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https://www.readbyqxmd.com/read/28636941/highly-aggressive-metastatic-melanoma-cells-unable-to-maintain-telomere-length
#1
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/28636901/the-effect-of-cd34-cell-telomere-length-and-htert-expression-on-the-outcome-of-autologous-cd34-cell-transplantation-in-patients-with-chronic-heart-failure
#2
Jasmina-Ziva Rozman, Maja Pohar Perme, Mojca Jez, Elvira Malicev, Metka Krasna, Srdjan Novakovic, Bojan Vrtovec, Primoz Rozman
Age-related telomere attrition in stem/progenitor cells may diminish their functional capacity and thereby impair the outcome of cell-based therapies. The aim of the present study was to investigate the effect of CD34(+) cell telomere length and hTERT expression on the clinical outcome of autologous CD34(+) cell transplantation. We studied 43 patients with cardiomyopathy. Their peripheral blood CD34(+) cells were mobilized with granulocyte colony-stimulating factor, enriched by immunoselection and delivered transendocardially...
June 18, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28630280/ki-67-contributes-to-normal-cell-cycle-progression-and-inactive-x-heterochromatin-in-p21-checkpoint-proficient-human-cells
#3
Xiaoming Sun, Aizhan Bizhanova, Timothy D Matheson, Jun Yu, Julie L Zhu, Paul D Kaufman
Ki-67 protein is widely used as a tumor proliferation marker. However, whether Ki-67 affects cell cycle progression has been controversial. Here, we demonstrate that depletion of Ki-67 in human hTERT-RPE1, WI-38, IMR90, hTERT-BJ cell lines and primary fibroblast cells slowed entry into S phase and coordinately downregulated genes related to DNA replication. Some gene expression changes were partially relieved in Ki-67-depleted hTERT-RPE1 cells by co-depletion of the Rb checkpoint protein, but more thorough suppression of the transcriptional and cell cycle defects was observed upon depletion of cell cycle inhibitor p21...
June 19, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28627695/targeted-cdx2-expression-inhibits-aggressive-phenotypes-of-colon-cancer-cells-in-vitro-and-in-vivo
#4
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
#5
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/28627633/robust-cancer-specific-gene-expression-by-a-novel-cassette-with-htert-and-cmv-promoter-elements
#6
Masakiyo Sakaguchi, Takuya Sadahira, Hideo Ueki, Rie Kinoshita, Hitoshi Murata, Ken-Ichi Yamamoto, Junichiro Futami, Yasutomo Nasu, Kazuhiko Ochiai, Hiromi Kumon, Nam-Ho Huh, Masami Watanabe
We developed and validated a novel hTERT/CMV promoter element-driven gene expression cassette that can robustly enhance cancer-specific gene expression. The following gene expressional elements were located in tandem within the plasmid construct: [hTERT core promoter, cytomegalovirus (CMV) minimized promoter, RU5' sequence, an inserted gene, BGH polyA, hTERT enhancer]; this is hereafter referred to as the hT/Cm-R-hT construct. Using various human cancer cell lines and normal cells, the cancer-specific transcription of the green fluorescent protein (GFP) gene was examined by western blotting and fluorescence microscopy...
June 12, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28627628/phosphorothioate%C3%A2-modified-antisense-oligonucleotides-against-human-telomerase-reverse-transcriptase-sensitize-cancer-cells-to-radiotherapy
#7
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/28623509/telomerase-and-drug-resistance-in-cancer
#8
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/28610415/synergistic-anticancer-effects-of-silibinin-and-chrysin-in-t47d-breast-cancer-cells
#9
Zahra Javan Maasomi, Younes Pilehvar Soltanahmadi, Mehdi Dadashpour, Shahriar Alipour, Somayeh Abolhasani, Nosratollah Zarghami
Objective: Breast cancer is one of the most significant causes of female cancer death worldwide. Although several chemotherapeutics have been developed to treat this type of cancer, issues remain such as low survival rates and high reoccurrence after chemotherapy and radiotherapy. To explore a chemopreventive approach to enhancing breast cancer treatment efficacy, the antiproliferative effects of a combination of chrysin and silibinin, two herbal substances, in T47D breast cancer cells were assessed. Materials and Methods: Cytotoxicity of the agents singly and in combination was evaluated by MTT assay...
