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p16 ink4a

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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
#1
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 11, 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
#2
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
#3
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 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28059099/biological-relevance-of-human-papillomaviruses-in-vulvar-cancer
#4
Gordana Halec, Laia Alemany, Beatriz Quiros, Omar Clavero, Daniela Höfler, Maria Alejo, Wim Quint, Michael Pawlita, Francesc X Bosch, Silvia de Sanjose
The carcinogenic role of high-risk human papillomavirus (HR-HPV) types in the increasing subset of vulvar intraepithelial neoplasia and vulvar cancer in young women has been established. However, the actual number of vulvar cancer cases attributed to HPV is still imprecisely defined. In an attempt to provide a more precise definition of HPV-driven vulvar cancer, we performed HPV-type-specific E6*I mRNA analyses available for 20 HR-/possible HR (pHR)-HPV types, on tissue samples from 447 cases of vulvar cancer...
January 6, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28035326/the-new-immortalized-uroepithelial-cell-line-hblak-contains-defined-genetic-aberrations-typical-of-early-stage-urothelial-tumors
#5
Michèle J Hoffmann, Evangelia Koutsogiannouli, Margaretha A Skowron, Maria Pinkerneil, Günter Niegisch, Artur Brandt, Stefanie Stepanow, Harald Rieder, Wolfgang A Schulz
Background: Cell culture models of normal urothelial cells are important for studying differentiation, disease mechanisms and anticancer drug development. Beyond primary cultures with their limitations in lifespan, interindividual heterogeneity and supply, few conditionally immortalized cell lines with limited applicability due to partial transformation or impaired differentiation capacity are available. We describe characteristics of the new spontaneously immortalized cell line HBLAK derived from a primary culture of uroepithelial cells...
October 27, 2016: Bladder Cancer
https://www.readbyqxmd.com/read/28032946/population-pharmacokinetics-modeling-of-unbound-efavirenz-atazanavir-and-ritonavir-in-hiv-infected-subjects-with-aging-biomarkers
#6
J B Dumond, J Chen, M Cottrell, C R Trezza, Hma Prince, C Sykes, C Torrice, N White, S Malone, R Wang, K B Patterson, N E Sharpless, A Forrest
Unbound drug is the pharmacodynamically relevant concentration. This study aimed to determine if chronologic age or markers of biologic aging, such as the frailty phenotype and p16(INK4a) gene expression, altered unbound pharmacokinetics (PKs) of efavirenz (EFV) and atazanavir/ritonavir (ATV/RTV). Sixty human immunodeficiency virus (HIV)-infected participants receiving EFV and 31 receiving ATV/RTV provided 1 to 11 samples to quantify total and unbound plasma concentrations. Population PK models with total and unbound concentrations simultaneously described are developed for each drug...
December 29, 2016: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28024722/the-role-of-hpv-on-the-risk-of-second-primary-neoplasia-in-patients-with-oropharyngeal-carcinoma
#7
María Martel, Laia Alemany, Miren Taberna, Marisa Mena, Sara Tous, Silvia Bagué, Xavier Castellsagué, Miquel Quer, Xavier León
OBJECTIVES: It has been reported that patients with HPV-positive oropharyngeal cancer (OPC) have a lower risk of appearance of second primary neoplasm (SPN) than HPV-negative OPC patients. The aim of our study was to analyze the risk of developing SPN in a large group of patients with OPC according to HPV status in the primary tumor. MATERIALS AND METHODS: We included 412 OPC patients treated at our center from 1991 to 2014 for which the HPV DNA positivity was evaluated by PCR in available tumor specimens...
January 2017: Oral Oncology
https://www.readbyqxmd.com/read/28019088/p16-ink4a-a-senescence-marker-influences-tenofovir-emtricitabine-metabolite-disposition-in-hiv-infected-subjects
#8
J B Dumond, J W Collins, M L Cottrell, C R Trezza, Hma Prince, C Sykes, C Torrice, N White, S Malone, R Wang, K B Patterson, N E Sharpless, A Forrest
The goal of this study was to explore the relationships between tenofovir (TFV) and emtricitabine (FTC) disposition and markers of biologic aging, such as the frailty phenotype and p16(INK4a) gene expression. Chronologic age is often explored in population pharmacokinetic (PK) analyses, and can be uninformative in capturing the impact of aging on physiology, particularly in human immunodeficiency virus (HIV)-infected patients. Ninety-one HIV-infected participants provided samples to quantify plasma concentrations of TFV/FTC, as well as peripheral blood mononuclear cell (PBMC) samples for intracellular metabolite concentrations; 12 participants provided 11 samples, and 79 participants provided 4 samples, over a dosing interval...
