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p16 ink4a

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https://www.readbyqxmd.com/read/28811900/slpi-and-anxa2-expression-in-neoplasm-free-palatine-tonsils-is-associated-with-smoking-habit-of-individuals
#1
Elgar S Quabius, Berit Bögershausen, Lukas Getzin, Tibor Görögh, Maximilian P Gebhard, Anna S Hoffmann, Markus Hoffmann
In order to confirm the inverse correlation between secretory leucocyte protease inhibitor (SLPI) expression, and human papillomavirus (HPV) infection previously observed in head and neck squamous-cell carcinoma, the present study retrospectively investigated the association between SLPI and Annexin A2 (AnxA2) expression, and HPV status in non-neoplastic chronic tonsillitis (n=118), and tonsillar hyperplasia (n=96) tissue. We hypothesised that smoking induces the upregulation of SLPI, resulting in reduced binding of HPV to AnxA2, a known modulator of HPV entry into the cell...
September 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28804534/mtor-inhibition-rejuvenates-the-aging-gingival-fibroblasts-through-alleviating-oxidative-stress
#2
Yiru Xia, Mengjun Sun, Yufeng Xie, Rong Shu
The aging periodontium may be vulnerable to periodontal pathogens and poor response to inflammation and susceptible to tumorigenesis. Human gingival fibroblasts (hGFs) through continuously replicative culture served as an in vitro surrogate for aging. To investigate the effects of the mechanistic target of rapamycin (mTOR) inhibition on the aging gingiva, we stimulated the high-passage hGFs with rapamycin (20 nmol/L) for 3 days and 30 days. The cellular and biological changes were examined by immunofluorescence, real-time PCR, ELISA, Western blotting, and flow cytometry...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28797447/evaluation-of-the-xpert%C3%A2-hpv-assay-in-the-detection-of-human-papillomavirus-in-formalin-fixed-paraffin-embedded-oropharyngeal-carcinomas
#3
Maria Gabriella Donà, Francesca Rollo, Barbara Pichi, Giuseppe Spriano, Raul Pellini, Renato Covello, Edoardo Pescarmona, Giulia Fabbri, Manuela Scalfari, Tarik Gheit, Maria Benevolo
OBJECTIVES: The increasing incidence of HPV-related Oropharyngeal Squamous Cell Carcinoma (OPSCC) and the improved survival of HPV-positive OPSCC highlight the need for effective tools in evaluating HPV status on formalin-fixed paraffin-embedded (FFPE) cancers. To date, there is no agreement regarding the most appropriate method for HPV testing on FFPE materials. We aimed to investigate the performance of the Xpert® HPV assay (Cepheid) on crude lysates from OPSCC FFPE tissues. MATERIALS AND METHODS: Crude lysates were obtained by proteinase K digestion of FFPE tissues that had already been analyzed by the INNO-LiPA HPV assay and p16(ink4a) immunostaining...
