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https://www.readbyqxmd.com/read/29047227/telomerase-reverse-transcriptase-tert-promoter-mutations-are-rare-in-urachal-cancer
#1
Sebastian Thiem, Thomas Herold, Ulrich Krafft, Felix Bremmer, Yuri Tolkach, Attila M Szász, Joerg Kriegsmann, Nadine T Gaisa, Christian Niedworok, Tibor Szarvas, Henning Reis
High rates of telomerase reverse transcriptase (TERT) promoter mutations have recently been described in urothelial carcinoma (UC). Unlike UC in the bladder, adenocarcinomas account for the majority of urachal cancer (UrC) cases. As data in UrC is unclear, we analyzed TERT promoter mutations in a large cohort of UrC for its differential diagnostic, clinicopathological and prognostic significance. UrC cases from six academic centers were analyzed for c.-146C>T (C250T) and c.-124C>T (C228T) TERT promoter mutations by PCR and Sanger sequencing...
October 19, 2017: Pathology International
https://www.readbyqxmd.com/read/29045785/programming-enzyme-initiated-autonomous-dnazyme-nanodevices-in-living-cells
#2
Feng Chen, Min Bai, Ke Cao, Yue Zhao, Xiaowen Cao, Jing Wei, Na Wu, Jiang Li, Lihua Wang, Chunhai Fan, Yongxi Zhao
Molecular nanodevices are computational assemblers that switch defined states upon external stimulation. However, interfacing artificial nanodevices with natural molecular machineries in living cells remains a great challenge. Here we delineate a generic method for programming assembly of enzyme-initiated DNAzyme nanodevices (DzNanos). Two programs including split assembly of two partzymes and toehold-exchange displacement assembly of one intact DNAzyme initiated by telomerase are computed. The intact one obtains higher assembly yield and catalytic performance ascribed to proper conformation folding and active misplaced assembly...
October 18, 2017: ACS Nano
https://www.readbyqxmd.com/read/29045464/tip60-represses-telomerase-expression-by-inhibiting-sp1-binding-to-the-tert-promoter
#3
Deepa Rajagopalan, Amit Kumar Pandey, Magdalene Claire Xiuzhen, Kwok Kin Lee, Shainan Hora, Yanzhou Zhang, Boon Haow Chua, Hui Si Kwok, Shreshtha Sailesh Bhatia, Lih Wen Deng, Daniel G Tenen, Dennis Kappei, Sudhakar Jha
HIV1-TAT interacting protein (TIP60) is a haploinsufficient tumor suppressor. However, the potential mechanisms endowing its tumor suppressor ability remain incompletely understood. It plays a vital role in virus-induced cancers where TIP60 down-regulates the expression of human papillomavirus (HPV) oncoprotein E6 which in turn destabilizes TIP60. This intrigued us to identify the role of TIP60, in the context of a viral infection, where it is targeted by oncoproteins. Through an array of molecular biology techniques such as Chromatin immunoprecipitation, expression analysis and mass spectrometry, we establish the hitherto unknown role of TIP60 in repressing the expression of the catalytic subunit of the human telomerase complex, TERT, a key driver for immortalization...
October 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29044824/replication-protein-a-1-has-a-preference-for-the-telomeric-g-rich-sequence-in-trypanosoma-cruzi
#4
Raphael Souza Pavani, Marcela O Vitarelli, Carlos A H Fernandes, Fabio F Mattioli, Mariana Morone, Milene C Menezes, Marcos R M Fontes, Maria Isabel N Cano, Maria Carolina Elias
Replication protein A (RPA), the major eukaryotic single-stranded binding protein, is a heterotrimeric complex formed by RPA-1, RPA-2 and RPA-3. RPA is a fundamental player in replication, repair, recombination and checkpoint signaling. In addition, increasing evidences have been adding functions to RPA in telomere maintenance, such as interaction with telomerase to facilitate its activity and also involvement in telomere capping in some conditions. Trypanosoma cruzi, the etiological agent of Chagas disease is a protozoa parasite that appears early in the evolution of eukaryotes...
