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https://www.readbyqxmd.com/read/29156824/37-kda-lrp-flag-enhances-telomerase-activity-and-reduces-senescent-markers-in-vitro
#1
Tyrone C Otgaar, Eloise Ferreira, Sibusiso Malindisa, Martin Bernert, Boitelo T Letsolo, Stefan F T Weiss
One of the core regulators of cellular aging are telomeres, repetitive DNA sequences at the ends of chromosomes that are maintained by the ribonucleoprotein DNA polymerase complex, telomerase. Recently, we demonstrated that knockdown of the 37kDa/ 67kDa laminin receptor (LRP/LR), a protein that promotes cell viability in tumorigenic and normal cells, reduces telomerase activity. We therefore hypothesized that upregulating LRP/LR might increase telomerase activity and impede aging. Here we show that overexpression of LRP::FLAG resulted in significantly elevated hTERT levels, telomerase activity and telomere length, respectively, with concomitantly reduced levels of senescence markers...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156735/telomerase-reverse-transcriptase-mediates-emt-through-nf-%C3%AE%C2%BAb-signaling-in-tongue-squamous-cell-carcinoma
#2
Yan Wu, Chunxiang Bian, Chunlin Zhen, Liu Liu, Zhenghong Lin, Muhammad Farrukh Nisar, Mei Wang, Jörg W Bartsch, Enyi Huang, Ping Ji, Li Yang, Yanhong Yu, Junfeng Yang, Xuemei Jiang, Julia Li Zhong
Locoregional lymph nodes metastasis in oral tongue squamous cell carcinoma represents one of important and common prognostic factors for poor clinical outcome. The human Telomerase Reverse Transcriptase (hTERT) is one of key players in cancer metastasis and stemness, but its exact function in tongue squamous cell carcinoma remains unknown. Here, we aim to understand the role of hTERT by utilizing the CRISPR/Cas9 gene editing system to deplete hTERT in the SCC-15 cell line. Functional comparison of SCC-15 control and knockout cells (hTERT(-/-)) showed that loss of hTERT suppressed cell proliferation and migration/invasion...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29145503/zinc-sulfate-contributes-to-promote-telomere-length-extension-via-increasing-telomerase-gene-expression-telomerase-activity-and-change-in-the-tert-gene-promoter-cpg-island-methylation-status-of-human-adipose-derived-mesenchymal-stem-cells
#3
Raheleh Farahzadi, Ezzatollah Fathi, Seyed Alireza Mesbah-Namin, Nosratollah Zarghami
The use of mesenchymal stem cells (MSCs) for cell therapy and regenerative medicine has received widespread attention over the past few years, but their application can be complicated by factors such as reduction in proliferation potential, the senescent tendency of the MSCs upon expansion and their age-dependent decline in number and function. It was shown that all the mentioned features were accompanied by a reduction in telomerase activity and telomere shortening. Furthermore, the role of epigenetic changes in aging, especially changes in promoter methylation, was reported...
2017: PloS One
https://www.readbyqxmd.com/read/29141053/clinical-and-prognostic-value-of-htert-mrna-expression-in-patients-with-non-small-cell-lung-cancer
#4
Marzena Zalewska-Ziob, Katarzyna Dobija-Kubica, Krzysztof Biernacki, Brygida Adamek, Janusz Kasperczyk, Krzysztof Bruliński, Zofia Ostrowska
Telomerase, undetectable in normal somatic cells, plays a critical role in carcinogenesis of the majority of human tumors including lung carcinoma. The aim of our study was to determine human telomerase reverse transcriptase (hTERT) mRNA expression in patients with non-small cell lung cancer (NSCLC) in order to estimate its usefulness as diagnostic and/or prognostic factor. hTERT expression was analyzed in a group of 12 females and 28 males with NSCLC using Quantitative Real-Time Polymerase Chain Reaction (QRT-PCR method) in cancerous and non-cancerous lung tissues...
