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https://www.readbyqxmd.com/read/28088790/intraperitoneal-immunotherapy-with-t-cells-stably-and-transiently-expressing-anti-epcam-car-in-xenograft-models-of-peritoneal-carcinomatosis
#1
Wei Xia Ang, Zhendong Li, Zhixia Chi, Shou-Hui Du, Can Chen, Johan C K Tay, Han Chong Toh, John E Connolly, Xue Hu Xu, Shu Wang
The epithelial cell adhesion molecule (EpCAM) is overexpressed in a wide variety of tumor types, including peritoneal carcinomatosis (PC) from gastrointestinal and gynecological malignancies. To develop a chimeric antigen receptor T (CART) cell therapy approach to treat patients with end-stage PC, we constructed third generation CARs specific to EpCAM using the 4D5MOC-B single chain variable fragment. CART cells were generated with lentiviral transduction and exhibited specific in vitro killing activity against EpCAM-positive human ovarian and colorectal cancer cells...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088294/suitability-of-small-diagnostic-peripheral-blood-samples-for-cell-therapy-studies
#2
Coralea Stephanou, Panayiota Papasavva, Myria Zachariou, Petros Patsali, Marilena Epitropou, Petros Ladas, Ruba Al-Abdulla, Soteroulla Christou, Michael N Antoniou, Carsten W Lederer, Marina Kleanthous
BACKGROUND AIMS: Primary hematopoietic stem and progenitor cells (HSPCs) are key components of cell-based therapies for blood disorders and are thus the authentic substrate for related research. We propose that ubiquitous small-volume diagnostic samples represent a readily available and as yet untapped resource of primary patient-derived cells for cell- and gene-therapy studies. METHODS: In the present study we compare isolation and storage methods for HSPCs from normal and thalassemic small-volume blood samples, considering genotype, density-gradient versus lysis-based cell isolation and cryostorage media with different serum contents...
February 2017: Cytotherapy
https://www.readbyqxmd.com/read/28087539/quantitative-stability-of-hematopoietic-stem-and-progenitor-cell-clonal-output-in-transplanted-rhesus-macaques
#3
Samson J Koelle, Diego A Espinoza, Chuanfeng Wu, Jason Xu, Rong Lu, Brian Li, Robert E Donahue, Cynthia E Dunbar
Autologous transplantation of hematopoietic stem and progenitor cells lentivirally labeled with unique oligonucleotide barcodes flanked by sequencing primer targets enables quantitative assessment of the self-renewal and differentiation patterns of these cells in a myeloablative rhesus macaque model. Compared with other approaches to clonal tracking, this approach is highly quantitative and reproducible. We documented very stable multipotent long-term hematopoietic clonal output of monocytes, granulocytes, B cells and T cells from a polyclonal pool of hematopoietic stem and progenitor cells in four macaques followed for up to 49 months post-transplantation...
January 13, 2017: Blood
https://www.readbyqxmd.com/read/28086964/anti-%C3%AE-synuclein-immunotherapy-reduces-%C3%AE-synuclein-propagation-in-the-axon-and-degeneration-in-a-combined-viral-vector-and-transgenic-model-of-synucleinopathy
#4
Brian Spencer, Elvira Valera, Edward Rockenstein, Cassia Overk, Michael Mante, Anthony Adame, Wagner Zago, Peter Seubert, Robin Barbour, Dale Schenk, Dora Games, Robert A Rissman, Eliezer Masliah
Neurodegenerative disorders such as Parkinson's Disease (PD), PD dementia (PDD) and Dementia with Lewy bodies (DLB) are characterized by progressive accumulation of α-synuclein (α-syn) in neurons. Recent studies have proposed that neuron-to-neuron propagation of α-syn plays a role in the pathogenesis of these disorders. We have previously shown that antibodies against the C-terminus of α-syn reduce the intra-neuronal accumulation of α-syn and related deficits in transgenic models of synucleinopathy, probably by abrogating the axonal transport and accumulation of α-syn in in vivo models...
January 13, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28077433/osteoprotegerin-disruption-attenuates-hysu-induced-pulmonary-hypertension-through-integrin-%C3%AE-v%C3%AE-3-fak-akt-pathway-suppression
#5
Daile Jia, Qian Zhu, Huan Liu, Caojian Zuo, Yuhu He, Guilin Chen, Ankang Lu
BACKGROUND: Pulmonary arterial remodeling characterized by increased vascular smooth muscle proliferation is commonly seen in life-threatening disease, pulmonary arterial hypertension (PAH). Clinical studies have suggested a correlation between osteoprotegerin serum levels and PAH severity. Here, we aimed to invhestigate vascular osteoprotegerin expression and its effects on pulmonary arterial smooth muscle cell proliferation in vitro and in vivo, as well as examine the signal transduction pathways mediating its activity...
