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Anna Pańczyszyn, Ewa Boniewska-Bernacka, Grzegorz Głąb
Human papillomaviruses (HPVs) belong to a small spherical virus family and are transmitted through direct contact, most often through sexual behavior. More than 200 types of HPV are known, a dozen or so of which are classified as high-risk viruses (HR HPV) and may contribute to the development of cervical cancer. HPV is a small virus with a capsid composed of L1 and L2 proteins, which are crucial for entry to the cell. The infection begins at the basal cell layer and progresses to involve cells from higher layers of the cervical epithelium...
May 18, 2018: Molecular Diagnosis & Therapy
Caroline Marrs, Kevin Chesmore, Ramkumar Menon, Scott Williams
OBJECTIVE: Premature aging and short telomere lengths of fetal tissues are associated with spontaneous preterm labor (PTL) and preterm premature rupture of membranes (pPROM). Maintenance of telomere length is performed by the enzyme telomerase. Human telomerase reverse transcriptase (hTERT) is a subunit of telomerase, and its dysfunction affects telomere shortening. This study assessed whether maternal or fetal genetic variations in the hTERT gene are associated with PTL or pPROM. METHODS: A case (PTL or pPROM) control (term birth) genetic association study was conducted in 654 non-Hispanic white mothers (438 term, 162 PTL, 54 pPROM) and 502 non-Hispanic white newborns (346 term, 116 PTB, 40 pPROM)...
2018: PloS One
Y-Q Zhang, J-H Pei, S-S Shi, J Zheng, J-M Wang, X-S Guo, G-Y Cui, X-Y Wang, H-P Zhang, W-Q Hu
OBJECTIVE: To investigate the expression of G-quadruplex antibody BG4 in human gastric cancer AGS cells and assess its functions in attenuating proliferation and promoting apoptosis in gastric cancer. MATERIALS AND METHODS: BG4 high-expression gastric cancer AGS cell line was established by pEGFP-N1-BG4 transient transfection. AGS cells transfected with pEGFP-N1 plasmids were included into the pEGFP-N1 group and those not transfected with plasmids were included into the negative control group...
May 2018: European Review for Medical and Pharmacological Sciences
Li Chai, Xiao-Jing Kang, Zhen-Zhu Sun, Ming-Feng Zeng, Shi-Rong Yu, Yuan Ding, Jun-Qin Liang, Ting-Ting Li, Juan Zhao
Background: hTERT gene plays an important role in melanoma, although the specific mechanism involved is unclear. The aim of this study was to screen and identify the relative miRNAs with the regulation of hTERT in melanoma. Materials and methods: Quantitative real-time polymerase chain reaction (q-PCR) and immunohistochemistry were performed to detect hTERT mRNA and protein expression in 36 formalin-fixed paraffin-embedded melanoma tissues and 36 age- and sex-matched pigmented nevi cases, respectively...
2018: Cancer Management and Research
Mrinal M Patnaik, Patrick S Kamath, Douglas A Simonetto
Clinical Case A 51 year old Caucasian male was referred for evaluation of variceal bleeding. Laboratory tests were remarkable for mild thrombocytopenia and moderate alkaline phosphatase elevation. Synthetic liver function was well preserved. Abdominal computed tomography scan revealed moderate splenomegaly, gastric varices, and normal hepatic contour. A transjugular liver biopsy was performed revealing findings of nodular regenerative hyperplasia (NRH) with no significant fibrosis or necroinflammatory activity...
May 11, 2018: Journal of Hepatology
Chuan Lin, Yu Qin, Hua Zhang, Ming-Yang Gao, Yan-Fu Wang
Activation of the epidermal growth factor receptor (EGFR) during tumor development can trigger the MEK signaling pathway. In the present study, we investigated the MEK signaling pathway in non‑small cell lung cancer (NSCLC) cells with respect to the effect of epidermal growth factor (EGF) on expression of Ret finger protein like 3 (RFPL3) and human telomerase reverse transcriptase (hTERT), and the effect of RFPL3 overexpression on other MEK signaling proteins. In vitro, A549 and H1299 cells were treated with different concentrations of EGF for 24 h or 48 h...
May 8, 2018: Oncology Reports
Ricarda Hannen, Jörg W Bartsch
Maintenance of chromosomal telomere length is a hallmark of cancer cells and a prerequisite for stemness. In 85-90% of all human cancers, telomere length maintenance is achieved by reactivation of telomerase, whereas in the remaining 10-15% cancers, alternative lengthening of telomeres (ALT) is observed. Reactivation of telomerase occurs by various mechanisms, one of which is accumulation of point mutations in the promoter region of the gene encoding the protein subunit hTERT. There are numerous studies linking either hTERT overexpression or the presence of hTERT mutations to an aggressive phenotype of several human cancers...
