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https://www.readbyqxmd.com/read/29214179/the-roles-of-thrombospondins-in-hemorrhagic-stroke
#1
REVIEW
Xuan Wu, Xu Luo, Qiquan Zhu, Jie Zhang, Yun Liu, Hansheng Luo, Yuan Cheng, Zongyi Xie
Hemorrhagic stroke is a devastating cerebrovascular disease with significant morbidity and mortality worldwide. Thrombospondins (TSPs), as matricellular proteins, belong to the TSP family which is comprised of five members. All TSPs modulate a variety of cellular functions by binding to various receptors. Recently, TSPs gained attention in the area of hemorrhagic stroke, especially TSP-1. TSP-1 participates in angiogenesis, the inflammatory response, apoptosis, and fibrosis after hemorrhagic stroke through binding to various molecules including but not limited to CD36, CD47, and TGF-β...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29213290/effect-of-isolation-technique-and-location-on-the-phenotype-of-human-corneal-stroma-derived-cells
#2
Richárd Nagymihály, Zoltán Veréb, Andrea Facskó, Morten C Moe, Goran Petrovski
Purpose: To determine the effect of the isolation technique and location upon the phenotype of human corneal stroma-derived cells (CSCs). Methods: CSCs were isolated from the corneal stroma center and periphery using the explant or enzymatic digestion technique. The native tissue was stained for functional markers, while cultured cells were analysed by FACS. PCR was used to determine gene expression in the cultured versus native cells. Results: The native stroma was positive for α-actinin, ALDH1A1, CD31, CD34, Collagen I, and Vimentin...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29203952/effect-of-intra-tumoral-magnetic-nanoparticle-hyperthermia-and-viral-nanoparticle-immunogenicity-on-primary-and-metastatic-cancer
#3
P Jack Hoopes, Courtney M Mazur, Bjorn Osterberg, Ailin Song, David J Gladstone, Nicole F Steinmetz, Frank A Veliz, Alicea A Bursey, Robert J Wagner, Steven N Fiering
Although there is long association of medical hyperthermia and immune stimulation, the relative lack of a quantifiable and reproducible effect has limited the utility and advancement of this relationship in preclinical/clinical cancer and non-cancer settings. Recent cancer-based immune findings (immune checkpoint modulators etc.) including improved mechanistic understanding and biological tools now make it possible to modify and exploit the immune system to benefit conventional cancer treatments such as radiation and hyperthermia...
January 2017: Proceedings of SPIE
https://www.readbyqxmd.com/read/29203951/hypo-fractionated-radiation-magnetic-nanoparticle-hyperthermia-and-a-viral-immunotherapy-treatment-of-spontaneous-canine-cancer
#4
P Jack Hoopes, Karen L Moodie, Alicia A Petryk, James D Petryk, Shawntel Sechrist, David J Gladstone, Nicole F Steinmetz, Frank A Veliz, Alicea A Bursey, Robert J Wagner, Ashish Rajan, Danielle Dugat, Margaret Crary-Burney, Steven N Fiering
It has recently been shown that cancer treatments such as radiation and hyperthermia, which have conventionally been viewed to have modest immune based anti-cancer effects, may, if used appropriately stimulate a significant and potentially effective local and systemic anti-cancer immune effect (abscopal effect) and improved prognosis. Using eight spontaneous canine cancers (2 oral melanoma, 3 oral amelioblastomas and 1 carcinomas), we have shown that hypofractionated radiation (6 x 6 Gy) and/or magnetic nanoparticle hyperthermia (2 X 43°C / 45 minutes) and/or an immunogenic virus-like nanoparticle (VLP, 2 x 200 μg) are capable of delivering a highly effective cancer treatment that includes an immunogenic component...
January 2017: Proceedings of SPIE
https://www.readbyqxmd.com/read/29188480/a-function-blocking-cd47-antibody-modulates-extracellular-vesicle-mediated-intercellular-signaling-between-breast-carcinoma-cells-and-endothelial-cells
#5
Sukhbir Kaur, Abdel G Elkahloun, Satya P Singh, Anush Arakelyan, David D Roberts
Tumor cells release extracellular vesicles (EVs) into the tumor microenvironment that may facilitate malignant progression and metastasis. Breast carcinoma EVs express high levels of the thrombospondin-1 and signal regulatory protein-α receptor CD47, which is the target of several experimental therapeutics currently in clinical trials. We analyzed changes in gene expression and function in human umbilical vein endothelial cells (HUVEC) induced by treatment with EVs derived from breast carcinoma cells and the effects of the function-blocking CD47 antibody B6H12 on the resulting intercellular communication...
