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https://www.readbyqxmd.com/read/28449469/cd90-positive-cells-exhibit-aggressive-radioresistance-in-esophageal-squamous-cell-carcinoma
#1
Yuandong Wang, Chi Zhang, Hongcheng Zhu, Junwei Tang, Shu Zhang, Jinhua Luo, Xinchen Sun
BACKGROUND: Cancer stem cells (CSCs) are widely abundant and considered to be an important factor in therapy resistance. They are also promising potential targets for conquering tumors. We explored the effects of radiation on stem cell-like tumor cells via the candidate marker CD90 to provide new ideas for the comprehensive treatment of esophageal squamous cell carcinoma (ESCC). METHODS: We constructed CD90 overexpression ESCC cells by lentiviral transfection and observed differences of toxicity, proliferation, clone number, apoptosis, migration, invasion, and in vivo tumor formation after irradiation...
March 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28449065/a-homozygous-missense-mutation-in-eral1-encoding-a-mitochondrial-rrna-chaperone-causes-perrault-syndrome
#2
Iliana A Chatzispyrou, Marielle Alders, Sergio Guerrero-Castillo, Ruben Zapata Perez, Martin A Haagmans, Laurent Mouchiroud, Janet Koster, Rob Ofman, Frank Baas, Hans R Waterham, Johannes N Spelbrink, Johan Auwerx, Marcel M Mannens, Riekelt H Houtkooper, Astrid S Plomp
Perrault syndrome (PS) is a rare recessive disorder characterized by ovarian dysgenesis and sensorineural deafness. It is clinically and genetically heterogeneous, and previously mutations have been described in different genes, mostly related to mitochondrial proteostasis. We diagnosed three unrelated females with PS and set out to identify the underlying genetic cause using exome sequencing. We excluded mutations in the known PS genes, but identified a single homozygous mutation in the ERAL1 gene (c.707A>T; p...
April 25, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28448437/sulfiredoxin-may-promote-cervical-cancer-metastasis-via-wnt-%C3%AE-catenin-signaling-pathway
#3
Kangyun Lan, Yuni Zhao, Yue Fan, Binbin Ma, Shanshan Yang, Qin Liu, Hua Linghu, Hui Wang
The abnormal elevation of sulfiredoxin (Srx/SRXN1)-an antioxidant enzyme whose main function is to protect against oxidative stress-has been shown to be closely correlated with the progression of several types of cancer, including human cervical cancer. However, the molecular mechanism by which Srx promotes tumor progression, especially cancer metastasis in cervical cancer, has not been elucidated. Here, we show that Srx expression gradually increases during the progression of human cervical cancer and its expression level is closely correlated with lymph node metastasis...
April 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28447889/bone-marrow-as-a-hematopoietic-stem-cell-source-for-gene-therapy-in-sickle-cell-disease-scd-evidence-from-rhesus-and-scd-patients
#4
Naoya Uchida, Atsushi Fujita, Matthew M Hsieh, Aylin Bonifacino, Allen E Krouse, Mark E Metzger, Robert E Donahue, John F Tisdale
Steady state bone marrow (BM) is the preferred hematopoietic stem cell (HSC) source for gene therapy in sickle cell disease (SCD) due to the recognized risk of vaso-occlusive crisis during granulocyte colony-stimulating factor mobilization. We previously established clinically relevant HSC gene transfer in the rhesus model following transplantation of mobilized peripheral blood (PB) CD34+ cells transduced with lentiviral vectors. In this study, we examined steady state bone marrow (BM) in the rhesus competitive repopulation model and demonstrate similar gene marking in vitro and in vivo, as compared to mobilized PB CD34+ cells...
April 27, 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28447728/high-expression-of-ubiquitin-specific-peptidase-39-is-associated-with-the-development-of-vascular-remodeling
#5
Shuai He, Wei Zhong, Li Yin, Yifei Wang, Zhibing Qiu, Gang Song
Vascular remodeling is the primary cause underlying the failure of angioplasty surgeries, including vascular stenting, transplant vasculopathy and vein grafts. Multiple restenosis‑associated proteins and genes have been identified to account for this. In the present study, the functions of ubiquitin‑specific peptidase 39 (USP39) were investigated in the context of two vascular remodeling models (a mouse common carotid artery ligation and a pig bilateral saphenous vein‑carotid artery interposition graft)...
