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https://www.readbyqxmd.com/read/28431961/ionizing-radiation-induces-long-term-senescence-in-endothelial-cells-through-mitochondrial-respiratory-complex-ii-dysfunction-and-superoxide-generation
#1
Audrey Lafargue, Charlotte Degorre, Isabelle Corre, Marie-Clotilde Alves-Guerra, Marie-Hélène Gaugler, François Vallette, Claire Pecqueur, François Paris
Ionizing radiation causes oxidative stress, leading to acute and late cellular responses. We previously demonstrated that irradiation of non-proliferating endothelial cells, as observed in normal tissues, induces early apoptosis, which can be inhibited by pretreatment with Sphingosine-1-Phosphate. We now propose to better characterize the long-term radiation response of endothelial cells by studying the molecular pathways associated with senescence and its link with acute apoptosis. First, senescence was validated in irradiated quiescent microvascular HMVEC-L in a dose- and time-dependent manner by SA β-galactosidase staining, p16(Ink4a) and p21(Waf1) expression, pro-inflammatory IL-8 secretion and DNA damage response activation...
April 18, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28418604/loss-of-ink4a-arf-gene-enhances-ultraviolet-radiation-induced-cutaneous-tumor-development
#2
Israr Ahmad, Purushotham Guroji, Amanda H DeBrot, Padma P Manapragada, Santosh K Katiyar, Craig A Elmets, Nabiha Yusuf
The CDKN2A locus encodes for tumor suppressor genes p16(INK)(4a) and p14(Arf) which are frequently inactivated in human skin tumors. The purpose of this study was to determine the relationship between loss of INK4a/Arf activity and inflammation in the development of ultraviolet (UV) radiation-induced skin tumors. Panels of INK4a/Arf(-/-) mice and wild type (WT) mice were treated with a single dose of UVB (200 mJ/cm(2) ). For long-term studies, these mice were irradiated with UVB (200 mJ/cm(2) ) three times weekly for 30 weeks...
April 18, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28410532/role-of-p16-ink4a-and-bmi-1-in-oxidative-stress-induced-premature-senescence-in-human-dental-pulp-stem-cells
#3
Cristina Mas-Bargues, José Viña-Almunia, Marta Inglés, Jorge Sanz-Ros, Juan Gambini, José Santiago Ibáñez-Cabellos, José Luis García-Giménez, José Viña, Consuelo Borrás
Human dental pulp stem cells (hDPSCs) are a source for cell therapy. Before implantation, an in vitro expansion step is necessary, with the inconvenience that hDPSCs undergo senescence following a certain number of passages, loosing their stemness properties. Long-term in vitro culture of hDPSCs at 21% (ambient oxygen tension) compared with 3-6% oxygen tension (physiological oxygen tension) caused an oxidative stress-related premature senescence, as evidenced by increased β-galactosidase activity and increased lysil oxidase expression, which is mediated by p16(INK4a) pathway...
April 7, 2017: Redox Biology
https://www.readbyqxmd.com/read/28408139/the-anti-inflammatory-effect-of-melatonin-in-sh-sy5y-neuroblastoma-cells-exposed-to-sublethal-dose-of-hydrogen-peroxide
#4
Chutikorn Nopparat, Varunya Chantadul, Kannika Permpoonputtana, Piyarat Govitrapong
Brain inflammaging is considered as one of the underlying factors of neurodegenerative diseases. The present study aimed to investigate the effects of melatonin, an endogenous indoleamine mainly synthesized by the pineal gland, on hydrogen peroxide (H2O2)-induced inflammaging state in SH-SY5Y cells. Our data showed that p21(Cip1) and p16(INK4a), cell cycle arrest markers, and the number of senescence-associated β-galactosidase (SA-βgal) staining increased significantly in H2O2-treated cells. Melatonin treatment could reverse this effect...
