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https://www.readbyqxmd.com/read/28078913/silibinin-loaded-magnetic-nanoparticles-inhibit-htert-gene-expression-and-proliferation-of-lung-cancer-cells
#1
Soumaye Amirsaadat, Younes Pilehvar-Soltanahmadi, Faraz Zarghami, Shahriar Alipour, Zohreh Ebrahimnezhad, Nosratollah Zarghami
Nanoparticle-based targeted drug delivery has the potential for rendering silibinin specifically at the favorite site using an external magnetic field. Also, it can circumvent the pitfalls of poor solubility. For this purpose, silibinin-loaded magnetic nanoparticles are fabricated, characterized and evaluated cytotoxicity and hTERT gene expression in A549 lung cancer cell line. silibinin-loaded PLGA-PEG-Fe3O4 had dose- and time-dependent cytotoxicity than pure silibinin. Additionally, hTERT expression is more efficiently reduced with increasing concentrations of nanosilibinin than pure silibinin...
January 12, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28076334/establishment-of-a-normal-derived-estrogen-receptor-positive-cell-line-comparable-to-the-prevailing-human-breast-cancer-subtype
#2
Branden M Hopkinson, Marie C Klitgaard, Ole William Petersen, René Villadsen, Lone Rønnov-Jessen, Jiyoung Kim
Understanding human cancer increasingly relies on insight gained from subtype specific comparisons between malignant and non-malignant cells. The most frequent subtype in breast cancer is the luminal. By far the most frequently used model for luminal breast cancer is the iconic estrogen receptor-positive (ERpos) MCF7 cell line. However, luminal specific comparisons have suffered from the lack of a relevant non-malignant counterpart. Our previous work has shown that transforming growth factor-β receptor (TGFβR) inhibition suffices to propagate prospectively isolated ERpos human breast luminal cells from reduction mammoplasties (HBEC)...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28062544/somatic-mutation-profiling-of-hobnail-variant-of-papillary-thyroid-carcinoma
#3
Luca Morandi, Alberto Righi, Francesca Maletta, Paola Rucci, Fabio Pagni, Marco Gallo, Sabrina Rossi, Leonardo Caporali, Anna Sapino, Ricardo Lloyd, Sofia Asioli
Hobnail variant of papillary thyroid carcinoma (HPTC) represents a recently described, aggressive and rare group of thyroid tumors with poorly understood pathogenesis. Molecular data about this group of cancers are few and a more detailed molecular characterization of these tumors is needed. The main objective of the study is to define a comprehensive molecular typing of HPTC. Eighteen patients affected by HPTC, including eighteen primary tumors and four lymph node metastases, were screened for NRAS, KRAS, HRAS, BRAF, TP53, PIK3CA, hTERT, PTEN, CDKN2A, EGFR, AKT1, CTNNB1, and NOTCH1 gene mutations...
January 6, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28054503/inhibition-of-telomerase-using-bibr1532-enhances-doxorubicin-induced-apoptosis-in-pre-b-acute-lymphoblastic-leukemia-cells
#4
Davood Bashash, Mohadeseh Zareii, Ava Safaroghli-Azar, Mir Davood Omrani, Seyed H Ghaffari
OBJECTIVES: Interest into targeting telomerase in cancer has increased by the recent disclosure that elevated telomerase activity is associated with disease recurrence and poor outcome in cancers. In addition, cellular acquisition of unlimited replicative potential, which is closely related to the maintenance of telomeres mostly via the reactivation of telomerase, has been shown to confer loss of sensitivity to a wide range of anti-neoplastic agents. METHODS: To evaluate whether telomerase inhibition using non-nucleosidic inhibitor of telomerase BIBR1532 could enhance cytotoxic effect of doxorubicin in acute lymphoblastic leukemia, Nalm-6 pre-B ALL cells were subjected to combination treatment and subsequent cell viability, growth kinetics, caspase-3 activity, and transcriptional alteration of p73, p21, FOXO3a, c-Myc, hTERT, and other apoptosis-related target genes were investigated...
January 5, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28039467/targeting-cancer-stem-cell-propagation-with-palbociclib-a-cdk4-6-inhibitor-telomerase-drives-tumor-cell-heterogeneity
#5
Gloria Bonuccelli, Maria Peiris-Pages, Bela Ozsvari, Ubaldo E Martinez-Outschoorn, Federica Sotgia, Michael P Lisanti
In this report, we systematically examined the role of telomerase activity in lung and ovarian cancer stem cell (CSC) propagation. For this purpose, we indirectly gauged telomerase activity, by linking the hTERT-promoter to eGFP. Using lung (A549) and ovarian (SKOV3) cancer cells, transduced with the hTERT-GFP reporter, we then employed GFP-expression levels to fractionate these cell lines into GFP-high and GFP-low populations. We functionally compared the phenotype of these GFP-high and GFP-low populations...
