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https://www.readbyqxmd.com/read/28730335/clinical-and-prognosis-value-of-the-cimp-status-combined-with-mlh1-or-p16-ink4a-methylation-in-colorectal-cancer
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28608263/molecular-markers-of-dna-damage-and-repair-in-cervical-cancer-patients-treated-with-cisplatin-neoadjuvant-chemotherapy-an-exploratory-study
#15
Nilda E Real, Gisela N Castro, F Darío Cuello-Carrión, Claudia Perinetti, Hanna Röhrich, Niubys Cayado-Gutiérrez, Martin E Guerrero-Gimenez, Daniel R Ciocca
Neoadjuvant (or induction) chemotherapy can be used for cervical cancer patients with locally advanced disease; this treatment is followed by radical surgery and/or radiation therapy. Cisplatin is considered to be the most active platinum agent drug for this cancer, with a response rate of 20%. In order to understand how the cisplatin treatment affects the stress response, in this work, we performed an exploratory study to analyze a number of stress proteins before and after cisplatin neoadjuvant chemotherapy...
June 12, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28595801/deregulation-of-hsa-mir-20b-expression-in-tnf-%C3%AE-induced-premature-senescence-of-human-pulmonary-microvascular-endothelial-cells
#16
Pooi-Fong Wong, Juliana Jamal, Kind-Leng Tong, Eng-Soon Khor, Chia-Earn Yeap, Hui-Lan Jong, Sui-Ting Lee, Mohd Rais Mustafa, Sazaly Abubakar
miRNAs are important regulators of cellular senescence yet the extent of their involvement remains to be investigated. We sought to identify miRNAs that are involved in cytokine-induced premature senescence (CIPS) in endothelial cells. CIPS was established in young human pulmonary microvascular endothelial cells (HMVEC-Ls) following treatment with a sublethal dose (20ng/ml) of tumor necrosis factor alpha (TNF-α) for 15days. In parallel, HMVEC-Ls were grown and routinely passaged until the onset of replicative senescence (RS)...
June 5, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28592523/germline-cdkn2a-p16ink4a-mutations-contribute-to-genetic-determinism-of-sarcoma
#17
Fanélie Jouenne, Isaure Chauvot de Beauchene, Emeline Bollaert, Marie-Françoise Avril, Olivier Caron, Olivier Ingster, Axel Lecesne, Patrick Benusiglio, Philippe Terrier, Vincent Caumette, Daniel Pissaloux, Arnaud de la Fouchardière, Odile Cabaret, Birama N'Diaye, Amélie Velghe, Gaelle Bougeard, Graham J Mann, Serge Koscielny, Jennifer H Barrett, Mark Harland, Julia Newton-Bishop, Nelleke Gruis, Remco Van Doorn, Marion Gauthier-Villars, Gaelle Pierron, Dominique Stoppa-Lyonnet, Isabelle Coupier, Rosine Guimbaud, Capucine Delnatte, Jean-Yves Scoazec, Alexander M Eggermont, Jean Feunteun, Luba Tchertanov, Jean-Baptiste Demoulin, Thierry Frebourg, Brigitte Bressac-de Paillerets
BACKGROUND: Sarcomas are rare mesenchymal malignancies whose pathogenesis is poorly understood; both environmental and genetic risk factors could contribute to their aetiology. METHODS AND RESULTS: We performed whole-exome sequencing (WES) in a familial aggregation of three individuals affected with soft-tissue sarcoma (STS) without TP53 mutation (Li-Fraumeni-like, LFL) and found a shared pathogenic mutation in CDKN2A tumour suppressor gene. We searched for individuals with sarcoma among 474 melanoma-prone families with a CDKN2A-/+ genotype and for CDKN2A mutations in 190 TP53-negative LFL families where the index case was a sarcoma...
June 7, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28584022/ikk%C3%AE-mediated-resistance-to-skin-cancer-development-is-ink4a-arf-dependent
#18
Angustias Page, Ana Bravo, Cristian Suárez-Cabrera, Josefa P Alameda, M LLanos Casanova, Corina Lorz, Carmen Segrelles, Jose C Segovia, Jesus M Paramio, Manuel Navarro, Angel Ramírez
IKKβ (encoded by IKBKB) is a protein kinase that regulates the activity of numerous proteins important in several signaling pathways, such as the nuclear factor kappa B (NF-κB) pathway. IKKβ exerts a pro-tumorigenic role in several animal models of lung, hepatic, intestinal and oral cancer. In addition, genomic and proteomic studies of human tumors also indicate that IKBKB gene is amplified or overexpressed in multiple tumor types. Here, the relevance of IKKβ in skin cancer was determined by performing carcinogenesis studies in animal models overexpressing IKKβ in the basal skin layer...
June 5, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28577303/hhex-regulates-hematopoietic-stem-cell-self-renewal-and-stress-hematopoiesis-via-repression-of-cdkn2a
#19
Jacob T Jackson, Benjamin J Shields, Wei Shi, Ladina Di Rago, Donald Metcalf, Nicos A Nicola, Matthew P McCormack
The hematopoietically expressed homeobox transcription factor (Hhex) is important for the maturation of definitive hematopoietic progenitors and B-cells during development. We have recently shown that in adult hematopoiesis, Hhex is dispensable for maintenance of hematopoietic stem cells (HSCs) and myeloid lineages but essential for the commitment of common lymphoid progenitors (CLPs) to lymphoid lineages. Here, we show that during serial bone marrow transplantation, Hhex-deleted HSCs are progressively lost, revealing an intrinsic defect in HSC self-renewal...
June 2, 2017: Stem Cells
https://www.readbyqxmd.com/read/28575665/senescence-in-health-and-disease
#20
REVIEW
Shenghui He, Norman E Sharpless
Many cellular stresses activate senescence, a persistent hyporeplicative state characterized in part by expression of the p16(INK4a) cell-cycle inhibitor. Senescent cell production occurs throughout life and plays beneficial roles in a variety of physiological and pathological processes including embryogenesis, wound healing, host immunity, and tumor suppression. Meanwhile, the steady accumulation of senescent cells with age also has adverse consequences. These non-proliferating cells occupy key cellular niches and elaborate pro-inflammatory cytokines, contributing to aging-related diseases and morbidity...
June 1, 2017: Cell
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