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https://www.readbyqxmd.com/read/28922619/identification-of-angiogenesis-inhibitors-using-a-co-culture-cell-model-in-a-high-content-and-high-throughput-screening-platform
#1
Shuaizhang Li, Chia-Wen Hsu, Srilatha Sakamuru, Chaozhong Zou, Ruili Huang, Menghang Xia
Angiogenesis is an important hallmark of cancer, contributing to tumor formation and metastasis. In vitro angiogenesis models for analyzing tube formation serve as useful tools to study these processes. However, current in vitro co-culture models using primary cells have limitations in usefulness and consistency. Therefore, in the present study, an in vitro co-culture assay system was optimized in a 1536-well format for high-throughput screening using human telomerase reverse transcriptase (hTERT)-immortalized mesenchymal stem cells and aortic endothelial cells...
September 1, 2017: SLAS Technology
https://www.readbyqxmd.com/read/28900814/sub-fertile-sperm-cells-exemplify-telomere-dysfunction
#2
Tal Biron-Shental, Amir Wiser, Anat Hershko-Klement, Ofer Markovitch, Aliza Amiel, Arie Berkovitch
PURPOSE: The purpose of this study was to evaluate telomere homeostasis in sub-fertile compared to fertile human sperm. METHODS: This observational, comparative study included 16 sub-fertile men who required intracytoplasmic sperm injection and 10 fertile men. At least 100 sperm cells from each participant were assessed. Main outcome measures were telomere length and telomere aggregates. Telomerase RNA component (TERC) copy number and telomere capture were assessed using fluorescence in situ hybridization technique and human telomerase reverse transcriptase (hTERT) using immunohistochemistry...
September 13, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28893481/telomerase-based-anticancer-immunotherapy-and-vaccines-approaches
#3
REVIEW
Chahal Kailashiya, Hanjabam Barun Sharma, Jyotsna Kailashiya
Telomerase is a Reverse Transcriptase that maintains the telomere length. It is absent in most somatic cells but is found in stem cells, germ cells and around 90% of cancers. It plays a crucial role in developing and maintaining cancer cells. Telomerase, a HLA class-I antigen, is able to stimulate cell mediated immune response by inducing cytotoxic T-cells. This property of telomerase is being exploited in targeting cancers by host's own immune responses; stimulated by various Human Telomerase Reverse Transcriptase (hTERT) derived vaccines...
September 8, 2017: Vaccine
https://www.readbyqxmd.com/read/28886883/alternative-splicing-of-telomerase-catalytic-subunit-htert-generated-by-apoptotic-endonuclease-endog-induces-human-cd4-t-cell-death
#4
Dmitry D Zhdanov, Daria A Vasina, Vladimir A Grachev, Elena V Orlova, Valentina S Orlova, Marina V Pokrovskaya, Svetlana S Alexandrova, Nikolai N Sokolov
Telomerase activity is regulated by alternative splicing of its catalytic subunit human Telomerase Reverse Transcriptase (hTERT) mRNA. Induction of a non-active spliced hTERT leads to inhibition of telomerase activity. However, very little is known about the mechanism of hTERT mRNA alternative splicing. The aim of this study was to determine the role of the apoptotic endonuclease EndoG in alternative splicing of hTERT and telomerase activity. A strong correlation was identified between EndoG expression levels and hTERT splice variants in human CD4(+) and CD8(+) T lymphocytes...