December 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/28025427/the-role-of-tert-clptm1l-snps-htert-expression-and-telomere-length-in-the-pathogenesis-of-oral-squamous-cell-carcinoma
#6
Jelena Carkic, Nadja Nikolic, Sanja Radojevic-Skodric, Jovana Kuzmanovic-Pficer, Gavrilo Brajovic, Marija Antunovic, Jelena Milasin, Branka Popovic
The aim of this study was to assess TERT-CLPTM1L single-nucleotide polymorphisms (SNPs) (rs402710 C/T in the CLPTM1L gene; rs2736100 A/C and rs2736098 G/A in the TERT gene) as risk factors for development of oral squamous cell carcinoma (OSCC), and to investigate the relationship between the analyzed polymorphisms, relative telomere length (RTL), telomerase expression and clinicopathologic characteristics of OSCC in a Serbian population. Paraffin-embedded tumor samples and buccal swabs from cancer-free controls were genotyped using PCR-RFLP, while tumor RTL values and telomerase expression were estimated by real-time PCR and immunohistochemistry, respectively...
2016: Journal of Oral Science
https://www.readbyqxmd.com/read/28011299/apoptosis-inducing-factor-gene-depletion-inhibits-zearalenone-induced-cell-death-in-a-goat-leydig-cell-line
#7
Diqi Yang, Tingting Jiang, Pengfei Lin, Huatao Chen, Lei Wang, Nan Wang, Fan Zhao, Keqiong Tang, Dong Zhou, Aihua Wang, Yaping Jin
Zearalenone (ZEA) is a contaminant of human food and animal feedstuffs that causes health hazards. However, the signal pathways underlying ZEA toxicity remain elusive. The aims of this study were to determine which pathways are involved in ZEA-induced cell death and investigate the effect of apoptosis inducing factor (AIF) on cell death during ZEA treatment in the immortalized goat Leydig cell line hTERT-GLC. This study showed that ZEA-induced cell death in hTERT-GLCs works via endoplasmic reticulum (ER) stress, the caspase-dependent pathway, the caspase-independent pathway and autophagy...
December 20, 2016: Reproductive Toxicology
https://www.readbyqxmd.com/read/28006764/telomere-dysfunction-in-nonalcoholic-fatty-liver-disease-and-cryptogenic-cirrhosis
#8
Ido Laish, Batya Mannasse-Green, Ruth Hadary, Tal Biron-Shental, Fred M Konikoff, Aliza Amiel, Yona Kitay-Cohen
Nonalcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis (CC) are considered preneoplastic conditions that might progress to hepatocellular carcinoma. We evaluated parameters of telomere dysfunction in these patient groups to study the correlation between telomere length and the progression of NAFLD. We analyzed peripheral lymphocytes from 22 patients with NAFLD, 20 patients with CC, and 20 healthy, age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization, and cellular senescence was evaluated by the percentage of cells with senescence-associated heterochromatin foci...
December 23, 2016: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28004350/identification-of-an-rna-aptamer-binding-htert-derived-peptide-and-inhibiting-telomerase-activity-in-mcf7-cells
#9
Akhil Varshney, Jyoti Bala, Baby Santosh, Ashima Bhaskar, Suresh Kumar, Pramod K Yadava
Human telomerase reverse transcriptase is an essential rate-limiting component of telomerase complex. hTERT protein in association with other proteins and the human telomerase RNA (hTR) shows telomerase activity, essential for maintaining genomic integrity in proliferating cells. hTERT binds hTR through a decapeptide located in the RID2 (RNA interactive domain 2) domain of N-terminal region. Since hTERT is essential for telomerase activity, inhibitors of hTERT are of great interest as potential anti-cancer agent...