February 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28077301/mir-124-down-regulation-is-critical-for-cancer-associated-fibroblasts-enhanced-tumor-growth-of-oral-carcinoma
#6
Xia Li, Qinqiao Fan, Jinyun Li, Jing Song, Yangcong Gu
Cancer associated fibroblasts (CAFs) are known to be involved in initiation, progression and metastasis of various cancers. However, the molecular mechanism of how CAFs affects the biological function of oral cancer (OC) has not been fully-addressed. In this study, we demonstrated that miR-124 was downregulated in oral CAFs and oral cancer cells (OCCs) when compared with matched normal fibroblasts (NFs). Hypermethylation in the promoter region of miR-124 genes was accounted for its downregulation. Interestingly, CAFs but not NFs exerted promotion effect on OCCs cell proliferation, migration and tumor growth in CAFs/NFs-OCCs co-culture...
January 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28076844/sulforaphane-inhibits-cancer-stem-like-cell-properties-and-cisplatin-resistance-through-mir-214-mediated-downregulation-of-c-myc-in-non-small-cell-lung-cancer
#7
Qian-Qian Li, You-Ke Xie, Yue Wu, Lin-Lin Li, Ying Liu, Xiao-Bo Miao, Qiu-Zhen Liu, Kai-Tai Yao, Guang-Hui Xiao
We herein report that sulforaphane (SFN), a potent anti-cancer and well-tolerated dietary compound, inhibits cancer stem-like cell (CSC) properties and enhances therapeutic efficacy of cisplatin in human non-small cell lung cancer (NSCLC). SFN exerted these functions through upregulation of miR-214, which in turn targets the coding region of c-MYC. This finding was further corroborated by our observations that plasmid or lentiviral vector-mediated expression of 3'UTR-less c-MYC cDNA and cisplatin- or doxorubicin-induced endogenous c-MYC accumulation was similarly suppressed by either SFN or miR-214...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28074855/mir-218-targets-mecp2-and-inhibits-heroin-seeking-behavior
#8
Biao Yan, Zhaoyang Hu, Wenqing Yao, Qiumin Le, Bo Xu, Xing Liu, Lan Ma
MicroRNAs (miRNAs) are a class of evolutionarily conserved, 18-25 nucleotide non-coding sequences that post-transcriptionally regulate gene expression. Recent studies implicated their roles in the regulation of neuronal functions, such as learning, cognition and memory formation. Here we report that miR-218 inhibits heroin-induced behavioral plasticity. First, network propagation-based method was used to predict candidate miRNAs that played potential key roles in regulating drug addiction-related genes. Microarray screening was also carried out to identify miRNAs responding to chronic heroin administration in the nucleus accumbens (NAc)...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28071969/curcumin-induces-apoptosis-in-human-leukemic-cell-lines-through-an-ifit2-dependent-pathway
#9
Yonglu Zhang, Yunyuan Kong, Shuyuan Liu, Lingbing Zeng, Lagen Wan, Zhanglin Zhang
Curcumin, the primary bioactive component isolated from turmeric, has been shown to possess variety of biological functions including anti-cancer activity. However, molecular mechanisms different cancer cells are various. In the present study, we demonstrated that curcumin induced G2/M cell cycle arrest and apoptosis by increasing the expression levels of cleaved caspase-3, cleaved PARP and decreasing the expression of BCL-2 in U937 human leukemic cells but not in K562 cells. We found some interferon induced genes, especially interferon-induced protein with tetratricopeptide repeats 2 (IFIT2), were significantly up-regulated when treated with curcumin in U937 cells by gene expression chip array, and further confirmed that the expression of IFIT2 was obviously higher in U937 than that in K562 cells by Western blot assay...
