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https://www.readbyqxmd.com/read/29763603/pim1-catalyzed-cbx8-phosphorylation-promotes-the-oncogene-induced-senescence-of-human-diploid-fibroblast
#1
Xiangwen Zhan, Jianming Yang, Zebin Mao, Wenhua Yu
The proto-oncogene PIM1 encodes Ser/Thr kinase and regulates cell growth, differentiation and apoptosis. However, more and more studies including ours have found that PIM1 can induce senescence in normal human diploid fibroblasts and behave as a tumor suppressor. But the relevant molecular mechanism of this process is not yet clear. It has been reported that Chromobox homolog 8 (CBX8) binds directly to INK4A as a transcriptional repressor, thereby suppressing stress-induced senescence. Here we report that PIM1 can phosphorylate CBX8 to promote its degradation, thereby up-regulating p16, during PIM1-induced cell senescence...
May 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29744680/association-of-antibody-to-e2-protein-of-human-papillomavirus-and-p16-ink4a-with-progression-of-hpv-infected-cervical-lesions
#2
Jureeporn Chuerduangphui, Chamsai Pientong, Piyawut Swangphon, Sanguanchoke Luanratanakorn, Ussanee Sangkomkamhang, Thumwadee Tungsiriwattana, Pilaiwan Kleebkaow, Ati Burassakarn, Tipaya Ekalaksananan
Human papillomavirus (HPV) E2 and L1 proteins are expressed in cervical cells during the lytic stage of infection. Overexpression of p16INK4A is a biomarker of HPV-associated cervical neoplasia. This study investigated antibodies to HPV16 E2, HPV16 L1, and p16INK4A in sera from women with no squamous intraepithelial lesion (No-SIL) of the cervix, low-grade SIL, high-grade SIL, and cervical squamous cell carcinoma (SCC). HPV DNA was detected by polymerase chain reaction. Anti-E2, -L1, and -p16INK4A antibodies in sera were determined by western blot...
May 9, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29708483/sexual-behaviour-hpv-status-and-p16-ink4a-expression-in-oropharyngeal-and-oral-cavity-squamous-cell-carcinomas-a-case-case-comparison-study
#3
Sarah Emmett, Samuel Boros, David C Whiteman, Sandro V Porceddu, Benedict J Panizza, Annika Antonsson
A significant proportion of mucosal squamous cell carcinomas of the head and neck (HNSCC; particularly of the oropharynx) are directly attributable to the human papillomavirus (HPV). The increase in the incidence of HPV-related tumours has been postulated to be due to changing sexual practices in the community. We analysed 136 formalin-fixed paraffin-embedded squamous cell carcinomas from the oral cavity (n=40) and oropharynx (n=96) recruited from the Princess Alexandra Hospital (Brisbane, Australia). Samples were analysed for the presence of HPV DNA using a combination of mucosal HPV general primer GP+ PCR and sequencing; p16INK4a expression was assessed by immunohistochemistry...
April 30, 2018: Journal of General Virology
https://www.readbyqxmd.com/read/29676649/asbestos-induces-epigenetic-repression-of-ras-association-domain-containing-protein-1-p16-kinase-4a-inhibitor-and-p14-alternative-reading-frame-in-normal-human-mesothelial-cells
#4
Sichuan Xi, Eden C Payabyab, David M Straughan, Emily S Reardon, Mary Zhang, Julie A Hong, R Taylor Ripley, Chuong D Hoang, David S Schrump
RATIONALE: Whereas asbestos burden has been linked to cytogenetic alterations in malignant pleural mesotheliomas, epigenetic aberrations induced by these fibers have not been fully delineated. OBJECTIVES: The objective of this study was to establish an in vitro model to characterize early epigenetic events potentially contributing to malignant pleural mesothelioma. METHODS: Normal human mesothelial cells (LP9 and LP3) were cultured with or without crocidolite asbestos fibers (1 or 2 μg/cm2 ) for up to 10 days...
April 2018: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29675777/inhibition-of-p16-ink4a-to-rejuvenate-aging-human-cardiac-progenitor-cells-via-the-upregulation-of-anti-oxidant-and-nf%C3%AE%C2%BAb-signal-pathways
#5
Roshni V Khatiwala, Shuning Zhang, Xiuchun Li, Neil Devejian, Edward Bennett, Chuanxi Cai
Autologous human cardiac stem/progenitor cell (hCPC) therapy is a promising treatment that has come into use in recent years for patients with cardiomyopathy. Though innovative in theory, a major hindrance to the practical application of this treatment is that the hCPCs of elderly patients, who are most susceptible to myocardial disease, are senescent and prone to cell death. Rejuvenating hCPCs from elderly patients may help overcome this obstacle, and can be accomplished by reversing entry into the cellular stage of senescence...