September 1, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28883651/the-role-of-transcriptional-factor-p63-in-regulation-of-epithelial-barrier-and-ciliogenesis-of-human-nasal-epithelial-cells
#5
Yakuto Kaneko, Takayuki Kohno, Takuya Kakuki, Ken-Ichi Takano, Noriko Ogasawara, Ryo Miyata, Shin Kikuchi, Takumi Konno, Tsuyoshi Ohkuni, Ryoto Yajima, Akito Kakiuchi, Shin-Ichi Yokota, Tetsuo Himi, Takashi Kojima
Disruption of nasal epithelial tight junctions (TJs) and ciliary dysfunction are found in patients with chronic rhinosinusitis (CRS) and nasal polyps (NPs), along with an increase of p63-positive basal cells and histone deacetylase (HDAC) activity. To investigate these mechanisms, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were transfected with siRNAs of TAp63 and ΔNp63, treated with the NF-kB inhibitor curucumin and inhibitors of HDACs, and infected with respiratory syncytial virus (RSV)...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28881756/mm-bmscs-induce-na%C3%A3-ve-cd4-t-lymphocytes-dysfunction-through-fibroblast-activation-protein-%C3%AE
#6
Xiaofei Wu, Yadan Wang, Jian Xu, Ting Luo, Jun Deng, Yu Hu
BACKGROUND: The tumor microenvironment plays a major role in multiple myelomas (MM). MM-BMSCs (bone marrow mesenchymal stromal cells) can support tumor growth and immune surveillance escape. On the other hand, fibroblast activation protein α, expressed by cancer stroma cells including BMSCs, has been shown to potentiate epithelial cancers growth and immune suppression. RESULTS: MM-BMSC inhibited proliferation of T cells (P = 0.0138), promoted senescence of T cells (P < 0...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878389/gas6-derived-from-cancer-associated-fibroblasts-promotes-migration-of-axl-expressing-lung-cancer-cells-during-chemotherapy
#7
Ryu Kanzaki, Hisamichi Naito, Kazuyoshi Kise, Kazuhiro Takara, Daisuke Eino, Masato Minami, Yasushi Shintani, Soichiro Funaki, Tomohiro Kawamura, Toru Kimura, Meinoshin Okumura, Nobuyuki Takakura
Alterations to the tumor stromal microenvironment induced by chemotherapy could influence the behavior of cancer cells. In the tumor stromal microenvironment, cancer-associated fibroblasts (CAFs) play an important role. Because the receptor tyrosine kinase Axl and its ligand Gas6 could be involved in promoting non-small cell lung cancer (NSCLC), we investigated the role of Gas6 secreted by CAFs during chemotherapy in NSCLC. In a murine model, we found that Gas6 expression by CAFs was upregulated following cisplatin treatment...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28870599/hepatocyte-nuclear-factor-4a-improves-hepatic-differentiation-of-immortalized-adult-human-hepatocytes-and-improves-liver-function-and-survival
#8
Hua-Lian Hang, Xin-Yu Liu, Hai-Tian Wang, Ning Xu, Jian-Min Bian, Jian-Jun Zhang, Lei Xia, Qiang Xia
Immortalized human hepatocytes (IHH) could provide an unlimited supply of hepatocytes, but insufficient differentiation and phenotypic instability restrict their clinical application. This study aimed to determine the role of hepatocyte nuclear factor 4A (HNF4A) in hepatic differentiation of IHH, and whether encapsulation of IHH overexpressing HNF4A could improve liver function and survival in rats with acute liver failure (ALF). Primary human hepatocytes were transduced with lentivirus-mediated catalytic subunit of human telomerase reverse transcriptase (hTERT) to establish IHH...
September 6, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28862599/-induction-of-apoptotic-endonuclease-endog-with-dna-damaging-agents-initiates-alternative-splicing-of-telomerase-catalytic-subunit-htert-and-inhibition-of-telomerase-activity-htert-in-human-cd4-and-cd8-t-lymphocytes
#9
D D Zhdanov, D A Vasina, V S Orlova, E V Orlova, D V Grishin, Yu A Gladilina, M V Pokrovskaya, S S Aleksandrova, N N Sokolov
Activity of telomerase catalytic subunit hTERT (human Telomerase Reverse Transcriptase) can be regulated by alternative splicing of its mRNA. At present time exact mechanism of hTERT splicing is not fully understood. Apoptotic endonuclease EndoG is known to participate this process. EndoG expression is induced by DNA damages. The aim of this work was to investigate the ability of DNA-damaging agents with different mechanism of action to induce EndoG expression and inhibit telomerase activity due to the activation of hTERT alternative splicing in normal activated human CD4+ and CD8+ T-lymphocytes...
July 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28843010/telomerase-activity-telomere-length-and-htert-dna-methylation-in-peripheral-blood-mononuclear-cells-from-monozygotic-twins-with-discordant-smoking-habits
#10
Francesca Marcon, Ester Siniscalchi, Cristina Andreoli, Alessandra Allione, Giovanni Fiorito, Emanuela Medda, Simonetta Guarrera, Giuseppe Matullo, Riccardo Crebelli
Increased telomerase expression has been implicated in the pathogenesis of lung cancer and, since the primary cause of lung cancer is smoking, an association between telomerase reactivation and tobacco smoke has been proposed. In this work an investigation has been performed to assess the relationship between tobacco smoke exposure and telomerase activity (TA) in peripheral blood mononuclear cells of healthy smokers. The methylation status of the catalytic subunit of telomerase hTERT was concurrently investigated to assess the possible association between epigenetic modifications of hTERT and TA...
