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p16 ink4a

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https://www.readbyqxmd.com/read/28915557/loss-of-p16-ink4a-stimulates-aberrant-mitochondrial-biogenesis-through-a-cdk4-rb-independent-pathway
#1
Ethika Tyagi, Bin Liu, Chelsea Li, Tong Liu, Jared Rutter, Douglas Grossman
The tumor suppressor p16INK4A (p16) inhibits cell cycle progression through the CDK4/Rb pathway. We have previously shown that p16 regulates cellular oxidative stress, independent of its role in cell cycle control. We investigated whether loss of p16 had a direct impact on the mitochondria. We found that p16-null primary mouse fibroblasts (PMFs) displayed increased mitochondrial mass and expression of mitochondrial respiratory subunit proteins compared to wild-type (WT) PMFs. These findings in p16-null PMFs were associated with increased expression of the mitochondrial biogenesis transcription factors PRC and TFAM...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28894253/atm-deficiency-increases-genomic-instability-and-metastatic-potential-in-a-mouse-model-of-pancreatic-cancer
#2
Yiannis Drosos, David Escobar, Ming-Yi Chiang, Kathryn Roys, Virginia Valentine, Marc B Valentine, Jerold E Rehg, Vaibhav Sahai, Lesa A Begley, Jianming Ye, Leena Paul, Peter J McKinnon, Beatriz Sosa-Pineda
Germline mutations in ATM (encoding the DNA-damage signaling kinase, ataxia-telangiectasia-mutated) increase Familial Pancreatic Cancer (FPC) susceptibility, and ATM somatic mutations have been identified in resected human pancreatic tumors. Here we investigated how Atm contributes to pancreatic cancer by deleting this gene in a murine model of the disease expressing oncogenic Kras (Kras(G12D)). We show that partial or total ATM deficiency cooperates with Kras(G12D) to promote highly metastatic pancreatic cancer...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28888905/selective-interference-of-mtorc1-raptor-protects-against-human-disc-cellular-apoptosis-senescence-and-extracellular-matrix-catabolism-with-akt-and-autophagy-induction
#3
M Ito, T Yurube, K Kakutani, K Maeno, T Takada, Y Terashima, Y Kakiuchi, Y Takeoka, S Miyazaki, R Kuroda, K Nishida
OBJECTIVE: The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that integrates nutrients to execute cell growth and protein synthesis. We hypothesized that mTOR is essential for the intervertebral disc, the largest avascular, low-nutrient organ. Our objective was to elucidate roles of mTOR signaling in human disc cells. DESIGN: The mTOR exists in two complexes: mTORC1 containing regulatory-associated protein of mTOR (RAPTOR) and mTORC2 containing rapamycin-insensitive companion of mTOR (RICTOR)...
September 6, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28884278/hpv-prevalence-in-vulvar-cancer-in-austria
#4
Sophie Pils, Lisa Gensthaler, Laia Alemany, Reinhard Horvat, Silvia de Sanjosé, Elmar A Joura
BACKGROUND: Even if vulvar cancer is not common, over one hundred women are affected in Austria per year. There is strong evidence that basaloid and warty variants are associated with types of human papillomavirus (HPV). METHODS: The aim of this study is to analyze the types of HPV in vulvar cancer in Austria. This cross-sectional period-prevalence international collaborative study on archival specimens was performed in cooperation with the Institut Catalan di Oncologia in Barcelona, Spain...
September 7, 2017: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/28871086/identification-of-hsp90-inhibitors-as-a-novel-class-of-senolytics
#5
Heike Fuhrmann-Stroissnigg, Yuan Yuan Ling, Jing Zhao, Sara J McGowan, Yi Zhu, Robert W Brooks, Diego Grassi, Siobhan Q Gregg, Jennifer L Stripay, Akaitz Dorronsoro, Lana Corbo, Priscilla Tang, Christina Bukata, Nadja Ring, Mauro Giacca, Xuesen Li, Tamara Tchkonia, James L Kirkland, Laura J Niedernhofer, Paul D Robbins
Aging is the main risk factor for many chronic degenerative diseases and cancer. Increased senescent cell burden in various tissues is a major contributor to aging and age-related diseases. Recently, a new class of drugs termed senolytics were demonstrated to extending healthspan, reducing frailty and improving stem cell function in multiple murine models of aging. To identify novel and more optimal senotherapeutic drugs and combinations, we established a senescence associated β-galactosidase assay as a screening platform to rapidly identify drugs that specifically affect senescent cells...
September 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28868898/the-tumour-suppressor-cdkn2a-p16-ink4a-regulates-adipogenesis-and-bone-marrow-dependent-development-of-perivascular-adipose-tissue
#6
Kristiaan Wouters, Yann Deleye, Sarah A Hannou, Jonathan Vanhoutte, Xavier Maréchal, Augustin Coisne, Madjid Tagzirt, Bruno Derudas, Emmanuel Bouchaert, Christian Duhem, Emmanuelle Vallez, Casper G Schalkwijk, François Pattou, David Montaigne, Bart Staels, Réjane Paumelle
The genomic CDKN2A/B locus, encoding p16(INK4a) among others, is linked to an increased risk for cardiovascular disease and type 2 diabetes. Obesity is a risk factor for both cardiovascular disease and type 2 diabetes. p16(INK4a) is a cell cycle regulator and tumour suppressor. Whether it plays a role in adipose tissue formation is unknown. p16(INK4a) knock-down in 3T3/L1 preadipocytes or p16(INK4a) deficiency in mouse embryonic fibroblasts enhanced adipogenesis, suggesting a role for p16(INK4a) in adipose tissue formation...
September 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28833816/depletion-of-hoxa5-inhibits-the-osteogenic-differentiation-and-proliferation-potential-of-stem-cells-from-the-apical-papilla
#7
Wenzhi Li, Xiao Lin, Haoqing Yang, Yangyang Cao, Chen Zhang, Zhipeng Fan
Mesenchymal stem cells (MSCs) are a prospective cell source for tissue regeneration due to their self-renewal abilities and potential to differentiate into different cell lineages, but the molecular mechanisms of the directed differentiation and proliferation are still unknown. Recently, multiple studies have indicated the crucial role of HOX genes in MSC differentiation and proliferation. However, the role of HOXA5 in MSCs remains unknown. Here, we investigated HOXA5 function in stem cells from the apical papilla (SCAPs)...
August 22, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28833798/expressions-of-programmed-death-pd-1-and-pd-1-ligand-pd-l1-in-cervical-intraepithelial-neoplasia-and-cervical-squamous-cell-carcinomas-are-of-prognostic-value-and-associated-with-human-papillomavirus-status
#8
Wen Yang, Yan-Ping Lu, Yi-Zhou Yang, Jia-Rui Kang, Yi-Duo Jin, Hong-Wei Wang
AIM: The programmed death 1/programmed death 1 ligand (PD-1/PD-L1) pathway can decrease the immune clearance effects of antigen-presenting cells and T lymphocytes to promote immune evasion of cervical cancer cells. However, the effects of this pathway on cervical intraepithelial neoplasia (CIN) progression and squamous cell carcinoma (SCC) metastasis are not clear. We herein investigated whether human papillomavirus infection could affect PD-1 and PD-L1 expression in CIN, and whether their expression is associated with CIN progression and SCC metastasis...
August 17, 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28811900/slpi-and-anxa2-expression-in-neoplasm-free-palatine-tonsils-is-associated-with-smoking-habit-of-individuals
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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...
August 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
#19
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
#20
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
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