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https://www.readbyqxmd.com/read/28641311/characterisation-of-blood-derived-exosomal-htert-mrna-secretion-in-cancer-patients-a-potential-pan-cancer-marker
#1
Hadar Goldvaser, Anna Gutkin, Einat Beery, Yonatan Edel, Jardena Nordenberg, Ofir Wolach, Ester Rabizadeh, Orit Uziel, Meir Lahav
BACKGROUND: Telomerase (human telomerase reverse transcriptase (hTERT)) is considered a hallmark of cancer. The aim of our study was to evaluate the feasibility of the detection of hTERT transcripts in serum as a 'pan-cancer' diagnostic method. METHODS: Human telomerase reverse transcriptase mRNA levels were determined in serum and serum-derived exosomes from 133 patients with different malignancies and 45 healthy controls. In four patients hTERT mRNA levels were measured in different clinical stages...
June 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28638472/advances-in-the-detection-of-telomerase-activity-using-isothermal-amplification
#2
REVIEW
Xiaojin Zhang, Xiaoding Lou, Fan Xia
Telomerase plays a significantly important role in keeping the telomere length of a chromosome. Telomerase overexpresses in nearly all tumor cells, suggesting that telomerase could be not only a promising biomarker but also a potential therapeutic target for cancers. Therefore, numerous efforts focusing on the detection of telomerase activity have been reported from polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assays to PCR-free assays such as isothermal amplification in recent decade...
2017: Theranostics
https://www.readbyqxmd.com/read/28637749/cell-cycle-dependent-spatial-segregation-of-telomerase-from-sites-of-dna-damage
#3
Faissal Ouenzar, Maxime Lalonde, Hadrien Laprade, Geneviève Morin, Franck Gallardo, Samuel Tremblay-Belzile, Pascal Chartrand
Telomerase can generate a novel telomere at DNA double-strand breaks (DSBs), an event called de novo telomere addition. How this activity is suppressed remains unclear. Combining single-molecule imaging and deep sequencing, we show that the budding yeast telomerase RNA (TLC1 RNA) is spatially segregated to the nucleolus and excluded from sites of DNA repair in a cell cycle-dependent manner. Although TLC1 RNA accumulates in the nucleoplasm in G1/S, Pif1 activity promotes TLC1 RNA localization in the nucleolus in G2/M...
June 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28636942/extensive-proliferation-of-human-cancer-cells-with-ever-shorter-telomeres
#4
Rebecca A Dagg, Hilda A Pickett, Axel A Neumann, Christine E Napier, Jeremy D Henson, Erdahl T Teber, Jonathan W Arthur, C Patrick Reynolds, Jayne Murray, Michelle Haber, Alexander P Sobinoff, Loretta M S Lau, Roger R Reddel
Acquisition of replicative immortality is currently regarded as essential for malignant transformation. This is achieved by activating a telomere lengthening mechanism (TLM), either telomerase or alternative lengthening of telomeres, to counter normal telomere attrition. However, a substantial proportion of some cancer types, including glioblastomas, liposarcomas, retinoblastomas, and osteosarcomas, are reportedly TLM-negative. As serial samples of human tumors cannot usually be obtained to monitor telomere length changes, it has previously been impossible to determine whether tumors are truly TLM-deficient, there is a previously unrecognized TLM, or the assay results are false-negative...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636941/highly-aggressive-metastatic-melanoma-cells-unable-to-maintain-telomere-length
#5
Nikenza Viceconte, Marie-Sophie Dheur, Eva Majerova, Christophe E Pierreux, Jean-François Baurain, Nicolas van Baren, Anabelle Decottignies
Unlimited replicative potential is one of the hallmarks of cancer cells. In melanoma, hTERT (telomerase reverse transcriptase) is frequently overexpressed because of activating mutations in its promoter, suggesting that telomerase is necessary for melanoma development. We observed, however, that a subset of melanoma metastases and derived cell lines had no telomere maintenance mechanism. Early passages of the latter displayed long telomeres that progressively shortened and fused before cell death. We propose that, during melanoma formation, oncogenic mutations occur in precursor melanocytes with long telomeres, providing cells with sufficient replicative potential, thereby bypassing the need to re-activate telomerase...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636312/combining-protein-and-mirna-quantification-for-bladder-cancer-analysis
#6
Ruixue Duan, Zhenyu Zhang, Fuxin Zheng, Longwang Wang, Ju Guo, Tianchi Zhang, Xiaomeng Dai, Shengwei Zhang, Dong Yang, Renrui Kuang, Gongxian Wang, Chaohong He, Abdul Hakeem, Chang Shu, Ping Yin, Xiaoding Lou, Fuqing Zeng, Huageng Liang, Fan Xia
We combine the telomerase extension reaction and microRNA (miRNA)-induced rolling circle amplification, followed by graphene oxide (GO) and nicking enzyme assisted signal amplification, to analyze telomerase and miRNA 21 in urine samples with following merits. Firstly, it is a binary assay and can simultaneously output double signals which corresponds to the quantities of telomerase and miRNA, respectively. Secondly, telomerase activity is firstly enhanced by using DNA molecular beacon probe to inhibit the formation of G-quadruplex...