August 26, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28842217/cytoskeleton-related-regulation-of-primary-cilia-shortening-mediated-by-melanin-concentrating-hormone-receptor-1
#11
Sakura Tomoshige, Yuki Kobayashi, Kosuke Hosoba, Akie Hamamoto, Tatsuo Miyamoto, Yumiko Saito
Primary cilia are specialized microtubule-based organelles. Their importance is highlighted by the gamut of ciliary diseases associated with various syndromes including diabetes and obesity. Primary cilia serve as signaling hubs through selective interactions with ion channels and conventional G-protein-coupled receptors (GPCRs). Melanin-concentrating hormone (MCH) receptor 1 (MCHR1), a key regulator of feeding, is selectively expressed in neuronal primary cilia in distinct regions of the mouse brain. We previously found that MCH acts on ciliary MCHR1 and induces cilia shortening through a Gi/o-dependent Akt pathway with no cell cycle progression...
August 23, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28839469/rbfox3-promotes-tumor-growth-and-progression-via-htert-signaling-and-predicts-a-poor-prognosis-in-hepatocellular-carcinoma
#12
Tianze Liu, Wenbin Li, Wenjing Lu, Miao Chen, Meihua Luo, Changlin Zhang, Yixin Li, Ge Qin, Dingbo Shi, Binyi Xiao, Huijuan Qiu, Wendan Yu, Lan Kang, Tiebang Kang, Wenlin Huang, Xinfa Yu, Xiaojun Wu, Wuguo Deng
Activation of the telomere maintenance mechanism is a key hallmark of cancer. Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase, which is highly expressed in more than 80% of tumors, including hepatocellular carcinoma (HCC). However, the exact mechanisms by which hTERT is up-regulated in HCCs and promotes tumor growth and progression is not fully understood. The aim of this study was to discover the novel molecular targets that modulate hTERT signaling and HCC growth. In this study, we pulled down and identified RBFOX3 (RNA binding protein fox-1 homolog 3) as a novel hTERT promoter-binding protein in HCC cells using biotin-streptavidin-agarose pull-down and proteomics approach, and validated it as a regulatory factor for hTERT signaling and tumor growth in HCCs...
2017: Theranostics
https://www.readbyqxmd.com/read/28837806/rhodospirillum-rubruml-asparaginase-targets-tumor-growth-by-a-dual-mechanism-involving-telomerase-inhibition
#13
Dmitry D Zhdanov, Vadim S Pokrovsky, Marina V Pokrovskaya, Svetlana S Alexandrova, Mikhail A Eldarov, Dmitry V Grishin, Marsel M Basharov, Yulia A Gladilina, Olga V Podobed, Nikolai N Sokolov
Rhodospirillum rubruml-asparaginase mutant RrA E149R, V150P, F151T (RrA) was previously identified to down-regulate telomerase activity along with catalyzing the hydrolysis of l-asparagine. The aim of this study was to define the effect of prolonged RrA exposure on telomerase activity, maintenance of telomeres and proliferation of cancer cells in vitro and in vivo. RrA could inhibit telomerase activity in SCOV-3, SkBr-3 and A549 human cancer cell lines due to its ability to down-regulate the expression of telomerase catalytic subunit hTERT...
October 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28837145/discovery-of-4-bromophenyl-3-hydroxy-4-methoxyphenyl-methanone-through-upregulating-htert-induces-cell-apoptosis-and-ers
#14
Xiu Cheng, Jing Bo Shi, Hao Liu, Liu Zeng Chen, Yang Wang, Wen Jian Tang, Xin Hua Liu
Dominant-negative mutants of telomerase hTERT were demonstrated to have selective effects in tumor cells. However, no any effective and highly selective hTERT inhibitor has been developed so far. We focused on developing new hTERT modulators and synthesized a small molecular compound, named (4-bromophenyl)(3-hydroxy-4-methoxyphenyl)methanone. Our in vitro studies found that title compound showed high inhibitory activity against telomerase, had high antiproliferative capacity on SMMC-7721 cells with IC50 value 88 nm, and had no obvious toxic effect on human normal hepatocyte cells with IC50 value 10 μM...
August 24, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28834761/novel-pan-pi3k-inhibitor-induced-apoptosis-in-apl-cells-correlates-with-suppression-of-telomerase-an-emerging-mechanism-of-action-of-bkm120
#15
Davood Bashash, Mahda Delshad, Ava Safaroghli-Azar, Majid Safa, Majid Momeny, Seyed H Ghaffari
The intertwining between cancer pathogenesis and perturbation of multitude signaling pathways ushered the cancer therapeutic approaches into an unbounded route of targeted therapies. For the nonce and among the plethora of promising inhibitors, intense interest has focused on small molecules targeting different component of PI3K axis. Intrigued by the constant activation of PI3K in leukemia, this study aimed to investigate the effects of BKM120, as the excelled member of pan PI3K inhibitors, in a panel of hematologic malignant cell lines...