December 21, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27997899/bufalin-inhibits-htert-expression-and-colorectal-cancer-cell-growth-by-targeting-cpsf4
#10
Ningning Zhang, Yunpeng Xie, Yidi Tai, Yingying Gao, Wei Guo, Wendan Yu, Jia Li, Xu Feng, Jiaojiao Hao, Yue Gao, Xinrui Zhao, Yina Liao, Wei Jiang, Ge Liu, Wuguo Deng, Xiaonan Cui
BACKGROUND/AIMS: Bufalin can induce apoptosis in certain human cancer cell lines, but bufalin has not yet been thoroughly evaluated in colorectal cancer cells. Cleavage and polyadenylation specific factor 4 (CPSF4) and human telomerase reverse transcriptase (hTERT) play important roles in colorectal cancer growth. The aim of this study was to investigate the roles and interactions of bufalin, CPSF4 and hTERT and the effects of bufalin in human colorectal cancer. METHODS: We treated LoVo and SW620 cells with bufalin to investigate the effect of bufalin on proliferation, apoptosis and migration...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27988335/cultured-human-amniocytes-express-htert-which-is-distributed-between-nucleus-and-cytoplasm-and-is-secreted-in-extracellular-vesicles
#11
Annalisa Radeghieri, Giulia Savio, Andrea Zendrini, Giuseppe Di Noto, Alessandro Salvi, Paolo Bergese, Giovanna Piovani
BACKGROUND: An increasing number of studies on stem cells suggests that the therapeutic effect they exert is primarily mediated by a paracrine regulation through extracellular vesicles (EVs) giving solid grounds for stem cell EVs to be exploited as agents for treating diseases or for restoring damaged tissues and organs. Due to their capacity to differentiate in all embryonic germ layers, amniotic fluid stem cells (AFCs), represent a highly promising cell type for tissue regeneration, which however is still poorly studied and in turn underutilized...
December 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27979861/bmi-1-extends-proliferative-potential-of-human-bronchial-epithelial-cells-whilst-retaining-their-mucociliary-differentiation-capacity
#12
Mustafa Mohamed Munye, Amelia Shoemark, Robert A Hirst, Juliette M Delhove, Tyson V Sharp, Tristan R McKay, Chistopher O'Callaghan, Deborah L Baines, Steven J Howe, Stephen L Hart
Air-liquid interface (ALI) culture of primary airway epithelial cells enables mucociliary differentiation providing an in vitro model of the human airway but their proliferative potential is limited. To extend proliferation, these cells were previously transduced with viral oncogenes or mouse Bmi-1 + hTERT but the resultant cell lines did not undergo mucociliary differentiation. We hypothesised that use of human BMI-1 alone would increase the proliferative potential of bronchial epithelial cells while retaining their mucociliary differentiation potential...
December 15, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27977688/regulation-of-the-human-telomerase-gene-tert-by-telomere-position-effect-over-long-distances-tpe-old-implications-for-aging-and-cancer
#13
Wanil Kim, Andrew T Ludlow, Jaewon Min, Jerome D Robin, Guido Stadler, Ilgen Mender, Tsung-Po Lai, Ning Zhang, Woodring E Wright, Jerry W Shay
Telomerase is expressed in early human development and then becomes silenced in most normal tissues. Because ~90% of primary human tumors express telomerase and generally maintain very short telomeres, telomerase is carefully regulated, particularly in large, long-lived mammals. In the current report, we provide substantial evidence for a new regulatory control mechanism of the rate limiting catalytic protein component of telomerase (hTERT) that is determined by the length of telomeres. We document that normal, young human cells with long telomeres have a repressed hTERT epigenetic status (chromatin and DNA methylation), but the epigenetic status is altered when telomeres become short...
December 2016: PLoS Biology
https://www.readbyqxmd.com/read/27956229/milk-fat-globule-egf-factor-8-secreted-by-mesenchymal-stem-cells-protects-against-liver-fibrosis-in-mice
#14
Su Yeon An, Yu Jin Jang, Hee-Joung Lim, Jiyou Han, Jaehun Lee, Gyunggyu Lee, Ji Young Park, Seo-Young Park, Ji Hyang Kim, Byung-Rok Do, Chugseong Han, Hee-Kyung Park, Ok-Hee Kim, Myeong Jun Song, Say-June Kim, Jong-Hoon Kim
BACKGROUND & AIMS: Mesenchymal stem cells (MSCs) mediate tissue repair and might be used to prevent or reduce liver fibrosis. However, little is known about the anti-fibrotic factors secreted from MSCs or their mechanisms. METHODS: Umbilical cord-derived MSCs (UCMSCs) were differentiated into hepatocyte-like cells (hpUCMSCs), medium was collected, and secretome proteins were identified and quantified using nanochip-liquid chromatography/quadruple time-of-flight mass spectrometry...
December 9, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27941629/the-telomerase-derived-anticancer-peptide-vaccine-gv1001-as-an-extracellular-heat-shock-protein-mediated-cell-penetrating-peptide
#15
REVIEW
Hong Kim, Eun-Hye Seo, Seung-Hyun Lee, Bum-Joon Kim
Cell-penetrating peptides (CPPs), which can facilitate the transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular delivery of macromolecules. GV1001, a peptide derived from a reverse-transcriptase subunit of telomerase (hTERT) and developed as a vaccine against various cancers, reportedly has unexpected CPP properties. Unlike typical CPPs, such as the HIV-1 TAT peptide, GV1001 enabled the cytosolic delivery of macromolecules such as proteins, DNA and siRNA via extracellular heat shock protein 90 (eHSP90) and 70 (eHSP70) complexes...
