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https://www.readbyqxmd.com/read/29332354/inhibition-of-telomerase-potentiates-enzalutamide-efficiency-of-androgen-sensitive-human-prostate-cancer-cells
#1
Karaca Kaan Gecgel, Mustafa Muduroglu, Suat Erdogan
PURPOSE: Androgen deprivation therapy (ADT) is one of the main strategies to treat prostate cancer (PCa) at various stages of its development. Androgen receptor (AR) antagonists such as enzalutamide are mainstay treatments for castration-sensitive prostate cancer. Though, a majority of patients initially respond to ADT, most will eventually progress to castrate-resistant, due to the development of different mutations on the AR. PCa cells express high telomerase activity, and there is a correlation between the total activity of telomerase and the Gleason score...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29332343/clinical-relevance-of-telomerase-polymorphism-for-breast-cancer-a-systematic-review
#2
Katherine de Souza Rodrigues, Joao Nunes de Matos Neto, Rodrigo Haddad, Diego Madureira de Oliveira
PURPOSE: To perform a systematic review to explore the clinical relevance of hTERT polymorphisms for breast cancer (BC). METHODS: Twenty-nine polymorphic regions were evaluated after comprehensive searching of 1236 articles, and selection of 9 publications (total of 12986 cases and 16758 controls). RESULTS: About the influence of hTERT variants in BC risk, 3 studies showed that the variant rs2736098 was associated with increasing risk. The variants rs10069690 and rs2853676 were also described as risk factors for BC...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29331373/establishment-and-characterization-of-five-immortalized-human-scalp-dermal-papilla-cell-lines
#3
Mi Hee Kwack, Jung Min Yang, Gong Hee Won, Moon Kyu Kim, Jung Chul Kim, Young Kwan Sung
Dermal papilla (DP) regulates the growth and cycling of hair follicles. Cultured DP cells are useful for the study of their role in relation to hair growth and regeneration. However, cultivation of human DP cells is tedious and difficult. In addition, cultured DP cells possess a relatively short replicative life span, requiring immortalized human DP cell lines. We previously established an immortalized human DP cell line, SV40T-hTERT-DPC, by introducing human telomerase reverse transcriptase (hTERT) gene into the transformed cell line, SV40T-DPC...
January 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29311615/hoxc5-and-mir-615-3p-target-newly-evolved-genomic-regions-to-repress-htert-and-inhibit-tumorigenesis
#4
TingDong Yan, Wen Fong Ooi, Aditi Qamra, Alice Cheung, DongLiang Ma, Gopinath Meenakshi Sundaram, Chang Xu, Manjie Xing, LaiFong Poon, Jing Wang, Yan Ping Loh, Jess Hui Jie Ho, Joscelyn Jun Quan Ng, Muhammad Khairul Ramlee, Luay Aswad, Steve G Rozen, Sujoy Ghosh, Frederic A Bard, Prabha Sampath, Vinay Tergaonkar, James O J Davies, Jim R Hughes, Eyleen Goh, Xuezhi Bi, Melissa Jane Fullwood, Patrick Tan, Shang Li
The repression of telomerase activity during cellular differentiation promotes replicative aging and functions as a physiological barrier for tumorigenesis in long-lived mammals, including humans. However, the underlying mechanisms remain largely unclear. Here we describe how miR-615-3p represses hTERT expression. mir-615-3p is located in an intron of the HOXC5 gene, a member of the highly conserved homeobox family of transcription factors controlling embryogenesis and development. Unexpectedly, we found that HoxC5 also represses hTERT expression by disrupting the long-range interaction between hTERT promoter and its distal enhancer...
January 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29307345/regulation-of-signal-transduction-cascades-by-pterostilbenes-in-different-cancers-is-it-a-death-knell-for-oncogenic-pathways
#5
Ghazala Butt, Rukset Attar, Sobia Tabassum, Aliye Aras, Muhammad Imran Qadir, Ulku Ozbey, Nada Alaaeddine, Beraat Ozcelik, Ammad Ahmad Farooqi
Interdisciplinary research has revolutionized the field of medicine and we have witnessed exponential increase in the high-impact research in past few decades. However, the road to this burgeoning research field is obstacle-ridden because of intratumor heterogeneity, loss of apoptosis and dysregulation of spatio-temporally controlled signaling pathways. Ground-breaking findings obtained through genetic, genomic and proteomic studies have considerably improved our concepts related to the complexity of protein network and excitingly, discovery of miRNAs has added another layer of intricacy to quantitatively regulated gene networks...
