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Shadi Foroughi, Nasrin Ziamajidi, Saman Javid, Roghayeh Abbasalipourkabir, Reza Aflatoonian, Mahnaz Ashrafi, Alireza Nourian
BACKGROUND: An in vivo study was carried out to study of telomerase reverse transcriptase and Uterine-Ovarian-specific genes expression in the endometrial tissue of ovariectomized female Sprague-Dawley rats. MATERIAL AND METHODS: Twenty-four female Sprague-Dawley rats divided into 4 groups of six rats. The first and second groups were ovariectomized and given tamoxifen and tamoxifen-loaded SLN respectively for six days continuously. Group 3 served as the untreated ovariectomized control group and group 4 was made up of untreated normal healthy rats...
February 19, 2018: International Journal of Biological Macromolecules
Jonathan K Alder, Vidya Sagar Hanumanthu, Margaret A Strong, Amy E DeZern, Susan E Stanley, Clifford M Takemoto, Ludmilla Danilova, Carolyn D Applegate, Stephen G Bolton, David W Mohr, Robert A Brodsky, James F Casella, Carol W Greider, J Brooks Jackson, Mary Armanios
Telomere length (TL) predicts the onset of cellular senescence in vitro but the diagnostic utility of TL measurement in clinical settings is not fully known. We tested the value of TL measurement by flow cytometry and FISH (flowFISH) in patients with mutations in telomerase and telomere maintenance genes. TL had a discrete and reproducible normal range with definable upper and lower boundaries. While TL above the 50th age-adjusted percentile had a 100% negative predictive value for clinically relevant mutations, the lower threshold in mutation carriers was age-dependent, and adult mutation carriers often overlapped with the lowest decile of controls...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Marco De Vitis, Francesco Berardinelli, Antonella Sgura
Eukaryotic cells undergo continuous telomere shortening as a consequence of multiple rounds of replications. During tumorigenesis, cells have to acquire telomere DNA maintenance mechanisms (TMMs) in order to counteract telomere shortening, to preserve telomeres from DNA damage repair systems and to avoid telomere-mediated senescence and/or apoptosis. For this reason, telomere maintenance is an essential step in cancer progression. Most human tumors maintain their telomeres expressing telomerase, whereas a lower but significant proportion activates the alternative lengthening of telomeres (ALT) pathway...
February 18, 2018: International Journal of Molecular Sciences
Jae-Il Roh, Yujin Kim, Jahyun Oh, Yunmi Kim, Jeehyun Lee, Jaehoon Lee, Kyung-Hee Chun, Han-Woong Lee
Autophagy is systematically regulated by upstream factors and nutrients. Recent studies reported that telomerase and hexokinase 2 [HK2) regulate autophagy through mTOR and that telomerase has the capacity to bind to the HK2 promoter. However, the molecular linkage among telomerase, HK2, and autophagy is not fully understood. Here, we show that HK2 connects telomerase to autophagy. HK2 inhibition in HepG2 cells suppressed TERT-induced autophagy activation and further enhancement by glucose deprivation. The HK2 downstream factor mTOR was responsible for the TERT-induced autophagy activation under glucose deprivation, implying that TERT promotes autophagy through an HK2-mTOR pathway...
2018: PloS One
Mangesh H Kaulage, Basudeb Maji, Sanjeev Pasadi, Asfa Ali, Santanu Bhattacharya, K Muniyappa
Recent studies support the idea that G-quadruplex structures in the promoter regions of oncogenes and telomere DNA can serve as potential therapeutic targets in the treatment of cancer. Accordingly, several different types of organic small molecules that stabilize G-quadruplex structures and inhibit telomerase activity have been discerned. Here, we describe the binding of benzimidazole-carbazole ligands to G-quadruplex structures formed in G-rich DNA sequences containing the promoter regions of human c-MYC, c-KIT1, c-KIT2, VEGF and BCL2 proto-oncogenes...
February 5, 2018: European Journal of Medicinal Chemistry
Kumar Padmapriya, Ritu Barthwal
Plant derived small molecules, which interact with and stabilize G-quadruplex DNA, act as inhibitors of telomere elongation and oncogene expression in humans. The inhibition of telomerase enzyme has immense potential since it is over expressed in most cancer cells. Interaction of palmatine, an antitumor alkaloid, to parallel G-quadruplex DNA, [d(TTGGGGT)]4 and [d(TTAGGGT)]4 , has been investigated using Nuclear Magnetic Resonance (NMR), fluorescence and Circular Dichroism (CD) spectroscopy. Titrations were monitored by1 H and31 P NMR spectra and solution structure of palmatine-[d(TTGGGGT)]4 complex was obtained by restrained Molecular Dynamics (rMD) simulations using distance restraints from 2D NOESY spectra...