November 15, 2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/29137220/stromal-cyclin-d1-promotes-heterotypic-immune-signaling-and-breast-cancer-growth
#5
Timothy G Pestell, Xuanmao Jiao, Mukesh Kumar, Amy R Peck, Marco Prisco, Shengqiong Deng, Zhiping Li, Adam Ertel, Mathew C Casimiro, Xiaoming Ju, Agnese Di Rocco, Gabriele Di Sante, Sanjay Katiyar, Alison Shupp, Michael P Lisanti, Pooja Jain, Kongming Wu, Hallgeir Rui, Douglas C Hooper, Zuoren Yu, Aaron R Goldman, David W Speicher, Lisa Laury-Kleintop, Richard G Pestell
The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that drives cell autonomous cell cycle progression and proliferation. Herein we show cyclin D1 abundance is increased >30-fold in the stromal fibroblasts of patients with invasive breast cancer, associated with poor outcome. Cyclin D1 transformed hTERT human fibroblast to a cancer-associated fibroblast phenotype. Stromal fibroblast expression of cyclin D1 (cyclin D1(Stroma)) in vivo, enhanced breast epithelial cancer tumor growth, restrained apoptosis, and increased autophagy...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29125889/pterostilbene-down-regulates-htert-at-physiological-concentrations-in-breast-cancer-cells-potentially-through-the-inhibition-of-cmyc
#6
Michael Daniel, Trygve O Tollefsbol
Human telomerase reverse transcriptase (hTERT) encodes the catalytic subunit of telomerase, which has been shown to be upregulated in many cancers. Pterostilbene is a naturally occurring stilbenoid and phytoalexin found primarily in blueberries that exhibits antioxidant activity and inhibits the growth of various cancer cell types. Therefore, the aim of this study was to determine whether treatment with pterostilbene, at physiologically achievable concentrations, can inhibit the proliferation of breast cancer cells and down-regulate the expression of hTERT...
November 10, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29109762/stability-analysis-on-the-radioactive-iodine-labelled-prostate-cancer-specific-recombinant-oncolytic-adenovirus
#7
Jiahe Zhou, Lin Hao, Zhenduo Shi, Songyi Ning, Houguang He, Yan Zhao, Yang Dong, Zhigang Li, Jiuxiang He, Guanghui Zang, Conghui Han
The aim of the present study was to construct the (125)I-replication-selective oncolytic adenovirus (RSOAds)-human telomerase reverse transcriptase (hTERT)/prostate specific antigen (PSA) nuclide-oncolytic virus marker by labelling the hTERT/PSA double-regulation replicative oncolytic adenovirus with (125)I nuclide, and investigate the influence of viral markers under various reaction conditions on labelling efficiency. N-bromosuccinimide (NBS) was used as the oxidizer for (125)I labelling, and the best conditions for labelling were identified through the reactions between oncolytic adenovirus at various concentrations and NBS...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29093759/increased-hydrophobic-block-length-of-ptdms-promotes-protein-internalization
#8
Coralie M Backlund, Federica Sgolastra, Ronja Otter, Lisa Minter, Toshihide Takeuchi, Shiroh Futaki, Gregory N Tew
The plasma membrane is a major obstacle in the development and use of biomacromolecules for intracellular therapeutic applications. Protein transduction domains (PTDs) have been used to overcome this barrier, but often require covalent conjugation to their cargo and can be time consuming to synthesize. Synthetic monomers can be designed to mimic the amino acid moieties in PTDs, and their resulting polymers provide a well-controlled platform to vary molecular composition for structure-activity relationship studies...
December 28, 2016: Polymer Chemistry
https://www.readbyqxmd.com/read/29083232/co-delivery-of-curcumin-and-chrysin-by-polymeric-nanoparticles-inhibit-synergistically-growth-and-htert-gene-expression-in-human-colorectal-cancer-cells
#9
Javid Lotfi-Attari, Younes Pilehvar-Soltanahmadi, Mehdi Dadashpour, Shahriar Alipour, Raana Farajzadeh, Shahrzad Javidfar, Nosratollah Zarghami
Nanoparticle (NP)-based combinational chemotherapy has been proposed as a potent approach for improving intracellular drug concentrations and attaining synergistic effects in colorectal cancer therapy. Here, two well-known herbal substances, Curcumin (Cur) and Chrysin (Chr), were co-encapsulated in PEGylated PLGA NPs and investigated their synergistic inhibitory effect against Caco-2 cancer cells. Characterization of nanoformulated drugs was determined using DLS, FTIR, TEM, and SEM. Drug release study was performed using dialysis method...