September 2017: Oral Oncology
https://www.readbyqxmd.com/read/28790310/p16-ink4a-deletion-ameliorated-renal-tubulointerstitial-injury-in-a-stress-induced-premature-senescence-model-of-bmi-1-deficiency
#4
Jianliang Jin, Jianguo Tao, Xin Gu, Zhenzhen Yu, Rong Wang, Guoping Zuo, Qing Li, Xianhui Lv, Dengshun Miao
To determine whether p16 (INK4a) deletion ameliorated renal tubulointerstitial injury by inhibiting a senescence-associated secretory phenotype (SASP) in Bmi-1-deficient (Bmi-1 (-/-)) mice, renal phenotypes were compared among 5-week-old Bmi-1 and p16 (INK4a) double-knockout, and Bmi-1 (-/-) and wild-type mice. Fifth-passage renal interstitial fibroblasts (RIFs) from the three groups were analyzed for senescence and proliferation. The effect of Bmi-1 deficiency on epithelial-to-mesenchymal transition (EMT) was examined in Bmi-1-knockdown human renal proximal tubular epithelial (HK2) cells, which were treated with concentrated conditioned medium (CM) from the fifth-passage renal interstitial fibroblasts (RIFs) of above three group mice or with exogenous TGF-β1...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28768895/p16-ink4a-and-senescence-associated-%C3%AE-galactosidase-can-be-induced-in-macrophages-as-part-of-a-reversible-response-to-physiological-stimuli
#5
Brandon M Hall, Vitaly Balan, Anatoli S Gleiberman, Evguenia Strom, Peter Krasnov, Lauren P Virtuoso, Elena Rydkina, Slavoljub Vujcic, Karina Balan, Ilya I Gitlin, Katerina I Leonova, Camila R Consiglio, Sandra O Gollnick, Olga B Chernova, Andrei V Gudkov
Constitutive p16(Ink4a) expression, along with senescence-associated β-galactosidase (SAβG), are commonly accepted biomarkers of senescent cells (SCs). Recent reports attributed improvement of the healthspan of aged mice following p16(Ink4a)-positive cell killing to the eradication of accumulated SCs. However, detection of p16(Ink4a)/SAβG-positive macrophages in the adipose tissue of old mice and in the peritoneal cavity of young animals following injection of alginate-encapsulated SCs has raised concerns about the exclusivity of these markers for SCs...
August 2, 2017: Aging
https://www.readbyqxmd.com/read/28737694/the-role-of-p16-ink4a-pathway-in-human-epidermal-stem-cell-self-renewal-aging-and-cancer
#6
REVIEW
Daniela D'Arcangelo, Lavinia Tinaburri, Elena Dellambra
The epidermis is a self-renewing tissue. The balance between proliferation and differentiation processes is tightly regulated to ensure the maintenance of the stem cell (SC) population in the epidermis during life. Aging and cancer may be considered related endpoints of accumulating damages within epidermal self-renewing compartment. p16(INK4a) is a potent inhibitor of the G1/S-phase transition of the cell cycle. p16(INK4a) governs the processes of SC self-renewal in several tissues and its deregulation may result in aging or tumor development...
July 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28730335/clinical-and-prognosis-value-of-the-cimp-status-combined-with-mlh1-or-p16-ink4a-methylation-in-colorectal-cancer
#7
Amana Saadallah-Kallel, Rania Abdelmaksoud-Dammak, Mouna Triki, Slim Charfi, Abdelmajid Khabir, Tahia Sallemi-Boudawara, Raja Mokdad-Gargouri
Aberrant DNA methylation of CpG islands occurred frequently in CRC and associated with transcriptional silencing of key genes. In this study, the CIMP combined with MLH1 or p16 (INK4a) methylation status was determined in CRC patients and correlated with clinicopathological parameters and overall survival. Our data showed that CIMP+ CRCs were identified in 32.9% of cases and that CACNAG1 is the most frequently methylated promoter. When we combined the CIMP with the MLH1 or the p16 (INK4a) methylation status, we found that CIMP-/MLH1-U (37...
August 2017: Medical Oncology
https://www.readbyqxmd.com/read/28722212/active-human-papillomavirus-involvement-in-barrett-s-dysplasia-and-oesophageal-adenocarcinoma-is-characterized-by-wild-type-p53-and-aberrations-of-the-retinoblastoma-protein-pathway
#8
Shanmugarajah Rajendra, Tao Yang, Wei Xuan, Prateek Sharma, Darren Pavey, Cheong Soon Lee, Son Le, Josephine Collins, Bin Wang
We have previously demonstrated that transcriptionally active high-risk HPV (hr-HPV) is strongly incriminated in Barrett's dysplasia (BD) and oesophageal adenocarcinoma (OAC) using mainly fresh frozen tissue. This study aimed to identify biomarkers of active HPV infection in Barrett's metaplasia, (BM)/BD/OAC by immunohistochemical staining (IHC) of formalin-fixed paraffin embedded (FFPE) tissue for aberrations of p53 and the retinoblastoma (pRb) pathway, which are targets for the viral oncoproteins, E6/E7, respectively...
