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https://www.readbyqxmd.com/read/28335889/human-papillomavirus-as-prognostic-marker-with-rising-prevalence-in-neck-squamous-cell-carcinoma-of-unknown-primary-a-retrospective-multicentre-study
#1
Lea Schroeder, Paolo Boscolo-Rizzo, Elisa Dal Cin, Salvatore Romeo, Lorena Baboci, Gerhard Dyckhoff, Jochen Hess, Carlota Lucena-Porcel, Anne Byl, Nikolaus Becker, Laia Alemany, Xavier Castellsagué, Miquel Quer, Xavier León, Manuel Wiesenfarth, Michael Pawlita, Dana Holzinger
Patients with neck squamous cell carcinomas of unknown primary tumour (NSCCUP) present with lymph node metastasis without evidence for a primary tumour. Most patients undergo an aggressive multimodal treatment, which induces severe, potentially unnecessary toxicity. Primary tumours of NSCCUP can be hidden in the oropharynx. Human papillomavirus (HPV) is causally involved in a subgroup of oropharyngeal squamous cell carcinomas (OPSCC) associated with early lymph node metastasis and good prognosis. Detection of markers for HPV transformation in NSCCUP could allow focussing on the oropharynx in primary tumour search and could be of value for choice and extent of treatment...
March 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28316325/silencing-of-the-small-gtpase-diras3-induces-cellular-senescence-in-human-white-adipose-stromal-progenitor-cells
#2
Asim Ejaz, Monika Mattesich, Werner Zwerschke
Inhibition of Akt-mTOR signaling protects from obesity and extends life span in animals. In the present study, we analyse the impact of the small GTPase, GTP-binding RAS-like 3 (DIRAS3), a recently identified weight-loss target gene, on cellular senescence in adipose stromal/progenitor cells (ASCs) derived from human subcutaneous white adipose tissue (sWAT). We demonstrate that DIRAS3 knock-down (KD) in ASCs induces activation of Akt-mTOR signaling and proliferation arrest. DIRAS3 KD ASCs lose the potential to form colonies and are negative for Ki-67...
March 17, 2017: Aging
https://www.readbyqxmd.com/read/28287250/changes-in-the-expression-of-cyclin-dependent-kinase-inhibitors-during-differentiation-of-immortalized-fibroblasts-into-adipocytes
#3
Ibon Alonso, Antonio Baroja, Blanca Fernández, Raquel Vielba, Jon Elorriaga, Jairo Pérez-Sanz, Juan Aréchaga, Juan J Goiriena de Gandarias, Carmen de la Hoz
The mechanisms implicated in the differentiation of fibroblastic precursors into adipocytes can be analyzed in vitro using cell models, such as the 3T3-L1 cell line. Since cell differentiation involves an exit from the cell cycle, it is likely that molecules that inhibit proliferation participate in the control of adipogenesis. This study was aimed at determining the role, if any, of several cyclin-dependent kinase (CDK)-inhibitors and the transcription factor C/EBPα in the process of adipocyte differentitation...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28286417/molecular-mechanism-of-g1-arrest-and-cellular-senescence-induced-by-lee011-a-novel-cdk4-cdk6-inhibitor-in-leukemia-cells
#4
Yan-Fang Tao, Na-Na Wang, Li-Xiao Xu, Zhi-Heng Li, Xiao-Lu Li, Yun-Yun Xu, Fang Fang, Mei Li, Guang-Hui Qian, Yan-Hong Li, Yi-Ping Li, Yi Wu, Jun-Li Ren, Wei-Wei Du, Jun Lu, Xing Feng, Jian Wang, Wei-Qi He, Shao-Yan Hu, Jian Pan