October 30, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/29081696/implication-of-gastric-cancer-molecular-genetic-markers-in-surgical-practice
#10
REVIEW
Marina V Nemtsova, Vladimir V Strelnikov, Alexander S Tanas, Igor I Bykov, Dmitry V Zaletaev, Viktoria V Rudenko, Alexander I Glukhov, Tatiana V Kchorobrich, Yi Li, Vadim V Tarasov, George E Barreto, Gjumrakch Aliev
INTRODUCTION: We have investigated aberrant methylation of genes CDH1, RASSF1A, MLH1, N33, DAPK, expression of genes hTERT, MMP7, MMP9, BIRC5 (survivin), PTGS2, and activity of telomerase of 106 gastric tumor samples obtained intra-operatively and 53 gastric tumor samples from the same group of patients obtained endoscopically before surgery. Biopsy specimens obtained from 50 patients with chronic calculous cholecystitis were used as a control group. Together with tissue samples obtained from different sites remote to tumors, a total of 727 samples have been studied...
October 2017: Current Genomics
https://www.readbyqxmd.com/read/29080039/myc-dependent-downregulation-of-telomerase-by-flt3-inhibitors-is-required-for-their-therapeutic-efficacy-on-acute-myeloid-leukemia
#11
Xiaolu Zhang, Bingnan Li, Jingya Yu, Jenny Dahlström, Anh Nhi Tran, Magnus Björkhom, Dawei Xu
The somatic mutation of FLT3 occurs in 30% of acute myeloid leukemia (AML), with the majority of mutations exhibiting internal tandem duplication (ITD). On the other hand, the induction of telomerase reverse transcriptase (hTERT) and the activation of telomerase is a key step in AML development. Here, we sought to determine whether FLT3ITD regulates hTERT expression in AML cells and whether hTERT expression affects FLT3 inhibitors' therapeutic efficacy on AML. FLT3ITD-harboring AML cell lines and primary cells treated with the FLT3 inhibitor PKC412 displayed a rapid decline in the levels of hTERT mRNA and telomerase activity...
October 27, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29079368/p14-methylation-an-epigenetic-signature-of-salivary-gland-mucoepidermoid-carcinoma-in-the-serbian-population
#12
Nadja Nikolic, Jelena Carkic, Ivana Ilic Dimitrijevic, Najib Eljabo, Milena Radunovic, Boban Anicic, Nasta Tanic, Markus Falk, Jelena Milasin
OBJECTIVE: To investigate the prevalence of p16(INK4 a), p14(ARF), tumor protein p53 (TP53), and human telomerase reverse transcriptase (hTERT) promoter hypermethylation in mucoepidermoid carcinomas (MECs) and search for a possible association between methylation status and clinicopathological parameters. STUDY DESIGN: DNA extracted from 35 formalin-fixed and paraffin-embedded MEC samples and 10 normal salivary gland (NSG) tissue samples was analyzed for the presence of promoter hypermethylation using methylation-specific polymerase chain reaction testing...
September 28, 2017: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/29074462/correlation-between-telomerase-and-mtor-pathway-in-cancer-stem-cells
#13
REVIEW
Fatma Dogan, Cigir Biray Avci
Cancer stem cells (CSCs), which are defined as a subset of tumor cells, are able to self-renew, proliferate, differentiate similar to normal stem cells. Therefore, targeting CSCs has been considered as a new approach in cancer therapy. The mammalian target of rapamycin (mTOR) is a receptor tyrosine kinase which plays an important role in regulating cell proliferation, differentiation, cell growth, self-renewal in CSCs. On the other hand, hTERT overactivation provides replicative feature and immortality to CSCs, so the stemness and replicative properties of CSCs depend on telomerase activity...
October 23, 2017: Gene
https://www.readbyqxmd.com/read/29068150/detection-of-circulating-tumor-cells-using-ohsv1-htert-gfp-in-lung-cancer
#14
Hongjun Gao, Wenjing Liu, Shaoxing Yang, Wen Zhang, Xiaoyan Li, Haifeng Qin, Weixia Wang, Changyun Zhao
BACKGROUND: This study was conducted to evaluate the clinical utility of the oHSV1-hTERT-GFP circulating tumor cell (CTC) detection method in the peripheral blood of patients with lung cancer by comparing its sensitivity to the CellSearch CTC detection method. METHODS: The oHSV1-hTERT-GFP and CellSearch CTC detection methods were compared using peripheral blood samples of patients pathologically diagnosed with lung cancer. RESULTS: A total of 240 patients with lung cancer were recruited, including 89 patients who were newly diagnosed and 151 patients who had previously received treatment...