December 15, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/29290038/tight-co-twin-similarity-of-monozygotic-twins-for-htert-protein-level-of-t-cell-subsets-for-telomere-length-and-mitochondrial-dna-copy-number-but-not-for-telomerase-activity
#6
Dóra Melicher, Anett Illés, Éva Pállinger, Árpád Ferenc Kovács, Levente Littvay, Ádám Domonkos Tárnoki, Dávid László Tárnoki, András Bikov, Mária Judit Molnár, Edit Irén Buzás, András Falus
Our study analyzed lymphocyte subpopulations of 32 monozygotic twins and compared the level of the catalytic reverse transcriptase protein subunit (hTERT) in T lymphocytes (Tly), helper- (Th), cytotoxic- (Tc) and regulatory T cell (Treg) subgroups. Four variables related to telomere and mitochondrial biology were simultaneously assessed, applying multi-parametric flow cytometry, TRAP-ELISA assay and qPCR standard curve method on peripheral blood mononuclear cell (PBMC) samples of genetically matched individuals...
December 30, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29288791/chromatin-modifications-of-htert-gene-in-htert-immortalized-human-mesenchymal-stem-cells-upon-exposure-to-radiation
#7
Nedime Serakinci, Pınar Mega Tiber, Oya Orun
Regulation of telomerase activity is thought to participate in the cellular response to ionizing radiation. Epigenetic mechanisms play a role in this regulation, as well as other mechanisms such as transcription, phosphorylation, etc. Here, we investigated chromatin modifications in telomerase promoter upon exposure to ionizing radiation in human mesenchymal stem cells (hMSC) and telomerase-immortalized hMSCs (hMSC-telo1) together with a hMSC-telo1 cell line in which TRF2 expression was partially repressed (siTRF2 hMSC-telo1)...
December 27, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/29288666/zeb1-stimulates-breast-cancer-growth-by-up-regulating-htert-expression
#8
Pan Yu, Xi Shen, Wen Yang, Yunke Zhang, Chunping Liu, Tao Huang
Dysfunctional cell proliferation and death are the foundation of the malignant biological characteristics of cancers. In this study, we discovered that ZEB1 was positively correlated with hTERT in breast invasive ductal carcinoma samples at both the mRNA and protein levels. Further, our in vitro study in breast cancer cell lines confirmed that ZEB1 regulates hTERT expression at the mRNA and protein levels; thus, hTERT promotes or inhibits telomerase activity, and telomere length is either protected or reduced...
December 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29286105/tsoong-induces-apoptosis-and-inhibits-proliferation-migration-and-invasion-of-pancreatic-ductal-adenocarcinoma-cells
#9
Yun-Peng Luan, Qi-Feng Li, Shi-Guo Wu, De-Chang Mao, Yan-Yun Deng, Rong-Wang Chen
The roots of Codonopsis cordifolioidea (classified as campanulaceae cordifolioidea), locally known as Tsoong, have been used as a tonic food. The major components isolated from Tsoong have been demonstrated to present anti‑human immunodeficiency virus‑1 activities and cytotoxicity against various tumor cell lines. However, the possible effects of the novel compound isolated from Tsoong, cordifoliketones A, on pancreatic ductal adenocarcinoma (PDAC) cells, are still unknown. In the present study, cordifoliketones A extractions were prepared from Tsoong, and the possible effects on PDAC cell growth, apoptosis, migration and invasion in vitro and in vivo were exlored...
December 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29280699/study-of-the-role-of-telomerase-in-colorectal-cancer-preliminary-report-and-literature-review
#10
M Minafra, R Laforgia, M G Sederino, S Fedele, A Delvecchio, S Lattarulo, G Carbotta, G Fabiano
AIM: The aim of our study is to focus on hTERT (human Telomerase Reverse Transcriptase) expression to identify tumoral tissue after a comparison to TP53 and KRAS. More than 85% of cancer cells contain genetic aberrations and also overexpression of hTERT, and, in fact, the promoter of hTERT characterizes all malignant cells. PATIENTS AND METHODS: Our sample is composed of 18 patients, including 10 with CRC that underwent surgical procedure and 8 patients without CRC, which represent the control group...
September 2017: Il Giornale di Chirurgia
https://www.readbyqxmd.com/read/29273061/diagnosis-and-treatment-of-alt-tumors-is-trabectedin-a-new-therapeutic-option
#11
REVIEW
Luca Pompili, Carlo Leonetti, Annamaria Biroccio, Erica Salvati
Telomeres are specialized nucleoprotein structures responsible for protecting chromosome ends in order to prevent the loss of genomic information. Telomere maintenance is required for achieving immortality by neoplastic cells. While most cancer cells rely on telomerase re-activation for linear chromosome maintenance and sustained proliferation, a significant population of cancers (10-15%) employs telomerase-independent strategies, collectively referred to as Alternative Lengthening of Telomeres (ALT). ALT mechanisms involve different types of homology-directed telomere recombination and synthesis...