July 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28705710/using-p16-immunohistochemistry-to-classify-morphologic-cervical-intraepithelial-neoplasia-2-correlation-of-ambiguous-staining-patterns-with-hpv-subtypes-and-clinical-outcome
#9
Yuxin Liu, Mahfood Alqatari, Kieran Sultan, Fei Ye, Dana Gao, Keith Sigel, David Zhang, Tamara Kalir
P16(INK4a) immunohistochemistry (IHC) is widely used to facilitate the diagnosis of human papillomavirus (HPV)-associated cervical precancerous lesions. While most p16 results are distinctly positive or negative, certain ones are ambiguous: they meet some but not all requirements for the "block-positive" pattern. It is unclear whether ambiguous p16 immunoreactivity indicates oncogenic HPV infection or risk of progression. Herein, we compared HPV genotypes and subsequent High-grade Squamous Intraepithelial Lesion (HSIL) outcomes among 220 cervical biopsies with a differential diagnosis of Cervical Intraepithelial Neoplasia 2 (CIN 2) based on hematoxylin and eosin morphology and varying degrees of p16 immunoreactivity...
July 10, 2017: Human Pathology
https://www.readbyqxmd.com/read/28704762/combined-inhibition-of-cdk4-6-and-pi3k-akt-mtor-pathways-induces-a-synergistic-anti-tumor-effect-in-malignant-pleural-mesothelioma-cells
#10
Mara A Bonelli, Graziana Digiacomo, Claudia Fumarola, Roberta Alfieri, Federico Quaini, Angela Falco, Denise Madeddu, Silvia La Monica, Daniele Cretella, Andrea Ravelli, Paola Ulivi, Michela Tebaldi, Daniele Calistri, Angelo Delmonte, Luca Ampollini, Paolo Carbognani, Marcello Tiseo, Andrea Cavazzoni, Pier Giorgio Petronini
Malignant pleural mesothelioma (MPM) is a progressive malignancy associated to the exposure of asbestos fibers. The most frequently inactivated tumor suppressor gene in MPM is CDKN2A/ARF, encoding for the cell cycle inhibitors p16(INK4a) and p14(ARF), deleted in about 70% of MPM cases. Considering the high frequency of alterations of this gene, we tested in MPM cells the efficacy of palbociclib (PD-0332991), a highly selective inhibitor of cyclin-dependent kinase (CDK) 4/6. The analyses were performed on a panel of MPM cell lines and on two primary culture cells from pleural effusion of patients with MPM...
July 10, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28693266/knockdown-of-glua2-induces-apoptosis-in-non-small-cell-lung-cancer-a549-cells-through-the-p53-signaling-pathway
#11
Hong-Yan Zhang, Wei Yang, Ji-Bin Lu
α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are important glutamatergic receptors that mediate fast excitatory synaptic transmission in the brain. Previous studies have demonstrated that glutamate ionotropic receptor AMPA type subunit 2 (GluA2), one of the four subunits that comprise AMPA receptors, is a potential novel marker for poor prognosis in patients with human lung cancer. However, the mechanisms of GluA2-induced apoptosis, proliferation and migration in lung cancer remain unknown...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28688373/deletion-of-rd-ink4-arf-enhancer-a-novel-mutation-to-inactivate-the-ink4-arf-locus
#12
REVIEW
Ming J Poi, Thomas J Knobloch, Junan Li
The presence of an enhancer element, RD(INK4/ARF) (RD), in the prominent INK4-ARF locus provides a novel en bloc mechanism to simultaneously regulate the transcription of the p15(INK4B) (p15), p16(INK4A) (p16), and p14(ARF) tumor suppressor genes. While genetic inactivation of p15, p16, and p14(ARF) in human cancers has been extensively studied, little is known about RD alteration and its potential contributions to cancer progression. In this review, we discuss recent developments in RD alteration and its association with p15, p16, and p14(ARF) alterations in human cancers, and demonstrate that RD deletion may represent a novel mechanism to simultaneously down-regulate p15, p16, and p14(ARF), thus promoting carcinogenesis...
