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https://www.readbyqxmd.com/read/28650466/ror2-mediated-alternative-wnt-signaling-regulates-cell-fate-and-adhesion-during-mammary-tumor-progression
#1
K Roarty, A D Pfefferle, C J Creighton, C M Perou, J M Rosen
Cellular heterogeneity is a common feature in breast cancer, yet an understanding of the coexistence and regulation of various tumor cell subpopulations remains a significant challenge in cancer biology. In the current study, we approached tumor cell heterogeneity from the perspective of Wnt pathway biology to address how different modes of Wnt signaling shape the behaviors of diverse cell populations within a heterogeneous tumor landscape. Using a syngeneic TP53-null mouse model of breast cancer, we identified distinctions in the topology of canonical Wnt β-catenin-dependent signaling activity and non-canonical β-catenin-independent Ror2-mediated Wnt signaling across subtypes and within tumor cell subpopulations in vivo...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28649577/in%C3%A2-vivo-murine-matured-human-cd3-cells-as-a-preclinical-model-for-t-cell-based-immunotherapies
#2
Kevin G Haworth, Christina Ironside, Zachary K Norgaard, Willimark M Obenza, Jennifer E Adair, Hans-Peter Kiem
Adoptive cellular immunotherapy is a promising and powerful method for the treatment of a broad range of malignant and infectious diseases. Although the concept of cellular immunotherapy was originally proposed in the 1990s, it has not seen successful clinical application until recent years. Despite significant progress in creating engineered receptors against both malignant and viral epitopes, no efficient preclinical animal models exist for rapidly testing and directly comparing these engineered receptors...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28647567/stearoyl-coa-desaturase-regulates-sorafenib-resistance-via-modulation-of-er-stress-induced-differentiation
#3
Mark Kin Fai Ma, Eunice Yuen Ting Lau, Doris Hoi Wing Leung, Jessica Lo, Nicole Pui Yu Ho, Lily Kwan Wai Cheng, Stephanie Ma, Chi Ho Lin, John A Copland, Jin Ding, Regina Cheuk Lam Lo, Irene Oi Lin Ng, Terence Kin Wah Lee
We investigated the functional role and clinical significance of Stearoyl CoA desaturase-1 (SCD1) mediated endoplasmic reticulum (ER) stress in regulation of liver tumor-initiating cells (T-ICs) and sorafenib resistance, aiming to develop a novel therapeutic strategy against hepatocellular carcinomas (HCCs) METHODS We evaluated the clinic-pathological relevance of SCD1 and its correlation with sorafenib resistance in large cohorts of HCC clinical samples by qPCR and immunohistochemical analyses. Lentiviral-based overexpression and knockdown approaches were performed to characterize functional roles of SCD1 in regulation of liver T-ICs and sorafenib resistance...
June 21, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28646491/sickle-cells-produce-functional-immune-modulators-and-cytotoxics
#4
Chiao-Wang Sun, Li-Chen Wu, Peter L Knopick, David S Bradley, Tim Townes, David S Terman
Sickle erythrocytes' (SSRBCs) unique physical adaptation to hypoxic conditions renders them able to home to hypoxic tumor niches in vivo, shut down tumor blood flow and induce tumoricidal responses. SSRBCs are also useful vehicles for transport of encapsulated drugs and oncolytic virus into hypoxic tumors with enhanced anti-tumor effects. In search of additional modes for arming sickle cells with cytotoxics, we turned to a lentiviral β-globin vector with optimized Locus Control Region/β-globin coding region/promoter/enhancers...
June 24, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28643325/surface-expression-of-anti-cd3scfv-stimulates-locoregional-immunotherapy-against-hepatocellular-carcinoma-depending-on-the-e1a-engineered-human-umbilical-cord-mesenchymal-stem-cells
#5
Qing Zhang, Xiang-Fei Yuan, Yang Lu, Zhen-Zhen Li, Shi-Qi Bao, Xiao-Long Zhang, Yuan-Yuan Yang, Dong-Mei Fan, Yi-Zhi Zhang, Chen-Xuan Wu, Hong-Xing Guo, Yan-Jun Zhang, Ye Zhou, Dong-Sheng Xiong
Tumor antigens is at the core of cancer immunotherapy, however, the ideal antigen selection is difficult especially in poorly immunogenic tumors. In this study, we designed a strategy to modify hepatocellular carcinoma (HCC) cells by surface expressing anti-CD3scfv within the tumor site strictly, which depended on the E1A-engineered human umbilical cord mesenchymal stem cells (HUMSC.E1A) delivery system. Subsequently, membrane-bound anti-CD3scfv actived the lymphocytes which lysed HCC cells bypassing the expression of antigens or MHC restriction...
