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Sara Pagotto, Angelo Veronese, Alessandra Soranno, Paola Lanuti, Mirco Di Marco, Marco Vincenzo Russo, Alice Ramassone, Marco Marchisio, Pasquale Simeone, Paolo E Guanciali Franchi, Giandomenico Palka, Renato Mariani Costantini, Carlo M Croce, Rosa Visone
Hsa-miR-155-5p (miR-155) is overexpressed in most solid and hematological malignancies. It promotes loss of genomic integrity in cancer cells by targeting genes involved in microsatellite instability and DNA repair; however, the link between miR-155 and aneuploidy has been scarcely investigated. Here we describe a novel mechanism by which miR-155 causes chromosomal instability. Using osteosarcoma cells (U2OS) and normal human dermal fibroblast (HDF), two well-established models for the study of chromosome congression, we demonstrate that miR-155 targets the spindle checkpoint proteins BUB1, CENP-F, and ZW10, thus compromising chromosome alignment at the metaphase plate...
February 27, 2018: Oncotarget
Kohei Nakamura, Kentaro Nakayama, Noriyoshi Ishikawa, Masako Ishikawa, Razia Sultana, Tohru Kiyono, Satoru Kyo
Fallopian tube secretory epithelial cells (FTSECs) have been suggested to be the source of high-grade serous ovarian carcinoma (HGSOC). Although several genetic alterations are known to be involved in HGSOC development, the minimal requirements remain unclear. We aimed to identify oncogenic mutations indispensable for HGSOC development in a stepwise model, using immortalized FTSECs. FTSECs were isolated from clinical samples and immortalized by overexpression of cyclin D1, CDK4R24C , and hTERT . Oncogenic mutations in the p53, c-Myc, and RAS/PI3K pathways were mimicked by lentiviral transduction...
February 27, 2018: Oncotarget
Alper Sayiner, Dinc Suren
PURPOSE: Distinction of thyroid neoplasms that include papillary carcinoma (PC) and follicular carcinoma (FC) from benign thyroid neoplasms can be performed successfully by histopathologic examination in most of the cases. However, in some cases it may be difficult to distinct PC and FC as well as FC and follicular adenoma (FA) and also FA and the dominant nodule of multinodular goiter (MNG) histopathologically. In this study, we aimed to determine the role of expression of the human telomerase reverse transcriptase (hTERT) in the distinction of thyroid neoplasms and its relation with prognostic factors by immunohistochemical methods...
January 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Ana Marzo-Mas, Eva Falomir, Juan Murga, Miguel Carda, J Alberto Marco
Several colchicine analogues in which the N-acetyl residue has been replaced by haloacetyl, cyclohexylacetyl, phenylacetyl and various aroyl moieties have been synthesized. The cytotoxic activities of the synthesized compounds have been measured on three tumor cell lines (HT-29, MCF-7 and A549) and on one non-tumor cell line (HEK-293). These compounds exhibit high antiproliferative activities at the nanomolar level, in many cases with a higher potency than colchicine itself. Some of the compounds, particularly the haloacetyl derivatives, inhibit the polymerization of tubulin in a similar manner as colchicine...
March 8, 2018: European Journal of Medicinal Chemistry
Jana Tomc, Katja Kološa, Bojana Žegura, Urška Kamenšek, Barbara Breznik, Tamara Lah Turnšek, Metka Filipič
The problem of the currently used routine genotoxicity tests is relatively low predictivity of in vitro tests for in vivo genotoxicity and carcinogenicity. An important reason is considered to be inadequate expression of xenobiotic-metabolizing enzymes in indicator cell lines. The aim of our study was to generate metabolically active differentiated hepatic progenies (hDHP) from human adipose tissue-derived mesenchymal stem cells (hASC) for genotoxicity testing. hDHP, generated using a three-step hepatic differentiation procedure, expressed hepatic properties such as glycogen storage and albumin secretion...