April 19, 2018: Stem Cell Reviews
https://www.readbyqxmd.com/read/29651745/correlations-between-age-functional-status-and-the-senescence-associated-proteins-hmgb2-and-p16-ink4a
#6
Ibiyonu Lawrence, Michael Bene, Timothy Nacarelli, Ashley Azar, Justin Z Cohen, Claudio Torres, Gregg Johannes, Christian Sell
Cellular senescence is a central component of the aging process. This cellular response has been found to be induced by multiple forms of molecular damage and senescent cells increase in number with age in all tissues examined to date. We have examined the correlation with age of two key proteins involved in the senescence program, p16INK4a and HMGB2. These proteins are involved in cell cycle arrest and chromatin remodeling during senescence. Circulating levels of these markers increases with age and correlates with functional status...
April 12, 2018: GeroScience
https://www.readbyqxmd.com/read/29625991/t-3-induces-both-markers-of-maturation-and-aging-in-pancreatic-%C3%AE-cells
#7
Cristina Aguayo-Mazzucato, Terence B Lee, Michelle Matzko, Amanda DiIenno, Habib Rezanejad, Preeti Ramadoss, Thomas Scanlan, Ann Marie Zavacki, P Reed Larsen, Anthony Hollenberg, Clark Colton, Arun Sharma, Susan Bonner-Weir
Previously we showed thyroid hormone (T3 ) enhanced β-cell functional maturation through induction of Mafa High levels of T3 have been linked to decreased lifespan in mammals, and low levels to lengthened lifespan, suggesting a relationship between thyroid hormone and aging. Here we show T3 increased p16 Ink4a (a β-cell senescence marker and effector) mRNA in rodent and human β-cells. The kinetics of Mafa and p16 Ink4a induction suggested both genes as targets of thyroid hormone via TH receptor (THR) binding to specific response elements (TRE)...
April 6, 2018: Diabetes
https://www.readbyqxmd.com/read/29572122/hpv-infection-and-p16-ink4a-and-tp53-expression-in-rare-cancers-of-the-uterine-cervix
#8
Nabiha Missaoui, Sarra Mestiri, Ahlem Bdioui, Thouraya Zahmoul, Hajer Hamchi, Moncef Mokni, Sihem Hmissa
Cervix cancer remains among most commonly diagnosed cancer in developing countries. Except squamous cell carcinoma and adenocarcinoma, the etiopathology and oncogenic mechanisms of rare cancers remain largely unknown. The study was performed to investigate the value of HPV infection and the expression of p16INK4A and TP53 in rare primitive cancers of the cervix. We conducted a retrospective study of rare primitive cancers of the cervix. Main clinicopathological features were reported. HPV infection was detected by in situ hybridization...
March 6, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29564021/high-fat-diet-modifies-expression-of-hepatic-cellular-senescence-gene-p16-ink4a-through-chromatin-modifications-in-adult-male-rats
#9
Xiyuan Zhang, Guanying Bianca Xu, Dan Zhou, Yuan-Xiang Pan
Background: Liver is the crucial organ as a hub for metabolic reactions. p16(INK4a) is a well-established cyclin-dependent kinase (CDK) inhibitor that plays important role in the molecular pathways of senescence, which lead to irreversible cell cycle arrest with secretion of proinflammatory cytokines and mitochondrial dysfunction. This study tested the hypothesis that cellular senescence regulated by p16(INK4a) is associated with high-fat diet in adult male rats. Methods: Sprague Dawley rats were fed a high-fat (HF) diet or a control (C) diet for 9 weeks after weaning...
2018: Genes & Nutrition
https://www.readbyqxmd.com/read/29548481/p16-ink4a-status-and-survival-benefit-of-egfr-inhibitors-in-head-and-neck-squamous-cell-cancer-a-systematic-review-and-meta-analysis
#10
REVIEW
Yapin Su, Jiuwei Cui, Dongsheng Xu, Mengmeng Wang, Tiankai Xu, Huimn Tian, Fujun Han
BACKGROUND: We conducted a systematic review and meta-analysis to investigate the impact of p16(INK4a) status on survival benefits in head and neck squamous cell cancer (HNSCC) after anti-epidermal growth factor receptor (EGFR) based treatments. METHODS: We identified studies assessing anti-EGFR based versus non-anti-EGFR based regimens in patients with unresectable locoregionally advanced, recurrent or metastatic HNSCC. The primary endpoint was progression-free survival (PFS)...