May 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28594907/gastrointestinal-cancer-cells-treatment-with-bevacizumab-activates-a-vegf-autoregulatory-mechanism-involving-telomerase-catalytic-subunit-htert-via-pi3k-akt-hif-1%C3%AE-and-vegf-receptors
#10
Nadine Mahfouz, Roula Tahtouh, Nada Alaaeddine, Joelle El Hajj, Riad Sarkis, Ray Hachem, Issam Raad, George Hilal
BACKGROUND: Targeting angiogenesis has been considered a promising treatment of choice for a large number of malignancies, including gastrointestinal cancers. Bevacizumab is an anti-vascular endothelial growth factor (anti-VEGF) being used for this purpose. However, treatment efficacy is largely questioned. Telomerase activity, responsible for cancer cell immortality, is detected in 85-95% of human cancers and is considered a potential regulator of VEGF. The aim of our study was to investigate the interrelationship between VEGF and hTERT in gastrointestinal cancers and to explore cell response to a combined inhibition of telomerase and VEGF...
2017: PloS One
https://www.readbyqxmd.com/read/28587932/preliminary-evidence-that-age-and-sex-affect-exercise-induced-htert-expression
#11
Travis G Cluckey, Nathan C Nieto, Bridger M Rodoni, Tinna Traustadóttir
The ability to repair cellular damage is reduced with aging, resulting in cellular senescence. Telomeres shorten as cells divide but the rate of telomere attrition is modulated by telomerase, an enzyme that adds nucleotides to the chromosome. Shelterin is a protein complex that acts as a negative regulator of telomerase. The aim of the present study was to investigate age-related differences in telomerase and shelterin responses to acute exercise. We hypothesized that acute exercise would stimulate an increased activity of telomerase (measured by telomerase reverse transcriptase, hTERT) without an increase in activity of shelterin (measured by telomeric repeat binding factor 2, TRF2) in both young and older individuals and that hTERT response would be attenuated in older individuals...
June 3, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28587656/the-correlations-between-dna-methylation-and-polymorphisms-in-the-promoter-region-of-the-human-telomerase-reverse-transcriptase-htert-gene-with-postoperative-recurrence-in-patients-with-thyroid-carcinoma-tc
#12
Jian-Jun Li, Ping Chen Jue-Ru Zheng, Yao-Zong Wang
BACKGROUND: This study aims at exploring the correlations between DNA methylation and polymorphisms in the promoter region of the human telomerase reverse transcriptase (hTERT) gene and postoperative recurrence in patients with thyroid carcinoma (TC). METHODS: A total of 312 patients diagnosed with TC were chosen for the study and categorized into recurrence (n = 75) and non-recurrence (n = 237) groups. The hTERT rs2736100 and rs2736098 polymorphisms were detected by performing polymerase chain reaction-restriction fragment length polymorphism...
June 6, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28584529/htert-immortalized-bone-mesenchymal-stromal-cells-expressing-rat-galanin-via-a-single-tetracycline-inducible-lentivirus-system
#13
Ke An, Hui-Ping Liu, Xiao-Long Zhong, David Y B Deng, Jing-Jun Zhang, Zhi-Heng Liu
The use of human telomerase reverse transcriptase-immortalized bone marrow mesenchymal stromal cells (hTERT-BMSCs) as vehicles to deliver antinociceptive galanin (GAL) molecules into pain-processing centers represents a novel cell therapy strategy for pain management. Here, an hTERT-BMSCs/Tet-on/GAL cell line was constructed using a single Tet-on-inducible lentivirus system, and subsequent experiments demonstrated that the secretion of rat GAL from hTERT-BMSCs/Tet-on/GAL was switched on and off under the control of an inducer in a dose-dependent manner...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28580306/enterolactone-reduces-telomerase-activity-and-the-level-of-its-catalytic-subunit-in-breast-cancer-cells
#14
Davod Ilbeigi, Mitra Nourbakhsh, Shahnaz Khaghani, Nahid Einollahi, Nejat Kheiripour, Zafar Gholinejad, Mohammad Alaee, Mostafa Saberian
OBJECTIVE: There is a positive correlation between higher serum phytoestrogen concentrations and lower risk of breast cancer. The activation of telomerase is crucial for the growth of cancer cells; therefore, the aim of this study was to examine the effects of enterolactone (ENL) and enterodiol (END) on this enzyme. MATERIALS AND METHODS: In this experimental study, we performed the viability assay to determine the effects of different concentrations of ENL and END on cell viability, and the effective concentrations of these two compounds on cell growth...
2017: Cell Journal
https://www.readbyqxmd.com/read/28577498/telomerase-reverse-transcriptase-genetically-modified-adipose-tissue-derived-stem-cells-improves-erectile-dysfunction-by-inhibiting-oxidative-stress-and-enhancing-proliferation-in-rat-model
#15
Xiao-Jun Wu, Wen-Hao Shen, Peng He, Xiao-Zhou Zhou, Yi Zhi, Qiang Dai, Zhi-Wen Chen, Zhan-Song Zhou
Erectile dysfunction (ED) is considered to be incapable of obtaining or/and keeping a sufficient erection function to receive the satisfactory during the sexual intercourse. This study aims to investigate the effects of telomerase reverse transcriptase (hTERT) modified adipose tissue derived stem cells (ADSCs) autologously injected into cavernosa of the ED rats on erectile function. The ADSCs were isolated form the rat subcutaneous adipose tissue sample, and identified by examining the CD29 and CD44 molecule...