May 10, 2018: FEBS Letters
Shanmugam Panneer Selvam, Braden M Roth, Rose Nganga, Jisun Kim, Marion A Cooley, Kristi L Helke, Charles D Smith, Besim Ogretmen
Telomerase activation protects cells from telomere damage by delaying senescence and inducing cell immortalization, whereas telomerase inhibition mediates rapid senescence or apoptosis. However, the cellular mechanisms that determine telomere damage-dependent senescence versus apoptosis induction are largely unknown. Here, we demonstrate that telomerase instability mediated by silencing of sphingosine kinase 2 (SPHK2) and sphingosine 1-phosphate (S1P), which binds and stabilizes telomerase, induces telomere damage-dependent caspase-3 activation and apoptosis, but not senescence, in p16-deficient lung cancer cells or tumors...
May 10, 2018: Journal of Biological Chemistry
Wei Chen, Kyung L Kang, Abdullah Alshaikh, Saaket Varma, Yi-Ling Lin, Ki-Hyuk Shin, Reuben Kim, Cun-Yu Wang, No-Hee Park, Katharina Walentin, Kai M Schmidt-Ott, Mo K Kang
Grainyhead-Like 2 (GRHL2) is an epithelial-specific transcription factor that regulates epithelial morphogenesis and differentiation. Prior studies suggested inverse regulation between GRHL2 and TGF-β in epithelial plasticity and potential carcinogenesis. Here, we report the role of GRHL2 in oral carcinogenesis in vivo using a novel Grhl2 knockout (KO) mouse model and the underlying mechanism involving its functional interaction with TGF-β signaling. We developed epithelial-specific Grhl2 conditional KO mice by crossing Grhl2 floxed mice with those expressing CreER driven by the K14 promoter...
May 8, 2018: Oncogenesis
Piera Rizzolo, Valentina Silvestri, Virginia Valentini, Veronica Zelli, Ines Zanna, Giovanna Masala, Simonetta Bianchi, Domenico Palli, Laura Ottini
Male breast cancer (MBC) is a rare disease. Due to its rarity, MBC research and clinical approach are mostly based upon data derived from female breast cancer (FBC). Increasing evidence indicate that on molecular level MBC may be an heterogeneous disease different from FBC. In order to investigate whether epigenetic signatures could define molecular subgroups of MBCs, we performed promoter methylation analysis of genes involved in signal transduction and hormone signalling in BRCA1/2 mutation-positive and -negative MBCs...
April 13, 2018: Oncotarget
E S Scarpa, M Mari, E Antonini, F Palma, P Ninfali
Avenanthramides (AVNs) are natural polyphenols obtained from oat sprouts and can also be chemically synthetized. The aim of the present study was to assess the anticancer, anti-inflammatory and antioxidant effects of individual synthetized AVNs (s-2c, s-2p, s-2f) and a natural AVN mixture (n-MIX) on CaCo-2 and Hep3B cancer cells. In CaCo-2, the AVN s-2c was found to be the most cytotoxic followed by the n-MIX. In Hep3B cells, a marked cytotoxic effect was found but no significant difference was observed between the synthesized AVNs and the n-MIX...
May 4, 2018: Food & Function
Rishi Kumar Jaiswal, Pramod Kumar, Manoj Kumar, Pramod Kumar Yadava
Telomerase complex maintains the length of the telomere and protects erosion of the physical ends of the eukaryotic chromosome in all actively dividing cells including cancer cells. Telomerase activation extends the lifespan of cells in culture by maintaining the length of the telomere. Compared to terminally differentiated somatic cells, telomerase activity remains high in over 90% of cancer cells. It has now become clear that the role of telomerase is much more complex than just telomere lengthening. The remaining 10% of cancers deploy ALT (alternative lengthening of telomeres) pathway to maintain telomere length...
May 2, 2018: Molecular Carcinogenesis
Bing Sun, Yun-Ling Zheng
Currently there is no sensitive, precise, and reproducible method to quantitate alternative splicing of mRNA transcripts. Droplet digital™ PCR (ddPCR™) analysis allows for accurate digital counting for quantification of gene expression. Human telomerase reverse transcriptase (hTERT) is one of the essential components required for telomerase activity and for the maintenance of telomeres. Several alternatively spliced forms of hTERT mRNA in human primary and tumor cells have been reported in the literature...