June 23, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28642327/declining-histone-acetyltransferase-gcn5-represses-bmsc-mediated-angiogenesis-during-osteoporosis
#6
Huan Jing, Li Liao, Xiaoxia Su, Yi Shuai, Xinjing Zhang, Zhihong Deng, Yan Jin
Angiogenesis is disrupted in age-related and postmenopausal osteoporosis. However, the mechanisms of the disorder remain elusive. We confirmed in this study that, in accordance with the decrease of H-type vessels, the proangiogenic potential of bone marrow-derived mesenchymal stem cells (BMSCs) declined during osteoporosis. Screening of the histone acetyltransferase family revealed that GCN5 decreased in BMSCs derived from osteoporotic femur. Further analysis identified that GCN5 plays important roles in regulating the proangiogenic potential of BMSCs...
June 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28635228/-mechanism-of-long-non-coding-rna-metastasis-associated-lung-adenocarcinoma-transcript-1-induced-invasion-and-metastasis-of-esophageal-cancer-cell-ec-109
#7
Q Q Zhang, Y H Cui, Y Wang, W Z Kou, F Cao, X J Cao, Z H Miao, X H Kang
Objective: To investigate the effect and mechanism of long non-coding RNA-metastasis associated lung adenocarcinoma transcript 1, (LncRNA-MALAT1) on invasion and metastasis of esophageal cancer cell EC-109. Methods: EC-109 cells were transfected with lentiviral vector carrying short hairpin RNA of MALAT1( shRNA-MALAT1) or a nonspecific shRNA control (shRNA-control). The expressions of MALAT1, microRNA-200a, ZEB1 and ZEB2 were detected by qRT-PCR. The effect of shRNA-MALAT1 on invasion of EC-109 cells was determined by transwell assay...
June 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28635133/critical-role-of-glioma-associated-oncogene-homolog-1-in-maintaining-invasive-and-mesenchymal-like-properties-of-melanoma-cells
#8
I Ketut Gunarta, Rong Li, Ryota Nakazato, Ryusuke Suzuki, Jambaldorj Boldbaatar, Takeshi Suzuki, Katsuji Yoshioka
Cutaneous melanoma is the most aggressive form of skin cancer. This aggressiveness appears to be due to the cancer cells' ability to reversibly switch between phenotypes with non-invasive and invasive potentials, and microphthalmia-associated transcription factor (MITF) is known to play a central role in this process. The transcription factor glioma-associated oncogene homolog 1 (GLI1) is a component of the canonical and noncanonical sonic hedgehog pathways. Although GLI1 has been suggested to be involved in melanoma progression, its precise role and the mechanism underlying invasion remain unclear...
June 21, 2017: Cancer Science
https://www.readbyqxmd.com/read/28632033/overexpression-of-alk5-induces-human-tenon-s-capsule-fibroblasts-transdifferentiation-and-fibrosis-in-vitro
#9
Shu-Hao Fu, Hui-Ying Wang, Jia-Ying Zhang, Hui-Min Shi, Nan Zhang, Wen Ye, Yi-Qin Xiao
PURPOSE: To investigate the involvement of activin receptor-like kinase 5 (ALK5) in human Tenon's capsule fibroblasts (HTFs) transdifferentiation and fibrosis. METHODS: (1) Cultured HTFs were treated with transforming growth factor beta 1 (TGF-β1) at different concentrations for different durations, mRNA expression of ALK5 and plasminogen activator inhibitor-1 (PAI-1) was measured by quantitative polymerase chain reaction (PCR) while protein expression of ALK5, α-smooth muscle actin (α-SMA), and extracellular matrix deposition including fibronectin (FN) and collagen I (Col1) was assessed by western blot...