March 16, 2018: Archives of Toxicology
Balal Brazvan, Abbas Ebrahimi-Kalan, Kobra Velaei, Ahmad Mehdipour, Zeynab Aliyari Serej, Ayyub Ebrahimi, Mohammad Ghorbani, Omid Cheraghi, Hojjatollah Nozad Charoudeh
The end of linear chromosomes is formed of a special nucleoprotein heterochromatin structure with repetitive TTAGGG sequences called telomere. Telomere length is regulated by a special enzyme called telomerase, a specific DNA polymerase that adds new telomeric sequences to the chromosome ends. Telomerase consists of two parts; the central protein part and the accessory part which is a RNA component transported by the central part. Regulation of telomere length by this enzyme is a multi-stage process. Telomere length elongation is strongly influenced by the level of telomerase and has a strong correlation with the activity of telomerase enzyme...
March 13, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
C Lavanya, Manjunatha M Venkataswamy, M K Sibin, M M Srinivas Bharath, G K Chetan
Increased telomerase activity can be blocked by targeting the hTERT activity at both RNA and catalytic subunits. Various inhibitors had been used to regulate hTERT activity in glioblastoma cell lines and showed promising results. The present study hypothesized that the telomerase specific inhibitor BIBR1532 can effectively down-regulate the telomerase activity in LN18 glioblastoma cell line. LN18 glioblastoma cell line was treated with various concentrations of BIBR1532 at different time intervals. MTT assay was performed to determine cell viability after BIBR1532 treatment...
March 15, 2018: Cytotechnology
Hua Zhou, Abdul Mondal, Aleksandra Dakic, Lama Alhawas, Xuefeng Liu, Zhixu He
The roles of protection of telomeres 1 (POT1) in human ovarian cancer have not been fully elucidated. Here, we investigated the impact of POT1 knockdown (POT1-KD) on in vitro cell proliferation, tumorigenesis, and histone deacetylase inhibitor (HDACi) response in human ovarian cancer-derived SK-OV3 cells. The POT1 gene was knocked down by infection with POT1 lenti-shRNA. POT1, c-Myc, and hTERT mRNA levels and relative telomere length were determined by qRT-PCR; POT1 protein levels were determined by western blot...
2018: BioMed Research International
Amanda Przespolewski, Andras Szeles, Eunice S Wang
Evasion of the host immune system is a key mechanism to promote malignant progression. Therapeutically targeting immune pathways has radically changed the treatment paradigm for solid and lymphoid tumors but has yet to be approved for myeloid malignancies. Here, we summarize the most recent advances in immunotherapy for acute myeloid leukemia. Topics reviewed here include adoptive cellular approaches (chimeric antigen receptor-T cells, natural killer and other immune cells), checkpoint inhibitors (anti-PD-1/PD-L1, anti-CTLA-4 and TIM-3) and vaccines (WT-1, HLA-A2 and hTERT)...
March 15, 2018: Future Oncology
Ricardo Leão, Joana Dias Apolónio, Donghyun Lee, Arnaldo Figueiredo, Uri Tabori, Pedro Castelo-Branco
BACKGROUND: Limitless self-renewal is one of the hallmarks of cancer and is attained by telomere maintenance, essentially through telomerase (hTERT) activation. Transcriptional regulation of hTERT is believed to play a major role in telomerase activation in human cancers. MAIN BODY: The dominant interest in telomerase results from its role in cancer. The role of telomeres and telomere maintenance mechanisms is well established as a major driving force in generating chromosomal and genomic instability...
March 12, 2018: Journal of Biomedical Science
Leyla Yurttas, Gulsen Akalin Ciftci
BACKGROUND: Quinoline is a privileged scaffold especially known with antimalarial and antibacterial drugs before, presently followed anticancer efficiency with a new group of protein kinase inhibitors. OBJECTIVE: In this work, combining quinoline ring, hydrazone and sulphonamide groups, we have synthesized N'-arylidene-2-[4-(quinolin-8-ylsulfonyl)piperazin-1-yl]acetohydrazide derivatives (3a-o) and evaluated their in vitro anticancer activity against cancerous cell lines PANC-1, CAPAN-1 and healthy cell line hTERT-HPNE...