December 22, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29251616/-the-influence-of-chorionic-gonadotropin-on-phenotype-conversion-and-htert-gene-expression-by-t-lymphocytes-of-different-degrees-of-differentiation
#12
M B Rayev, S A Zamorina, L S Litvinova, K A Yurova, O G Khaziakhmatova, V P Timganova, M S Bochkova, M D Kropaneva, P V Khramtsov
The effects of chorionic gonadotropin (hCG) on the expression of the hTERT gene in combination with the conversion of the phenotype of naive T-cells and T-cells of immune memory in vitro were studied. hCG inhibited expression of hTERT mRNA in naive T-cells (CD45RA+) and immune memory T cells (CD45RO+), causing a decrease in the replicative potential of the cells. The presence of hCG in the culture led to the conversion of the phenotype of T-lymphocytes. hCG reduced the number of proliferating T-cells of immune memory, estimated by phenotypic signs by differential gating...
November 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/29242210/reversible-immortalisation-enables-genetic-correction-of-human-muscle-progenitors-and-engineering-of-next-generation-human-artificial-chromosomes-for-duchenne-muscular-dystrophy
#13
Sara Benedetti, Narumi Uno, Hidetoshi Hoshiya, Martina Ragazzi, Giulia Ferrari, Yasuhiro Kazuki, Louise Anne Moyle, Rossana Tonlorenzi, Angelo Lombardo, Soraya Chaouch, Vincent Mouly, Marc Moore, Linda Popplewell, Kanako Kazuki, Motonobu Katoh, Luigi Naldini, George Dickson, Graziella Messina, Mitsuo Oshimura, Giulio Cossu, Francesco Saverio Tedesco
Transferring large or multiple genes into primary human stem/progenitor cells is challenged by restrictions in vector capacity, and this hurdle limits the success of gene therapy. A paradigm is Duchenne muscular dystrophy (DMD), an incurable disorder caused by mutations in the largest human gene: dystrophin. The combination of large-capacity vectors, such as human artificial chromosomes (HACs), with stem/progenitor cells may overcome this limitation. We previously reported amelioration of the dystrophic phenotype in mice transplanted with murine muscle progenitors containing a HAC with the entire dystrophin locus (DYS-HAC)...
December 14, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29230433/proangiogenic-activity-of-endometrial-epithelial-and-stromal-cells-in-response-to-estradiol-in-gelatin-hydrogels
#14
Jacquelyn C Pence, Kathryn B H Clancy, Brendan A C Harley
Biomaterial vascularization remains a major focus in the field of tissue engineering. Biomaterial culture of endometrial cells is described as a platform to inform the design of proangiogenic biomaterials. The endometrium undergoes rapid growth and shedding of dense vascular networks during each menstrual cycle mediated via estradiol and progesterone in vivo. Cocultures of endometrial epithelial and stromal cells encapsulated within a methacrylamide-functionalized gelatin hydrogel are employed. It is reported that proangiogenic gene expression profiles and vascular endothelial growth factor production are hormone dependent in endometrial epithelial cells, but that hormone signals have no effect on human telomerase reverse transcriptase (hTERT)-immortalized endometrial stromal cells...
September 2017: Advanced Biosystems
https://www.readbyqxmd.com/read/29228527/synergistic-effects-of-resistin-and-visfatin-as-adipocyte-derived-hormones-on-telomerase-gene-expression-in-ags-gastric-cancer-cell-line
#15
Masoumeh Mohammadi, Nosratollah Zarghami, Mehdi Hedayati, Sara Ghaemmaghami
Recently suggested that adipocytokines may play a role in pathogenesis and progression of certain cancers, especially in gastric cancer. The previous study showed Resistin and Visfatin, as adipocyte derived hormones, separately increases telomerase (hTERT) gene, the aim of this study is investigating synergic effects of Resistin and Visfatin on telomerase gene expression, in AGS gastric cancer cell line. In this study, human gastric cancer AGS cell line was selected. After stimulation with increasing concentrations of Resistin and Visfatin recombinant proteins for 24 and 48 hours, cell proliferation was assessed by XTT assay...