December 26, 2016: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28000027/meta-analysis-demonstrates-no-association-between-p16-ink4a-promoter-methylation-and-epithelial-ovarian-cancer
#9
Yi Jiang, Fangrong Yan, Li Liang, Yicong Wan, Jinsong Liu, Wenjun Cheng
BACKGROUND: p16 (INK4A) (p16) functions as a tumor suppressor gene in various malignancies. Aberrant p16 methylation has been proposed to be essential in ovarian carcinogenesis. However, it is unclear whether p16 can be used as a diagnostic marker owing to the small sample sizes in previous studies. METHODS: To determine whether p16 promoter methylation is associated with epithelial ovarian cancer and can thus be used as a diagnostic marker, we performed a meta-analysis of published studies...
December 20, 2016: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/27965321/suppressing-p16ink4a-and-p14arf-pathways-overcomes-apoptosis-in-individualized-human-embryonic-stem-cells
#10
Wenqian Wang, Yanling Zhu, Ke Huang, Yongli Shan, Juan Du, Xiaoya Dong, Ping Ma, Penafei Wu, Jian Zhang, Wenhao Huang, Tian Zhang, Baojian Liao, Deyang Yao, Guangjin Pan, Jiajun Liu
Dissociation-induced apoptosis is a striking phenomenon in human embryonic stem cells (hESCs), but not in naïve mouse ESCs. Rho-associated kinase-dependent actin-myosin hyperactivation is an underlying mechanism that triggers apoptosis in dissociated hESCs; however, in this study, we show that the Ink4A-ARF-mediated senescence pathway is another mechanism to cause apoptosis in individualized hESCs. We show that P16(INK4A) and P14(ARF) are immediately induced in hESCs upon dissociation, but not in mouse ESCs...
December 13, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27958341/downregulation-of-peroxiredoxin-3-by-hydrophobic-bile-acid-induces-mitochondrial-dysfunction-and-cellular-senescence-in-human-trophoblasts
#11
Wei-Bin Wu, Ramkumar Menon, Yue-Ying Xu, Jiu-Ru Zhao, Yan-Lin Wang, Yuan Liu, Hui-Juan Zhang
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disorder characterised by raised bile acids in foetal-maternal circulation, which threatens perinatal health. During the progression of ICP, the effect of oxidative stress is underscored. Peroxiredoxin-3 (PRDX3) is a mitochondrial antioxidant enzyme that is crucial to balance intracellular oxidative stress. However, the role of PRDX3 in placental trophoblast cells under ICP is not fully understood. We demonstrated that the level of PRDX3 was downregulated in ICP placentas as well as bile acids-treated trophoblast cells and villous explant in vitro...
December 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27937072/altered-expression-of-g1-s-phase-cell-cycle-regulators-in-placental-mesenchymal-stromal-cells-derived-from-preeclamptic-pregnancies-with-fetal-placental-compromise
#12
Anna Maria Nuzzo, Domenica Giuffrida, Bianca Masturzo, Paolo Mele, Ettore Piccoli, Carola Eva, Tullia Todros, Alessandro Rolfo
Herein, we evaluated whether Placental Mesenchymal Stromal Cells (PDMSCs) derived from normal and Preeclamptic (PE) placentae presented differences in the expression of G1/S-phase regulators p16(INK4A), p18(INK4C), CDK4 and CDK6. Finally, we investigated normal and PE-PDMSCs paracrine effects on JunB, Cyclin D1, p16(INK4A), p18(INK4C), CDK4 and CDK6 expressions in physiological term villous explants. PDMSCs were isolated from physiological (n = 20) and PE (n = 24) placentae. Passage three normal and PE-PDMSC and conditioned media (CM) were collected after 48h...