June 24, 2017: DNA Repair
https://www.readbyqxmd.com/read/28680533/cyclin-dependent-kinase-4-and-6-inhibitors-as-novel-therapeutic-agents-for-targeted-treatment-of-malignant-mesothelioma
#13
Navid Sobhani, Silvia P Corona, Fabrizio Zanconati, Daniele Generali
Malignant Mesothelioma (MM) is a rare and aggressive form of tumour that affects the lining of the internal organs for which current treatments have not been proven to be very effective. P16(INK4A) tumour suppressor encoding CDKN2A gene is often downregulated in MM. This protein is a cyclin dependent kinase 4 and 6 inhibitor, that normally phosphorylates RB1, which has to be un-phosphorylated in order to block cell-cycle at G1 in normal cells. Adding CDK inhibitor molecules to MM in pre-clinical studies has been proven to restore the normal function of p16(INK4A), blocking thereby MM cell cycle at G1...
March 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28668968/cigarette-smoke-extract-changes-expression-of-endothelial-nitric-oxide-synthase-enos-and-p16-ink4a-and-is-related-to-endothelial-progenitor-cell-dysfunction
#14
Zhihui He, Yan Chen, Can Hou, Wenfang He, Ping Chen
BACKGROUND Endothelial dysfunction is an important pathophysiologic feature in many smoke-related diseases. Endothelial progenitor cells (EPCs) are the precursors of endothelial cells and play a fundamental role in the maintenance of endothelial integrity and function. Endothelial nitric oxide synthase (eNOS) is the dominant NOS isoform in the vasculature and plays a central role in the maintenance of endothelial homeostasis. p16(INK4a) is a cyclin-dependent kinase inhibitor and could be regarded as a major dominant senescence gene...
July 2, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28658942/cellular-senescence-biomarker-p16ink4a-cell-burden-in-thigh-adipose-is-associated-with-poor-physical-function-in-older-women
#15
Jamie N Justice, Heather Gregory, Tamar Tchkonia, Nathan K LeBrasseur, James L Kirkland, Stephen B Kritchevsky, Barbara J Nicklas
Background: Ample evidence implicates cellular senescence as a contributor to frailty and functional decline in rodents, but considerable effort remains to translate these findings to human aging. Methods: We quantified senescence biomarker p16INK4a-expressing cells in thigh adipose tissue obtained from older women previously enrolled in a 5-month resistance training intervention, with or without caloric restriction (RT±CR, n=11 baseline, 8 pre-post-intervention pairs)...
June 27, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28650766/murine-mesenchymal-cells-that-express-elevated-levels-of-the-cdk-inhibitor-p16-ink4a-in-vivo-are-not-necessarily-senescent
#16
David Frescas, Brandon Hall, Evguenia Strom, Lauren P Virtuoso, Mahima Gupta, Anatoli S Gleiberman, Elena Rydkina, Vitaly Balan, Slavoljub Vujcic, Olga B Chernova, Andrei V Gudkov
Age-related health decline has been attributed to the accumulation of senescent cells recognized in vivo by p16(Ink4a) expression. The pharmacological elimination of p16(Ink4a)-positive cells from the tissues of mice was shown to extend a healthy lifespan. Here, we describe a population of mesenchymal cells isolated from mice that are highly p16(INK4a)-positive are proficient in proliferation but lack other properties of cellular senescence. These data, along with earlier reports on p16(Ink4a)-positive macrophages, indicate that p16(Ink4a)-positive and senescent cell populations only partially intersect, therefore, extending the list of potential cellular targets for anti- aging therapies...
