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https://www.readbyqxmd.com/read/29778758/major-traits-of-the-senescent-phenotype-of-nucleus-pulposus-intervertebral-disc-cells-persist-under-the-specific-microenvironmental-conditions-of-the-tissue
#1
Anastasios Kouroumalis, Eleni Mavrogonatou, Olga D Savvidou, Panayiotis J Papagelopoulos, Harris Pratsinis, Dimitris Kletsas
Intervertebral discs (IVDs) are the joints of the spine, mainly consisting of extracellular matrix (ECM) with a low number of cells embedded therein. Low cellularity stems from nutrient deprivation due to the lack of blood supply, as well as from the hypoxic and hyperosmotic conditions prevailing in the tissue. Intervertebral disc degeneration (IDD) has been firmly connected with low back pain, a major age-related disease, whereas degenerated discs have been characterized by increased proteolytic activity and accumulation of senescent cells...
May 17, 2018: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/29775409/transactivation-domain-of-p53-regulates-dna-repair-and-integrity-in-human-ips-cells
#2
Ramaswamy Kannappan, Saidulu Mattapally, Pooja A Wagle, Jianyi Zhang
The role of p53 transactivation domain (p53-TAD), a multifunctional and dynamic domain, on DNA repair and retaining DNA integrity in human iPS cells has never been studied. p53-TAD was knocked out in iPS cells using CRISPR/Cas9 and was confirmed by DNA sequencing. p53-TAD KO cells were characterized by: accelerated proliferation, decreased population doubling time, and unaltered Bcl2, BBC3, IGF1R, Bax and altered Mdm2, p21, and PIDD transcripts expression. In p53-TAD KO cells p53 regulated DNA repair proteins XPA, DNA polH and DDB2 expression were found to be reduced compared to p53-WT cells...
May 18, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29765418/isolation-and-characterisation-of-mesenchymal-stem-cells-from-rat-bone-marrow-and-the-endosteal-niche-a-comparative-study
#3
Norhayati Yusop, Paul Battersby, Amr Alraies, Alastair J Sloan, Ryan Moseley, Rachel J Waddington
Within bone, mesenchymal stromal cells (MSCs) exist within the bone marrow stroma (BM-MSC) and the endosteal niche, as cells lining compact bone (CB-MSCs). This study isolated and characterised heterogeneous MSC populations from each niche and subsequently investigated the effects of extensive cell expansion, analysing population doublings (PDs)/cellular senescence, colony-forming efficiencies (CFEs), MSC cell marker expression, and osteogenic/adipogenic differentiation. CB-MSCs and BM-MSCs demonstrated similar morphologies and PDs, reaching 100 PDs...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29764277/human-papillomavirus-hpv-is-absent-in-branchial-cleft-cysts-of-the-neck-distinguishing-them-from-hpv-positive-cystic-metastasis
#4
Lars Sivars, David Landin, Marzia Rizzo, Linnea Haeggblom, Cinzia Bersani, Eva Munck-Wikland, Anders Näsman, Tina Dalianis, Linda Marklund
BACKGROUND: Distinguishing branchial cleft cysts (BCCs) from cystic metastases of a human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (OPSCC) is challenging. Fine needle aspirates (FNAs) from cystic metastasis may be non-representative, while reactive squamous cells from BCC can be atypic. Based on cytology and with the support of HPV DNA positivity many centers treat cystic metastasis oncological and thus patients are spared neck dissection. To do so safely, one must investigate whether HPV DNA and p16INK4a overexpression is found exclusively in cystic metastases and not in BCC...
May 15, 2018: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/29750271/ape1-deficiency-promotes-cellular-senescence-and-premature-aging-features
#5
Mengxia Li, Xiao Yang, Xianfeng Lu, Nan Dai, Shiheng Zhang, Yi Cheng, Lei Zhang, Yuxin Yang, Yie Liu, Zhenzhou Yang, Dong Wang, David M Wilson
Base excision repair (BER) handles many forms of endogenous DNA damage, and apurinic/apyrimidinic endonuclease 1 (APE1) is central to this process. Deletion of both alleles of APE1 (a.k.a. Apex1) in mice leads to embryonic lethality, and deficiency in cells can promote cell death. Unlike most other BER proteins, APE1 expression is inversely correlated with cellular senescence in primary human fibroblasts. Depletion of APE1 via shRNA induced senescence in normal human BJ fibroblasts, a phenotype that was not seen in counterpart cells expressing telomerase...
