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https://www.readbyqxmd.com/read/29679665/comparison-of-exosomes-and-ferritin-protein-nanocages-for-the-delivery-of-membrane-protein-therapeutics
#1
Eunji Cho, Gi-Hoon Nam, Yeonsun Hong, Yoon Kyoung Kim, Dong-Hwee Kim, Yoosoo Yang, In-San Kim
Exosomes are small membrane vesicles secreted by most cell types that play an important role in intercellular communication. Due to the characteristic of transferring their biomacromolecules, exosomes have potential as a new alternative for delivering protein therapeutics. Here, we investigate whether exosomes provide crucial advantages over other nanoparticles, in particular protein nanocage formulations, as a delivery system for membrane protein therapeutics. We characterized membrane-scaffold-based exosomes and protein-scaffold-based ferritin nanocages, both harboring SIRPα (signal regulatory protein α), an antagonist of CD47 on tumor cells...
April 18, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29667847/cd47-is-a-novel-potent-immunotherapy-target-in-human-malignancies-current-studies-and-future-promises
#2
Bing Tong, Mengzhao Wang
Recently, many immunosuppressive checkpoints such as PD-L1, CTLA-4 and CD47, were identified in succession and serve as potential immunotherapy targets in human cancers. Among them, CD47, a 'marker-of-self' protein that is overexpressed broadly across tumor types, is emerging as a novel potent macrophage immune checkpoint for cancer immunotherapy. In this review, we highlight the prominent role of CD47 as a 'don't-eat-me' signal that inhibits macrophage phagocytosis for immune evasion of a tumor and presents the opportunities and challenges for CD47 inhibitors both as monotherapy and in combination treatments for hematological cancers and solid tumors; some of these agents are currently in clinical trials...
April 18, 2018: Future Oncology
https://www.readbyqxmd.com/read/29653288/ph-protective-y-1-receptor-ligand-functionalized-antiphagocytosis-bplp-wpu-micelles-for-enhanced-tumor-imaging-and-therapy-with-prolonged-survival-time
#3
Zhenqi Jiang, Yuchen Tian, Dingying Shan, Yinjie Wang, Ethan Gerhard, Jianbi Xia, Rong Huang, Yan He, Aiguo Li, Jianchao Tang, Huimin Ruan, Yong Li, Juan Li, Jian Yang, Aiguo Wu
Nanoparticle-based tumor therapies are extensively studied; however, few are capable of improving patient survival time due to premature drug leakage, off target effects, and poor tissue penetration. Previously, we successfully synthesized a novel family of Y1 receptor (Y1 R) ligand modified, photoluminescent BPLP nanobubbles and nanoparticles for targeted breast cancer ultrasound imaging; however, increased accumulation could also be observed in the liver, kidney, and spleen, suggesting significant interaction of the particles with macrophages in vivo...
April 4, 2018: Biomaterials
https://www.readbyqxmd.com/read/29625402/effect-of-tropical-thermal-stress-on-peri-implantation-immune-responses-in-cows
#4
Mohanned Naif Alhussien, Aarti Kamboj, Mustafa Ahmad Aljader, Bibhudatta S K Panda, Munna Lal Yadav, Lakshit Sharma, Seid Mohammed, Aasif Ahmad Sheikh, Masoud Lotfan, Rajeev Kapila, A K Mohanty, Ajay Kumar Dang
Pregnancy losses during the peri-implantation period cause a negative impact on the reproductive and economic performance of dairy herds. In this study, we investigated the possible immunological factors which may contribute to pregnancy loss during the peri-implantation period under different seasons of tropical conditions. Eighteen Karan Fries cows, six cows in each season (W: winter; HH: hot-humid; HD: hot-dry) were selected. These cows exhibited heat and were brought for artificial insemination (AI; day 0)...
March 29, 2018: Theriogenology
https://www.readbyqxmd.com/read/29615814/the-impact-of-circulating-preeclampsia-associated-extracellular-vesicles-on-the-migratory-activity-and-phenotype-of-thp-1-monocytic-cells
#5
Árpád Ferenc Kovács, Orsolya Láng, Lilla Turiák, András Ács, László Kőhidai, Nóra Fekete, Bálint Alasztics, Tamás Mészáros, Edit Irén Buzás, János Rigó, Éva Pállinger
Intercellular communication via extracellular vesicles (EVs) and their target cells, especially immune cells, results in functional and phenotype changes that consequently may play a significant role in various physiological states and the pathogenesis of immune-mediated disorders. Monocytes are the most prominent environment-sensing immune cells in circulation, skilled to shape their microenvironments via cytokine secretion and further differentiation. Both the circulating monocyte subset distribution and the blood plasma EV pattern are characteristic for preeclampsia, a pregnancy induced immune-mediated hypertensive disorder...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29600425/a-novel-bispecific-antibody-fusion-protein-co-targeting-egfr-and-cd47-with-enhanced-therapeutic-index
#6
Yun Yang, Rui Guo, Qi Chen, Youxun Liu, Pengfei Zhang, Ziheng Zhang, Xi Chen, Tianyun Wang
OBJECTIVE: To promote targeting specificity of anti-CD47 agents, we have constructed a novel bispecific antibody fusion protein against EGFR and CD47, which may minimize the "off-target" effects caused by CD47 expression on red blood cells. RESULTS: The novel bispecific antibody fusion protein, denoted as Bi-SP could simultaneously bind to EGFR and CD47 and exhibited potent phagocytosis-stimulation effects in vitro. Bi-SP treatment with a low dose more effectively inhibited tumor growth than either EGFR-targeting antibody, Pan or the SIRPα variant-Fc (SIRPαV-Fc) in the A431 xenograft tumor model...