BACKGROUND: Overexpression of cyclin D1 dependent kinases 4 and 6 (CDK4/6) is a common feature of many human cancers including leukemia. LEE011 is a novel inhibitor of both CDK4 and 6. To date, the molecular function of LEE011 in leukemia remains unclear. METHODS: Leukemia cell growth and apoptosis following LEE011 treatment was assessed through CCK-8 and annexin V/propidium iodide staining assays. Cell senescence was assessed by β-galactosidase staining and p16(INK4a) expression analysis...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28263309/ezh2-is-a-potential-therapeutic-target-for-h3k27m-mutant-pediatric-gliomas
#5
Faizaan Mohammad, Simon Weissmann, Benjamin Leblanc, Deo P Pandey, Jonas W Højfeldt, Itys Comet, Chunqin Zheng, Jens Vilstrup Johansen, Nicolas Rapin, Bo T Porse, Andrey Tvardovskiy, Ole N Jensen, Nagore G Olaciregui, Cinzia Lavarino, Mariona Suñol, Carmen de Torres, Jaume Mora, Angel M Carcaboso, Kristian Helin
Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumor that is located in the pons and primarily affects children. Nearly 80% of DIPGs harbor mutations in histone H3 genes, wherein lysine 27 is substituted with methionine (H3K27M). H3K27M has been shown to inhibit polycomb repressive complex 2 (PRC2), a multiprotein complex responsible for the methylation of H3 at lysine 27 (H3K27me), by binding to its catalytic subunit EZH2. Although DIPGs with the H3K27M mutation show global loss of H3K27me3, several genes retain H3K27me3...
February 27, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28249161/the-setd8-pr-set7-methyltransferase-functions-as-a-barrier-to-prevent-senescence-associated-metabolic-remodeling
#6
Hiroshi Tanaka, Shin-Ichiro Takebayashi, Akihisa Sakamoto, Tomoka Igata, Yuko Nakatsu, Noriko Saitoh, Shinjiro Hino, Mitsuyoshi Nakao
Cellular senescence is an irreversible growth arrest that contributes to development, tumor suppression, and age-related conditions. Senescent cells show active metabolism compared with proliferating cells, but the underlying mechanisms remain unclear. Here we show that the SETD8/PR-Set7 methyltransferase, which catalyzes mono-methylation of histone H4 at lysine 20 (H4K20me1), suppresses nucleolar and mitochondrial activities to prevent cellular senescence. SETD8 protein was selectively downregulated in both oncogene-induced and replicative senescence...
February 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28245508/immunohistochemical-expression-of-the-tumor-suppressor-protein-p16ink4a-in-cervical-adenocarcinoma
#7
José Eleutério, Thiago Silva Lima, Maria do Perpétuo Socorro Cunha, Diane Isabelle Magno Cavalcante, Angélica Maria Holanda Silva
Objective To evaluate the diagnostic utility of the p16(ink4a) protein expression as a marker for adenocarcinoma of the cervix. Methods In a cross-sectional study, p16(ink4a) expression was evaluated in 30 cervical biopsies from patients diagnosed with invasive adenocarcinoma from 2 reference clinics in Brazil, and compared with 18 biopsies of endocervical polyps (control cases). The performance of the tests for p16(ink4a) was evaluated using a conventional contingency table, and the Kappa (κ) index was used to evaluate the agreement of the marker with the tissue diagnosis...