October 16, 2017: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/29043869/identifying-the-biomarker-potential-of-telomerase-activity-and-shelterin-complex-molecule-telomeric-repeat-binding-factor-2-terf2-in-multiple-myeloma
#5
Raman Kumar, Rehan Khan, Nidhi Gupta, Tulika Seth, Atul Sharma, Mani Kalaivani, Alpana Sharma
Telomere length (TL) is maintained by telomere capping protein complex called shelterin complex. We studied the possible involvement and biomarker potential of shelterin complex molecules in naive multiple myeloma (MM) patients and controls. TL, relative telomerase activity (RTA), real-time PCR and Western blotting were performed in bonemarrow sample of 70 study subjects (patients = 50; controls = 20). Significantly lowered mean TL, increased RTA and higher mRNA expression of shelterin molecules were observed in patients, while PIN2/TERF1 interacting telomerase inhibitor 1 (PINX1) showed lower mRNA expression...
October 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29043638/telomerase-rna-imaging-in-budding-yeast-and-human-cells-by-fluorescent-in-situ-hybridization
#6
David Guérit, Maxime Lalonde, Pascal Chartrand
Telomerase, the enzyme that elongates telomeres in most eukaryotes, is a ribonucleoprotein complex composed of a reverse transcriptase catalytic subunit (TERT in human, Est2 in the budding yeast S. cerevisiae), regulatory factors and a noncoding RNA called hTERC (in human) or TLC1 (in budding yeast). Telomerase trafficking is a major process in the biogenesis and regulation of telomerase action at telomeres. Due to its higher signal-to-noise ratio, imaging of the telomerase RNA moiety is frequently used to determine telomerase intracellular localization...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29043636/analysis-of-de-novo-telomere-addition-by-southern-blot
#7
Diego Bonetti, Maria Pia Longhese
Telomere length is maintained in most eukaryotes by the action of a specialized enzyme, the telomerase. However, the complexity of mechanisms regulating telomeric DNA length as well as the heterogeneity in length of each telomere in a population of cells has made it very difficult to understand how telomerase is regulated in vivo. Here, we describe a method developed in Saccharomyces cerevisiae to monitor the addition of telomeric sequences to a single newly generated telomere in vivo. The primary strain consists of a HO endonuclease cleavage site that is placed directly adjacent to an 81-base-pair stretch of telomeric DNA inserted into the ADH4 locus of chromosome VII...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29043077/recent-advances-in-understanding-werner-syndrome
#8
REVIEW
Raghavendra A Shamanna, Deborah L Croteau, Jong-Hyuk Lee, Vilhelm A Bohr
Aging, the universal phenomenon, affects human health and is the primary risk factor for major disease pathologies. Progeroid diseases, which mimic aging at an accelerated rate, have provided cues in understanding the hallmarks of aging. Mutations in DNA repair genes as well as in telomerase subunits are known to cause progeroid syndromes. Werner syndrome (WS), which is characterized by accelerated aging, is an autosomal-recessive genetic disorder. Hallmarks that define the aging process include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication...
2017: F1000Research
https://www.readbyqxmd.com/read/29041955/pluripotent-nontumorigenic-multilineage-differentiating-stress-enduring-cells-muse-cells-a-seven-year-retrospective
#9
REVIEW
Samantha C Fisch, María L Gimeno, Julia D Phan, Ariel A Simerman, Daniel A Dumesic, Marcelo J Perone, Gregorio D Chazenbalk
Multilineage differentiating stress enduring (Muse) cells, discovered in the spring of 2010 at Tohoku University in Sendai, Japan, were quickly recognized by scientists as a possible source of pluripotent cells naturally present within mesenchymal tissues. Muse cells normally exist in a quiescent state, singularly activated by severe cellular stress in vitro and in vivo. Muse cells have the capacity for self-renewal while maintaining pluripotent cell characteristics indicated by the expression of pluripotent stem cell markers...
October 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29041825/cathepsin-l-deficiency-results-in-reactive-oxygen-species-ros-accumulation-and-vascular-cells-activation
#10
Guo-Xiang Fu, Alex F Chen, Qiu-Mei Xu, Bei-Bei Han, Gao-Zhong Huang, Yuan Zhong
Recent evidence suggests a link between cathepsin L (CTSL) and vascular diseases. However, its contribution to reactive oxygen species (ROS) homeostasis in the vasculature remains unknown. p66shc is a redox enzyme implicated in mitochondrial ROS generation and translation of oxidative signals. In this study, we explored the relationship between CTSL and oxidative damage in vasculature and whether the oxidative damage is mediated by p66shc.Carotid arteries from aged mice (24 months old) showed a reduction in CTSL expression compared with young wild-type mice (4 months old)...