February 28, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28630892/disruption-of-the-axonal-trafficking-of-tyrosine-hydroxylase-mrna-impairs-catecholamine-biosynthesis-in-the-axons-of-sympathetic-neurons
#10
Armaz Aschrafi, Anthony E Gioio, Lijin Dong, Barry B Kaplan
Tyrosine hydroxylase (TH) is the enzyme that catalyzes the rate-limiting step in the biosynthesis of the catecholamine neurotransmitters. In a previous communication, evidence was provided that TH mRNA is trafficked to the axon, where it is locally translated. In addition, a 50-bp sequence element in the 3'untranslated region (3'UTR) of TH mRNA was identified that directs TH mRNA to distal axons (i.e., zip-code). In the present study, the hypothesis was tested that local translation of TH plays an important role in the biosynthesis of the catecholamine neurotransmitters in the axon and/or presynaptic nerve terminal...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28628776/3d-printed-lattices-as-an-activation-and-expansion-platform-for-t-cell-therapy
#11
Bahman Delalat, Frances Harding, Batjargal Gundsambuu, Elena M De-Juan-Pardo, Felix M Wunner, Marie-Luise Wille, Marek Jasieniak, Kristen A L Malatesta, Hans J Griesser, Antonio Simula, Dietmar W Hutmacher, Nicolas H Voelcker, Simon C Barry
One of the most significant hurdles to the affordable, accessible delivery of cell therapy is the cost and difficulty of expanding cells to clinically relevant numbers. Immunotherapy to prevent autoimmune disease, tolerate organ transplants or target cancer critically relies on the expansion of specialized T cell populations. We have designed 3D-printed cell culture lattices with highly organized micron-scale architectures, functionalized via plasma polymerization to bind monoclonal antibodies that trigger cell proliferation...
June 7, 2017: Biomaterials
https://www.readbyqxmd.com/read/28627702/lentivirus%C3%A2-mediated-knockdown-of-chondroitin-polymerizing-factor-inhibits-glioma-cell-growth-in%C3%A2-vitro
#12
Yang-Hua Fan, Bing Xiao, Shi-Gang Lv, Min-Hua Ye, Xin-Gen Zhu, Miao-Jing Wu
Glioma is the most common primary tumor in the central nervous system, characterized by rapid progression, aggressive behavior, frequent recurrence and poor prognosis. In the present study we demonstrated that chondroitin polymerizing factor (CHPF) is highly expressed in human glioma tissues and 4 glioma cell lines. To explore the role of CHPF in glioma, a lentiviral vector expressing CHPF shRNA was constructed and transfected into the glioma U251 cells, which stably downregulated the expression levels of the CHPF gene in U251 cells in vitro...
June 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28627681/b7-h3-promotes-the-proliferation-migration-and-invasiveness-of-cervical-cancer-cells-and-is-an-indicator-of-poor-prognosis
#13
Yi Li, Jingjing Zhang, Sai Han, Qiuhong Qian, Qian Chen, Lu Liu, Youzhong Zhang
B7-H3 is an immune regulatory molecule whose aberrant expression in tumors is associated with adverse outcomes. Upregulation of B7-H3 may promote tumor cell proliferation and metastasis in vitro, but the role of B7-H3 in cervical cancer has not yet been investigated. We measured B7-H3 expression in 90 cervical cancer patient and 20 non‑cervical lesion patient tissues using immunohistochemistry and in 30 cervical cancer patient and 30 healthy donor blood samples using ELISA. The association of B7-H3 expression and the prognosis of cervical cancer patients was investigated...
June 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28627666/expression-pattern-of-zinc-finger-protein-185-in-mouse-testis-and-its-role-in-regulation-of-testosterone-secretion
#14
Xinguo You, Lu Wei, Shutong Fan, Weiwei Yang, Xiaoying Liu, Guohui Wang, Yi Man, Zhifang Pan, Weiguo Feng
Zinc finger protein 185 (ZNF185) belongs to the ZNF family and is involved in cell proliferation and differentiation. To the best of our knowledge, the association between ZNF185 and male reproduction is unknown. In the present study, the expression and localization of ZNF185 in mouse testis, as well as its role in testosterone secretion, cell cycle progression and apoptosis of mouse Leydig cells were investigated. The results of the immunofluorescence analysis indicated that ZNF185 was highly expressed in Leydig cells of the mouse testis, and primarily localized in the cytoplasm...
June 16, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627637/lentiviral-vector-mediated-co-overexpression-of-vegf-and-bcl-2-improves-mesenchymal-stem-cell-survival-and-enhances-paracrine-effects-in%C3%A2-vitro
#15
Xiaobin Ni, Caiwen Ou, Jingbin Guo, Bei Liu, Jianwu Zhang, Zhiye Wu, Hekai Li, Minsheng Chen
Mesenchymal stem cell (MSC) transplantation has emerged as a promising therapy for ischemic heart disease; however, the low survival rate of transplanted cells limits their therapeutic efficacy. The aim of this study was to investigate whether the dual genetic modification of vascular endothelial growth factor (VEGF) and B‑cell lymphoma‑2 (Bcl‑2) confers a higher expression level of the target genes, better survival and a stronger paracrine effect in MSCs in an adverse environment than the modification of the individual genes...
