SPS) was applied to create the models of PTSD in rats. The expression levels of CRT, CNX and ERp57 were examined using immunohistochemistry or immunofluorescence, western blot analysis and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR)...
November 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29108228/cbp501-induces-immunogenic-tumor-cell-death-and-cd8-t-cell-infiltration-into-tumors-in-combination-with-platinum-and-increases-the-efficacy-of-immune-checkpoint-inhibitors-against-tumors-in-mice
#10
Keiichi Sakakibara, Takuji Sato, Donald W Kufe, Daniel D VonHoff, Takumi Kawabe
CBP501, a calmodulin-binding peptide, is an anti-cancer drug candidate and functions as an enhancer of platinum uptake into cancer cells. Here we show that CBP501 promotes immunogenic cell death (ICD) in combination with platinum agents. CBP501 enhanced a clinically relevant low dose of cisplatin (CDDP) in vitro as evidenced by upregulation of ICD markers, including cell surface calreticulin exposure and release of high-mobility group protein box-1. Synergistic induction of ICD by CDDP plus CBP501 as compared to CDDP alone was confirmed in the well-established vaccination assay...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29107940/structure-of-the-human-mhc-i-peptide-loading-complex
#11
Andreas Blees, Dovile Januliene, Tommy Hofmann, Nicole Koller, Carla Schmidt, Simon Trowitzsch, Arne Moeller, Robert Tampé
The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response. The PLC coordinates peptide translocation into the endoplasmic reticulum with loading and editing of major histocompatibility complex class I (MHC-I) molecules. After final proofreading in the PLC, stable peptide-MHC-I complexes are released to the cell surface to evoke a T-cell response against infected or malignant cells. Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin...
November 6, 2017: Nature
https://www.readbyqxmd.com/read/29104090/two-novel-calreticulin-related-molecules-with-microbial-binding-and-phagocytosis-enhancing-capacity-in-the-half-smooth-tongue-sole-cynoglossus-semilaevis
#12
Guanghua Wang, Zengjie Jiang, Shuwen He, Min Zhang
Calreticulin (CRT) is highly conserved chaperone located in the endoplasmic reticulum. It plays important roles in innate immunity. Although various immune-related functions of CRT have been reported in vertebrates and invertebrates, information on the potential functions of teleost CRT is very limited. In the present study, we characterized two calreticulin-related molecules from tongue sole (Cynoglossus semilaevis), calreticulin-like1 and calreticulin-like2 (CsCRTL1 and CsCRTL2). CsCRTL1and CsCRTL2 contain signature CRT motifs that are highly conserved in different species...
November 6, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29080087/the-role-of-the-endoplasmic-reticulum-protein-calreticulin-in-mediating-tgf-%C3%AE-stimulated-extracellular-matrix-production-in-fibrotic-disease
#13
REVIEW
Benjamin Y Owusu, Kurt A Zimmerman, Joanne E Murphy-Ullrich
Endoplasmic reticulum (ER) stress is a key factor contributing to fibrotic disease. Although ER stress is a short-term adaptive response, with chronic stimulation, it can activate pathways leading to fibrosis. ER stress can induce TGF-β signaling, a central driver of extracellular matrix production in fibrosis. This review will discuss the role of an ER protein, calreticulin (CRT), which has both chaperone and calcium regulatory functions, in fibrosis. CRT expression is upregulated in multiple different fibrotic diseases...
October 28, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29075268/calreticulin-fragment-39-272-promotes-b16-melanoma-malignancy-through-myeloid-derived-suppressor-cells-in-vivo
#14
Xiao-Yan He, Fang-Yuan Gong, Yong Chen, Zhe Zhou, Zheng Gong, Xiao-Ming Gao
Calreticulin (CRT), a multifunctional Ca(2+)-binding glycoprotein mainly located in the endoplasmic reticulum, is a tumor-associated antigen that has been shown to play protective roles in angiogenesis suppression and anti-tumor immunity. We previously reported that soluble CRT (sCRT) was functionally similar to heat shock proteins or damage-associated molecular patterns in terms of ability to activate myeloid cells and elicit strong inflammatory cytokine production. In the present study, B16 melanoma cell lines expressing recombinant CRT fragment 39-272 (sCRT/39-272) in secreted form (B16-CRT), or recombinant enhanced green fluorescence protein (rEGFP) (B16-EGFP), were constructed for investigation on the roles of sCRT in tumor development...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29072694/calreticulin-promotes-egf-induced-emt-in-pancreatic-cancer-cells-via-integrin-egfr-erk-mapk-signaling-pathway
#15
Weiwei Sheng, Chuanping Chen, Ming Dong, Guosen Wang, Jianping Zhou, He Song, Yang Li, Jian Zhang, Shuangning Ding
Our previous study showed that Calreticulin (CRT) promoted the development of pancreatic cancer (PC) through ERK/MAPK pathway. We next investigate whether CRT promotes EGF-induced epithelial-mesenchymal transition (EMT) in PC via Integrin/EGFR-ERK/MAPK signaling, which has not been reported yet to our knowledge. EGF simultaneously induced EMT and activated Integrin/EGFR-ERK/MAPK signaling pathway in 3 PC cells. However, CRT silencing significantly inhibited EGF function, including inhibiting EGF-induced EMT-like cell morphology, EGF-enhanced cell invasion and migration, and EGF induced the decrease of E-cadherin, ZO-1, and β-catenin and the increase of the key proteins in Integrin/EGFR-ERK/MAPK signaling (pEGFR-tyr1173, Fibronectin, Integrinβ1, c-Myc and pERK)...