May 10, 2018: Nucleic Acids Research
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
#6
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/29739873/p16-controls-p53-protein-expression-through-mir-dependent-destabilization-of-mdm2
#7
Huda Al-Khalaf, Abdelilah Aboussekhra
p16INK4A and p53 are two major tumor suppressor proteins, which are both up-regulated in response to various cellular stresses and during senescence and aging. p53 is a well characterized transcription factor, while p16INK4A a cyclin-dependent kinase inhibitor encoded by the CDKN2A gene, controls the expression of several genes through protein-protein interactions and also via microRNAs (miRs). This report demonstrates a p16INK4A-dependent positive regulation of p53 expression, at the protein level, in various human cells as well as in mouse embryonic fibroblasts (MEFs)...
May 8, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29737207/restoring-effects-of-natural-anti-oxidant-quercetin-on-cellular-senescent-human-dermal-fibroblasts
#8
Eun-Ju Sohn, Jung Min Kim, Se-Hui Kang, Joseph Kwon, Hyun Joo An, Jung-Suk Sung, Kyung A Cho, Ik-Soon Jang, Jong-Soon Choi
The oxidative damage initiated by reactive oxygen species (ROS) is a major contributor to the functional decline and disability that characterizes aging. The anti-oxidant flavonoid, quercetin, is a plant polyphenol that may be beneficial for retarding the aging process. We examined the restoring properties of quercetin on human dermal fibroblasts (HDFs). Quercetin directly reduced either intracellular or extracellular ROS levels in aged HDFs. To find the aging-related target genes by quercetin, microarray analysis was performed and two up-regulated genes LPL and KCNE2 were identified...
May 8, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29734247/clinical-and-economic-value-of-p16ink4a-for-the-differential-diagnosis-of-morphologic-cervical-intraepithelial-neoplasia-2
#9
Vanina S Fishkel, Fernando C Monge, Felicitas M von Petery, Karen E Tapper, Teresa M Peña, Florencia Torres, Fernando A Poletta, Jorge F Elgart, Alejandra Avagnina, Valeria Denninghoff
The detection of high-grade intraepithelial lesions requires highly sensitive and specific methods that allow more accurate diagnoses. This contributes to a proper management of preneoplastic lesions, thus avoiding overtreatment. The purpose of this study was to analyze the value of immunostaining for p16 in the morphologic assessment of cervical intraepithelial neoplasia 2 lesions, to help differentiate between low-grade (p16-negative) and high-grade (p16-positive) squamous intraepithelial lesions. The direct medical cost of the treatment of cervical intraepithelial neoplasia 2 morphologic lesions was estimated...
May 4, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29728850/liquid-based-cytology-do-ancillary-techniques-enhance-detection-of-epithelial-abnormalities
#10
Sridhar Mishra, Nuzhat Husain, Namrata P Awasthi, Yashodhara Pradeep, Roohi Roohi, Sarita Saxena
PURPOSE: Cervical cancer is the fourth most common cancer in women worldwide with very high incidence in India. Liquid-based cytology (LBC) provides the use of ancillary techniques in addition to a good morphology and detection of cytologic abnormalities. The current study was designed to assess the diagnostics of P16INK4a immunoexpression, p16 promoter hypermethylation, human papilloma virus (HPV), and DNA ploidy in LBC samples with cervical precancer and cancer. METHODS: A series of LBC samples categorised by Bethesda system including 22 atypical squamous cells of undetermined significance (ASC-US), 21 low-grade squamous intraepithelial lesion (LSIL), 41 high-grade squamous intraepithelial lesion (HSIL), 54 squamous cell carcinoma (SCC), and 26 controls with normal cytology were included...
May 4, 2018: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/29718136/molecular-insights-to-withaferin-a-induced-senescence-bioinformatics-and-experimental-evidence-to-the-role-of-nf-kappa-b-and-carf
#11
Priyanshu Bhargava, Vidhi Malik, Ye Liu, Jihoon Ryu, Sunil C Kaul, Durai Sundar, Renu Wadhwa
Withaferin-A (Wi-A) has been shown to possess anticancer activity. Molecular mechanism(s) of its action have not been fully resolved. We recruited low dose of Wi-A that caused slow growth arrest in cancer cells, and was relatively safe for normal cells. Consistently, we detected nuclear translocation of NFκB and activation of p38MAPK selectively in cancer cells. Bioinformatics analyses revealed that Wi-A did not disrupt IKK/IKKβ-Nemo complex that regulates NFκB activity. However, it caused moderate change in the conformation of IKKβ-Nemo interacting domain...
April 28, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
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
#12
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/29706499/ink4a-arf-expression-impairs-neurogenesis-in-the-brain-of-irradiated-mice
#13
Oanh Le, Lina Palacio, Gilbert Bernier, Ines Batinic-Haberle, Gilles Hickson, Christian Beauséjour
Brain neurogenesis is severely impaired following exposure to ionizing radiation (IR). We and others have shown that the expression of the tumor suppressor gene p16INK4a is increased in tissues exposed to IR and thus hypothesized that its expression could limit neurogenesis in the irradiated brain. Here, we found that exposure to IR leads to persistent DNA damage and the expression of p16INK4a in the hippocampus and subventricular zone regions. This was accompanied by a decline in neurogenesis, as determined by doublecortin expression and bromodeoxyuridine incorporation, an effect partially restored in Ink4a/arf-null mice...