November 29, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29182441/elimination-of-tumor-by-cd47-pd-l1-dual-targeting-fusion-protein-that-engages-innate-and-adaptive-immune-responses
#6
Boning Liu, Huaizu Guo, Jin Xu, Ting Qin, Qingcheng Guo, Nana Gu, Dapeng Zhang, Weizhu Qian, Jianxin Dai, Sheng Hou, Hao Wang, Yajun Guo
The host immune system generally serves as a barrier against tumor formation. Programmed death-ligand 1 (PD-L1) is a critical "don't find me" signal to the adaptive immune system, whereas CD47 transmits an anti-phagocytic signal, known as the "don't eat me" signal, to the innate immune system. These and similar immune checkpoints are often overexpressed on human tumors. Thus, dual targeting both innate and adaptive immune checkpoints would likely maximize anti-tumor therapeutic effect and elicit more durable responses...
November 28, 2017: MAbs
https://www.readbyqxmd.com/read/29180808/engagement-of-mhc-class-i-by-the-inhibitory-receptor-lilrb1-suppresses-macrophages-and-is-a-target-of-cancer-immunotherapy
#7
Amira A Barkal, Kipp Weiskopf, Kevin S Kao, Sydney R Gordon, Benyamin Rosental, Ying Y Yiu, Benson M George, Maxim Markovic, Nan G Ring, Jonathan M Tsai, Kelly M McKenna, Po Yi Ho, Robin Z Cheng, James Y Chen, Layla J Barkal, Aaron M Ring, Irving L Weissman, Roy L Maute
Exciting progress in the field of cancer immunotherapy has renewed the urgency of the need for basic studies of immunoregulation in both adaptive cell lineages and innate cell lineages. Here we found a central role for major histocompatibility complex (MHC) class I in controlling the phagocytic function of macrophages. Our results demonstrated that expression of the common MHC class I component β2-microglobulin (β2M) by cancer cells directly protected them from phagocytosis. We further showed that this protection was mediated by the inhibitory receptor LILRB1, whose expression was upregulated on the surface of macrophages, including tumor-associated macrophages...
November 27, 2017: Nature Immunology
https://www.readbyqxmd.com/read/29158380/anti-sirp%C3%AE-antibody-immunotherapy-enhances-neutrophil-and-macrophage-antitumor-activity
#8
Nan Guo Ring, Dietmar Herndler-Brandstetter, Kipp Weiskopf, Liang Shan, Jens-Peter Volkmer, Benson M George, Melanie Lietzenmayer, Kelly M McKenna, Tejaswitha J Naik, Aaron McCarty, Yunjiang Zheng, Aaron M Ring, Richard A Flavell, Irving L Weissman
Cancer immunotherapy has emerged as a promising therapeutic intervention. However, complete and durable responses are only seen in a fraction of patients who have cancer. A key factor that limits therapeutic success is the infiltration of tumors by cells of the myeloid lineage. The inhibitory receptor signal regulatory protein-α (SIRPα) is a myeloid-specific immune checkpoint that engages the "don't eat me" signal CD47 expressed on tumors and normal tissues. We therefore developed the monoclonal antibody KWAR23, which binds human SIRPα with high affinity and disrupts its binding to CD47...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29153131/donor-sirp-%C3%AE-polymorphisms-widening-the-innate-to-adaptive-continuum-in-allograft-rejection
#9
Madhav C Menon, Peter S Heeger
In the usual paradigm, self:nonself recognition is attributed to calls of the adaptive immune system, owing to variations in specialized genes encoded within the major histocompatibility complex loci. However, an increasing body of data has shown that cells of the innate immune system also have self:nonself recognition functions relevant to organ transplantation, and this trait may derive from genes located outside the major histocompatibility complex loci. A recent publication identifies the donor SIRP-α gene as a non-major histocompatibility complex locus responsible for nonself recognition by monocytes, with variability resulting in changes in the surface interaction of SIRP-α with its ligand CD47...
December 2017: Kidney International
https://www.readbyqxmd.com/read/29147614/exploiting-a-new-strategy-to-induce-immunogenic-cell-death-to-improve-dendritic-cell-based-vaccines-for-lymphoma-immunotherapy
#10
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/29143228/effect-of-exosome-biomarkers-for-diagnosis-and-prognosis-of-breast-cancer-patients
#11
REVIEW
M Wang, S Ji, G Shao, J Zhang, K Zhao, Z Wang, A Wu
PURPOSE: Exosomes are gradually detected as an indicator for diagnosis and prognosis of breast cancer in clinic and a systematic review was conducted. METHODS: A search for clinical studies published before July 1, 2017 was performed. Methods of exosome purification and identification from all studies were extracted. For diagnosis evaluation, the comparison of exosome biomarkers expression between breast cancer patients and healthy women was obtained; for prognosis prediction, the correlation between exosome biomarkers expression and chemotherapy resistance, overall survival (OS), disease-free survival (DFS), recurrence and metastasis of breast cancer was also extracted...