April 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29511060/p16-ink4a-overexpression-as-a-predictor-of-survival-in-ocular-surface-squamous-neoplasia
#11
Sheetal Chauhan, Seema Sen, Anjana Sharma, Seema Kashyap, Radhika Tandon, Mandeep S Bajaj, Neelam Pushker, Murugesan Vanathi, Shyam S Chauhan
AIMS: To evaluate the expression and methylation status of the p16INK4a gene in early and advanced American Joint Committee on Cancer (AJCC) stages of ocular surface squamous neoplasia (OSSN) and to correlate its association with clinicopathological features and survival. METHODS: Sixty-four (35 early and 29 advanced AJCC stage) patients with OSSN formed part of this study and were followed up for 36-58 (mean 48±3.6) months. Immunohistochemical expression of the p16INK4a protein and methylation status of the p16INK4a gene were determined by methylation-specific PCR...
March 6, 2018: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/29496041/double-positivity-for-hpv-dna-p16-ink4a-is-the-biomarker-with-strongest-diagnostic-accuracy-and-prognostic-value-for-human-papillomavirus-related-oropharyngeal-cancer-patients
#12
Marisa Mena, Miren Taberna, Sara Tous, Sandra Marquez, Omar Clavero, Beatriz Quiros, Belen Lloveras, Maria Alejo, Xavier Leon, Miquel Quer, Silvia Bagué, Ricard Mesia, Julio Nogués, Montserrat Gomà, Anton Aguila, Teresa Bonfill, Carmen Blazquez, Marta Guix, Rafael Hijano, Montserrat Torres, Dana Holzinger, Michael Pawlita, Miguel Angel Pavon, Ignacio G Bravo, Silvia de Sanjosé, Francesc Xavier Bosch, Laia Alemany
BACKGROUND: The etiologic role of human papillomaviruses (HPV) in oropharyngeal cancer (OPC) is well established. Nevertheless, information on survival differences by anatomic sub-site or treatment remains scarce, and it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value. METHODS: We conducted a retrospective cohort study of all patients diagnosed with a primary OPC in four Catalonian hospitals from 1990 to 2013. Formalin-fixed, paraffin-embedded cancer tissues were subjected to histopathological evaluation, DNA quality control, HPV-DNA detection, and p16INK4a /pRb/p53/Cyclin-D1 immunohistochemistry...
March 2018: Oral Oncology
https://www.readbyqxmd.com/read/29484109/a-novel-suicide-gene-therapy-for-the-treatment-of-p16-ink4a-overexpressing-tumors
#13
Jaskaren Kohli, Judith Campisi, Marco Demaria
p16Ink4a is a potent cell cycle inhibitor engaged to support cell cycle arrest during cellular senescence. However, in tumors carrying mutations in key downstream effectors, p16Ink4a is highly expressed but fails to block cell proliferation. p16Ink4a -overexpressing tumor cells are highly aggressive and no targeted interventions are available. To study the effect of specific therapies, we generated murine sarcomas by overexpressing RAS oncogene and disrupting p53 activity. We observed that p16Ink4a -overxpressing murine sarcoma cells were resistant to ABT-263 and ABT-737, anti-cancer small molecules previously shown to eliminate p16Ink4a+ senescent cells...
January 26, 2018: Oncotarget
https://www.readbyqxmd.com/read/29482580/upregulation-of-lactate-inducible-snail-protein-suppresses-oncogene-mediated-senescence-through-p16-ink4a-inactivation
#14
Xiangrui Li, Zhijian Zhang, Yao Zhang, Yuxiang Cao, Huijun Wei, Zhihao Wu
BACKGROUND: The preferential use of aerobic glycolysis by tumor cells lead to high accumulation of lactate in tumor microenvironment. Clinical evidence has linked elevated lactate concentration with cancer outcomes. However, the role and molecular mechanisms of lactate in cellular senescence and tumor progression remain elusive. METHODS: The function of Snail in lactate-induced EMT in lung cancer cells was explored by wound healing assay and cell invasion assay...
February 26, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29453249/hhex-induces-promyelocyte-self-renewal-and-cooperates-with-growth-factor-independence-to-cause-myeloid-leukemia-in-mice
#15
Jacob T Jackson, Ashley P Ng, Benjamin J Shields, Sue Haupt, Ygal Haupt, Matthew P McCormack
The hematopoietically expressed homeobox (Hhex) transcription factor is overexpressed in human myeloid leukemias. Conditional knockout models of murine acute myeloid leukemia indicate that Hhex maintains leukemia stem cell self-renewal by enabling Polycomb-mediated epigenetic repression of the Cdkn2a tumor suppressor locus, encoding p16Ink4a and p19Arf However, whether Hhex overexpression also affects hematopoietic differentiation is unknown. To study this, we retrovirally overexpressed Hhex in hematopoietic progenitors...