October 2017: Acta Medica Iranica
https://www.readbyqxmd.com/read/29221209/direct-hpv-e6-myc-interactions-induce-histone-modifications-pol-ii-phosphorylation-and-htert-promoter-activation
#16
Yiyu Zhang, Aleksandra Dakic, Renxiang Chen, Yuhai Dai, Richard Schlegel, Xuefeng Liu
Human Papillomavirus Viruses (HPVs) are associated with the majority of human cervical and anal cancers and 10-30% of head and neck squamous carcinomas. E6 oncoprotein from high risk HPVs interacts with the p53 tumor suppressor protein to facilitate its degradation and increases telomerase activity for extending the life span of host cells. We published previously that the Myc cellular transcription factor associates with the high-risk HPV E6 protein in vivo and participates in the transactivation of the hTERT promoter...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221158/epigenetic-silencing-of-mir-296-and-mir-512-ensures-htert-dependent-apoptosis-protection-and-telomere-maintenance-in-basal-type-breast-cancer-cells
#17
Roberto Dinami, Valentina Buemi, Rosanna Sestito, Antonina Zappone, Yari Ciani, Miguel Mano, Eleonora Petti, Andrea Sacconi, Giovanni Blandino, Mauro Giacca, Silvano Piazza, Roberta Benetti, Stefan Schoeftner
The catalytic subunit of the telomerase complex, hTERT, ensures unlimited proliferative potential of cancer cells by maintaining telomere function and protecting from apoptosis. Using a miRNA screening approach we identified miR-296-5p and miR-512-5p as miRNAs that target hTERT in breast cancer cells. Ectopic miR-296-5p and miR-512-5p reduce telomerase activity, drive telomere shortening and cause proliferation defects by enhancing senescence and apoptosis in breast cancer cells. In line with the relevance of hTERT expression for human cancer we found that miR-296-5p and miR-512-5p expression is reduced in human breast cancer...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220510/ciliopathy-associated-mutations-of-ift122-impair-ciliary-protein-trafficking-but-not-ciliogenesis
#18
Mariko Takahara, Yohei Katoh, Kentaro Nakamura, Tomoaki Hirano, Maho Sugawa, Yuta Tsurumi, Kazuhisa Nakayama
The intraflagellar transport (IFT) machinery containing the IFT-A and IFT-B complexes mediates ciliary protein trafficking. Mutations in the genes encoding the six subunits of the IFT-A complex (IFT43, IFT121, IFT122, IFT139, IFT140, and IFT144) are known to cause skeletal ciliopathies, including cranioectodermal dysplasia (CED). As the IFT122 subunit connects the core and peripheral subcomplexes of the IFT-A complex, it is expected to play a pivotal role in the complex. Indeed, we here showed that knockout (KO) of the IFT122 gene in hTERT-RPE1 cells using the CRISPR/Cas9 system led to a severe ciliogenesis defect, whereas KO of other IFT-A genes had minor effects on ciliogenesis but impaired ciliary protein trafficking...
December 6, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29215790/inhibition-of-fucosylation-in-human-invasive-ductal-carcinoma-reduces-e-selectin-ligand-expression-cell-proliferation-and-erk1-2-and-p38-mapk-activation
#19
M A Carrascal, M Silva, J S Ramalho, C Pen, M Martins, C Pascoal, C Amaral, I Serrano, M J Oliveira, R Sackstein, P A Videira
Breast cancer tissue overexpresses fucosylated glycans, such as sialyl-Lewis X/A (sLeX/A ), and α-1,3/4-fucosyltransferases in relation to increased disease progression and metastasis. These glycans in tumor circulating cells mediate binding to vascular E-selectin, initiating tumor extravasation. However, their role(s) in breast carcinogenesis is still unknown. Here, we aimed to define the contribution of the fucosylated structures, including sLeX/A , to cell adhesion, cell signaling and proliferation in invasive ductal carcinomas (IDC), the most frequent type of breast cancer...
December 7, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29203363/mechanism-of-action-of-g-quadruplex-forming-oligonucleotide-homologous-to-the-telomere-overhang-in-melanoma
#20
Gagan Chhabra, Luke Wojdyla, Mark Frakes, Zachary Schrank, Brandon Leviskas, Marko Ivancich, Pooja Vinay, Ramesh Ganapathy, Benjamin E Ramirez, Neelu Puri
T-oligo, a guanine-rich oligonucleotide (GRO) homologous to the 3'-telomeric overhang of telomeres, elicits potent DNA-damage responses in melanoma cells; however, its mechanism of action is largely unknown. GROs can form G-quadruplexes (G4) which are stabilized by the hydrogen-bonding of guanine residues. In this study, we confirmed the G4-forming capabilities of T-oligo using non-denaturing PAGE, NMR and immunofluorescence. Using an anti-G-quadruplex antibody (BG4) we showed that T-oligo can form G4 in the nuclei of melanoma cells...
December 1, 2017: Journal of Investigative Dermatology
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