January 2017: Revista Brasileira de Ginecologia e Obstetrícia
https://www.readbyqxmd.com/read/28218424/p16-ink4a-enhances-the-transcriptional-and-the-apoptotic-functions-of-p53-through-dna-dependent-interaction
#8
Huda H Al-Khalaf, Shreeram C Nallar, Dhananjaya V Kalvakolanu, Abdelilah Aboussekhra
p16(INK4A) and p53 are two important tumor suppressor proteins that play essential roles during cell proliferation and aging through regulating the expression of several genes. Here, we report that p16(INK4A) and p53 co-regulate a plethora of transcripts. Furthermore, both proteins colocalize in the nucleus of human primary skin fibroblasts and breast luminal cells, and form a heteromer whose level increases in response to genotoxic stress as well as aging of human fibroblasts and various mouse organs. CDK4 is also present in this heteromeric complex, which is formed only in the presence of DNA both in vitro using pure recombinant proteins and in vivo...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28213009/immunohistochemical-detection-of-mtap-and-bap1-protein-loss-for-mesothelioma-diagnosis-comparison-with-9p21-fish-and-bap1-immunohistochemistry
#9
Tomoyuki Hida, Makoto Hamasaki, Shinji Matsumoto, Ayuko Sato, Tohru Tsujimura, Kunimitsu Kawahara, Akinori Iwasaki, Tatsuro Okamoto, Yoshinao Oda, Hiroshi Honda, Kazuki Nabeshima
OBJECTIVES: Differentiating malignant pleural mesothelioma (MPM) from reactive mesothelial hyperplasia (RMH) is still challenging. Detection of homozygous deletion (HD) of 9p21 region including p16(INK4A) (p16) by fluorescence in situ hybridization (FISH) and immunohistochemical detection of loss of BRCA1 associated protein 1 (BAP1), are reliable markers for MPM diagnosis. However, not all laboratories are equipped to perform 9p21 FISH; immunohistochemistry (IHC) is a more common and feasible technique...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28192277/cdkn2a-p16ink4-a-expression-is-associated-with-vascular-progeria-in-chronic-kidney-disease
#10
Peter Stenvinkel, Karin Luttropp, Dagmara McGuinness, Anna Witasp, Abdul Rashid Qureshi, Annika Wernerson, Louise Nordfors, Martin Schalling, Jonaz Ripsweden, Lars Wennberg, Magnus Söderberg, Peter Bárány, Hannes Olauson, Paul G Shiels
Patients with chronic kidney disease (CKD) display a progeric vascular phenotype linked to apoptosis, cellular senescence and osteogenic transformation. This has proven intractable to modelling appropriately in model organisms. We have therefore investigated this directly in man, using for the first time validated cellular biomarkers of ageing (CDKN2A/p16(INK4a), SA-β-Gal) in arterial biopsies from 61 CKD patients undergoing living donor renal transplantation. We demonstrate that in the uremic milieu, increased arterial expression of CDKN2A/p16(INK4a) associated with vascular progeria in CKD, independently of chronological age...
February 9, 2017: Aging
https://www.readbyqxmd.com/read/28191769/suppression-of-transforming-growth-factor-%C3%AE-signaling-delays-cellular-senescence-and-preserves-the-function-of-endothelial-cells-derived-from-human-pluripotent-stem-cells
#11
Hao Bai, Yongxing Gao, Dixie L Hoyle, Tao Cheng, Zack Z Wang
Transplantation of vascular cells derived from human pluripotent stem cells (hPSCs) offers an attractive noninvasive method for repairing the ischemic tissues and for preventing the progression of vascular diseases. Here, we found that in a serum-free condition, the proliferation rate of hPSC-derived endothelial cells is quickly decreased, accompanied with an increased cellular senescence, resulting in impaired gene expression of endothelial nitric oxide synthase (eNOS) and impaired vessel forming capability in vitro and in vivo...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28186864/within-day-baseline-variation-in-salivary-biomarkers-in-healthy-men
#12
Firman Prathama Idris, Yunxia Wan, Xi Zhang, Chamindie Punyadeera
Saliva is an easily accessible sample and offers practical and noninvasive biomarker solutions as an alternative to blood and urine-based diagnostics. Saliva contains a plethora of biomolecules such as nucleic acids, hormones, proteins, and electrolytes. On the other hand, little is known on the extent to which the biomolecules in saliva vary over time within a given person. This baseline information is crucial for future development of robust saliva-based diagnostics. We have collected unstimulated whole mouth saliva from 20 healthy young men at four times during the day, including before and after a meal...
February 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28179162/loss-of-p16-ink4a-expression-and-homozygous-cdkn2a-deletion-are-associated-with-worse-outcome-and-younger-age-in-thymic-carcinomas
#13
Scott W Aesif, Marie Christine Aubry, Eunhee S Yi, Sara M Kloft-Nelson, Sarah M Jenkins, Grant M Spears, Patricia T Greipp, William R Sukov, Anja C Roden
INTRODUCTION: Thymic carcinomas are aggressive tumors. Biomarkers and alternative treatment modalities are needed. We studied the expression of p16 and cytogenetic abnormalities of cyclin-dependent kinase inhibitor 2A gene (CDKN2A) and correlated findings with clinical features and outcome in a large cohort of thymic carcinomas. METHODS: Thymic carcinomas (1963-2013) were stained with p16. Fluorescence in situ hybridization was utilized to assess for the presence of CDKN2A gene (at 9p21)...