April 10, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28405521/human-papilloma-virus-load-and-pd-1-pd-l1-cd8-and-foxp3-in-anal-cancer-patients-treated-with-chemoradiotherapy-rationale-for-immunotherapy
#5
Panagiotis Balermpas, Daniel Martin, Ulrike Wieland, Margret Rave-Fränk, Klaus Strebhardt, Claus Rödel, Emmanouil Fokas, Franz Rödel
We examined the prognostic role of immune markers programmed cell death protein-1 (PD-1) and its ligand (PD-L1), CD8(+) tumor-infiltrating lymphocytes (TILs), FOXP3+ Tregs and phosphorylated Caspase-8 (T273) in patients with anal squamous cell cancer (ASCC) treated with standard chemoradiotherapy (CRT). The baseline immunohistochemical expression of immune markers was correlated with clinicopathologic characteristics, and cumulative incidence of local failure, disease-free survival (DFS) and overall survival (OS) in 150 patients, also in the context of human papilloma virus 16 (HPV16) DNA load and p16(INK4a) expression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28403538/human-papillomavirus-epstein-barr-virus-and-methylation-status-of-p16-ink4a-in-penile-cancer
#6
L A Afonso, F N Carestiato, A A Ornellas, P Ornellas, W M Rocha, T I Cordeiro, D C Lisboa, G Alves, Smb Cavalcanti
Little is known about penile carcinogenesis. The aim of this study was to evaluate the prevalence of HPV and EBV, and the methylation status of p16(ink4a) in penile cancer samples, and to contribute to the understanding of the mechanisms responsible for penile cancer development. HPV DNA was detected in 63.6% of 122 cases, with HPV16 being the most prevalent type. EBV DNA was detected in 47.7%, with EBV-1 being the most prevalent type. HPV/EBV co-infections were found in 27.3% of the cases. Hypermethylation in p16(ink4a) was detected in 64...
April 12, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28395715/-subcellular-re-distribution-of-f-actin-in-mcf7-cells-upon-inducible-expression-of-cdkn2a-p16-ink4a
#7
Jianqing Liang, Manna Wang, Zhengrong Zhang, Long Yuan, You Zheng, Hongyan Huang, Qiang Sun, Jufang Wang, Xiaoning Wang
Objective To investigate the effect of CDKN2A/p16(INK4a), a cyclin-dependent kinase inhibitor, on cell morphology and cytoskeleton in MCF7 breast cancer cells by tetracycline operon (Tet-on) inducible gene expression system. Methods MCF7 cells, genetically null for p16(INK4a) expression, were sequentially infected with two viruses of Tet-on systems to make MCF7-pTet-on-p16(INK4a) cells, which were induced to express p16NK4a by doxycycline (Dox) treatment. Cell growth was evaluated by cell counting. To observe the effect of p16(INK4a) on cell adhesion and cytoskeleton, intercellular adhesion and intracellular F-actin were examined by fluorescent staining with anti-E-cadherin antibody and phalloidin, respectively...
April 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28387325/hpv-negative-penile-squamous-cell-carcinoma-disruptive-mutations-in-the-tp53-gene-are-common
#8
Karl Kashofer, Elke Winter, Iris Halbwedl, Andrea Thueringer, Marisa Kreiner, Stefan Sauer, Sigrid Regauer
The majority of penile squamous cell carcinomas is caused by transforming human papilloma virus (HPV) infection. The etiology of HPV-negative cancers is unclear, but TP53 mutations have been implicated. Archival tissues of 108 invasive squamous cell carcinoma from a single pathology institution in a low-incidence area were analyzed for HPV-DNA and p16(ink4a) overexpression and for TP53 mutations by ion torrent next-generation sequencing. Library preparation failed in 32/108 squamous cell carcinomas. Institutional review board approval was obtained...
April 7, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28380379/%C3%AE-cell-aging-markers-have-heterogeneous-distribution-and-are-induced-by-insulin-resistance
#9
Cristina Aguayo-Mazzucato, Mark van Haaren, Magdalena Mruk, Terence B Lee, Caitlin Crawford, Jennifer Hollister-Lock, Brooke A Sullivan, James W Johnson, Aref Ebrahimi, Jonathan M Dreyfuss, Jan Van Deursen, Gordon C Weir, Susan Bonner-Weir
We hypothesized that the known heterogeneity of pancreatic β cells was due to subpopulations of β cells at different stages of their life cycle with different functional capacities and that further changes occur with metabolic stress and aging. We identified new markers of aging in β cells, including IGF1R. In β cells IGF1R expression correlated with age, dysfunction, and expression of known age markers p16(ink4a), p53BP1, and senescence-associated β-galactosidase. The new markers showed striking heterogeneity both within and between islets in both mouse and human pancreas...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28376081/human-papillomavirus-16-is-an-aetiological-factor-of-scrotal-cancer
#10
Núria Guimerà, Laia Alemany, Gordana Halec, Michael Pawlita, Gerard Vincent Wain, José Santos Salas Vailén, Jerome E Azike, David Jenkins, Silvia de Sanjosé, Wim Quint, F Xavier Bosch
BACKGROUND: Squamous cell scrotal carcinoma (SCSC) is an infrequent skin cancer associated historically with occupational carcinogens. Human papillomavirus (HPV) DNA has been associated with SCSC but there is no definitive proof of its oncogenic role. METHODS: Human papillomavirus-DNA and -E6*I mRNA were analysed in six invasive histologically typed SCSC. LCM-PCR was used to localise HPV DNA to tumour cells. P16(INK4a)and p53 expression were studied by immunohistochemistry...