October 17, 2017: Free Radical Research
https://www.readbyqxmd.com/read/29040642/dynamic-dna-binding-junction-recognition-and-g4-melting-activity-underlie-the-telomeric-and-genome-wide-roles-of-human-cst
#11
Anukana Bhattacharjee, Yongyao Wang, Jiajie Diao, Carolyn M Price
Human CST (CTC1-STN1-TEN1) is a ssDNA-binding complex that helps resolve replication problems both at telomeres and genome-wide. CST resembles Replication Protein A (RPA) in that the two complexes harbor comparable arrays of OB-folds and have structurally similar small subunits. However, the overall architecture and functions of CST and RPA are distinct. Currently, the mechanism underlying CST action at diverse replication issues remains unclear. To clarify CST mechanism, we examined the capacity of CST to bind and resolve DNA structures found at sites of CST activity...
October 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29029466/a-comparative-study-of-anti-aging-properties-and-mechanism-resveratrol-and-caloric-restriction
#12
Juan Li, Chun-Xia Zhang, Yi-Mei Liu, Ke-Li Chen, Gang Chen
Resveratrol and caloric restriction (CR) are the powerful therapeutic options for anti-aging. Here, their comparative effect on longevity-associated gene silencing information regulator (SIRT1) were evaluated in vitro and in vivo. IMR-90 cells treated with 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) were applied to establish a cellular senescence model, and rats treated with D-galactose (D-gal) were used as an aging animal model. Resveratrol and CR exhibited similar anti-aging activities, evidenced by inhibiting senescence and apoptosis, and restoring cognitive impairment and oxidative damage...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29028335/metallo-supramolecular-complexes-enantioselectively-eradicate-cancer-stem-cells-in-vivo
#13
Hongshuang Qin, Chuanqi Zhao, Yuhuan Sun, Jinsong Ren, Xiaogang Qu
Cancer stem cells (CSCs) are responsible for drug resistance, metastasis and recurrence of cancers. However, there is still no clinically approved drug that can effectively eradicate CSCs. Thus, it is crucial and important to develop specific CSC-targeting agents. Chiral molecular recognition of DNA plays an important role in rational drug design. Among them, poly-morphic telomeric G-quadruplex DNA has received much attention due to its significant roles in telomerase activity and chromosome stability. Herein, we find that one enantiomer of zinc-finger-like chiral metallohelices, [Ni2L3]4+-P, a telomeric G-quadruplex-targeting ligand, can preferentially reduce cell growth in breast CSCs compared to the bulk cancer cells...
October 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29026176/primary-astrocytic-tumours-and-paired-recurrences-have-similar-biological-features-in-idh1-tp53-and-tertp-mutation-and-mgmt-atrx-loss
#14
Xia Li, Jie Wei, Yixiong Liu, Peifeng Li, Linni Fan, Yingmei Wang, Mingyang Li, Danhui Zhao, Zhou Yu, Jing Ye, Ying Guo, Qingguo Yan, Shuangping Guo, Zhe Wang
Astrocytic tumours are the most common type of primary malignant brain tumour. Most astrocytic tumours will recur at some point after surgery. Currently, the combination of radiotherapy and chemotherapy does not prevent the recurrence of astrocytic tumours. In this study, we investigated the consistency in isocitrate dehydrogenase 1 (IDH1), tumour protein p53 (TP53) and telomerase reverse transcriptase promoter (TERTp) mutations during astrocytic tumour recurrence. We also evaluated the protein loss of O-6-methylguanine-DNA methyltransferase (MGMT) and alpha-thalassemia/mental retardation, X-linked (ATRX) during disease recurrence...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29022488/characterization-of-immortalized-human-mammary-epithelial-cell-line-hmec-2-6
#15
Pooja S Joshi, Vishnu Modur, JiMing Cheng, Kathy Robinson, Krishna Rao
Primary human mammary epithelial cells have a limited life span which makes it difficult to study them in vitro for most purposes. To overcome this problem, we have developed a cell line that was immortalized using defined genetic elements, and we have characterized this immortalized non-tumorigenic human mammary epithelial cell line to establish it as a potential model system. human mammary epithelial cells were obtained from a healthy individual undergoing reduction mammoplasty at SIU School of Medicine. The cells were transduced with CDK4R24C followed by transduction with human telomerase reverse transcriptase...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29020403/cardiac-and-systemic-rejuvenation-after-cardiosphere-derived-cell-therapy-in-senescent-rats
#16
Lilian Grigorian-Shamagian, Weixin Liu, Soraya Fereydooni, Ryan C Middleton, Jackelyn Valle, Jae Hyung Cho, Eduardo Marbán
Aim: The aim is to assess the effects of CDCs on heart structure, function, gene expression, and systemic parameters in aged rats. Diastolic dysfunction is characteristic of aged hearts. Cardiosphere-derived cell (CDC) therapy has exhibited several favourable effects on heart structure and function in humans and in preclinical models; however, the effects of CDCs on aging have not been evaluated. Methods and Results: We compared intra-cardiac injections of neonatal rat CDCs to vehicle (phosphate-buffered saline, PBS) in 21...