February 16, 2018: Biochimie
Yaping Wang, Zhen Zhao, Zhiyong Zhu, Pingying Li, Xiaolin Li, Xiaohong Xue, Jie Duo, Yingcai Ma
BACKGROUND: The effects of acute hypoxia at high altitude on the telomere length of the cells in the heart and lung tissues remain unclear. This study aimed to investigate the change in telomere length of rat heart and lung tissue cells in response to acute exposure to severe hypoxia and its role in hypoxia-induced damage to heart and lung tissues. METHODS: Forty male Wistar rats (6-week old) were randomized into control group (n = 10) and hypoxia group (n = 30)...
February 17, 2018: Journal of Physiological Anthropology
Esther Aix, Alex Gallinat, Ignacio Flores
Although recent advances have overturned the old view of the human heart as an inert postmitotic organ, it is clear that the adult heart´s capacity to regenerate after an ischemic episode is very limited. Unlike humans, zebrafish and other lower vertebrates vigorously regenerate damaged myocardium after cardiac injury. Understanding how the zebrafish is able to conserve life-long cardiac regeneration capacity while mammals lose it soon after birth is crucial for the development of new treatments for myocardial infarction...
February 3, 2018: Differentiation; Research in Biological Diversity
Jessica A Pilsworth, Dawn R Cochrane, Zhouchunyang Xia, Geraldine Aubert, Anniina E M Färkkilä, Hugo M Horlings, Satoshi Yanagida, Winnie Yang, Jamie L P Lim, Yi Kan Wang, Ali Bashashati, Jacqueline Keul, Adele Wong, Kevin Norris, Sara Y Brucker, Florin-Andrei Taran, Bernhard Krämer, Annette Staebler, Esther Oliva, Sohrab P Shah, Stefan Kommoss, Friedrich Kommoss, C Blake Gilks, Duncan M Baird, David G Huntsman
The telomerase reverse transcriptase (TERT) gene is highly expressed in stem cells and silenced upon differentiation. Cancer cells can attain immortality by activating TERT to maintain telomere length and telomerase activity, which is a crucial step of tumorigenesis. Two somatic mutations in the TERT promoter (C228T; C250T) have been identified as gain-of-function mutations that promote transcriptional activation of TERT in multiple cancers, such as melanoma and glioblastoma. A recent study investigating TERT promoter mutations in ovarian carcinomas found C228T and C250T mutations in 15...
February 15, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Enrica Rampazzo, Paola Del Bianco, Roberta Bertorelle, Caterina Boso, Alessandro Perin, Giovanna Spiro, Francesca Bergamo, Claudio Belluco, Angela Buonadonna, Elisa Palazzari, Sara Leonardi, Antonino De Paoli, Salvatore Pucciarelli, Anita De Rossi
BACKGROUND: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome. METHODS: 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT=T0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4-8 months after surgery (T3) time points...
February 15, 2018: British Journal of Cancer
Xiaowen Xu, Lei Wang, Kan Li, Qihong Huang, Wei Jiang
Reliable and accurate detection of telomerase activity is crucial for better understanding its role in cancer cells and further exploring its function in cancer diagnosis and treatment. Here, we construct a smart DNA tweezer (DT) for detection of telomerase activity. The DT is assembled by three specially-designed single-stranded oligonucleotides: a central strand dually-labeled with donor/acceptor fluorophores and two arm strands containing overhangs complementary to telomerase reaction products (TRPs). It can get closed through hybridization with TRPs and get reopen through strand displacement reaction by TRPs' complementary sequences...
February 15, 2018: Analytical Chemistry
Yi Liu, Feng Liu, Yizhao Cao, Huimin Xu, Yangxiu Wu, Su Wu, Dan Liu, Yong Zhao, Zhou Songyang, Wenbin Ma
Shwachman-Diamond syndrome (SDS) is a rare pediatric disease characterized by various systemic disorders, including hematopoietic dysfunction. The mutation of Shwachman-Bodian-Diamond syndrome (SBDS) gene has been proposed to be a major causative reason for SDS. Although SBDS patients were reported to have shorter telomere length in granulocytes, the underlying mechanism is still unclear. Here we provide data to elucidate the role of SBDS in telomere protection. We demonstrate that SBDS deficiency leads to telomere shortening...
February 13, 2018: Cell Reports
Jana Majerská, Petra Procházková Schrumpfová, Ladislav Dokládal, Šárka Schořová, Karel Stejskal, Michal Obořil, David Honys, Lucie Kozáková, Pavla Sováková Polanská, Eva Sýkorová
In the published online version, the affiliations were mixed up. Corrected affiliation section is shown below. Also, the update has also been reflected in the author group section above.
February 14, 2018: Protoplasma
Collin Matsumoto, Yan Jiang, Jacqueline Emathinger, Pearl Quijada, Nathalie Nguyen, Andrea De La Torre, Maryam Moshref, Jonathan Nguyen, Aimee B Levinson, Minyoung Shin, Mark A Sussman, Nirmala Hariharan
Aging severely limits myocardial repair and regeneration. Delineating the impact of age-associated factors such as short telomeres is critical to enhance the regenerative potential of cardiac progenitor cells (CPCs). We hypothesized that short telomeres activate p53 and induce autophagy to elicit the age-associated change in CPC fate. We isolated CPCs and compared mouse strains with different telomere lengths for phenotypic characteristics of aging. Wild mouse strain Mus musculus castaneus (CAST) possessing short telomeres exhibits early cardiac aging with cardiac dysfunction, hypertrophy, fibrosis and senescence, as compared to common lab strains FVB and C57 bearing longer telomeres...