June 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28631564/indole-3-carbinol-induces-apoptosis-of-chronic-myelogenous-leukemia-cells-through-suppression-of-stat5-and-akt-signaling-pathways
#7
Majid Safa, Leila Jafari, Fatemeh Alikarami, Rima Manafi Shabestari, Ahmad Kazemi
Signal transducer and activator of transcription 5 and Akt pathways, implicated in signaling transduction downstream of BCR-ABL, play critical roles in the pathogenesis of chronic myeloid leukemia. Therefore, idenication of novel compounds that modulate the activity of such pathways could be a new approach in the treatment of chronic myeloid leukemia. Previous studies have demonstrated that indole-3-carbinol inhibits the proliferation and induces apoptosis of various tumor cells. However, its anticancer activity against chronic myeloid leukemia cells and the underlying mechanism remain unclear...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28627695/targeted-cdx2-expression-inhibits-aggressive-phenotypes-of-colon-cancer-cells-in-vitro-and-in-vivo
#8
Jianbao Zheng, Sai He, Jie Qi, Xiaolong Wang, Junhui Yu, Yunhua Wu, Qi Gao, Kai Wang, Xuejun Sun
Loss of caudal type homeobox 2 (CDX2) is associated with the development of human colorectal cancer, while human telomerase reverse transcriptase (hTERT) frequently occurs in variety of human cancers. We investigated the effects of restoration of CDX2 expression using a hypoxia-inducible hTERT promoter-driven vector (pLVX-5HRE-hTERTp-CDX2-3FLAG) on colon cancer cell viability, cell cycle distribution, apoptosis, colony formation, invasion ability and xenograft tumor growth in nude mice. CDX2 overexpression significantly inhibited viability, colony formation, and the invasion and migration ability of LoVo cells, and induced cell cycle arrest and apoptosis in vitro, especially under hypoxic culture conditions...
June 13, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28627647/differences-in-telomerase-activity-and-the-effects-of-azt-in-aneuploid-and-euploid-cells-in-colon-cancer
#9
Xiao Fang, Tenghui Hu, Hua Yin, Junjun Yang, Weian Tang, Siqi Hu, Xingxiang Xu
Telomerase-targeted treatments for cancer have received a great deal of attention because telomerase is detected in nearly all cancer cells but is not expressed in most normal tissues. Aneuploidy refers to a chromosome number that is not a multiple of the base chromosome number and can indicate either hypo- or hyperploid chromosome numbers. Most solid tumors are aneuploid. In the present study, we sought to determine whether there are differences in telomerase activity and hTERT gene expression between aneuploid and euploid cells...
June 14, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28627628/phosphorothioate%C3%A2-modified-antisense-oligonucleotides-against-human-telomerase-reverse-transcriptase-sensitize-cancer-cells-to-radiotherapy
#10
Fei Cao, Xiaoping Ju, Di Chen, Lingong Jiang, Xiaofei Zhu, Shuiwang Qing, Fang Fang, Yuxin Shen, Zhen Jia, Huojun Zhang
Emergence of resistance, unavoidable systemic toxicity and unsatisfactory efficacy arethe main obstacles for traditional cancer therapy. Combination with phosphorothioate modified antisense oligonucleotides (PS‑ASODN) against human telomerase reverse transcriptase (hTERT) may enhance the therapeutic effect of irradiation. However, the effect of PS‑ASODN against hTERT on the anti‑tumor effects of irradiation in liver cancer remain unclear. In the current study, Walker 256 cells were transfected with hTERT PS‑ASODN...