November 15, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29109283/sirp%C3%AE-dendritic-cells-regulate-homeostasis-of-fibroblastic-reticular-cells-via-tnf-receptor-ligands-in-the-adult-spleen
#12
Yasuyuki Saito, Datu Respatika, Satomi Komori, Ken Washio, Taichi Nishimura, Takenori Kotani, Yoji Murata, Hideki Okazawa, Hiroshi Ohnishi, Yoriaki Kaneko, Katsuyuki Yui, Koji Yasutomo, Chikako Nishigori, Yoshihisa Nojima, Takashi Matozaki
In secondary lymphoid organs, development and homeostasis of stromal cells such as podoplanin (Pdpn)-positive fibroblastic reticular cells (FRCs) are regulated by hematopoietic cells, but the cellular and molecular mechanisms of such regulation have remained unclear. Here we show that ablation of either signal regulatory protein α (SIRPα), an Ig superfamily protein, or its ligand CD47 in conventional dendritic cells (cDCs) markedly reduced the number of CD4(+) cDCs as well as that of Pdpn(+) FRCs and T cells in the adult mouse spleen...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29096246/isolation-of-stem-like-cancer-cells-in-primary-endometrial-cancer-using-cell-surface-markers-cd133-and-cxcr4
#13
Yi Sun, Toshiko Yoshida, Motonori Okabe, Kaixuan Zhou, Fang Wang, Chika Soko, Sigeru Saito, Toshio Nikaido
Endometrial cancer (EC) is the most common familiar gynecologic malignant tumor identified in the female reproductive system and has been increasing yearly. In this study, we will identify the surface markers and stem cell markers related with cancer stem cells (CSCs) of EC. Tissue samples were obtained from endometrial cancer patients during surgical procedures. Single cells were isolated from the tissues for culturing, transfection into nude mice, and histopathology analysis. RT-PCR demonstrated that the cultured cells strongly expressed stemness-related genes, such as c-Myc, Sox-2, Nanog, Oct 4A, ABCG2, BMI-1, CK-18, Nestin and β-actin...
December 2017: Translational Oncology
https://www.readbyqxmd.com/read/29090279/selenium-nanoparticles-induce-suppressed-function-of-tumor-associated-macrophages-and-inhibit-dalton-s-lymphoma-proliferation
#14
Pramod Kumar Gautam, Sanjay Kumar, M S Tomar, Rishi Kant Singh, A Acharya, Sanjay Kumar, B Ram
Selenium Nanoparticle (SeNPs) is reported that it enhances and maintains optimal immune during infection and malignancies. To this end, we examined the role of selenium on TAMS whose anti-tumor function suppressed which favor tumor progression. BALB/c (H2d) strain of mice non-Hodgkin type of Dalton's cell line was used to check the role of carboxlic group induced, synthesized SeNPs on TAMs. Screening of IC50 value was done primarily trypen blue exclusion assay and 50% proliferation of DL cells inhibited 40 ng/ml to 50 ng/...
December 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29084248/tti-621-sirp%C3%AE-fc-a-cd47-blocking-cancer-immunotherapeutic-triggers-phagocytosis-of-lymphoma-cells-by-multiple-polarized-macrophage-subsets
#15
Gloria H Y Lin, Vien Chai, Vivian Lee, Karen Dodge, Tran Truong, Mark Wong, Lisa D Johnson, Emma Linderoth, Xinli Pang, Jeff Winston, Penka S Petrova, Robert A Uger, Natasja N Viller
Tumor-associated macrophages (TAMs) are heterogeneous and can adopt a spectrum of activation states between pro-inflammatory and pro-tumorigenic in response to the microenvironment. We have previously shown that TTI-621, a soluble SIRPαFc fusion protein that blocks the CD47 "do-not-eat" signal, promotes tumor cell phagocytosis by IFN-γ-primed macrophages. To assess the impact of CD47 blockade on diverse types of macrophages that are found within the tumor microenvironment, six different polarized human macrophage subsets (M(-), M(IFN-γ), M(IFN-γ+LPS), M(IL-4), M(HAGG+IL-1β), M(IL-10 + TGFβ)) with distinct cell surface markers and cytokine profiles were generated...