March 29, 2018: Biotechnology Letters
https://www.readbyqxmd.com/read/29559519/overhydrated-stomatocytosis-associated-with-a-complex-rhag-genotype-including-a-novel-de-novo-mutation
#7
Manu Jamwal, Anu Aggarwal, Man Updesh Singh Sachdeva, Prashant Sharma, Pankaj Malhotra, Arindam Maitra, Reena Das
Overhydrated stomatocytosis is a rare autosomal dominant disorder known to cause variably severe haemolytic anaemia due to heterozygous mutations in the RHAG gene. We report a 26-year-old man with recurring jaundice, splenohepatomegaly and mild chronic haemolytic anaemia with significant stomatocytosis. Extensive haemolytic work-up including flow cytometry for eosin-5'-maleimide and CD47 expression levels was carried out. Targeted resequencing revealed two probably causative heterozygous mutations in RHAG (Leu336Ser and Ile149Met) and one heterozygous mutation in ANK1 (Glu1046Lys) ...
March 20, 2018: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29538621/disrupting-cd47-sirp%C3%AE-axis-alone-or-combined-with-autophagy-depletion-for-the-therapy-of-glioblastoma
#8
Xuyao Zhang, Wei Chen, Jiajun Fan, Shaofei Wang, Zongshu Xian, Jingyun Luan, Yubin Li, Yichen Wang, Yanyang Nan, Man Luo, Song Li, Wenzhi Tian, Dianwen Ju
CD47-targeting immune checkpoint inhibitors have been investigated for immunotherapy of several cancers, glioblastoma, one of the most common tumors in brain, was still a challenge for CD47-targeting therapy. Herein, we reported novel strategies for glioblastoma therapy via blocking CD47-SIRPα by SIRPα-Fc alone or in combination with autophagy inhibition. Our results showed that SIRPα-Fc increased macrophages-triggered cytotoxicity and phagocytosis of glioblastoma cells then elicited potent anti-tumor efficacy...
March 10, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29536167/cd47-expression-in-epstein-barr-virus-associated-gastric-carcinoma-coexistence-with-tumor-immunity-lowering-the-ratio-of-cd8-foxp3-t-cells
#9
Hiroyuki Abe, Ruri Saito, Takashi Ichimura, Akiko Iwasaki, Sho Yamazawa, Aya Shinozaki-Ushiku, Teppei Morikawa, Tetsuo Ushiku, Hiroharu Yamashita, Yasuyuki Seto, Masashi Fukayama
Epstein-Barr virus-associated gastric carcinoma (EBVaGC) frequently harbors dense lymphocytic infiltration, suggesting a specific microenvironment allowing coexistence with tumor immunity. CD47, which mediates the "do not eat me" signal in innate immunity, is also important in adaptive anti-tumor immunity. We investigated the significance of CD47 in EBVaGC compared with EBV-negative gastric cancer and the correlation with various immune cells. By immunohistochemistry of CD47, high, low, and negative expression was observed in 24, 63, and 12% of EBVaGC (n = 41), while 11, 49, and 39% of EBV-negative gastric cancer (n = 262), respectively, indicating that high expression of CD47 in cancer cells was significantly frequent and increased in EBVaGC (P = 0...
March 13, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29514782/the-myc-oncogene-is-a-global-regulator-of-the-immune-response
#10
Stephanie C Casey, Virginie Baylot, Dean W Felsher
The MYC proto-oncogene is a gene product that coordinates the transcriptional regulation of a multitude of genes that are essential to cellular programs required for normal as well as neoplastic cellular growth and proliferation, including cell cycle, self-renewal, survival, cell growth, metabolism, protein and ribosomal biogenesis, and differentiation. Here we propose that MYC regulates these programs in a manner that is coordinated with a global influence on the host immune response. MYC had been presumed to contribute to tumorigenesis through tumor cell intrinsic influences...
