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Telomerases

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https://www.readbyqxmd.com/read/28432274/sensitive-detection-of-viable-circulating-tumor-cells-using-a-novel-conditionally-telomerase-selective-replicating-adenovirus-in-non-small-cell-lung-cancer-patients
#1
Shinsaku Togo, Nobuyoshi Katagiri, Yukiko Namba, Miniwan Tulafu, Kumi Nagahama, Kotarou Kadoya, Kazuya Takamochi, Siaki Oh, Kenji Suzuki, Fuminori Sakurai, Hiroyuki Mizuguchi, Yasuo Urata, Kazuhisa Takahashi
Circulating tumor cells (CTCs) have a crucial role in the clinical outcome of cancer patients. Detection of non-small cell lung cancer (NSCLC) using an antibody against epithelial cell adhesion molecule (EpCAM) in captured CTCs has low sensitivity; the loss of epithelial markers leads to underestimation of CTCs with mesenchymal phenotype. We propose a new approach for detection of viable CTCs, including those with epithelial-mesenchymal transition status (EMT-CTCs), using the new telomerase-specific replication-selective adenovirus (OBP-1101), TelomeScan F35...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427283/break-induced-replication-in-eukaryotes-mechanisms-functions-and-consequences
#2
Cynthia J Sakofsky, Anna Malkova
Break-induced replication (BIR) is an important pathway specializing in repair of one-ended double-strand DNA breaks (DSBs). This type of DSB break typically arises at collapsed replication forks or at eroded telomeres. BIR initiates by invasion of a broken DNA end into a homologous template followed by initiation of DNA synthesis that can proceed for hundreds of kilobases. This synthesis is drastically different from S-phase replication in that instead of a replication fork, BIR proceeds via a migrating bubble and is associated with conservative inheritance of newly synthesized DNA...
April 21, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28427205/mns16a-tandem-repeat-minisatellite-of-human-telomerase-gene-functional-studies-in-colorectal-lung-and-prostate-cancer
#3
Philipp Hofer, Cornelia Zöchmeister, Christian Behm, Stefanie Brezina, Andreas Baierl, Angelina Doriguzzi, Vanita Vanas, Klaus Holzmann, Hedwig Sutterlüty-Fall, Andrea Gsur
MNS16A, a functional polymorphic tandem repeat minisatellite, is located in the promoter region of an antisense transcript of the human telomerase reverse transcriptase gene. MNS16A promoter activity depends on the variable number of tandem repeats (VNTR) presenting varying numbers of transcription factor binding sites for GATA binding protein 1. Although MNS16A has been investigated in multiple cancer epidemiology studies with incongruent findings, functional data of only two VNTRs (VNTR-243 and VNTR-302) were available thus far, linking the shorter VNTR to higher promoter activity...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425985/the-cellular-senescence-of-leukemia-initiating-cells-from-acute-lymphoblastic-leukemia-is-postponed-by-%C3%AE-arrestin1-binding-with-p300-sp1-to-regulate-htert-transcription
#4
Shan Liu, Haiyan Liu, Ru Qin, Yi Shu, Zhidai Liu, Penghui Zhang, Caiwen Duan, Dengli Hong, Jie Yu, Lin Zou
Although we previously reported that the self-renewal of leukemia-initiating cells of B-lineage acute lymphoblastic leukemia (B-ALL LICs) was regulated by β-Arrestin1, a multiple-function protein, the cellular senescence is critical for LICs fate and leukemia progress, and worthy for further investigation. Here we found that depletion of β-Arrestin1 extended the population doubling time and the percentage of senile cells, the signatures of cellular senescence, of B-ALL LICs. Moreover, lack of β-Arrestin1 enhanced the expression of proteins (CBX, HIRA) and genes (P53, P16) related to senescence in leukemic Reh cells and B-ALL-LICs-derived leukemic mice...
April 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28425984/withaferin-a-kills-cancer-cells-with-and-without-telomerase-chemical-computational-and-experimental-evidences
#5
Yue Yu, Shashank P Katiyar, Durai Sundar, Zeenia Kaul, Eijiro Miyako, Zhenya Zhang, Sunil C Kaul, Roger R Reddel, Renu Wadhwa
Maintenance of telomere length is the most consistent attribute of cancer cells. Tightly connected to their capacity to overcome replicative mortality, it is achieved either by activation of telomerase or an Alternative mechanism of Lengthening of Telomeres (ALT). Disruption of either of these mechanisms has been shown to induce DNA damage signalling leading to senescence or apoptosis. Telomerase inhibitors are considered as potential anticancer drugs but are ineffective for ALT cancers (~15% of all cancers)...