August 14, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29017500/nf-%C3%AE%C2%BAb-potentiates-tumor-growth-by-suppressing-a-novel-target-lpts
#17
Dongbo Liu, Hongping Miao, Yuanyin Zhao, Xia Kang, Shenglan Shang, Wei Xiang, Rongchen Shi, Along Hou, Rui Wang, Kun Zhao, Yingzhe Liu, Yue Ma, Huan Luo, Hongming Miao, Fengtian He
BACKGROUND: Chronic inflammation is causally linked to the carcinogenesis and progression of most solid tumors. LPTS is a well-identified tumor suppressor by inhibiting telomerase activity and cancer cell growth. However, whether and how LPTS is regulated by inflammation signaling is still incompletely elucidated. METHODS: Real-time PCR and western blotting were used to determine the expression of p65 and LPTS. Reporter gene assay, electrophoretic mobility shift assay and chromatin immunoprecipitation were performed to decipher the regulatory mechanism between p65 and LPTS...
October 10, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29017189/curcumin-affects-adipose-tissue-derived-mesenchymal-stem-cell-aging-through-tert-gene-expression
#18
Samaneh Pirmoradi, Ezzatollah Fathi, Raheleh Farahzadi, Younes Pilehvar-Soltanahmadi, Nosratollah Zarghami
Aging and losing cell survival is one of the main problems in cell therapy. Aging of Mesenchymal Stem Cells (MSCs) is associated with a rise in intracellular reactive oxygen species, decrease in telomerase reverse transcriptase (TERT) expression and finally eroded telomere ends. Given that the production of free radicals in the aging process is effective, the use of antioxidants can help in scavenging free radicals and prevent the aging of cells. The aim of this study is to evaluate the effects of curcumin on proliferation, aging and TERT expression of rat adipose tissue-derived stem cells (rADSC)...
October 10, 2017: Drug Research
https://www.readbyqxmd.com/read/28992682/nanocurcumin-mediated-down-regulation-of-telomerase-via-stimulating-tgf%C3%AE-1-signaling-pathway-in-hepatocellular-carcinoma-cells
#19
Molood Shariati, Samira Hajigholami, Ziba Veisi Malekshahi, Maliheh Entezari, Narges Bodaghabadi, Majid Sadeghizadeh
Background: Curcumin, extracted from turmeric, represents enormous potential to serve as an anticancer agent. Telomerase is viewed as a prominent molecular target of curcumin, and Transforming growth factor-β1 (TGFβ1) has proven to be a major inhibitory signaling pathway for telomerase activity. In the current study, we aimed to explore suppressive effects of nanocurcumin on telomerase expression through TGFβ1 pathway in a hepatocellular carcinoma cell line (Huh7). Methods: MTT assay was used to determine the effect of nonocurcumin on viability of Huh7 cells...
October 10, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28990525/a-human-proximal-tubular-epithelial-cell-model-to-explore-a-knowledge-gap-on-neonatal-drug-disposition
#20
Ahmed Reda, Anke Raaijmakers, Saskia van Dorst, Charlotte G G M Pauwels, Karel Allegaert, Mohamed A Elmonem, Rosalinde Masereeuw, Lambertus van den Heuvel, Elena Levtchenko, Fanny Oliveira Arcolino
BACKGROUND: Finding the right drug-dosage for neonates is still a challenge. Until now, neonatal doses are extrapolated from adults and children doses. However, there are differences between neonatal and adult kidney physiology that should be considered, especially when it comes to drug metabolism and/or transport. Studying renal drug disposition in neonates is limited by the lack of reliable human cell models. OBJECTIVE: To illustrate the feasibility of developing an in vitro model for neonatal proximal tubule epithelial cells (nPTECs) to study renal drug disposition at this age...
October 9, 2017: Current Pharmaceutical Design
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