February 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29447461/genetic-ablation-of-p16-ink4a-does-not-protect-against-cellular-senescence-in-mouse-models-of-copd-emphysema
#16
Isaac K Sundar, Kahkashan Rashid, Janice Gerloff, Dongmei Li, Irfan Rahman
Cigarette smoke (CS) affects DNA damage and cellular senescence signaling pathways in the pathogenesis of chronic obstructive pulmonary disease (COPD). p16(INK4a) (p16: a cyclin-dependent kinase inhibitor) is a key marker of cellular senescence, which is induced by CS in lung cells. It is thought that removal of p16 attenuates premature aging by removing senesced cells. However, the role of p16 in CS-induced stress induce premature senescence (SIPS) and senescence-associated secretory phenotype (SASP during the development of COPD/emphysema is not known...
February 15, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29290803/glutathione-peroxidase-3-delivered-by-hipsc-mscs-ameliorated-hepatic-ir-injury-via-inhibition-of-hepatic-senescence
#17
Xiang Qi, Kevin Tak-Pan Ng, Qizhou Lian, Chang Xian Li, Wei Geng, Chang Chun Ling, Wai Ho Yeung, Yuen Yuen Ma, Xiao Bing Liu, Hui Liu, Jiang Liu, Xin Xiang Yang, Chung Mau Lo, Kwan Man
Background and Aims: Down-regulation of GPx3 accelerated hepatic senescence, which further caused overwhelming inflammation and severe liver graft injury. MSCs derived from human induced pluripotent stem cells (hiPSC-MSCs) have been developed as more efficient delivery vehicle with the property of injury tropism. Here, we aimed to explore the suppressive role of GPx3 in hepatic IR injury using novel delivery system of hiPSC-MSCs. Methods: The mice IR injury model with partial hepatectomy was established. The engineered hiPSC-MSCs delivering GPx3 was constructed...
2018: Theranostics
https://www.readbyqxmd.com/read/29234059/p16-ink4a-and-p21-cip1-waf1-promote-tumour-growth-by-enhancing-myeloid-derived-suppressor-cells-chemotaxis
#18
Atsushi Okuma, Aki Hanyu, Sugiko Watanabe, Eiji Hara
p16Ink4a and p21Cip1/Waf1 act as tumour suppressors through induction of cellular senescence. However, senescence-independent roles of these CDK inhibitors are not well understood. Here, we report an unexpected function of p16Ink4 and p21Cip1/Waf1 , namely, tumour promotion through chemotaxis. In monocytic myeloid-derived suppressor cells (Mo-MDSCs), p16Ink4 and p21Cip1/Waf1 are highly expressed and stimulate CX3CR1 chemokine receptor expression by preventing CDK-mediated phosphorylation and inactivation of SMAD3...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29161981/presenting-symptoms-and-clinical-findings-in-hpv-positive-and-hpv-negative-oropharyngeal-cancer-patients
#19
Timo Carpén, Anni Sjöblom, Marie Lundberg, Caj Haglund, Antti Markkola, Stina Syrjänen, Jussi Tarkkanen, Antti Mäkitie, Jaana Hagström, Petri Mattila
OBJECTIVES: Oropharyngeal squamous cell carcinoma (OPSCC) is divided in two different disease entities depending on HPV involvement. We investigated differences in presenting symptoms and clinical findings in patients with HPV-positive and -negative OPSCC tumors. METHODS: Altogether 118 consecutive patients diagnosed with primary OPSCC between 2012 and 2014 at the Helsinki University Hospital were included. HPV-status of the tumors was assessed by PCR detection of HPV DNA and immunostaining with p16-INK4a antibody...
May 2018: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/29159804/antibodies-against-human-papillomaviruses-as-diagnostic-and-prognostic-biomarker-in-patients-with-neck-squamous-cell-carcinoma-from-unknown-primary-tumor
#20
Lea Schroeder, Gunnar Wichmann, Maria Willner, Angelika Michel, Manuel Wiesenfarth, Christa Flechtenmacher, Tanja Gradistanac, Michael Pawlita, Andreas Dietz, Tim Waterboer, Dana Holzinger
Treatment of patients with neck lymph node metastasis of squamous cell carcinoma (SCC) from unknown primary tumor (NSCCUP) is challenging due to the risk of missing occult tumors or inducing toxicity to unaffected sites. Human papillomavirus (HPV) is a promising biomarker given its causal link to oropharyngeal SCC and superior survival of patients with HPV-driven oropharyngeal SCC and NSCCUP. Identification of HPV-driven NSCCUP could focus diagnostic work-up and treatment on the oropharynx. For the first time, we assessed HPV antibodies and their prognostic value in NSCCUP patients...
April 1, 2018: International Journal of Cancer. Journal International du Cancer
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