June 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28624356/vascular-ageing-underlying-mechanisms-and-clinical-implications
#11
REVIEW
Ageliki Laina, Konstantinos Stellos, Kimon Stamatelopoulos
Epidemiological studies have shown that ageing is a major non-reversible risk factor for cardiovascular disease. Vascular ageing starts early in life and is characterized by a gradual change of vascular structure and function resulting in increased arterial stiffening. At the present review we discuss the role of the most important molecular pathways involved in vascular ageing, their association with arterial stiffening and possible novel therapeutic targets that may delay this otherwise irreversible degenerating process...
June 14, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28623509/telomerase-and-drug-resistance-in-cancer
#12
REVIEW
Natalia Lipinska, Aleksandra Romaniuk, Anna Paszel-Jaworska, Ewa Toton, Przemyslaw Kopczynski, Blazej Rubis
It is well known that a decreased expression or inhibited activity of telomerase in cancer cells is accompanied by an increased sensitivity to some drugs (e.g., doxorubicin, cisplatin, or 5-fluorouracil). However, the mechanism of the resistance resulting from telomerase alteration remains elusive. There are theories claiming that it might be associated with telomere shortening, genome instability, hTERT translocation, mitochondria functioning modulation, or even alterations in ABC family gene expression. However, association of those mechanisms, i...
June 16, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28622077/a-comparative-study-of-the-effects-of-sodium-selenite-and-glutathione-mono-ethyl-ester-on-aged-adipose-derived-stem-cells-the-telomerase-and-cellular-responses
#13
N Aminizadeh, Taki M Tiraihi, S A Mesbah-Namin, Taher Taheri
The proliferation and differentiation potential of adipose derived stem cells (ADSCs) declines with ageing. Moreover, Alzheimer's disease is associated with progressive decline in cholinergic neurons. The purpose of this study is to enhance the proliferation potential of aged rat ADSCs and their differentiation into cholinergic neurons. The ADSCs were collected from aged male rats cultured and treated with different concentrations of sodium selenite for 3 days or glutathione mono ethyl ester (GSH-MEE) for 1 day...
June 16, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28621624/use-of-telomerase-promoter-mutations-to-mark-specific-molecular-subsets-with-reciprocal-clinical-behavior-in-idh-mutant-and-idh-wild-type-diffuse-gliomas
#14
Cemaliye B Akyerli, Şirin Yüksel, Özge Can, E Zeynep Erson-Omay, Yavuz Oktay, Erdal Coşgun, Ege Ülgen, Yiğit Erdemgil, Aydın Sav, Andreas von Deimling, Murat Günel, M Cengiz Yakıcıer, M Necmettin Pamir, Koray Özduman
OBJECTIVE Recent studies have established that hemispheric diffuse gliomas may be grouped into subsets on the basis of molecular markers; these subsets are loosely correlated with the histopathological diagnosis but are strong predictors of clinical tumor behavior. Based on an analysis of molecular and clinical parameters, the authors hypothesized that mutations of the telomerase promoter (TERTp-mut) mark separate oncogenic programs among isocitrate dehydrogenase 1 and/or 2 (IDH) mutant (IDH-mut) and IDH wild-type (IDH-wt) diffuse gliomas independent of histopathology or WHO grade...
June 16, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28616852/ultrasonographic-prediction-of-highly-aggressive-telomerase-reverse-transcriptase-tert-promoter-mutated-papillary-thyroid-cancer
#15
Tae Hyuk Kim, Chang-Seok Ki, Soo Yeon Hahn, Young Lyun Oh, Hye Won Jang, Sun Wook Kim, Jae Hoon Chung, Jung Hee Shin
PURPOSE: Telomerase reverse transcriptase promoter mutations are found in highly aggressive thyroid malignancies. Our aim was to define the ultrasonographic features of telomerase reverse transcriptase promoter-mutated papillary thyroid cancer and to evaluate their predictive performances. METHODS: Ultrasonographic findings were reviewed for 185 patients with surgically confirmed papillary thyroid cancer between 1994 and 2004. Genomic DNA to identify telomerase reverse transcriptase promoter mutations was extracted from archived surgical specimens...