February 5, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28129785/human-umbilical-cord-derived-mesenchymal-stromal-cells-protect-against-premature-renal-senescence-resulting-from-oxidative-stress-in-rats-with-acute-kidney-injury
#14
Camila Eleuterio Rodrigues, José Manuel Condor Capcha, Ana Carolina de Bragança, Talita Rojas Sanches, Priscila Queiroz Gouveia, Patrícia Aparecida Ferreira de Oliveira, Denise Maria Avancini Costa Malheiros, Rildo Aparecido Volpini, Mirela Aparecida Rodrigues Santinho, Bárbara Amélia Aparecida Santana, Rodrigo do Tocantins Calado, Irene de Lourdes Noronha, Lúcia Andrade
BACKGROUND: Mesenchymal stromal cells (MSCs) represent an option for the treatment of acute kidney injury (AKI). It is known that young stem cells are better than are aged stem cells at reducing the incidence of the senescent phenotype in the kidneys. The objective of this study was to determine whether AKI leads to premature, stress-induced senescence, as well as whether human umbilical cord-derived MSCs (huMSCs) can prevent ischaemia/reperfusion injury (IRI)-induced renal senescence in rats...
January 28, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28127745/5-fluorouracil-causes-endothelial-cell-senescence-potential-protective-role-of-glucagon-like-peptide-1
#15
Paola Altieri, Roberto Murialdo, Chiara Barisione, Edoardo Lazzarini, Silvano Garibaldi, Patrizia Fabbi, Clarissa Ruggeri, Silvia Borile, Federico Carbone, Andrea Armirotti, Marco Canepa, Alberto Ballestrero, Claudio Brunelli, Fabrizio Montecucco, Pietro Ameri, Paolo Spallarossa
BACKGROUND AND PURPOSE: 5-fluorouracil (5FU) and its prodrug, capecitabine, can damage endothelial cells, whilst endothelial integrity is preserved by glucagon-like peptide 1 (GLP-1). Here, we studied the effect of 5FU on endothelial senescence and whether GLP-1 antagonizes it. EXPERIMENTAL APPROACH: EA.hy926 cells were exposed to 5FU or sera from patients taking capecitabine, with or without pre-incubation with GLP-1. Senescence was identified by expression of senescence-associated β-galactosidase and p16(INK4a) and reduced cell proliferation...
January 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28120917/the-interplay-between-p16-serine-phosphorylation-and-arginine-methylation-determines-its-function-in-modulating-cellular-apoptosis-and-senescence
#16
Yang Lu, Wenlong Ma, Zhongwei Li, Jun Lu, Xiuli Wang
Cyclin-dependent kinase inhibitor p16(INK4a) (p16) primarily functions as a negative regulator of the retinoblastoma protein (Rb) -E2F pathway, thus plays critical role in cell cycle progression, cellular senescence and apoptosis. In this study, we showed that the methylation of Arg 138 and the phosphorylation of Ser 140 on p16 were critical for the control of cell proliferation and apoptosis. Compared to wild type p16, mutant p16R138K possessed improved function in preventing cell proliferation and inducing apoptosis, while the Ser 140 mutation (p16S140A) exhibited the opposite alteration...