March 8, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447717/knockdown-of-zfpl1-results-in-increased-autophagy-and-autophagy%C3%A2-related-cell-death-in-nci%C3%A2-n87-and-bgc%C3%A2-823-human-gastric-carcinoma-cell-lines
#6
Yong-Zheng Xie, Wan-Li Ma, Ji-Ming Meng, Xue-Qun Ren
Macroautophagy, which will hereafter be referred to as autophagy, is an evolutionarily conserved process, during which cells recycle and remove damaged organelles and proteins in response to cellular stress. However, the mechanisms underlying the regulation of autophagy remain to be fully elucidated. The present study demonstrated that knockdown of zinc finger protein like 1 (ZFPL1) induces autophagy and increases autophagic cell death in NCI‑N87 and BGC‑823 human gastric carcinoma cell lines. To examine the role of ZFPL1 in gastric carcinoma cells, ZFPL1 expression was downregulated by lentiviral infection...
March 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447574/optimized-longitudinal-monitoring-of-stem-cell-grafts-in-mouse-brain-using-a-novel-bioluminescent-near-infrared-fluorescent-fusion-reporter
#7
Laura Mezzanotte, Juvita Delancy Iljas, Ivo Que, Alan Chan, Eric Kaijzel, Rob Hoeben, Clemens Löwik
<p>Biodistribution and fate of transplanted stem cells via longitudinal monitoring has been successfully achievedin the last decade using optical imaging. However, sensitive longitudinal imaging of transplanted stem cells in deep tissue like the brain remains challenging not only due to low light penetration but because of other factors such as low or inferior expression levels of optical reporters in stem cells and stem cell death after transplantation. Here we describe an optimized imaging protocol for sensitive long term monitoring of human bone marrow derived mesenchymal stem cells (hMSCs) expressing a novel bioluminescent/near infrared fluorescent (NIRF) fusion reporter transplanted in mouse brain cortex...
April 26, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28447263/design-of-a-lentiviral-vector-for-the-inducible-expression-of-myc-a-new-strategy-for-construction-approach
#8
Onur Tokgun, Francesco Paolo Fiorentino, Pervin Elvan Tokgun, Jun Yokota, Hakan Akca
Lentiviral vectors are powerful tools for gene expression studies. Here we report the construction of pTIJ, a vector for inducible gene expression. pTIJ was generated from pTRIPZ backbone, which is designed for the inducible expression of shRNA sequences, by the introducing of a multiple cloning site upstream of the Tet promoter and the removal of miR30 flanking sequences. To evaluate pTIJ as a tool for the inducible expression of genes of interest, we introduced MYC cDNA into pTIJ and infected two small cell lung cancer cell lines, H209 and H345...
April 26, 2017: Molecular Biotechnology
https://www.readbyqxmd.com/read/28446712/aspirin-inhibits-the-shh-gli1-signaling-pathway-and-sensitizes-malignant-glioma-cells-to-temozolomide-therapy
#9
Jianguang Ming, Bo Sun, Ziwei Li, Lin Lin, Xiangqi Meng, Bo Han, Ruijia Wang, Pengfei Wu, Jianlong Li, Jinquan Cai, Chuanlu Jiang
Aberrant activation of sonic hedgehog (SHH)/glioma-associated oncogene homolog 1 (GLI1) pathway plays an important role in the tumorigenicity of malignant glioma cells and resistance to temozolomide (TMZ). Here we investigated the aspirin's antineoplastic molecular route by targeting SHH/GLI1 pathway and examined the feasibility of aspirin combined with TMZ therapy. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) revealed that the activity of the SHH/GLI1 pathway was strongly inhibited by aspirin...
April 17, 2017: Aging
https://www.readbyqxmd.com/read/28446707/deterministic-versus-stochastic-model-of-reprogramming-new-evidence-from-cellular-barcoding-technique
#10
Anastasia M Yunusova, Veniamin S Fishman, Gennady V Vasiliev, Nariman R Battulin
Factor-mediated reprogramming of somatic cells towards pluripotency is a low-efficiency process during which only small subsets of cells are successfully reprogrammed. Previous analyses of the determinants of the reprogramming potential are based on average measurements across a large population of cells or on monitoring a relatively small number of single cells with live imaging. Here, we applied lentiviral genetic barcoding, a powerful tool enabling the identification of familiar relationships in thousands of cells...