April 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28425274/profile-of-pot1-as-telomerase-shelterin-component-discriminatesbetween-cervical-cancer-and-normal-cervical-cells
#6
Andreas Budi Wijaya, Furqan Hidayatullah, Verina Veronica Setyabudhi, Faizal Reza Pahlevi, Rasyad Indra, Tatit Nurseta
BACKGROUND/AIM: Telomerase activity is influenced by hTERT transcriptional regulation, shelterin, and posttranscriptional alternative splicing. Telomerase shelterin such as POT1 is highly correlated with various cancers. However, the profile of POT1 in cervical cancer has not been clearly identified. Therefore, it is important to identify its profile in cervical cancer biopsy tissue and normal cervical smears. MATERIALS AND METHODS: Biopsy tissue of cervical cancer patients and normal cervical smears were characterized using SDS-PAGE and western blot...
April 18, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28423629/polymorphisms-in-human-telomerase-reverse-transcriptase-htert-gene-gene-gene-and-gene-smoking-interaction-with-susceptibility-to-gastric-cancer-in-chinese-han-population
#7
Jian Zhang, Hui Ju, Jun-Ru Gao, Xue-Long Jiao, Yun Lu
AIMS: To investigate the association of telomerase reverse transcriptase (TERT) gene polymorphisms and additional gene-gene and gene- environment interaction with gastric cancer (GC) risk. RESULTS: GC risk was significantly higher in carriers of G allele of rs2736100 than those with TT genotype (TG+ GG versus TT), adjusted OR (95%CI) =1.68 (1.26-2.17), and higher in carriers of G allele of rs2853669 than those with AA genotype (AG+ GG versus AA), adjusted OR (95%CI) = 1...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420995/quantum-dots-sirna-nanoplexes-for-gene-silencing-in-central-nervous-system-tumor-cells
#8
Guimiao Lin, Ting Chen, Jinyun Zou, Yucheng Wang, Xiaomei Wang, Jiefeng Li, Qijun Huang, Zicai Fu, Yingying Zhao, Marie Chia-Mi Lin, Gaixia Xu, Ken-Tye Yong
RNA interfering (RNAi) using short interfering RNA (siRNA) is becoming a promising approach for cancer gene therapy. However, owing to the lack of safe and efficient carriers, the application of RNAi for clinical use is still very limited. In this study, we have developed cadmium sulphoselenide/Zinc sulfide quantum dots (CdSSe/ZnS QDs)-based nanocarriers for in vitro gene delivery. These CdSSe/ZnS QDs are functionalized with polyethyleneimine (PEI) to form stable nanoplex (QD-PEI) and subsequently they are used for siRNA loading which specially targets human telomerase reverse transcriptase (TERT)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28420430/chronic-stress-induces-cd99-suppresses-autophagy-and-affects-spontaneous-adipogenesis-in-human-bone-marrow-stromal-cells
#9
Zvenyslava Husak, Michael N Dworzak
BACKGROUND: Bone marrow-derived mesenchymal stromal cells (MSCs) are multipotent cells with a high constitutive level of autophagy and low expression of CD99. Under certain conditions, MSCs may develop tumorigenic properties. However, these transformation-induced conditions are largely unknown. Recently, we have identified an association between Hsp70, a main participant in cellular stress response and tumorigenesis, and CD99. Preliminary observations had revealed upregulation of both proteins in stressed long-term cultured MSCs...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28419269/dual-genotype-diffuse-low-grade-glioma-is-it-really-time-to-abandon-oligoastrocytoma-as-a-distinct-entity
#10
Valeria Barresi, Simona Lionti, Laura Valori, Giovanna Gallina, Maria Caffo, Sabrina Rossi
We report a unique case of dual-genotype oligoastrocytoma characterized by IDH2 gene mutation. The tumor was resected from the temporal lobe of a 25-year-old man. At histological examination with hematoxylin and eosin stain, it showed distinct oligodendroglial and astrocytic areas. The former retained alpha-thalassaemia/mental retardation X-linked (ATRX) immuno-expression and had absent staining for p53, while the latter had ATRX loss and p53 over-expression. Molecular analyses were separately assessed in the 2 tumor components...