December 7, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27940549/repression-of-telomerase-gene-promoter-requires-human-specific-genomic-context-and-is-mediated-by-multiple-hdac1-containing-corepressor-complexes
#16
De Cheng, Yuanjun Zhao, Shuwen Wang, Fan Zhang, Mariano Russo, Steven B McMahon, Jiyue Zhu
The human telomerase reverse transcriptase (hTERT) gene is repressed in most somatic cells, whereas the expression of the mouse mTert gene is widely detected. To understand the mechanisms of this human-specific repression, we constructed bacterial artificial chromosome (BAC) reporters using human and mouse genomic DNAs encompassing the TERT genes and neighboring loci. Upon chromosomal integration, the hTERT, but not the mTert, reporter was stringently repressed in telomerase-negative human cells in a histone deacetylase (HDAC)-dependent manner, replicating the expression of their respective endogenous genes...
December 9, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27936398/microrna138-regulates-keratin-17-protein-expression-to-affect-hacat-cell-proliferation-and-apoptosis-by-targeting-htert-in-psoriasis-vulgaris
#17
Shi-Jun Feng, Rui-Qi Chu, Jing Ma, Zheng-Xiang Wang, Guang-Jing Zhang, Xiu-Fang Yang, Zhi Song, Yun-Yi Ma
The purpose of this study is to explore the how microRNA-138 (miR-138) affects the expression of keratin 17 (K17) and psoriasis development. Twenty-eight skin lesions from patients with psoriasis vulgaris and twenty-four normal skin tissues from healthy controls were collected. The HaCaT cells were assigned into blank, negative control (NC), miR-138 mimic, miR-138 inhibitor, hTERT siRNA and miR-138 inhibitor+hTERT siRNA groups. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the miR-138 expression...
January 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27935866/hic1-hypermethylated-in-cancer-1-sumoylation-is-dispensable-for-dna-repair-but-is-essential-for-the-apoptotic-dna-damage-response-ddr-to-irreparable-dna-double-strand-breaks-dsbs
#18
Sonia Paget, Marion Dubuissez, Vanessa Dehennaut, Joe Nassour, Brennan T Harmon, Nathalie Spruyt, Ingrid Loison, Corinne Abbadie, Brian R Rood, Dominique Leprince
The tumor suppressor gene HIC1 (Hypermethylated In Cancer 1) encodes a transcriptional repressor mediating the p53-dependent apoptotic response to irreparable DNA double-strand breaks (DSBs) through direct transcriptional repression of SIRT1. HIC1 is also essential for DSB repair as silencing of endogenous HIC1 in BJ-hTERT fibroblasts significantly delays DNA repair in functional Comet assays. HIC1 SUMOylation favours its interaction with MTA1, a component of NuRD complexes. In contrast with irreparable DSBs induced by 16-hours of etoposide treatment, we show that repairable DSBs induced by 1 h etoposide treatment do not increase HIC1 SUMOylation or its interaction with MTA1...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27931240/skeletal-muscle-characteristics-are-preserved-in-htert-cdk4-human-myogenic-cell-lines
#19
Matthew Thorley, Stéphanie Duguez, Emilia Maria Cristina Mazza, Sara Valsoni, Anne Bigot, Kamel Mamchaoui, Brennan Harmon, Thomas Voit, Vincent Mouly, William Duddy
BACKGROUND: hTERT/cdk4 immortalized myogenic human cell lines represent an important tool for skeletal muscle research, being used as therapeutically pertinent models of various neuromuscular disorders and in numerous fundamental studies of muscle cell function. However, the cell cycle is linked to other cellular processes such as integrin regulation, the PI3K/Akt pathway, and microtubule stability, raising the question as to whether genetic modification related to the cell cycle results in secondary effects that could undermine the validity of these cell models...
December 8, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27928113/a-combination-of-%C3%AE-tocotrienol-and-ferulic-acid-synergistically-inhibits-telomerase-activity-in-dld-1-human-colorectal-adenocarcinoma-cells
#20
Takahiro Eitsuka, Naoto Tatewaki, Hiroshi Nishida, Kiyotaka Nakagawa, Teruo Miyazawa
Rice bran is a rich source of functional compounds, including tocotrienol (T3) and ferulic acid (FA). We previously investigated the anti-cancer properties of T3, and reported on the potent inhibitory effects of δ-T3 on angiogenesis and telomerase activity. In this study, we examined the synergistic suppressive effects of the combination of δ-T3 and FA on telomerase activity in DLD-1 human colorectal adenocarcinoma cells. Co-treatment with δ-T3 and FA significantly decreased cellular telomerase activity compared to treatment with δ-T3 alone, whereas FA alone had no inhibitory effect...
2016: Journal of Nutritional Science and Vitaminology
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