March 7, 2018: Anti-cancer Agents in Medicinal Chemistry
Sibel Azizenur Ozturk, Ebru Alp, Atiye Seda Yar Saglam, Ece Konac, Emine Sevda Menevse
Context: Thyroid cancers (TCs) are the most common endocrine malignancies. There were two problems with the current cancer chemotherapy: the ineffectiveness of treatment due to resistance to cancer cell, and the toxic effect on normal cells. Aims: This study was aimed to determine the effects of thymoquinone (TQ) and genistein (Gen) phytotherapeutics on telomerase activity, angiogenesis, and apoptosis in follicular and anaplastic thyroid cancer cells (TCCs). Materials and Methods: Cell viability, caspase-3 (CASP-3) activity, and messenger RNA (mRNA) expression levels of human telomerase reverse transcriptase (hTERT), phosphatase and tensin homolog (PTEN), nuclear factor-kappa B (NF-kB), cyclin-dependent kinase inhibitor 1 (p21), and vascular endothelial growth factor-A (VEGF-A) genes were analyzed...
January 2018: Journal of Cancer Research and Therapeutics
Mohammad Houshmand, Narjes Yazdi, Alireza Kazemi, Amir Atashi, Amir Ali Hamidieh, Ali Anjam Najemdini, Mahshid Mohammadi Pour, Mahin Nikougoftar Zarif
Cancerous cells show resistance to various forms of therapy, so applying up to the minute targeted therapy is crucial. For this purpose, long non-coding RNA PVT1 as shown by recent studies is an important oncogene that interacts with vital cellular signaling pathways and different proteins such as c-Myc, NOP2 and LATS2. Due to the enormous role of long non-coding RNAs in development of leukemias, we aimed to show the role of PVT1 knock-down on fate of different hematologic cell lines. owing to this matter, various experiments such as Real-time PCR, cell cycle analysis and apoptosis assay were performed...
March 3, 2018: International Journal of Biochemistry & Cell Biology
Muhsin Aydin, Ahmet Taner Sümbül, Günay Camuz Hilaloğullari, Süleyman Bayram
Breast cancer (BC) is encountered most frequently in developed or developing countries. It is the most common cancer in humans following lung cancer, and it is the most common cancer type resulting in mortality in women. Genetic polymorphisms are among the genetic factors that play an important role in the development of the breast cancer. The purpose of this study was to investigate the effect of five functional single nucleotide polymorphisms (SNPs) of hTERT (rs2736109 G>A, rs2735940 T>C, rs2853669 A>G, rs2736098 G>A, and rs2736100 T>G) on susceptibility to BC in Turkish population...
February 28, 2018: Cellular and Molecular Biology
D D Zhdanov, Yu A Gladilina, M V Pokrovskaya, S S Aleksandrova, D V Grishin, O V Podobed, N N Sokolov
The effect of apoptotic endonuclease EndoG on alternative splicing of mRNA of human telomerase catalytic subunit hTERT (human telomerase reverse transcriptase) and telomerase activity in normal human lymphocytes were studied. Human CD4+ , CD8+ , B, and NK cells were transfected with a plasmid pEndoG-GFP containing EndoG gene or control plasmid pGFP. The levels of mRNA of EndoG or hTERT splicing variants were analyzed by real-time PCR. Protein content was assessed by Western blotting. Telomerase activity was measured by the telomere repeats amplification protocol...