January 10, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28070500/chimeric-influenza-haemagglutinins-generation-and-use-in-pseudotype-neutralization-assays
#10
Francesca Ferrara, Nigel Temperton
Recently chimeric influenza haemagglutinins (cHAs) have been generated as potential 'universal' vaccination antigens and as tools to identify HA stalk-directed antibodies via their use as antigens in ELISA, and virus or pseudotype-based neutralization assays. The original methods [1], [2] used for their generation require the amplification of regions of interest (head and stalk) using primers containing SapI sites and subsequent cloning into pDZ plasmid. This requires precise primer design, checking for the absence of SapI sites in the sequence of interest, and multi-segment ligation...
2017: MethodsX
https://www.readbyqxmd.com/read/28069043/fgf19-fgfr4-signaling-contributes-to-the-resistance-of-hepatocellular-carcinoma-to-sorafenib
#11
Lixia Gao, Xuli Wang, Yaoliang Tang, Shuang Huang, Chien-An Andy Hu, Yong Teng
BACKGROUND: Sorafenib, a multi-kinase inhibitor, is used as a standard therapy for advanced hepatocellular carcinoma (HCC). However, complete remission has not been achieved and the molecular basis of HCC resistance to sorafenib remains largely unknown. Previous studies have shown that fibroblast growth factor 19 (FGF19) expression correlates with tumor progression and poor prognosis of HCC. Here, we demonstrate the novel role of FGF19 in HCC resistance to sorafenib therapy. METHODS: FGF19 Knockdown cells were achieved by lentiviral-mediated interference, and FGFR4 knockout cells were achieved by CRISPR-Cas9...
January 9, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28067416/a-novel-technique-of-delivering-viral-vectors-to-trigeminal-ganglia-in-rats
#12
Hu Long, Lina Liao, Yang Zhou, Di Shan, Meiya Gao, Renhuan Huang, Xin Yang, Wenli Lai
The objective of this study was to develop a viable and reliable technique of delivering viral vectors to rat trigeminal ganglia. Adult Sprague-Dawley rats (200-300 g) were used, and lentiviral vectors containing enhanced green fluorescence protein and calcitonin gene-related peptide short hairpin RNA (shRNA) were generated. Following general anesthesia, viral vectors were delivered to rat trigeminal ganglia using the technique described in this study. Both X-ray and micro-computed tomography (micro-CT) were employed to verify the position of the needles when injecting the vectors...
January 9, 2017: European Journal of Oral Sciences
https://www.readbyqxmd.com/read/28067166/stem-cell-genetic-therapy-for-fanconi-anemia-a-new-hope
#13
Helmut Hanenberg, Katharina Roellecke, Constanze Wiek
Fanconi anemia (FA) is a rare inherited DNA disorder clinically characterized by congenital malformations, progressive bone marrow failure, and cancer susceptibility. Due to a strong survival advantage of spontaneously corrected 'normal' hematopoietic stem cells (HSCs) in a few patients, FA is considered a model disorder for genetic correction of autologous stem cells, where genetically corrected stem cells and their progeny have a strong in vivo selective advantage, ultimately leading to normal hematopoiesis...
January 9, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28067165/gene-therapy-in-fanconi-anemia-a-matter-of-time-safety-and-gene-transfer-tool-efficiency
#14
Verhoeyen Els, Francisco José Román Rodríguez, François-Loïc Cosset, Camille Lévy, Paula Rio
Fanconi anemia (FA) is a rare genetic syndrome characterized by progressive marrow failure. Gene therapy by infusion of FA-corrected autologous hematopoietic stem cells (HSCs) may offer a potential cure since it is a monogenetic disease with mutations in the FANC genes, coding for DNA repair enzymes (See review[1]). However, the collection of hCD34 +-cells in FA patients implies particular challenges because of the reduced numbers of progenitor cells present in their bone marrow (BM)[2] or mobilized peripheral blood[3-5]...
January 9, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28067096/differential-response-of-normal-and-transformed-mammary-epithelial-cells-to-combined-treatment-of-anti-mir-21-and-radiation
#15
Vanja Radulovic, Theresa Heider, Sabine Richter, Simone Moertl, Michael J Atkinson, Nataša Anastasov
PURPOSE: MicroRNA miR-21 has emerged as a therapeutic target in the treatment of breast cancer. This study was designed to compare the responses of breast cancer cells and non-transformed breast epithelial cells to a combined regimen of miR-21 inhibition and radiation. MATERIALS AND METHODS: The MDA-MB-361 (breast cancer) and MCF-10A (non-transformed mammary epithelial) cell lines were used for the comparison in this in vitro study. The stable knockdown of miR-21 was performed by using lentiviral approach...