December 12, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27926800/interobserver-reproducibility-of-cytologic-p16-ink4a-ki-67-dual-immunostaining-in-human-papillomavirus-positive-women
#13
Maria Benevolo, Elena Allia, Daniela Gustinucci, Francesca Rollo, Simonetta Bulletti, Elena Cesarini, Basilio Passamonti, Maria Rosaria Giovagnoli, Elisabetta Carico, Francesca M Carozzi, Alessandra Mongia, Giulia Fantacci, Massimo Confortini, Teresa Rubino, Cristina Fodero, Sonia Prandi, Natalina Marchi, Angelo Farruggio, Anna Coccia, Luigia Macrì, Bruno Ghiringhello, Guglielmo Ronco, Emma Bragantini, Enzo Polla, Vincenzo Maccallini, Giovanni Negri, Paolo Giorgi Rossi
BACKGROUND: The accumulation of cyclin-dependent kinase inhibitor 2A (p16(ink4a) ) protein in a cell is associated with neoplastic progression in precancerous cervical lesions. Dual staining for p16(ink4a) and Ki-67 has been proposed as a triage test in cervical cancer screening for women who test positive for human papillomavirus DNA. In this study, interobserver reproducibility of the interpretation of this test was assessed. METHODS: Forty-two immunostained, liquid-based cytology slides were divided into 2 sets and were interpreted by 17 to 21 readers from 9 different laboratories, yielding a total of 816 reports...
December 7, 2016: Cancer
https://www.readbyqxmd.com/read/27893710/muc1-c-activates-bmi1-in-human-cancer-cells
#14
M Hiraki, T Maeda, A Bouillez, M Alam, A Tagde, K Hinohara, Y Suzuki, T Markert, M Miyo, K Komura, R Ahmad, H Rajabi, D Kufe
B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) is a component of the polycomb repressive complex 1 (PRC1) complex that is overexpressed in breast and other cancers, and promotes self-renewal of cancer stem-like cells. The oncogenic mucin 1 (MUC1) C-terminal (MUC1-C) subunit is similarly overexpressed in human carcinoma cells and has been linked to their self-renewal. There is no known relationship between MUC1-C and BMI1 in cancer. The present studies demonstrate that MUC1-C drives BMI1 transcription by a MYC-dependent mechanism in breast and other cancer cells...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27889388/cellular-aging-contributes-to-failure-of-cold-induced-beige-adipocyte-formation-in-old-mice-and-humans
#15
Daniel C Berry, Yuwei Jiang, Robert W Arpke, Elizabeth L Close, Aki Uchida, David Reading, Eric D Berglund, Michael Kyba, Jonathan M Graff
Cold temperatures induce progenitor cells within white adipose tissue to form beige adipocytes that burn energy and generate heat; this is a potential anti-diabesity therapy. However, the potential to form cold-induced beige adipocytes declines with age. This creates a clinical roadblock to potential therapeutic use in older individuals, who constitute a large percentage of the obesity epidemic. Here we show that aging murine and human beige progenitor cells display a cellular aging, senescence-like phenotype that accounts for their age-dependent failure...
January 10, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/27865368/effect-of-hpv-on-head-and-neck-cancer-patient-survival-by-region-and-tumor-site-a-comparison-of-1362-cases-across-three-continents
#16
Gypsyamber D'Souza, Devasena Anantharaman, Tarik Gheit, Behnoush Abedi-Ardekani, Daniel C Beachler, David I Conway, Andrew F Olshan, Victor Wunsch-Filho, Tatiana N Toporcov, Wolfgang Ahrens, Kathy Wisniewski, Franco Merletti, Stefania Boccia, Eloiza H Tajara, Jose P Zevallos, José Eduardo Levi, Mark C Weissler, Sylvia Wright, Ghislaine Scelo, Angela L Mazul, Massimo Tommasino, Paul Brennan, Gabriella Cadoni
OBJECTIVES: To explore whether HPV-related biomarkers predict oropharyngeal squamous cell cancer (OPSCC) survival similarly across different global regions, and to explore their prognostic utility among non-oropharyngeal (non-OP) head and neck cancers. METHODS: Data from 1362 head and neck SCC (HNSCC) diagnosed 2002-2011 was used from epidemiologic studies in: Brazil (GENCAPO study, n=388), U.S. (CHANCE study, n=472), and Europe (ARCAGE study, n=502). Tumors were centrally tested for p16(INK4a) and HPV16 DNA (by PCR)...