2017: PloS One
https://www.readbyqxmd.com/read/29079706/genome-wide-association-study-identified-copy-number-variants-associated-with-sporadic-colorectal-cancer-risk
#16
Lai Fun Thean, Yee Syuen Low, Michelle Lo, Yik-Ying Teo, Woon-Puay Koh, Jian-Min Yuan, Min Hoe Chew, Choong Leong Tang, Peh Yean Cheah
BACKGROUND: Multiple single nucleotide polymorphisms (SNPs) have been associated with colorectal cancer (CRC) risk. The role of structural or copy number variants (CNV) in CRC, however, remained unclear. We investigated the role of CNVs in patients with sporadic CRC. METHODS: A genome-wide association study (GWAS) was performed on 1000 Singapore Chinese patients aged 50 years or more with no family history of CRC and 1000 ethnicity-matched, age-matched and gender-matched healthy controls using the Affymetrix SNP 6 platform...
October 27, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29078731/immune-regulation-effect-of-lienal-polypeptides-extract-in-lewis-lung-carcinoma-bearing-mice-treated-with-cyclophosphamide
#17
Yan-Ping Wu, Jie Deng, Shu-Hua Ouyang, Zhong-Fu Mao, Guo-En Wang, Hiroshi Kurihara, Rong-Rong He, Yi-Fang Li
Polypeptides extracted from animal immune organs have been proved to exert immunomodulatory activities in previous reports. However, relative experimental data regarding the influence of a polypeptide mixture extracted from healthy calf spleen (lienal polypeptide [LP]) on the immune function in tumor therapy are limited, and the components in LP remain unclear. In the present study, the immune regulatory effect of LP was investigated in normal mice and Lewis lung carcinoma (LLC)-bearing mice treated with cyclophosphamide (CTX)...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29065481/cd47-car-t-cells-effectively-kill-target-cancer-cells-and-block-pancreatic-tumor-growth
#18
Vita Golubovskaya, Robert Berahovich, Hua Zhou, Shirley Xu, Hizkia Harto, Le Li, Cheng-Chi Chao, Mike Ming Mao, Lijun Wu
CD47 is a glycoprotein of the immunoglobulin superfamily that is often overexpressed in different types of hematological and solid cancer tumors and plays important role in blocking phagocytosis, increased tumor survival, metastasis and angiogenesis. In the present report, we designed CAR (chimeric antigen receptor)-T cells that bind CD47 antigen. We used ScFv (single chain variable fragment) from mouse CD47 antibody to generate CD47-CAR-T cells for targeting different cancer cell lines. CD47-CAR-T cells effectively killed ovarian, pancreatic and other cancer cells and produced high level of cytokines that correlated with expression of CD47 antigen...
October 21, 2017: Cancers
https://www.readbyqxmd.com/read/29056539/tumor-cell-associated-immune-checkpoint-molecules-drivers-of-malignancy-and-stemness
#19
REVIEW
Fabrizio Marcucci, Cristiano Rumio, Angelo Corti
Inhibitory or stimulatory immune checkpoint molecules are expressed on a sizeable fraction of tumor cells in different tumor types. It was thought that the main function of tumor cell-associated immune checkpoint molecules would be the modulation (down- or upregulation) of antitumor immune responses. In recent years, however, it has become clear that the expression of immune checkpoint molecules on tumor cells has important consequences on the biology of the tumor cells themselves. In particular, a causal relationship between the expression of these molecules and the acquisition of malignant traits has been demonstrated...
October 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29050218/braf-mek-inhibitors-promote-cd47-expression-that-is-reversible-by-erk-inhibition-in-melanoma
#20
Fen Liu, Chen Chen Jiang, Xu Guang Yan, Hsin-Yi Tseng, Chun Yan Wang, Yuan Yuan Zhang, Hamed Yari, Ting La, Margaret Farrelly, Su Tang Guo, Rick F Thorne, Lei Jin, Qi Wang, Xu Dong Zhang
The expression of CD47 on the cancer cell surface transmits "don't eat me" signalling that not only inhibits phagocytosis of cancer cells by phagocytes but also impairs anti-cancer T cell responses. Here we report that oncogenic activation of ERK plays an important role in transcriptional activation of CD47 through nuclear respiratory factor 1 (NRF-1) in melanoma cells. Treatment with BRAF/MEK inhibitors upregulated CD47 in cultured melanoma cells and fresh melanoma isolates. Similarly, melanoma cells selected for resistance to the BRAF inhibitor vemurafenib expressed higher levels of CD47...
September 19, 2017: Oncotarget
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