April 17, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28418989/impact-of-antiretroviral-treatment-containing-tenofovir-difumarate-on-the-telomere-length-of-aviremic-hiv-infected-patients
#11
Rocio Montejano, Natalia Stella-Ascariz, Susana Monge, José I Bernardino, Ignacio Pérez-Valero, MaLuisa Montes, Eulalia Valencia, Luz Martín-Carbonero, Victoria Moreno, Juan González-García, Francisco Arnalich, Jesús Mingorance, Laura Pintado Berniches, Rosario Perona, José R Arribas
OBJECTIVE: To evaluate the in vivo relevance of the inhibitory effect of tenofovir upon telomerase activity observed in vitro. DESIGN: Cross sectional study of HIV-infected patients with suppressed virological replication (HIV RNA < 50 copies/mL for more than one year) Methods: Telomere length in whole blood was measured by quantitative real time PCR. We performed a multivariate analysis to elucidate variables associated with telomere length and also evaluated the association between telomere length and use of tenofovir difumarate (TDF) adjusted by significant confounders RESULTS:: 200 patients included, 72% male, median age 49 (IQR 45-54...
April 7, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28418878/the-tert-rs2736100-polymorphism-increases-cancer-risk-a-meta-analysis
#12
Hui Li, Yanyan Xu, Hua Mei, Liang Peng, Xiaojie Li, Jianzhou Tang
Abnormal telomerase activity is implicated in cancer initiation and development. The rs2736100 T > G polymorphism in the telomerase reverse transcriptase (TERT) gene, which encodes the telomerase catalytic subunit, has been associated with increased cancer risk. We conducted a meta-analysis to more precisely assess this association. After a comprehensive literature search of the PubMed and EMBASE databases up to November 1, 2016, 61 articles with 72 studies comprising 108,248 cases and 161,472 controls were included in our meta-analysis...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416747/the-tert-promoter-mutation-incidence-is-modified-by-germline-tert-rs2736098-and-rs2736100-polymorphisms-in-hepatocellular-carcinoma
#13
Xiaotian Yuan, Guanghui Cheng, Jingya Yu, Shunzhen Zheng, Chao Sun, Qing Sun, Kailin Li, Zhaomin Lin, Tiantian Liu, Ping Li, Yiteng Xu, Feng Kong, Magnus Bjorkholm, Dawei Xu
Telomerase activation via induction of the catalytic component telomerase reverse transcriptase (TERT) plays essential roles in malignant transformation. TERT promoter-activating mutations were recently identified as a novel mechanism to activate telomerase in hepatocellular carcinoma (HCC) and many other malignancies. In addition, single nucleotide polymorphisms (SNPs) in the TERT rs2736098 and rs2736100 are significantly associated with cancer susceptibility. It is currently unclear whether different germline TERT variants modify TERT promoter mutations...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416343/pigmented-epithelioid-melanocytoma-animal-type-melanoma-an-institutional-experience
#14
Michael J Bax, Marc D Brown, Paul G Rothberg, Todd S Laughlin, Glynis A Scott
BACKGROUND: Pigmented epithelioid melanocytoma (PEM) is an uncommon, recently described entity with unknown biologic behavior. There is a high rate of regional metastases, but limited evidence of distant metastases or disease-related death. OBJECTIVE: We sought to report our series of patients given a diagnosis of PEM at our institution and provide mutational analysis of genes commonly implicated in melanoma in 2 cases. METHODS: The pathology database was queried for cases of PEM diagnosed at the University of Rochester...
April 14, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28412741/opposite-effects-of-gcn5-and-pcaf-knockdowns-on-the-alternative-mechanism-of-telomere-maintenance
#15
Maya Jeitany, Dalal Bakhos-Douaihy, David C Silvestre, Jose R Pineda, Nicolas Ugolin, Angela Moussa, Laurent R Gauthier, Didier Busso, Marie-Pierre Junier, Hervé Chneiweiss, Sylvie Chevillard, Chantal Desmaze, François D Boussin
Cancer cells can use a telomerase-independent mechanism, known as alternative lengthening of telomeres (ALT), to elongate their telomeres. General control non-derepressible 5 (GCN5) and P300/CBP-associated factor (PCAF) are two homologous acetyltransferases that are mutually exclusive subunits in SAGA-like complexes. Here, we reveal that down regulation of GCN5 and PCAF had differential effects on some phenotypic characteristics of ALT cells. Our results suggest that GCN5 is present at telomeres and opposes telomere recombination, in contrast to PCAF that may indirectly favour them in ALT cells...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411413/sexual-intimacy-in-couples-is-associated-with-longer-telomere-length
#16
Tomás Cabeza de Baca, Elissa S Epel, Theodore F Robles, Michael Coccia, Amanda Gilbert, Eli Puterman, Aric A Prather
High-quality relationships have been shown to be beneficial for physical and mental health. This study examined overall relationship satisfaction and perceived stress as well as daily reports of partner support, partner conflict, and physical intimacy obtained over the course of one week in a sample of 129 high and low stress mothers. Telomere length was examined in whole blood, as well as the two cell subpopulations: peripheral blood mononuclear cells (PBMCs) and granulocytes. Telomerase activity was measured in PBMCs...