June 26, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28639061/oral-and-oropharyngeal-papillomas-are-not-associated-with-high-risk-human-papillomavirus-infection
#17
Miroslaw Snietura, Roman Lamch, Agnieszka Kopec, Dariusz Waniczek, Wirginia Likus, Dariusz Lange, Jaroslaw Markowski
The role of different types of human papillomavirus (HPV) in the development of oral and oropharyngeal papillomas remains unclear. High-risk HPV (HR-HPV) was shown to be involved in the pathogenesis of significant proportion of squamous cell carcinomas of the oropharynx. In this study, we hypothesized that in some oropharyngeal papillomas, low-risk HPV (LR-HPV) and HR-HPV infection could co-exist, similar to what is observed in genital warts, and thus contribute to the elevated risk of malignancy. To test this hypothesis, we used real-time PCR to assess the presence of HPV DNA of 16 types (2 LR-HPV and 14 HR-HPV), in 75 formalin-fixed and paraffin-embedded histopathological samples of oral and oropharyngeal papillomas and in 57 squamous cell carcinomas from the same regions...
June 21, 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/28630279/obesity-and-p16-ink4a-down-regulation-activate-breast-adipocytes-and-promote-their-pro-tumorigenicity
#18
Huda H Al-Khalaf, Mrad Amir, Falah Al-Mohanna, Asma Tulbah, Adher Al-Sayed, Abdelilah Aboussekhra
Obesity is increasingly recognized as a risk factor for breast cancer development. However, the molecular basis of obesity-related breast carcinogenesis remains elusive. In this study, we have shown that obesity reduces the level of the tumor suppressor p16(INK4A) protein in breast adipocytes, which showed active features and strong pro-carcinogenic potential both in vitro and in orthotopic tumor xenografts, as compared to mature adipocytes from lean women. Furthermore, obesity triggered epithelial-to-mesenchymal transition (EMT) in breast ductal epithelial cells...
June 19, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28622890/evaluation-of-type-specific-antibodies-to-high-risk-human-papillomavirus-hpv-proteins-in-patients-with-oropharyngeal-cancer
#19
Martina A Broglie, Wolfram Jochum, Angelika Michel, Tim Waterboer, Diana Foerbs, René Schoenegg, Sandro J Stoeckli, Michael Pawlita, Dana Holzinger
OBJECTIVES: High risk human papillomavirus (HR-HPV) infection leads to a subgroup of oropharyngeal cancer (OPSCC) characterized by improved treatment response. However an universally accepted definition of an HR-HPV-attributable cancer is lacking. METHODS: Detailed, type-specific HPV antibody responses were analyzed by multiplex serology in HR-HPV-attributable OPSCC patients, defined by p16(INK4A) overexpression and HR-HPV DNA detection by PCR amplification and sequencing...
July 2017: Oral Oncology
https://www.readbyqxmd.com/read/28608850/cellular-senescence-drives-age-dependent-hepatic-steatosis
#20
Mikolaj Ogrodnik, Satomi Miwa, Tamar Tchkonia, Dina Tiniakos, Caroline L Wilson, Albert Lahat, Christoper P Day, Alastair Burt, Allyson Palmer, Quentin M Anstee, Sushma Nagaraja Grellscheid, Jan H J Hoeijmakers, Sander Barnhoorn, Derek A Mann, Thomas G Bird, Wilbert P Vermeij, James L Kirkland, João F Passos, Thomas von Zglinicki, Diana Jurk
The incidence of non-alcoholic fatty liver disease (NAFLD) increases with age. Cellular senescence refers to a state of irreversible cell-cycle arrest combined with the secretion of proinflammatory cytokines and mitochondrial dysfunction. Senescent cells contribute to age-related tissue degeneration. Here we show that the accumulation of senescent cells promotes hepatic fat accumulation and steatosis. We report a close correlation between hepatic fat accumulation and markers of hepatocyte senescence. The elimination of senescent cells by suicide gene-meditated ablation of p16(Ink4a)-expressing senescent cells in INK-ATTAC mice or by treatment with a combination of the senolytic drugs dasatinib and quercetin (D+Q) reduces overall hepatic steatosis...
June 13, 2017: Nature Communications
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