April 2017: Open Biology
https://www.readbyqxmd.com/read/28445693/high-content-analysis-screening-for-cell-cycle-regulators-using-arrayed-synthetic-crrna-libraries
#11
Žaklina Strezoska, Matthew R Perkett, Eldon T Chou, Elena Maksimova, Emily M Anderson, Shawn McClelland, Melissa L Kelley, Annaleen Vermeulen, Anja van Brabant Smith
The CRISPR-Cas9 system has been utilized for large-scale, loss-of-function screens mainly using lentiviral pooled formats and cell-survival phenotypic assays. Screening in an arrayed format expands the types of phenotypic readouts that can be used to now include high-content, morphology-based assays, and with the recent availability of synthetic crRNA libraries, new studies are emerging. Here, we use a cell cycle reporter cell line to perform an arrayed, synthetic crRNA:tracrRNA screen targeting 169 genes (> 600 crRNAs) and used high content analysis (HCA) to identify genes that regulate the cell cycle...
April 23, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28445362/effect-of-human-fat-graft-on-breast-cancer-metastasis-in-a-murine-model
#12
Roberto Moltó-García, Virina González-Alonso, María Eloísa Villaverde-Doménech, Edurne Novella-Maestre
BACKGROUND: Isolated adipose stem cells have been reported to encourage migration and early metastasis of breast cancer. Mimicking a surgical situation, the authors developed a human breast cancer model to evaluate in vivo whether human adipose tissue promotes tumor growth and invasion. METHODS: Human adipose tissue was obtained from four patients. The MDA-MB-468 cell line was cultured with a lentiviral vector encoding a puromycin resistance gene and mCherry fluorescent protein...
May 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28442011/-ck2%C3%AE-regulates-the-metastases-and-migration-of-lung-adenocarcinoma-%C3%A2-a549-cell-line-through-pi3k-akt-gsk-3%C3%AE-signal-pathway
#13
Aibing Wu, Mingchun Li, Zongjiong Mai, Shujun Li, Zhixiong Yang
BACKGROUND: Lung cancer is the leading cancer-related death worldwide. Patients with lung cancer mainly died of tumor metastasis and invasion. Protein kinase CK2 is an ubiquitous serine/threonine protein kinase and is frequently upregulated in various human tumors. This study aims to explore the effect and molecular mechanism of the invasion and migration of lung adenocarcinoma A549 cells after knock-down of CK2α expression. METHODS: The pSilencerTM 4.1-siCK2α-eGFP of lentiviral-mediated shRNA was constructed...
April 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28442010/-effect-of-nm23-h1-nuclear-localization-on-proliferation-of-%C3%A2-human-lung-adenocarcinoma-cell-line-a549
#14
Ya Sheng, Yanli Xiong, Mingfang Xu, Xunjie Kuang, Dong Wang, Xueqin Yang
BACKGROUND: Recent studies have indicated that Nm23-H1 is found in the nucleus, but previous studies have been based on the overexpression or suppression of Nm23-H1 in the cytoplasm. Due to the lacking nuclear localization signal of Nm23-H1, these results cannot reflect or repeat cells in which Nm23-H1 mainly positioned in nuclei and whether they cause clinical biological effects. Therefore, to explore the effects of transposing Nm23-H1 from the cytoplasm to the nucleus during lung cancer cell proliferation, a vector with a nuclear localization signal of Nm23-H1 was constructed and A549 cells were transfected...
April 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28439947/sirt1-hsf1-hsps-pathway-is-essential-for-exenatide-alleviated-lipid-induced-hepatic-endoplasmic-reticulum-stress
#15
Xiaobin Zheng, Fen Xu, Hua Liang, Huanyi Cao, Mengyin Cai, Wen Xu, Jianping Weng
Recent studies have indicated lipid-induced endoplasmic reticulum (ER) stress to be a major contributor to the progression of hepatic steatosis. Exenatide (Exendin-4), a glucagon-like peptide-1 receptor agonist, is known to improve hepatic steatosis with accumulating evidence. In this study, we investigated whether exenatide could alleviate lipid-induced hepatic ER stress through mammal sirtuin1 (SIRT1) and illustrated the detailed mechanisms. Male C57BL/6J mice challenged with a high-fat diet (HFD) were then treated with exenatide or normal saline by intraperitoneal injection for 4 weeks...
April 25, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28438967/immune-induced-fever-is-dependent-on-local-but-not-generalized-prostaglandin-e2-synthesis-in-the-brain
#16
Anna Eskilsson, Takashi Matsuwaki, Kiseko Shionoya, Elahe Mirrasekhian, Joanna Zajdel, Markus Schwaninger, David Engblom, Anders Blomqvist
Fever occurs upon binding of prostaglandin E2 (PGE2) to EP3 receptors in the median preoptic nucleus of the hypothalamus, but the origin of the pyrogenic PGE2 has not been clearly determined. Here, using mice of both sexes, we examined the role of local vs generalized PGE2 production in the brain for the febrile response. In wild-type mice and in mice with genetic deletion of the prostaglandin synthesizing enzyme cyclooxygenase-2 in the brain endothelium, generated with an inducible CreER(T2) under the Slco1c1 promoter, PGE2 levels in the cerebrospinal fluid were only weakly related to the magnitude of the febrile response, whereas the PGE2 synthesizing capacity in the hypothalamus, as reflected in the levels of cyclooxygenase-2 mRNA, showed strong correlation with the immune-induced fever...