March 5, 2018: Bulletin of Experimental Biology and Medicine
Rita Cardoso, Junhua Wang, Joachim Müller, Sebastian Rupp, Alexandre Leitão, Andrew Hemphill
Like most intracellular pathogens, the apicomplexan parasites Besnoitia besnoiti, Toxoplasma gondii and Neospora caninum scavenge metabolites from their host cells. Recruitment of the Golgi complex to the vicinity of the parasitophorous vacuole (PV) is likely to aid in this process. In this work, we comparatively assessed B. besnoiti, T. gondii and N. caninum infected human retinal pigmented epithelial (hTERT-RPE-1) cells at 24 h post-infection and used antibodies to confirm Golgi ribbon compaction in B. besnoiti, and Golgi ribbon dispersion in T...
February 27, 2018: Experimental Parasitology
Igor Khlusov, Larisa Litvinova, Valeria Shupletsova, Olga Khaziakhmatova, Elena Melashchenko, Kristina Yurova, Vladimir Leitsin, Marina Khlusova, Vladimir Pichugin, Yurii Sharkeev
The response of the human Jurkat T cell leukemia-derived cell line (Jurkat T cells) after 24 h of in vitro exposure to a titanium substrate (12 × 12 × 1 mm³) with a bilateral rough ( Ra = 2.2-3.7 μm) titanium oxide coating (rTOC) applied using the micro-arc method in a 20% orthophosphoric acid solution was studied. A 1.5-fold down-regulation of hTERT mRNA expression and decreases in CD3, CD4, CD8, and CD95 presentation and IL-4 and TNFα secretion were observed. Jurkat T cell inactivation was not correlated with the generation of intracellular reactive oxygen species (ROS) and was not mediated by TiO₂ nanoparticles with a diameter of 14 ± 8 nm at doses of 1 mg/L or 10 mg/L...
February 28, 2018: Materials
Zongjuan Li, Xiangdong Xu, Yizhuo Li, Kun Zou, Zhuo Zhang, Xiaoying Xu, Yina Liao, Xinrui Zhao, Wei Jiang, Wendan Yu, Wei Guo, Yiming Chen, Yixin Li, Miao Chen, Wu-Guo Deng, Liren Li, Lijuan Zou
BACKGROUND/AIMS: PI3KCA and mutant p53 are associated with tumorigenesis and the development of cancers. NVP-BKM120, a selective pan-PI3K inhibitor, exerts the antitumor activity by suppressing the PI3K signaling pathway. Prima-1Met, a low molecular weight compound, can rescue the gain-of-function of mutant p53 by restoring its transcriptional function. In this study, we investigated whether PI3K inhibition combined with mutant p53 reactivation could enhance the antitumor effect in thyroid cancer cells...
February 23, 2018: Cellular Physiology and Biochemistry
Paula M De Angelis, Aasa R Schjølberg, Juliana B Hughes, Henrik S Huitfeldt, Solveig Norheim Andersen, Anne Carine Østvold
Background: The colon and rectum are continuously exposed to oxidative stress that generates reactive oxygen species, which are a major cause of DNA double-strand breaks (DSB). Furthermore, chronic inflammatory diseases such as ulcerative colitis (UC) are characterized by an excess of reactive nitrogen species that can also lead to DNA double-strand breakage and genomic instability. We investigated the expression of the nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) protein in UC and sporadic colorectal cancer (CRC) due to its involvement in both DNA double-strand break repair and inflammatory signaling...
February 15, 2018: Inflammatory Bowel Diseases
Raneem Habib, Heidemarie Neitzel, Aurelie Ernst, John K L Wong, Bozenna Goryluk-Kozakiewicz, Antje Gerlach, Ilja Demuth, Karl Sperling, Krystyna Chrzanowska
Background: Nijmegen breakage syndrome is an autosomal recessive disorder characterized by microcephaly, immunodeficiency, hypersensitivity to X-irradiation, and a high predisposition to cancer. Nibrin, the product of the NBN gene, is part of the MRE11/RAD50 (MRN) complex that is involved in the repair of DNA double strand breaks (DSBs), and plays a critical role in the processing of DSBs in immune gene rearrangements, telomere maintenance, and meiotic recombination. NBS skin fibroblasts grow slowly in culture and enter early into senescence...
2018: Molecular Cytogenetics
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