February 14, 2018: Stem Cells
Yinnan Chen, Joshua D Podlevsky, Dhenugen Logeswaran, Julian J-L Chen
Human telomerase synthesizes telomeric DNA repeats (GGTTAG) n onto chromosome ends using a short template from its integral telomerase RNA (hTR). However, telomerase is markedly slow for processive DNA synthesis among DNA polymerases. We report here that the unique template-embedded pause signal restricts the first nucleotide incorporation for each repeat synthesized, imparting a significantly greater K M This slow nucleotide incorporation step drastically limits repeat addition processivity and rate under physiological conditions, which is alleviated with augmented concentrations of dGTP or dGDP, and not with dGMP nor other nucleotides...
February 12, 2018: EMBO Journal
Gary Lam, Karen Beemon
Avian leukosis virus (ALV) is a simple retrovirus that can induce B-cell lymphoma in chicken(s) and other birds by insertional mutagenesis. The promoter region of telomerase reverse transcriptase (TERT) has been identified as an important integration site for tumorigenesis. Tumors with TERT promoter integrations are associated with increased TERT expression. The mechanism of this activation is still under investigation. We asked whether insertion of proviral DNA perturbs the epigenome of the integration site and, subsequently, impacts the regulation of neighboring genes...
February 10, 2018: Viruses
Jianmin Shi, Lianglong Pang, Shouguo Jiao
BACKGROUND: Mechanical stimuli obviously affect disc nucleus pulposus (NP) biology. Previous studies have indicate that static compression exhibits detrimental effects on disc biology compared with dynamic compression. OBJECTIVE: To study disc NP cell senescence under static compression and dynamic compression in a disc organ culture. METHODS: Porcine discs were cultured and subjected to compression (static compression: 0.4 MPa for 4 hours once per day; dynamic compression: 0...
February 5, 2018: Bioscience Reports
Yong-Li Song, Ke-Yong Tian, Wen-Juan Mi, Zhong-Jia Ding, Yang Qiu, Fu-Quan Chen, Ding-Jun Zha, Jian-Hua Qiu
Cochlear progenitor cells are considered as one of the best candidates for hair cell regeneration, thus, the regulation of cochlear progenitor cell proliferation has become a focus in this field. Several genes expressed in the inner ear during postnatal development have been demonstrated to be involved in maintaining the proliferative potential of progenitor cells, but the mechanism for regulating the proliferation and differentiation of cochlear progenitor cells remains poorly understood. Telomerase reverse transcriptase (TERT) has rate limiting telomerase activity and the overexpression of TERT has been shown to promote cell proliferation in series of cell lines...
February 6, 2018: Molecular Medicine Reports
Feng Liu, Kaya Xu, Hua Yang, Yuming Li, Jian Liu, Jixiang Wang, Zhizhong Guan
Gliomas are the most common type of primary brain tumor in adults, where more than half of the cases are malignant, and the prognosis is poor. The early viral 1A (E1A) protein has been widely recognized to be essential for adenoviral replication and production of progeny virions in human cells, a process that is regulated by human telomerase reverse transcriptase. The p53 gene, as a tumor suppressor, regulates diverse cellular processes, including cell cycle arrest, cell autophagy, senescence and apoptosis...
March 2018: Oncology Letters
Halin Bao, Tuya Bai, Koji Takata, Takehiko Yokobori, Takashi Ohnaga, Takeshi Hisada, Toshitaka Maeno, Pinjie Bao, Tomonori Yoshida, Yuji Kumakura, Hiroaki Honjo, Makoto Sakai, Makoto Sohda, Minoru Fukuchi, Bolag Altan, Tadashi Handa, Munenori Ide, Tatsuya Miyazaki, Kyoichi Ogata, Tetsunari Oyama, Kimihiro Shimizu, Akira Mogi, Takayuki Asao, Ken Shirabe, Hiroyuki Kuwano, Kyoichi Kaira
The present study aimed to enrich circulating tumor cells (CTCs) from blood samples using a new size-sorting CTC chip. The present study also set out to identify a blood sensitivity marker for the immune checkpoint inhibitor nivolumab in patients with advanced, pre-treatment lung cancer. The CTC sorting efficacy of the chip was investigated and the large cell fraction of blood samples from 15 patients with pre-treatment lung cancer who were later administered nivolumab were purified. The expression levels of carcinoembryonic antigen ( CEA ), human Telomerase Reverse Transcriptase ( hTERT ), cytokeratin19 ( CK19 ), and programmed death ligand-1 ( PD-L1 ) were investigated to clarify the association between these CTC markers and the clinical response to nivolumab...
March 2018: Oncology Letters
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