April 20, 2018: Stem Cell Reports
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
#14
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
#15
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/29673160/mechanisms-of-diabetes-induced-endothelial-cell-senescence-role-of-arginase-1
#16
Esraa Shosha, Zhimin Xu, S Priya Narayanan, Tahira Lemtalsi, Abdelrahman Y Fouda, Modesto Rojas, Ji Xing, David Fulton, R William Caldwell, Ruth B Caldwell
We have recently found that diabetes-induced premature senescence of retinal endothelial cells is accompanied by NOX2-NADPH oxidase-induced increases in the ureohydrolase enzyme arginase 1 (A1). Here, we used genetic strategies to determine the specific involvement of A1 in diabetes-induced endothelial cell senescence. We used A1 knockout mice and wild type mice that were rendered diabetic with streptozotocin and retinal endothelial cells (ECs) exposed to high glucose or transduced with adenovirus to overexpress A1 for these experiments...
April 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29664911/hpv-relatedness-definitions-for-classifying-hpv-related-oropharyngeal-cancer-patient-do-impact-on-tnm-classification-and-patients-survival
#17
Miren Taberna, Marisa Mena, Sara Tous, Miquel Angel Pavón, Marc Oliva, Xavier León, Jacinto Garcia, Marta Guix, Rafael Hijano, Teresa Bonfill, Antón Aguilà, Laia Alemany, Ricard Mesía
BACKGROUND: Given the different nature and better outcomes of oropharyngeal carcinoma (OPC) associated with human papillomavirus (HPV) infection, a novel clinical stage classification for HPV-related OPC has been accepted for the 8th edition AJCC TNM (ICON-S model). However, it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value. MATERIAL AND METHODS: The aim of this study was to compare different staging system models proposed for HPV-related OPC patients: 7th edition AJCC TNM, RPA stage with non-anatomic factors (Princess Margaret), RPA with N categories for nasopharyngeal cancer (MD-Anderson) and AHR-new (ICON-S), according to different HPV-relatedness definitions: HPV-DNA detection plus an additional positive marker (p16INK4a or HPV-mRNA), p16INK4a positivity alone or the combination of HPV-DNA/p16INK4a positivity as diagnostic tests...
2018: PloS One
https://www.readbyqxmd.com/read/29661169/rna-seq-reveals-the-existence-of-a-cdkn1c-e2f1-tp53-axis-that-is-altered-in-human-t-cell-lymphoblastic-lymphomas
#18
Pilar López-Nieva, Pablo Fernández-Navarro, Concepción Vaquero-Lorenzo, María Villa-Morales, Osvaldo Graña-Castro, María Ángeles Cobos-Fernández, José Luis López-Lorenzo, Pilar Llamas, Laura González-Sanchez, Isabel Sastre, Marina Pollan, Marcos Malumbres, Javier Santos, José Fernández-Piqueras
BACKGROUND: Precursor T-cell lymphoblastic lymphomas (T-LBL) are rare aggressive hematological malignancies that mainly develop in children. As in other cancers, the loss of cell cycle control plays a prominent role in the pathogenesis in these malignancies that is primarily attributed to loss of CDKN2A (encoding protein p16INK4A). However, the impact of the deregulation of other genes such as CDKN1C, E2F1, and TP53 remains to be clarified. Interestingly, experiments in mouse models have proven that conditional T-cell specific deletion of Cdkn1c gene may induce a differentiation block at the DN3 to DN4 transition, and that the loss of this gene in the absence of Tp53 led to aggressive thymic lymphomas...
April 16, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29652189/a-review-and-update-on-papillary-immature-metaplasia-of-the-uterine-cervix-a-distinct-subset-of-low-grade-squamous-intraepithelial-lesion-proposing-a-possible-cell-of-origin
#19
Soon Auck Hong, Su Hyun Yoo, Jene Choi, Stanley J Robboy, Kyu-Rae Kim
CONTEXT: - Papillary immature metaplasia (PIM) is a known papillary cervical lesion associated with low-risk human papilloma virus (LR-HPV). OBJECTIVE: - To evaluate additional clinicopathologic features and the HPV genotypes of PIM and discuss the presumptive cell of origin. DESIGN: - A total of 26 PIM cases were evaluated by p16INK4a , cytokeratin (CK) 7, and CK17 immunohistochemical stainings. Human papilloma virus genotyping was performed, by using HPV DNA Chip, HPV polymerase chain reaction (PCR), and real-time PCR...
April 13, 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29651745/correlations-between-age-functional-status-and-the-senescence-associated-proteins-hmgb2-and-p16-ink4a
#20
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
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