March 7, 2018: Blood
https://www.readbyqxmd.com/read/29508634/on-target-and-direct-modulation-of-alloreactive-t-cells-by-a-nanoparticle-carrying-mhc-alloantigen-regulatory-molecules-and-cd47-in-a-murine-model-of-alloskin-transplantation
#11
Khawar Ali Shahzad, Xin Wan, Lei Zhang, Weiya Pei, Aifeng Zhang, Muhammad Younis, Wei Wang, Chuanlai Shen
Biomimetic nanoparticles have been reported as immune modulators in autoimmune diseases and allograft rejections by numerous researchers. However, most of the therapeutics carrying antigens, toxins or cytokines underlay the mechanism of antigen presentation by cellular uptake of NPs through pinocytosis and phagocytosis. Few researches focus on the direct and antigen-specific modulation on T cells by NPs and combined use of multiple regulatory molecules. Here, polylactic-co-glycolic acid nanoparticles (PLGA-NPs) were fabricated as scaffold to cocoupling H-2Kb -Ig dimer, anti-Fas mAb, PD-L1-Fc, TGF-β and CD47-Fc for the generation of alloantigen-presenting and tolerance-inducing NPs, termed killer NPs and followed by i...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29495147/-the-roles-of-tsp-1-and-its-receptor-cd47-in-pathogenesis-of-paraquat-induced-pulmonary-fibrosis-in-rats
#12
J Zhang, K X Liu, W Gao, X S Xie
Objective: To establish a rat model of paraquat (PQ) -induced pulmonary fibrosis and observe the changes in thrombospondin-1 (TSP-1) and its receptor CD47 in lung tissue, and to investigate their roles in the pathogenesis of PQ-induced pulmonary fibrosis. Methods: Fifty-four clean adult male Sprague-Dawley rats were randomly divided into normal control group ( n =6) and 2 h, 12 h, 1 d, 3 d, 7 d, and 14 d PQ poisoning groups ( n =8 per group). A rat model of PQ poisoning was established by a single gavage of 20 wt...
December 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
https://www.readbyqxmd.com/read/29473266/anti-human-sirp%C3%AE-antibody-is-a-new-tool-for-cancer-immunotherapy
#13
Yoji Murata, Daisuke Tanaka, Daisuke Hazama, Tadahiko Yanagita, Yasuyuki Saito, Takenori Kotani, Per-Arne Oldenborg, Takashi Matozaki
Interaction of signal regulatory protein α (SIRPα) expressed on the surface of macrophages with its ligand CD47 expressed on target cells negatively regulates phagocytosis of the latter cells by the former. We recently showed that blocking Abs to mouse SIRPα enhanced both the Ab-dependent cellular phagocytosis (ADCP) activity of mouse macrophages for Burkitt's lymphoma Raji cells opsonized with an Ab to CD20 (rituximab) in vitro as well as the inhibitory effect of rituximab on the growth of tumors formed by Raji cells in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice...
February 23, 2018: Cancer Science
https://www.readbyqxmd.com/read/29463646/mutant-idh1-disrupts-pkm2-%C3%AE-catenin-brg1-transcriptional-network-driven-cd47-expression
#14
Pruthvi Gowda, Shruti Patrick, Ankita Singh, Touseef Sheikh, Ellora Sen
Gain-of-function mutation in isocitrate dehydrogenase1 (IDH1) affects immune-surveillance in gliomas. As elevated CD47 is associated with immune evasion in cancers, its status in gliomas harboring IDH1-MT was investigated. Decreased CD47 expression in IDH1-R132H overexpressing cells was accompanied by diminished nuclear β-catenin, PKM2 and TCF4 levels as compared to IDH1-WT. Inhibition of β-catenin in IDH1-WT abrogated CD47 expression, β-catenin-TCF4 interaction and transactivational activity of β-catenin/TCF4...
February 20, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29444453/efferocytosis-in-atherosclerotic-lesions-malfunctioning-regulatory-pathways-and-control-mechanisms
#15
REVIEW
Amir Tajbakhsh, Mehdi Rezaee, Petri T Kovanen, Amirhossein Sahebkar
Atherosclerosis is a dynamic and progressive inflammatory process in the intimal layer of large and medium-sized arteries, and it is the major contributor to the atherosclerotic cardiovascular disease (ACVD), the leading cause of death worldwide. In an atherosclerotic plaque, phagocytosis of apoptotic cells occurs through an intricate process designated efferocytosis. Defective efferocytosis has emerged as a causal factor in the etiopathogenesis of atherosclerosis and its progression into overt ACVD. Both specialized phagocytes (macrophages and dendritic cells) and non-specialized cells with phagocytic capabilities (smooth muscle and endothelial cells) are involved in the efferocytotic process...