April 4, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28371465/p16-ki-67-dual-labeling-and-urinary-cytology-results-according-to-the-new-paris-system-for-reporting-urinary-cytology-impact-of-extended-follow-up
#11
Eric Piaton, Anne-Sophie Advenier, Christian Carré, Myriam Decaussin-Petrucci, Florence Mège-Lechevallier, Karine Hutin, Cindy Nennig, Marc Colombel, Alain Ruffion
BACKGROUND: Overexpression of p16(INK4a) has been identified in urothelial malignancies both cytologically and histologically. In addition, p16/Ki-67 dual labeling has been shown to identify high-grade urothelial cancer cells and some progression cases within a 12-month delay. The Paris System for Reporting Urinary Cytology (TPS) was published in late 2015. Its aim is to clarify the criteria for diagnosing or, conversely, excluding high-grade urothelial carcinoma (HGUC). METHODS: Dual labeling was performed on archived ThinPrep-based Papanicolaou slides...
April 3, 2017: Cancer
https://www.readbyqxmd.com/read/28371015/p16-ink4a-a-surrogate-marker-of-high-risk-human-papillomavirus-infection-in-squamous-cell-carcinoma-of-the-nasal-vestibule
#12
Domenic Vital, David Holzmann, Gerhard F Huber, Michael B Soyka, Holger Moch, Dieter R Zimmermann, Kristian Ikenberg
BACKGROUND: The purpose of this study was to analyze the role of p16(INK4a) and the prevalence of human papillomavirus (HPV) in squamous cell carcinoma (SCC) of the nasal vestibule. METHODS: Patients diagnosed from 1995 to 2014 were included in this study. Assessment of p16(INK4a) and HPV-DNA polymerase chain reaction (PCR) was performed and analyzed with respect to baseline, clinicopathological, and outcome parameters. The p16(INK4a) positivity was defined as unequivocal nuclear and cytoplasmic staining of ≥70% of the cells, whereas 50%-69% was considered to be a "borderline" result...
March 28, 2017: Head & Neck
https://www.readbyqxmd.com/read/28369859/role-of-mucosal-high-risk-human-papillomavirus-types-in-head-and-neck-cancers-in-central-india
#13
Tarik Gheit, Devasena Anantharaman, Dana Holzinger, Laia Alemany, Sara Tous, Eric Lucas, Priya R Prabhu, Michael Pawlita, Ruediger Ridder, Susanne Rehm, Johannes Bogers, Fausto Maffini, Susanna Chiocca, Belén Lloveras, Rekha Vijay Kumar, Thara Somanathan, Silvia de Sanjosé, Xavier Castellsagué, Marc Arbyn, Paul Brennan, Rengaswamy Sankaranarayanan, Madhavan Radhakrishna Pillai, Nitin Gangane, Massimo Tommasino
Mucosal high-risk (HR) human papillomaviruses (HPV) cause a subset of head and neck cancers (HNC). The HPV-attributable fraction of HNC varies substantially between countries. Although HNC has a very high incidence in the Indian sub-continent, information on the contribution of HPV infection is limited. Here, we evaluated the HPV-attributable fraction in HNC (N=364) collected in a central region of India. HNC from three different anatomical subsites were included, namely oral cavity (n=252), oropharynx (n=53) and hypopharynx/larynx (n=59)...
March 29, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28367025/role-of-p16-ink4a-and-ki-67-as-specific-biomarkers-for-cervical-intraepithelial-neoplasia-an-institutional-study
#14
Ankitha Hebbar, Venkataramappa Srinivasa Murthy
BACKGROUND: P16/INK4a and Ki-67 have emerged as important biomarkers for the detection of high-risk human papilloma virus (HR-HPV) associated dysplastic changes in the cervical biopsy samples. The increasing inter- and intra-observer variability in the diagnosis of dysplastic lesions and immature squamous metaplasia on histopathology has led to the advent of these biomarkers. This study was taken up with an aim to study their role in increasing the diagnostic accuracy in equivocal cases on histopathology...
April 2017: Journal of Laboratory Physicians
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
#15
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
#16
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
#17
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
#18
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
#19
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...
April 2017: Nature Medicine
https://www.readbyqxmd.com/read/28249161/the-setd8-pr-set7-methyltransferase-functions-as-a-barrier-to-prevent-senescence-associated-metabolic-remodeling
#20
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
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