April 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28437526/prominin-1-is-a-novel-regulator-of-autophagy-in-the-human-retinal-pigment-epithelium
#17
Sujoy Bhattacharya, Jinggang Yin, Christina S Winborn, Qiuhua Zhang, Junming Yue, Edward Chaum
Purpose: Prominin-1 (Prom1) is a transmembrane glycoprotein, which is expressed in stem cell lineages, and has recently been implicated in cancer stem cell survival. Mutations in the Prom1 gene have been shown to disrupt photoreceptor disk morphogenesis and cause an autosomal dominant form of Stargardt-like macular dystrophy (STGD4). Despite the apparent structural role of Prom1 in photoreceptors, its role in other cells of the retina is unknown. The purpose of this study is to investigate the role of Prom1 in the highly metabolically active cells of the retinal pigment epithelium (RPE)...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28435021/the-mtorc2-pkc-pathway-sustains-compensatory-insulin-secretion-of-pancreatic-%C3%AE-cells-in-response-to-metabolic-stress
#18
Yun Xie, Canqi Cui, Aifang Nie, Yan Wang, Qicheng Ni, Yun Liu, Qinglei Yin, Hongli Zhang, Yong Li, Qidi Wang, Yanyun Gu, Guang Ning
BACKGROUND: Compensation of the pancreatic β cell functional mass in response to metabolic stress is key to the pathogenesis of Type 2 Diabetes. The mTORC2 pathway governs fuel metabolism and β cell functional mass. It is unknown whether mTORC2 is required for regulating metabolic stress-induced β cell compensation. METHODS: We challenged four-week-old β-cell-specific Rictor (a key component of mTORC2)-knockout mice with a high fat diet (HFD) for 4weeks and measured metabolic and pancreatic morphological parameters...
April 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28434868/hif-1%C3%AE-dependent-wound-healing-angiogenesis-in%C3%A2-vivo-can-be-controlled-by-site-specific-lentiviral-magnetic-targeting-of-shp-2
#19
Yvonn Heun, Kristin Pogoda, Martina Anton, Joachim Pircher, Alexander Pfeifer, Markus Woernle, Andrea Ribeiro, Petra Kameritsch, Olga Mykhaylyk, Christian Plank, Florian Kroetz, Ulrich Pohl, Hanna Mannell
Hypoxia promotes vascularization by stabilization and activation of the hypoxia inducible factor 1α (HIF-1α), which constitutes a target for angiogenic gene therapy. However, gene therapy is hampered by low gene delivery efficiency and non-specific side effects. Here, we developed a gene transfer technique based on magnetic targeting of magnetic nanoparticle-lentivirus (MNP-LV) complexes allowing site-directed gene delivery to individual wounds in the dorsal skin of mice. Using this technique, we were able to control HIF-1α dependent wound healing angiogenesis in vivo via site-specific modulation of the tyrosine phosphatase activity of SHP-2...
April 20, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28434866/lentiviral-vectors-with-cellular-promoters-correct-anemia-and-lethal-bone-marrow-failure-in-a-mouse-model-for-diamond-blackfan-anemia
#20
Shubhranshu Debnath, Pekka Jaako, Kavitha Siva, Michael Rothe, Jun Chen, Maria Dahl, H Bobby Gaspar, Johan Flygare, Axel Schambach, Stefan Karlsson
Diamond-Blackfan anemia is a congenital erythroid hypoplasia and is associated with physical malformations and a predisposition to cancer. Twenty-five percent of patients with Diamond-Blackfan anemia have mutations in a gene encoding ribosomal protein S19 (RPS19). Through overexpression of RPS19 using a lentiviral vector with the spleen focus-forming virus promoter, we demonstrated that the Diamond-Blackfan anemia phenotype can be successfully treated in Rps19-deficient mice. In our present study, we assessed the efficacy of a clinically relevant promoter, the human elongation factor 1α short promoter, with or without the locus control region of the β-globin gene for treatment of RPS19-deficient Diamond-Blackfan anemia...
April 20, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
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