November 2016: Oral Oncology
https://www.readbyqxmd.com/read/27861555/p16ink4a-expression-and-immunologic-aging-in-chronic-hiv-infection
#17
Susan Pereira Ribeiro, Jeffrey M Milush, Edecio Cunha-Neto, Esper G Kallas, Jorge Kalil, Luiz Felipe D Passero, Peter W Hunt, Steven G Deeks, Douglas F Nixon, Devi SenGupta
Chronic HIV infection is characterized by increased immune activation and immunosenescence. p16 INK4a (p16) is a member of the cyclin-dependent kinase antagonist family that inhibits cellular proliferation, and its protein expression increases during normal chronological aging. However, some infectious diseases can increase the expression of this anti-proliferative protein, potentially accelerating immunological aging and dysfunction. In order to investigate the immunological aging in HIV patients, p16 protein expression was evaluated by flow cytometry, in T cell subsets in a cohort of chronically HIV-infected patients on and off ART as well as age-matched healthy controls...
2016: PloS One
https://www.readbyqxmd.com/read/27859428/low-p16-ink4a-expression-in-early-passage-human-prostate-basal-epithelial-cells-enables-immortalization-by-telomerase-expression-alone
#18
Mindy Kim Graham, Lorenzo Principessa, Lizamma Antony, Alan K Meeker, John T Isaacs
BACKGROUND: There are two principal senescence barriers that must be overcome to successfully immortalize primary human epithelial cells in culture, stress-induced senescence, and replicative senescence. The p16(INK4a) /retinoblastoma protein (p16/Rb) pathway mediates stress-induced senescence, and is generally upregulated by primary epithelial cells in response to the artificial conditions from tissue culture. Replicative senescence is associated with telomere loss. Following each round of cell division, telomeres progressively shorten...
November 8, 2016: Prostate
https://www.readbyqxmd.com/read/27859245/diagnostic-accuracy-of-p16-ink4a-immunohistochemistry-in-oropharyngeal-squamous-cell-carcinomas-a-systematic-review-and-meta-analysis
#19
Elena-Sophie Prigge, Marc Arbyn, Magnus von Knebel Doeberitz, Miriam Reuschenbach
The accurate diagnosis of human papillomavirus (HPV) causality in oropharyngeal squamous cell carcinomas (OPSCC) is likely to influence therapeutic decisions in affected patients in the near future. We conducted a systematic review and meta-analysis to determine the diagnostic accuracy of p16(INK4a) immunohistochemistry (IHC) to identify HPV-induced OPSCC. We identified all studies that performed p16(INK4a) IHC (index test) and HPV E6/E7 mRNA detection using an amplification-based method (gold standard to indicate a transforming relevance of HPV) in OPSCC...
March 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27844328/molecular-profiling-of-thymoma-and-thymic-carcinoma-genetic-differences-and-potential-novel-therapeutic-targets
#20
Franz Enkner, Bettina Pichlhöfer, Alexandru Teodor Zaharie, Milica Krunic, Tina Maria Holper, Stefan Janik, Bernhard Moser, Karin Schlangen, Barbara Neudert, Karin Walter, Brigitte Migschitz, Leonhard Müllauer
Thymoma and thymic carcinoma are thymic epithelial tumors (TETs). We performed a molecular profiling to investigate the pathogenesis of TETs and identify novel targets for therapy. We analyzed 37 thymomas (18 type A, 19 type B3) and 35 thymic carcinomas. The sequencing of 50 genes detected nonsynonymous mutations in 16 carcinomas affecting ALK, ATM, CDKN2A, ERBB4, FGFR3, KIT, NRAS and TP53. Only two B3 thymomas had a mutation in noncoding regions of the SMARCB1 and STK11 gene respectively. Three type A thymomas harbored a nonsynonymous HRAS mutation...
November 14, 2016: Pathology Oncology Research: POR
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