2018: Methods in Molecular Biology
Yingbo Lin, Nelly Seger, Panagiotis Tsagkozis, Asle C Hesla, Mehran Ghaderi, Yi Chen, Monika Ehnman, Dudi Warsito, Johan Wejde, Olle Larsson, Felix Haglund
AIMS: Solitary fibrous tumour (SFT) is an infrequently metastasising mesenchymal tumour defined by the NAB2-STAT6 fusion gene. Activating mutations in the telomerase reverse transcriptase ( hTERT ) gene promoter has been reported to associate with adverse patient outcome in SFTs. METHODS: We analysed the hTERT gene for promoter mutations and copy number alterations in 43 primary extrameningeal SFTs (9 malignant and 34 benign tumours according to WHO 2013 criteria), six local recurrences and three metastatic lesions...
April 27, 2018: Journal of Clinical Pathology
Joëlle El Hajj, Eric Nguyen, Qingyuan Liu, Claire Bouyer, Eric Adriaenssens, George Hilal, Evelyne Ségal-Bendirdjian
BACKGROUND: Since tumor growth requires reactivation of telomerase (hTERT), this enzyme is a challenging target for drug development. Therefore, it is of great interest to identify telomerase expression and activity regulators. Retinoids are well-known inducers of granulocytic maturation associated with hTERT repression in acute promyelocytic leukemia (APL) blasts. In a maturation-resistant APL cell line, we have previously identified a new pathway of retinoid-induced hTERT transcriptional repression independent of differentiation...
April 27, 2018: Molecular Cancer
Changhee Kang, C-Yoon Kim, Hyuk Soon Kim, Se-Pill Park, Hyung-Min Chung
All- trans retinoic acid (ATRA) is a highly effective treatment for acute promyelocytic leukemia (APL), a cytogenetically distinct subtype of acute myeloid leukemia (AML). However, ATRA-based treatment is not effective in other subtypes of AML. In non-APL AML, ATRA signaling pathway is impaired or downmodulated, and consequently fails to respond to pharmacological doses of ATRA. Therefore, complementary treatment strategies are needed to improve ATRA responsiveness in non-APL AML. In this study, we investigated the combined effect of ATRA and bromodomain inhibitor JQ1, proven to have potent anti-cancer activity mainly through inhibition of c-Myc...
April 30, 2018: International Journal of Stem Cells
Sara Rasouli, Nosratollah Zarghami
Objective: To explore the possibility of a novel chemopreventive strategy for improving breast cancer treatment, the anticancer effects of a combination two natural compounds, Chrysin and Metformin, against T47D breast cancer cells were investigated. Materials and Methods: After treatment of T47D cells with Metformin, Chrysin and the two drugs in combination, toxicity to cancer cells was evaluated by MTT assay. Real time PCR was then used to determine the expression levels of hTERT and cyclin D1 genes. Results: The MTT test findings showed that the combination of metformin and chrysin had high synergistic effects in killing cancer cells...
April 25, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Suresh Singh Yadav, Rohini Ravindran Nair, Pramod Kumar Yadava
Gene expression is crucial and tightly regulated to steer the development, differentiation, proliferation and even apoptosis of a cell. Each cell and tissue type shows a unique repertoire of transcription factors. Tissue micro-environmental regulation of epigenetic signature of a gene has been documented in many cases. Epigenetic factors play a significant role in the regulation of gene expression. KLF4 is a well-known transcription factor regulating the expression of several genes including hTERT. KLF4 functions both as a tumor suppressor and oncogene depending on cell type...
June 2018: Medical Hypotheses
Yutaka Suehiro, Shinichi Hashimoto, Shingo Higaki, Ikuei Fujii, Chieko Suzuki, Tomomi Hoshida, Toshihiko Matsumoto, Yuko Yamaoka, Taro Takami, Isao Sakaida, Takahiro Yamasaki
Although methylated TWIST1 is a biomarker of colorectal neoplasia, its detection from serum samples is very difficult by conventional bisulfite-based methylation assays. Therefore, we have developed a new methylation assay that enables counting of even one copy of a methylated gene in a small DNA sample amount without DNA bisulfite treatment. We performed this study to evaluate the sensitivity and specificity of serum DNA testing by the new methylation assay in combination with and without the fecal immunochemical test for hemoglobin for the detection of colorectal neoplasia...
March 30, 2018: Oncotarget
Long Wu, Huan Zhang, Yixing Jiang, Robert C Gallo, Hua Cheng
Dendritic cell (DC)-based cancer immunotherapy has achieved modest clinical benefits, but several technical hurdles in DC preparation, activation, and cancer/testis antigen (CTA) delivery limit its broad applications. Here, we report the development of immortalized and constitutively activated human primary blood dendritic cell lines (ihv-DCs). The ihv-DCs are a subset of CD11c+ /CD205+ DCs that constitutively display costimulatory molecules. The ihv-DCs can be genetically modified to express human telomerase reverse transcriptase (hTERT) or the testis antigen MAGEA3 in generating CTA-specific cytotoxic T lymphocytes (CTLs)...
April 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
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