June 12, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28627582/mir%C3%A2-27-inhibits-the-nf-%C3%AE%C2%BAb-signaling-pathway-by-targeting-leptin-in-osteoarthritic-chondrocytes
#16
Bin Zhou, Hongwei Li, Jide Shi
Osteoarthritis (OA) is a chronic degenerative joint disease. An increasing number of studies point to the role of microRNAs (miRNAs or miRs) in the pathogenesis of OA. An earlier study suggested that miR‑27b was associated with OA; however, the precise mechanisms regarding the involvement of the miR‑27 in the progression of OA remain unclear. In the present study, we first analyzed the effects of miR‑27 on OA. In vitro, the degree of miR‑27 expression was decreased in chondrocytes obtained from patients with OA...
June 13, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28627344/-protective-effect-of-bag-1l-mediated-by-lentivirus-in-human-neuroblastoma-cells-induced-by-hypoxia
#17
Yun Wang, Qingshu Li, Chao Jia, Chunyu Xie, Yankun Song, Nan Zhang, Yan Qu
OBJECTIVE: To investigate the protective effects of lentivirus mediated Bcl-2-associated athanogene 1L (BAG-1L) over-expression on human neuroblastoma cells (SH-SY5Y) induced by hypoxia/re-oxygenation, and to study its effect on the phosphoinositide 3 kinase serine/threonine protein kinase (PI3K/AKT) pathway. METHODS: SH-SY5Y cells were cultured in vitro, and the cells at logarithmic phase were collected, and they were divided into recombined lentiviral infection group [infected by lentivirus containing BAG-1L and green fluorescent protein (GFP) gene], vector control group (infected by lentivirus containing GFP without BAG-1L gene) and cell control group (non-infection)...
March 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28626608/c-kit-modifies-the-inflammatory-status-of-smooth-muscle-cells
#18
Lei Song, Laisel Martinez, Zachary M Zigmond, Diana R Hernandez, Roberta M Lassance-Soares, Guillermo Selman, Roberto I Vazquez-Padron
BACKGROUND: c-Kit is a receptor tyrosine kinase present in multiple cell types, including vascular smooth muscle cells (SMC). However, little is known about how c-Kit influences SMC biology and vascular pathogenesis. METHODS: High-throughput microarray assays and in silico pathway analysis were used to identify differentially expressed genes between primary c-Kit deficient (Kit(W/W-v)) and control (Kit(+/+)) SMC. Quantitative real-time RT-PCR and functional assays further confirmed the differences in gene expression and pro-inflammatory pathway regulation between both SMC populations...
2017: PeerJ
https://www.readbyqxmd.com/read/28626364/ex-vivo-generation-of-genetically-modified-macrophages-from-human-induced-pluripotent-stem-cells
#19
Mania Ackermann, Alexandra Kuhn, Jessica Kunkiel, Sylvia Merkert, Ulrich Martin, Thomas Moritz, Nico Lachmann
BACKGROUND: Pluripotent stem cells, including induced pluripotent stem cells (iPSCs), have the capacity to differentiate towards all three germ layers and have been highlighted as an attractive cell source for the field of regenerative medicine. Thus, stable expression of therapeutic transgenes in iPSCs, as well as thereof derived progeny of hematopoietic lineage, may lay the foundation for innovative cell replacement therapies. METHODS: We have utilized human iPSC lines genetically modified by lentiviral vector technology or targeted integration of reporter genes to evaluate transgene expression during hematopoietic specification and differentiation towards macrophages...
June 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/28624579/epigenome-wide-association-study-identifies-methylation-sites-associated-with-liver-enzymes-and-hepatic-steatosis
#20
Jana Nano, Mohsen Ghanbari, Wenshi Wang, Paul S de Vries, Klodian Dhana, Taulant Muka, André G Uitterlinden, Joyce B J van Meurs, Albert Hofman, Oscar H Franco, Qiuwei Pan, Sarwa Darwish Murad, Abbas Dehghan
BACKGROUND & AIMS: Epigenetic mechanisms might be involved in the regulation of liver enzyme level. We aimed to identify CpG sites at which DNA methylation levels are associated with blood levels of liver enzymes and hepatic steatosis. METHODS: We conducted an epigenome-wide association study in whole blood for liver enzymes levels including gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), among a discovery set of 731 participants of the Rotterdam Study and sought replication in a non-overlapping sample of 719 individuals...
June 14, 2017: Gastroenterology
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