March 25, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28411378/immune-responses-and-long-term-disease-recurrence-status-after-telomerase-based-dendritic-cell-immunotherapy-in-patients-with-acute-myeloid-leukemia
#17
Hanna J Khoury, Robert H Collins, William Blum, Patrick S Stiff, Laurence Elias, Jane S Lebkowski, Anita Reddy, Kevin P Nishimoto, Debasish Sen, Edward D Wirth, Casey C Case, John F DiPersio
BACKGROUND: Telomerase activity in leukemic blasts frequently is increased among patients with high-risk acute myeloid leukemia (AML). In the current study, the authors evaluated the feasibility, safety, immunogenicity, and therapeutic potential of human telomerase reverse transcriptase (hTERT)-expressing autologous dendritic cells (hTERT-DCs) in adult patients with AML. METHODS: hTERT-DCs were produced from patient-specific leukapheresis, electroporated with an mRNA-encoding hTERT and a lysosomal-targeting sequence, and cryopreserved...
April 14, 2017: Cancer
https://www.readbyqxmd.com/read/28410238/physical-activity-and-telomere-length-impact-of-aging-and-potential-mechanisms-of-action
#18
REVIEW
Nicole C Arsenis, Tongjian You, Elisa F Ogawa, Grant M Tinsley, Li Zuo
Telomeres protect the integrity of information-carrying DNA by serving as caps on the terminal portions of chromosomes. Telomere length decreases with aging, and this contributes to cell senescence. Recent evidence supports that telomere length of leukocytes and skeletal muscle cells may be positively associated with healthy living and inversely correlated with the risk of several age-related diseases, including cancer, cardiovascular disease, obesity, diabetes, chronic pain, and stress. In observational studies, higher levels of physical activity or exercise are related to longer telomere lengths in various populations, and athletes tend to have longer telomere lengths than non-athletes...
March 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408741/establishment-of-a-novel-human-lymphoblastic-cell-strain-with-the-long-arm-of-chromosome-11-aberration-without-mll-rearrangement
#19
Qian Wang, Lin Zhuang, Pei Li, Qiang Niu, Ping Zhu, Miao-Xia He, Hui Jiang, Chang-Cheng Liu, Min-Jun Wang, Li Chen, Hui Cheng, Yan Ma, Xiao-Xia Hu, Yi-Ping Hu, Xiao-Ping Xu
At present, all cell strains derived from acute lymphoblastic leukemia (ALL) patients with the long arm of chromosome 11 aberration are accompanied with mixed lineage leukemia (MLL) gene rearrangement. In this study, we established a permanent ALL cell strain CHH-1 with the long arm of chromosome 11 aberration and without MLL rearrangement, hoping that it could be used for the research of ALL with such genetic abnormality. CHH-1 cell strain was certified through morphology, immunophenotype, genetics and immunoglobulin (Ig) gene rearrangement analysis...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28408374/expression-of-biglycan-in-first-trimester-chorionic-villous-sampling-placental-samples-and-altered-function-in-telomerase-immortalized-microvascular-endothelial-cells
#20
Amy Chui, Tilini Gunatillake, Shaun P Brennecke, Vera Ignjatovic, Paul T Monagle, John M Whitelock, Dagmar E van Zanten, Jasper Eijsink, Yao Wang, James Deane, Anthony J Borg, Janet Stevenson, Jan Jaap Erwich, Joanne M Said, Padma Murthi
OBJECTIVE: Biglycan (BGN) has reduced expression in placentae from pregnancies complicated by fetal growth restriction (FGR). We used first trimester placental samples from pregnancies with later small for gestational age (SGA) infants as a surrogate for FGR. The functional consequences of reduced BGN and the downstream targets of BGN were determined. Furthermore, the expression of targets was validated in primary placental endothelial cells isolated from FGR or control pregnancies. APPROACH AND RESULTS: BGN expression was determined using real-time polymerase chain reaction in placental tissues collected during chorionic villous sampling performed at 10 to 12 weeks' gestation from pregnancies that had known clinical outcomes, including SGA...
April 13, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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