January 9, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28065762/characterisation-of-early-changes-in-ovine-cln5-and-cln6-batten-disease-neural-cultures-for-the-rapid-screening-of-therapeutics
#16
Hannah L Best, Nicole J Neverman, Hollie E Wicky, Nadia L Mitchell, Beulah Leitch, Stephanie M Hughes
Batten disease (neuronal ceroid lipofuscinosis) refers to a group of neurodegenerative lysosomal storage diseases predominantly affecting children. There are currently no effective treatments, and the functions of many of the associated gene products are unknown. Here we characterise fetal neural cultures from two genetically distinct sheep forms of Batten disease, with mutations in the lysosomal protein encoding gene CLN5 and endoplasmic reticulum membrane protein encoding gene CLN6, respectively. We found similar reductions in autophagy, acidic organelles and synaptic recycling in both forms compared to unaffected cells...
January 5, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28063225/purification-of-small-molecule-induced-cardiomyocytes-from-human-induced-pluripotent-stem-cells-using-a-reporter-system
#17
Geun Hye Hwang, So Mi Park, Ho Jae Han, Joong Sun Kim, Seung Pil Yun, Jung Min Ryu, Ho Jin Lee, Woochul Chang, Su-Jin Lee, Jeong-Hee Choi, Jin-Sung Choi, Min Young Lee
In order to realize the practical use of human pluripotent stem cell (hPSC)-derived cardiomyocytes for the purpose of clinical use or cardiovascular research, the generation of large numbers of highly purified cardiomyocytes should be achieved. Here, we show an efficient method for cardiac differentiation of human induced pluripotent stem cells (hiPSCs) in chemically defined conditions and purification of hiPSC-derived cardiomyocytes using a reporter system. Regulation of the Wnt/β-catenin signaling pathway is implicated in the induction of the cardiac differentiation of hPSCs...
January 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28063212/regulation-of-chondrocyte-functions-by-transient-receptor-potential-cation-channel-v6-in-osteoarthritis
#18
Tengfei Song, Jun Ma, Lei Guo, Peng Yang, Xuhui Zhou, Tianwen Ye
Transient receptor potential vanilloid (TRPV) channels function to maintain the dynamic balance of calcium signaling and calcium metabolism in bones. The goal of this study was to determine the potential role of TRPV6 in regulation of chondrocytes. The level of TRPV6 expression was analyzed by western blot in articular cartilage derived from the knee joints of osteoarthritis (OA) rat models and OA patients. Bone structure and osteoarthritic changes in the knee joints of TRPV6 knockout mice were examined using micro-computed and histological analysis at the age of 6 and 12 months old...
January 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28062688/piggybac-mediates-efficient-in-vivo-crispr-library-screening-for-tumorigenesis-in-mice
#19
Chunlong Xu, Xiaolan Qi, Xuguang Du, Huiying Zou, Fei Gao, Tao Feng, Hengxing Lu, Shenglan Li, Xiaomeng An, Lijun Zhang, Yuanyuan Wu, Ying Liu, Ning Li, Mario R Capecchi, Sen Wu
CRISPR/Cas9 is becoming an increasingly important tool to functionally annotate genomes. However, because genome-wide CRISPR libraries are mostly constructed in lentiviral vectors, in vivo applications are severely limited as a result of difficulties in delivery. Here, we examined the piggyBac (PB) transposon as an alternative vehicle to deliver a guide RNA (gRNA) library for in vivo screening. Although tumor induction has previously been achieved in mice by targeting cancer genes with the CRISPR/Cas9 system, in vivo genome-scale screening has not been reported...
January 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28061838/cryptotanshinone-activates-ampk-tsc2-axis-leading-to-inhibition-of-mtorc1-signaling-in-cancer-cells
#20
Wenxing Chen, Yanhong Pan, Siliang Wang, Yuping Liu, Guangying Chen, Liang Zhou, Wenting Ni, Aiyun Wang, Yin Lu
BACKGROUND: Cryptotanshinone (CPT), a fat-soluble phenanthraquinone from Salvia miltiorrhiza Bunge, has been demonstrated to inhibit phosphorylation of p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1), a couple of direct downstream effectors of the mammalian target of rapamycin complex 1 (mTORC1), resulting in cancer cell arrested in G0 phase and subsequent inhibition of proliferation. However, its concrete molecular mechanism about how CPT inhibits mTORC1 signaling pathway is unclear...
January 7, 2017: BMC Cancer
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