June 14, 2017: Endocrine
https://www.readbyqxmd.com/read/28615534/functional-dissection-of-breast-cancer-risk-associated-tert-promoter-variants
#16
Sonja Helbig, Leesa Wockner, Annick Bouendeu, Ursula Hille-Betz, Karen McCue, Juliet D French, Stacey L Edwards, Hilda A Pickett, Roger R Reddel, Georgia Chenevix-Trench, Thilo Dörk, Jonathan Beesley
The multi-cancer susceptibility locus at 5p15.33 includes TERT, encoding the telomerase catalytic subunit. Genome-wide association studies (GWAS) have identified six single nucleotide polymorphisms (SNPs) in the TERT promoter associated with decreased breast cancer risk, although the precise causal variants and their mechanisms of action have remained elusive. Luciferase reporter assays indicated that the protective haplotype reduced TERT promoter activity in human mammary epithelial and cancer cells in an estrogen-independent manner...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611443/identification-of-a-gene-cluster-for-telomestatin-biosynthesis-and-heterologous-expression-using-a-specific-promoter-in-a-clean-host
#17
Keita Amagai, Haruo Ikeda, Junko Hashimoto, Ikuko Kozone, Miho Izumikawa, Fumitaka Kudo, Tadashi Eguchi, Takemichi Nakamura, Hiroyuki Osada, Shunji Takahashi, Kazuo Shin-Ya
Telomestatin, a strong telomerase inhibitor with G-quadruplex stabilizing activity, is a potential therapeutic agent for treating cancers. Difficulties in isolating telomestatin from microbial cultures and in chemical synthesis are bottlenecks impeding the wider use. Therefore, improvement in telomestatin production and structural diversification are required for further utilization and application. Here, we discovered the gene cluster responsible for telomestatin biosynthesis, and achieved production of telomestatin by heterologous expression of this cluster in the engineered Streptomyces avermitilis SUKA strain...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28607398/epstein-barr-virus-induced-up-regulation-of-tcab1-is-involved-in-the-dna-damage-response-in-nasopharyngeal-carcinoma
#18
Kun Wang, Yichen Ge, Chao Ni, Bomiao Cui, Jintao Du, Bo Zhang, Xiaoyu Hu, Jiao Chen, Liying Xiao, Chongkui Sun, Yan Li
Telomerase Cajal body protein 1 (TCAB1), which is involved in Cajal body maintenance, telomere elongation and ribonucleoprotein biogenesis, has been linked to cancer predisposition, including nasopharyngeal carcinoma (NPC), due to its oncogenic properties. However, there are no specific reports to date on the functional relevance of TCAB1 and Epstein-Barr virus (EBV), which is considered to be a risk factor for NPC. In this study, we first examined NPC clinical tissues and found a notable overexpression of TCAB1 in EBV-positive specimens...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28604726/rif1-maintains-telomeres-and-mediates-dna-repair-by-encasing-dna-ends
#19
Stefano Mattarocci, Julia K Reinert, Richard D Bunker, Gabriele A Fontana, Tianlai Shi, Dominique Klein, Simone Cavadini, Mahamadou Faty, Maksym Shyian, Lukas Hafner, David Shore, Nicolas H Thomä, Ulrich Rass
In yeast, Rif1 is part of the telosome, where it inhibits telomerase and checkpoint signaling at chromosome ends. In mammalian cells, Rif1 is not telomeric, but it suppresses DNA end resection at chromosomal breaks, promoting repair by nonhomologous end joining (NHEJ). Here, we describe crystal structures for the uncharacterized and conserved ∼125-kDa N-terminal domain of Rif1 from Saccharomyces cerevisiae (Rif1-NTD), revealing an α-helical fold shaped like a shepherd's crook. We identify a high-affinity DNA-binding site in the Rif1-NTD that fully encases DNA as a head-to-tail dimer...
June 12, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28602428/influence-of-amalaki-rasayana-on-telomerase-activity-and-telomere-length-in-human-blood-mononuclear-cells
#20
Kanive P Guruprasad, Sweta Dash, Marigowda B Shivakumar, Pavithra R Shetty, Kothanahalli S Raghu, Bhanuvalli R Shamprasad, Vishwanatha Udupi, Raviraj V Acharya, Prasanna B Vidya, Jayakrishna Nayak, Anandan E Mana, Rajesh Moni, Muraleedharan T Sankaran, Kapaettu Satyamoorthy
BACKGROUND: Indian traditional medicine practices use defined rasayana preparations to improve the quality of health in aged individuals. Amalaki Rasayana is one such rasayana prepared from the fruits of Phyllanthus emblica and is popularly used to prevent or treat various age related health conditions. Telomerase activity in the cells maintains telomere length and is implicated in ageing and various diseases wherein the shortening of telomere during ageing is controlled chiefly by the telomerase activity...
June 8, 2017: Journal of Ayurveda and Integrative Medicine
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