January 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28108990/geographic-heterogeneity-in-the-prevalence-of-human-papillomavirus-in-head-and-neck-cancer
#17
Devasena Anantharaman, Behnoush Abedi-Ardekani, Daniel C Beachler, Tarik Gheit, Andrew F Olshan, Kathy Wisniewski, Victor Wunsch-Filho, Tatiana N Toporcov, Eloiza H Tajara, José Eduardo Levi, Raquel A Moyses, Stefania Boccia, Gabriella Cadoni, Guido Rindi, Wolfgang Ahrens, Franco Merletti, David I Conway, Sylvia Wright, Christine Carreira, Helene Renard, Priscilia Chopard, Sandrine McKay-Chopin, Ghislaine Scelo, Massimo Tommasino, Paul Brennan, Gypsyamber D'Souza
Human papillomavirus (HPV) causes oropharyngeal squamous cell carcinoma (OPSCC), although strongly divergent results have been reported regarding the prevalence of HPV16 in different countries, whether this represents important differences in etiology remains unclear. Applying rigorous protocols for sample processing, we centrally evaluated 1,420 head and neck tumors (533 oropharynx, 395 oral cavity and 482 larynx) from studies conducted in the US, Europe and Brazil for mucosal HPV DNA and p16(INK4a) expression to evaluate regional heterogeneity in the proportion of HPV16-associated OPSCC and other head and neck cancer, and to assess covariates associated with the risk of HPV16-positive OPSCC...
May 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28088318/correlation-of-the-hpv-detection-protein-expression-and-dna-content-in-cutaneous-pre-invasive-and-invasive-carcinoma-among-croatian-patients
#18
Kristina Meljanac Salopek, Stanko Jukić, Damir Babić
Development of cutaneous carcinomas has been associated with HPV infection. There have been various reports on p16, p53 and pRb expression in cutaneous carcinomas and on its linkage to HPV status. Association of protein expression and HPV infection with DNA content is not clear. The aim of this study was to determine a possible correlation between HPV type, protein expression and DNA content in both pre-invasive and invasive squamous cell carcinoma, as well as differences between studied groups in these parameters...
January 12, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28074012/reduced-abundance-of-the-e3-ubiquitin-ligase-e6ap-contributes-to-decreased-expression-of-the-ink4-arf-locus-in-non-small-cell-lung-cancer
#19
Cristina Gamell, Twishi Gulati, Yaara Levav-Cohen, Richard J Young, Hongdo Do, Pat Pilling, Elena Takano, Neil Watkins, Stephen B Fox, Prudence Russell, Doron Ginsberg, Brendon J Monahan, Gavin Wright, Alex Dobrovic, Sue Haupt, Ben Solomon, Ygal Haupt
The tumor suppressor p16(INK4a), one protein encoded by the INK4/ARF locus, is frequently absent in multiple cancers, including non-small cell lung cancer (NSCLC). Whereas increased methylation of the encoding gene (CDKN2A) accounts for its loss in a third of patients, no molecular explanation exists for the remainder. We unraveled an alternative mechanism for the silencing of the INK4/ARF locus involving the E3 ubiquitin ligase and transcriptional cofactor E6AP (also known as UBE3A). We found that the expression of three tumor suppressor genes encoded in the INK4/ARF locus (p15(INK4b), p16(INK4a), and p19(ARF)) was decreased in E6AP(-/-) mouse embryo fibroblasts...
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28072763/epithelial-to-mesenchymal-transition-and-hpv-infection-in-squamous-cell-oropharyngeal-carcinomas-the-papillophar-study
#20
Marine Lefevre, Alexandra Rousseau, Thomas Rayon, Véronique Dalstein, Christine Clavel, Agnès Beby-Defaux, Jean-Luc Pretet, Patrick Soussan, Myriam Polette, Jean Lacau Saint Guily, Philippe Birembaut
BACKGROUND: Human Papillomavirus (HPV) infection is recognised as aetiological factor of carcinogenesis in oropharyngeal squamous cell carcinomas (OPC). HPV-related OPC respond better to treatments and have a significantly favourable outcome. Epithelial to mesenchymal transition (EMT) implicated in tumour invasion, is a hallmark of a poor prognosis in carcinomas. METHODS: We have studied the relationship of EMT markers (E-cadherin, β-catenin and vimentin) with HPV infection (DNA and E6/E7 mRNA detection), p16(INK4a) expression and survival outcomes in a cohort of 296 patients with OPC...
January 2017: British Journal of Cancer
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