October 26, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29058591/proteomic-analysis-of-trochophore-and-veliger-larvae-development-in-the-small-abalone-haliotis-diversicolor
#16
Guilan Di, Xianghui Kong, Xiulian Miao, Yifang Zhang, Miaoqin Huang, Yuting Gu, Weiwei You, Jianxin Zhang, Caihuan Ke
BACKGROUND: Haliotis diversicolor is commercially important species. The trochophore and veliger are distinct larval stages in gastropod development. Their development involves complex morphological and physiological changes. We studied protein changes during the embryonic development of H. diversicolor using two dimensional electrophoresis (2-DE) and label-free methods, tandem mass spectrometry (MS/ MS), and Mascot for protein identification. RESULTS: A total of 150 2-DE gel spots were identified...
October 23, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29054890/natural-killer-t-cell-immunotherapy-in-combination-with-chemotherapy-induced-immunogenic-cell-death-targets-metastatic-breast-cancer
#17
Simon Gebremeskel, Lynnea Lobert, Kaitlyn Tanner, Brynn Walker, Tora Oliphant, Livia E Clarke, Graham Dellaire, Brent Johnston
Natural killer T (NKT) cells are glycolipid-reactive lymphocytes that promote cancer control. In previous studies, NKT-cell activation improved survival and antitumor immunity in a post-surgical mouse model of metastatic breast cancer. Herein, we investigated whether NKT-cell activation could be combined with chemotherapeutic agents to augment therapeutic outcomes. Gemcitabine and cyclophosphamide analogs enhanced the potential immunogenicity of 4T1 mammary carcinoma cells by increasing the expression of antigen-presenting molecules (MHC-I, MHC-II, and CD1d) and promoting exposure or release of immunogenic cell death markers (calreticulin, HMGB1 and ATP)...
October 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29042925/calreticulin-is-an-effective-immunologic-adjuvant-to-tumor-associated-antigens
#18
Jun Wang, Zhi Peng Gao, Song Qin, Chang Bai Liu, Li Li Zou
As a key molecule involved in cell recognition, calreticulin (CRT) may be expressed on the surface of (pre-) apoptotic cells and provide the signal that is recognized by dendritic cells (DCs) or other antigen presenting cells (APCs), which results in phagocytosis. Within the APCs, tumor-associated antigens (TAAs) may be subsequently presented to T lymphocytes, which triggers a specific antitumor immune response. It has been hypothesized that CRT is able to act as the immunologic adjuvant and translocate itself and TAAs to the cell surface and induce a specific antitumor immune response...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29040188/phagocytosis-of-extracellular-vesicles-extruded-from-the-placenta-by-ovarian-cancer-cells-inhibits-growth-of-the-cancer-cells
#19
Qi Chen, Victoria Rutten, Wei-Tzu Cheng, Mancy Tong, Jia Wei, Peter Stone, Lai-Ming Ching, Lawrence W Chamley
OBJECTIVE: Ovarian cancer is a common gynecological cancer, and parity is negatively associated with the incidence of this disease. This negative association is hypothesized to be due in part to shifting the balance of estrogen and progesterone toward more progesterone and reduced ovulation during pregnancy. However, studies suggested that parity is also associated with estrogen-independent gynecological cancers suggesting balance of hormones may not be the only protective factor. Extracellular vesicles (EVs) play an important role in cell-to-cell communication in physiological and pathological conditions...
October 17, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/29036211/orally-administered-taenia-solium-calreticulin-prevents-experimental-intestinal-inflammation-and-is-associated-with-a-type-2-immune-response
#20
Fela Mendlovic, Mayra Cruz-Rivera, Jose Alfredo Diaz-Gandarilla, Marco Antonio Flores-Torres, Guillermina Avila, Maria Perfiliev, Ana Maria Salazar, Lourdes Arriaga-Pizano, Patricia Ostrosky-Wegman, Ana Flisser
Intestinal helminth antigens are inducers of type 2 responses and can elicit regulatory immune responses, resulting in dampened inflammation. Several platyhelminth proteins with anti-inflammatory activity have been reported. We have identified, cloned and expressed the Taenia solium calreticulin (rTsCRT) and shown that it predominantly induces a type 2 response characterized by IgG1, IL-4 and IL-5 production in mice. Here, we report the rTsCRT anti-inflammatory activity in a well-known experimental colitis murine model...
2017: PloS One
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