May 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28576827/the-transcriptional-repressor-gatad2b-mediates-progesterone-receptor-suppression-of-myometrial-contractile-gene-expression
#16
Chien-Cheng Chen, Alina P Montalbano, Imran Hussain, Wan-Ru Lee, Carole R Mendelson
The mechanisms whereby progesterone (P4) acting via progesterone receptor (PR) inhibits proinflammatory/contractile gene expression during pregnancy are incompletely defined. Using immortalized human myometrial (hTERT-HM) cells stably expressing wild-type PR-A or PR-B (PRWT), we found that P4 significantly inhibited IL-1β induction of the NF-κB target genes, COX-2 and IL-8 P4/PRWT transrepression occurred at the level of transcription initiation and was mediated by decreased recruitment of NF-κB p65 and RNA Pol II to COX-2 and IL-8 promoters...
June 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28572671/interaction-studies-of-carbon-nanomaterials-and-plasma-activated-carbon-nanomaterials-solution-with-telomere-binding-protein
#17
Pankaj Attri, Jitender Gaur, Sooho Choi, Minsup Kim, Rohit Bhatia, Naresh Kumar, Ji Hoon Park, Art E Cho, Eun Ha Choi, Weontae Lee
Most cancer cells have telomerase activity because they can express the human telomerase reverse transcriptase (hTERT) gene. Therefore, the inhibition of the hTERT expression can play an important role in controlling cancer cell proliferation. Our current study aims to inhibit hTERT expression. For this, we synthesized graphene oxide (GO) and a functionalized multiwall carbon nanotube (f-MWCNT), latter treated them with cold atmospheric pressure plasma for further analysis of the hTERT expression. The inhibition of hTERT expression by GO, f-MWCNT, plasma activated GO solution (PGOS), and plasma activated f-MWCNT solution (PCNTS), was studied using two lung cancer cell lines, A549 and H460...
June 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28570625/an-androgen-response-element-driven-reporter-assay-for-the-detection-of-androgen-receptor-activity-in-prostate-cells
#18
Waqas Azeem, Margrete Reime Hellem, Jan Roger Olsen, Yaping Hua, Kristo Marvyin, Yi Qu, Biaoyang Lin, Xisong Ke, Anne Margrete Øyan, Karl-Henning Kalland
The androgen receptor (AR) transcription factor plays a key role in the development and progression of prostate cancer, as is evident from the efficacy of androgen-deprivation therapy, AR is also the most frequently mutated gene, in castration resistant prostate cancer (CRPC). AR has therefore become an even more attractive therapeutic target in aggressive and disseminated prostate cancer. To investigate mechanisms of AR and AR target gene activation in different subpopulations of prostate cancer cells, a toolkit of AR expressor and androgen response element (ARE) reporter vectors were developed...
2017: PloS One
https://www.readbyqxmd.com/read/28559013/establishment-and-genomic-characterization-of-primary-salivary-duct-carcinoma-cell-line
#19
Jie Li, Yohitsugu Mitani, Pulivarthi H Rao, Laszlo Perlaky, Bin Liu, Randal S Weber, Adel K El-Naggar
OBJECTIVES: To develop and characterize in vitro salivary duct carcinoma as a surrogate for functional studies. MATERIALS AND METHODS: Cells were dispersed from tumor tissue fragments under sterile conditions in RPMI media. Disassociated cells were cultivated, immortalized with hTERT and propagated for more than 100 passages. Morphologic, linage, cytogenetic and genomic analyses were performed on different passages of cell line and primary tumor. Soft agar growth was performed...
June 2017: Oral Oncology
https://www.readbyqxmd.com/read/28544703/high-ubiquitin-specific-protease-44-expression-induces-dna-aneuploidy-and-provides-independent-prognostic-information-in-gastric-cancer
#20
Sho Nishimura, Eiji Oki, Koji Ando, Makoto Iimori, Yu Nakaji, Yuichiro Nakashima, Hiroshi Saeki, Yoshinao Oda, Yoshihiko Maehara
Chromosomal instability (CIN), characterized by aneuploidy, is a major molecular subtype of gastric cancer. The deubiquitinase USP44 is an important regulator of APC activation in the spindle checkpoint and leads to proper chromosome separation to prevent aneuploidy. Aberrant expression of USP44 leads CIN in cells; however, the correlation between USP44 and DNA aneuploidy in gastric cancer is largely unknown. We analyzed USP44 expression in 207 patients with gastric cancer by immunohistochemistry and found that the proportion of USP44 expression was higher in gastric cancer tumors (mean, 39...
June 2017: Cancer Medicine
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