October 25, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/29066480/detection-of-the-single-nucleotide-polymorphism-at-position-rs2735940-in-the-human-telomerase-reverse-transcriptase-gene-by-the-introduction-of-a-new-restriction-enzyme-site-for-the-pcr-rflp-assay
#15
Sihua Wang, Mingcui Ding, Xiaoran Duan, Tuanwei Wang, Xiaolei Feng, Pengpeng Wang, Wu Yao, Yongjun Wu, Zhen Yan, Feifei Feng, Songcheng Yu, Wei Wang
It has been shown that the single nucleotide polymorphism (SNP) of the rs2735940 site in the human telomerase reverse transcriptase (hTERT) gene is associated with increased cancer risk. The traditional method to detect SNP genotypes is polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). However, there is a limitation to utilizing PCR-RFLP due to a lack of proper restriction enzyme sites at many polymorphic loci. This study used an improved PCR-RFLP method with a mismatched base for detection of the SNP rs2735940...
September 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/29039521/antitumoral-effect-of-arsenic-compound-sodium-metaarsenite-kml001-on-multiple-myeloma-cells
#16
Seo Ju Kim, Eun Shil Kim, Sujong Kim, Jieun Uhm, Young Woong Won, Byeong Bae Park, Jung Hye Choi, Young Yiul Lee
KML001 (sodium metaarsenite;NaAs2O3) is known to have antitumor activity against a variety of cancers. In this study, we examined its effect on multiple myeloma (MM). KML001 reduced the growth of all MM cell lines examined with an IC50 of 5x10‑8 M. Exposure to KML001 (5x10‑8 M) decreased levels of cyclins A/B1/D1/E1, CDK2/4/6 in U266 cells and increased the p21 and p27 levels. Furthermore, p21 became bound to CDK2/4/6, resulting in a reduction of CDK2/4/6 kinase activity. The cleaved forms of Bcl-2, and caspases‑3, ‑8 and ‑9 were detected, and the anti-apoptotic molecule, Bax, also increased...
October 16, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29028335/metallo-supramolecular-complexes-enantioselectively-eradicate-cancer-stem-cells-in-vivo
#17
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, polymorphic 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...
November 1, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28992336/molecular-and-cytogenetic-effects-of-thai-royal-jelly-modulation-through-c-myc-h-tert-nrf2-ho-1-bcl2-bax-and-cyclins-in-human-lymphocytes-in-vitro
#18
Wantha Jenkhetkan, Sumon Thitiorul, Chalerm Jansom, Treetip Ratanavalachai
Royal jelly (RJ) is widely used as a food supplement for anti-aging and beauty. However, its use has been linked to asthma and hemorrhagic colitis. Since its mechanisms of toxicity have not been fully identified, we conducted an investigation to elucidate its molecular and cytogenetic effects. Using human lymphocytes in vitro, treatments with RJ (0.0005-5 mg/ml) for 3 h did not induce sister chromatid exchanges until 5 mg/ml was used. Treatments for 24 h showed a dose-dependent reduction in BCL2/BAX, c-MYC/BAX and HO-1/BAX ratios...
September 15, 2017: Mutagenesis
https://www.readbyqxmd.com/read/28990525/a-human-proximal-tubular-epithelial-cell-model-to-explore-a-knowledge-gap-on-neonatal-drug-disposition
#19
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
https://www.readbyqxmd.com/read/28984046/inhibition-of-telomerase-activity-and-induction-of-apoptosis-by-rhodospirillum-rubrum-l-asparaginase-in-cancer-jurkat-cell-line-and-normal-human-cd4-%C3%A2-t-lymphocytes
#20
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 rubrum L-asparaginase mutant E149R, V150P, F151T (RrA) down-regulates telomerase activity due to its ability to inhibit the expression of telomerase catalytic subunit hTERT. The aim of this study was to define the effect of short-term and long-term RrA exposure on proliferation of cancer Jurkat cell line and normal human CD4(+) T lymphocytes. RrA could inhibit telomerase activity in dose- and time-dependent manner in both Jurkat and normal CD4(+) T cells. Continuous RrA exposure of these cells resulted in shortening of telomeres followed by cell cycle inhibition, replicative senescence, and development of apoptosis...
November 2017: Cancer Medicine
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