February 11, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29429992/srsf10-mediated-il1rap-alternative-splicing-regulates-cervical-cancer-oncogenesis-via-mil1rap-nf-%C3%AE%C2%BAb-cd47-axis
#16
Fei Liu, Miao Dai, Qinyang Xu, Xiaolu Zhu, Yang Zhou, Shuheng Jiang, Yahui Wang, Zhihong Ai, Li Ma, Yanli Zhang, Lipeng Hu, Qin Yang, Jun Li, Shujie Zhao, Zhigang Zhang, Yincheng Teng
High-risk human papillomavirus oncoproteins E6 and E7 are the major etiological factors of cervical cancer but are insufficient for malignant transformation of cervical cancer. Dysregulated alternative splicing, mainly ascribed to aberrant splicing factor levels and activities, contributes to most cancer hallmarks. However, do E6 and E7 regulate the expression of splicing factors? Does alternative splicing acts as an "accomplice" of E6E7 to promote cervical cancer progression? Here, we identified that the splicing factor SRSF10, which promotes tumorigenesis of cervix, was upregulated by E6E7 via E2F1 transcriptional activation...
February 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29425774/a-membrane-type-surfactant-protein-d-sp-d-suppresses-macrophage-mediated-cytotoxicity-in-swine-endothelial-cells
#17
Patmika Jiaravuthisan, Akira Maeda, Chihiro Takakura, Han-Tang Wang, Rieko Sakai, Afifah Mohd Shabri, Pei-Chi Lo, Rei Matsuura, Tasuku Kodama, Hiroshi Eguchi, Hiroomi Okuyama, Shuji Miyagawa
OBJECTIVE: Surfactant protein D (SP-D), which is secreted mainly in the lung, is an oligometric C type lectin that promotes phagocytosis by binding to carbohydrates on microbial surfaces. SP-D can also bind SIRPα, leading to a decrease in cytokine production by monocytes/macrophages. In the present study, we examined the possibility that SP-D suppresses macrophage-mediated xenogeneic cytotoxicity, by creating a membrane-type SP-D. METHODS: The cDNA for the carbohydrate recognition domain (CRD) of human SP-D was switched to that of a membrane-type protein, collectin placenta 1 (CL-P1), with a Flag-tag...
February 6, 2018: Transplant Immunology
https://www.readbyqxmd.com/read/29416769/roles-of-malat1-in-development-and-migration-of-triple-negative-and-her-2-positive-breast-cancer
#18
Zhang Xiping, Chen Bo, Yang Shifeng, Yu Feijiang, Yang Hongjian, Cheng Qihui, Tang Binbin
Background: As a type of new targets for prognosis of malignancies, long non-coding RNA MALAT1 (metastasis-associated lung adenocarcinoma transcription 1) is associated with proliferation and metastatic abilities of several malignancies. However, its relations to development and migration of triple negative and human epidermal growth factor receptor 2 (Her-2) positive breast cancers haven't been reported. Objectives: In this paper, we aimed to discuss how MALAT1 is connected with and affects proliferation and invasion abilities of cells in Her-2 positive and triple-negative breast cancers (TNBC)...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416092/cd63-mhc-class-1-and-cd47-identify-subsets-of-extracellular-vesicles-containing-distinct-populations-of-noncoding-rnas
#19
Sukhbir Kaur, Abdel G Elkahloun, Anush Arakelyan, Lynn Young, Timothy G Myers, Francisco Otaizo-Carrasquero, Weiwei Wu, Leonid Margolis, David D Roberts
Extracellular vesicles (EVs) mediate the intercellular transfer of RNAs, which alter gene expression in target cells. EV heterogeneity has limited progress towards defining their physiological functions and utility as disease-specific biomarkers. CD63 and MHC1 are widely used as markers to purify EVs. CD47 is also present on EVs and alters their effects on target cells, suggesting that specific surface markers define functionally distinct EVs. This hypothesis was addressed by comparing Jurkat T cell EVs captured using CD47, CD63, and MHC1 antibodies...
February 7, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29414673/evolving-targets-for-the-treatment-of-atherosclerosis
#20
REVIEW
Ankita Solanki, Lokesh Kumar Bhatt, Thomas P Johnston
Atherosclerosis is a progressive disease of large arteries and a leading cause of cardiovascular diseases and stroke. Chronic inflammation, aberrant immune response, and disturbances to key enzymes involved with lipid metabolism are characteristic features of atherosclerosis. Apart from targeting the derangements in lipid metabolism, therapeutic modulation to regulate chronic inflammation and the immune system response may prove to be very promising strategies in the management of atherosclerosis. In recent years, various targets have been studied for the treatment of atherosclerosis...
February 4, 2018: Pharmacology & Therapeutics
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