August 20, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28833505/aberrant-levels-of-suv39h1-and-suv39h2-methyltransferase-are-associated-with-genomic-instability-in-chronic-lymphocytic-leukemia
#16
Juliana Carvalho Alves-Silva, Doralina do Amaral Rabello, Martha Oliveira Bravo, Antônio Roberto Lucena-Araujo, Diego Madureira de Oliveira, Fábio Morato de Oliveira, Eduardo Magalhaes Rego, Fábio Pittella-Silva, Felipe Saldanha-Araujo
Chromosomal alterations are commonly detected in patients with chronic lymphocytic leukemia (CLL) and impact disease pathogenesis, prognosis, and progression. Telomerase expression (hTERT), its activity and the telomere length are other important predictors of survival and multiple outcomes in CLL. SUV39H and SUV420H enzymes are histone methyltransferases (HMTases) involved in several cellular processes, including regulation of telomere length, heterochromatin organization, and genome stability. Here, we investigated whether SUV39H1, SUV39H2, SUV420H1, SUV420H2, and hTERT are associated with genomic instability of CLL...
August 19, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28833137/tert-ezh2-network-regulates-lipid-metabolism-and-dna-damage-responses-in-glioblastoma
#17
Fahim Ahmad, Shruti Patrick, Touseef Sheikh, Vikas Sharma, Pankaj Pathak, Prit Benny Malgulwar, Anupam Kumar, Shanker Datt Joshi, Chitra Sarkar, Ellora Sen
Elevated expression of enhancer of zeste homolog 2 (EZH2) - a histone H3K27 methyltransferase was observed in gliomas harboring telomerase reverse transcriptase (TERT) promoter mutations. Given the known involvement of TERT and EZH2 in glioma progression, the co-relation between the two and subsequently its involvement in metabolic programming was investigated. Inhibition of hTERT either pharmacologically or through genetic manipulation not only decreased EZH2 expression, but also (i) abrogated FASN levels, (ii) decreased de novo fatty acid accumulation, and (iii) increased Ataxia-telangiectasia mutated (ATM) phosphorylation levels...
August 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28832026/tgf-%C3%AE-1-alters-esophageal-epithelial-barrier-function-by-attenuation-of-claudin-7-in-eosinophilic-esophagitis
#18
N Nguyen, S D Fernando, K A Biette, J A Hammer, K E Capocelli, D A Kitzenberg, L E Glover, S P Colgan, G T Furuta, J C Masterson
Barrier dysfunction has been implicated in the pathophysiology of eosinophilic esophagitis (EoE). Transforming growth factor-β1 (TGF-β1), a potent pleiotropic molecule, is increased in EoE; however, no study has evaluated its influence on esophageal epithelial barrier. We hypothesized that TGF-β1 regulates barrier dysfunction in EoE. We aimed to determine the role of TGF-β1 in the epithelial barrier in models of EoE. To examine the impact of TGF-β1 on esophageal barrier, immortalized human esophageal epithelial (EPC2-hTERT) cells were exposed to TGF-β1 during the three-dimensional air-liquid interface (3D-ALI) model in vitro...
August 23, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28819549/metastatic-state-of-parent-cells-influences-the-uptake-and-functionality-of-prostate-cancer-cell-derived-extracellular-vesicles
#19
Elisa Lázaro-Ibáñez, Maarit Neuvonen, Maarit Takatalo, Uma Thanigai Arasu, Cristian Capasso, Vincenzo Cerullo, Johng S Rhim, Kirsi Rilla, Marjo Yliperttula, Pia R-M Siljander
Extracellular vesicles (EVs), including microvesicles and exosomes, mediate intercellular signalling which has a profound role in cancer progression and in the development of metastasis. Internalisation of EVs can prompt functional changes in the recipient cells, the nature of which depends on the molecular composition and the cargo of the EVs. We hypothesised that the metastatic stage of cancerous parent cells would determine the uptake efficacy and the subsequent functional effects of the respective cancer cell-derived EVs...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28813465/long-term-persistent-infection-of-hpv-16-e6-up-regulate-sp1-and-htert-by-inhibiting-lkb1-in-lung-cancer-cells
#20
Jing-Hua Yang, Xiao-Yan Li, Xin Wang, Wei-Jian Hou, Xue-Shan Qiu, En-Hua Wang, Guang-Ping Wu
HPV 16 E6 upregulates hTERT expression in lung cancer cells. However, the underlying molecular mechanism is unclear. In this paper, E6, LKB1, SP1, and hTERT mRNA expression levels were detected in brushing cells of patients with lung cancer (n = 106) and with benign lung disease (n = 68) by qRT-PCR. The mRNA expression levels of E6, SP1, and hTERT were significantly increased in the malignant group compared with the benign group (P < 0.01). Conversely, the mRNA expression level of LKB1 was significantly decreased in the malignant group (P < 0...
2017: PloS One
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