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https://www.readbyqxmd.com/read/28549747/increased-dipeptidyl-peptidase-4-accelerates-diet-related-vascular-aging-and-atherosclerosis-in-apoe-deficient-mice-under-chronic-stress
#1
Yanna Lei, Guang Yang, Lina Hu, Limei Piao, Aiko Inoue, Haiying Jiang, Takeshi Sasaki, Guangxian Zhao, Maimaiti Yisireyili, Chenglin Yu, Wenhu Xu, Kyosuke Takeshita, Kenji Okumura, Masafumi Kuzuya, Xian Wu Cheng
OBJECTIVES: Exposure to psychosocial stress is a risk factor for cardiovascular disease. Given that dipeptidyl peptidase-4 (DPP4) regulates several intracellular signaling pathways associated with glucagon-like peptide-1 (GLP-1) metabolism, we investigated the role of DPP4 in stress-related vascular senescence and atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice. METHODS AND RESULTS: ApoE(-/-) mice fed a high-fat (HF) diet were randomly assigned to one of non-stress and immobilized stress groups for 12weeks...
May 16, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28544727/ultraviolet-radiation-accelerates-nras-mutant-melanomagenesis-a-cooperative-effect-blocked-by-sunscreen
#2
Rebecca C Hennessey, Andrea M Holderbaum, Anamaria Bonilla, Conor Delaney, James E Gillahan, Kathleen L Tober, Tatiana M Oberyszyn, Jonathan H Zippin, Christin E Burd
To mitigate melanoma risk, sunscreen use is widely advocated; yet, the ability of sunscreens to prevent melanoma remains controversial. Here, we test the tenet that sunscreens limit melanoma risk by blocking ultraviolet radiation (UV)-induced DNA damage using murine models that recapitulate the genetics and spontaneous evolution of human melanoma. We find that a single, non-erythematous dose of UV dramatically accelerates melanoma onset and increases tumor multiplicity in mice carrying an endogenous, melanocyte-specific NRas(61R) allele...
May 24, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28522693/histone-h3-3k27m-represses-p16-to-accelerate-gliomagenesis-in-a-murine-model-of-dipg
#3
Francisco J Cordero, Zhiqing Huang, Carole Grenier, Xingyao He, Guo Hu, Roger E McLendon, Susan K Murphy, Rintaro Hashizume, Oren J Becher
Diffuse Intrinsic Pontine Glioma (DIPG) is a highly aggressive pediatric brainstem tumor genetically distinguished from adult GBM by the high prevalence of the K27M mutation in the histone H3 variant H3.3 (H3F3A). This mutation reprograms the H3K27me3 epigenetic landscape of DIPG by inhibiting the H3K27-specific histone methyltransferase EZH2. This globally reduces H3K27me2/3, critical repressive marks responsible for cell fate decisions, and also causes focal gain of H3K27me3 throughout the epigenome. To date the tumor-driving effects of H3...
May 18, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28518126/techniques-to-induce-and-quantify-cellular-senescence
#4
Nicole Noren Hooten, Michele K Evans
In response to cellular stress or damage, proliferating cells can induce a specific program that initiates a state of long-term cell-cycle arrest, termed cellular senescence. Accumulation of senescent cells occurs with organismal aging and through continual culturing in vitro. Senescent cells influence many biological processes, including embryonic development, tissue repair and regeneration, tumor suppression, and aging. Hallmarks of senescent cells include, but are not limited to, increased senescence-associated β-galactosidase activity (SA-β-gal); p16(INK4A), p53, and p21 levels; higher levels of DNA damage, including γ-H2AX; the formation of Senescence-associated Heterochromatin Foci (SAHF); and the acquisition of a Senescence-associated Secretory Phenotype (SASP), a phenomenon characterized by the secretion of a number of pro-inflammatory cytokines and signaling molecules...
May 1, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28512399/protein-s-negatively-regulates-neural-stem-cell-self-renewal-through-bmi-1-signaling
#5
Katya Zelentsova-Levytskyi, Ziv Talmi, Ghada Abboud-Jarrous, Tal Capucha, Tamar Sapir, Tal Burstyn-Cohen
Revealing the molecular mechanisms underlying neural stem cell self-renewal is a major goal toward understanding adult brain homeostasis. The self-renewing potential of neural stem and progenitor cells (NSPCs) must be tightly regulated to maintain brain homeostasis. We recently reported the expression of Protein S (PROS1) in adult hippocampal NSPCs, and revealed its role in regulation of NSPC quiescence and neuronal differentiation. Here, we investigate the effect of PROS1 on NSPC self-renewal and show that genetic ablation of Pros1 in neural progenitors increased NSPC self-renewal by 50%...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28509346/role-of-quantitative-p16-ink4a-mrna-assay-and-digital-reading-of-p16-ink4a-immunostained-sections-in-diagnosis-of-cervical-intraepithelial-neoplasia
#6
Nataša Vasiljević, Paul D Carter, Caroline Reuter, Rhian Warman, Adam R Brentnall, James R Carton, Jack Cuzick, Attila T Lorincz
Visual interpretation of cervical biopsies is subjective and variable, generally showing fair to moderate inter-reader agreement in distinguishing high from low grade cervical intraepithelial neoplasia (CIN). We investigated the performance of two objective p16 quantitative tests in comparison with visual assessment: 1) p16-mRNA assay and 2) digital analysis of sections stained for p16 protein. The primary analysis considered 232 high-risk HPV+ samples from diagnostic cervical specimens. A p16 RT-qPCR (p16-mRNA assay) was run on mRNA extracted from formalin-fixed paraffin-embedded sections...
May 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28491095/angelica-sinensis-polysaccharide-prevents-hematopoietic-stem-cells-senescence-in-d-galactose-induced-aging-mouse-model
#7
Xinyi Mu, Yanyan Zhang, Jing Li, Jieyu Xia, Xiongbin Chen, Pengwei Jing, Xiaoying Song, Lu Wang, Yaping Wang
Age-related regression in hematopoietic stem/progenitor cells (HSC/HPCs) limits replenishment of the blood and immune system and hence contributes to hematopoietic diseases and declined immunity. In this study, we employed D-gal-induced aging mouse model and observed the antiaging effects of Angelica Sinensis Polysaccharide (ASP), a major active ingredient in dong quai (Chinese Angelica Sinensis), on the Sca-1(+) HSC/HPCs in vivo. ASP treatment prevents HSC/HPCs senescence with decreased AGEs levels in the serum, reduced SA-β-Gal positive cells, and promoted CFU-Mix formation in the D-gal administrated mouse...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28479691/prevalence-of-human-papillomavirus16-dna-and-p16-ink4a-protein-in-oral-squamous-cell-carcinoma-a-systematic-review-and-meta-analysis
#8
T Smitha, C V Mohan, S Hemavathy
BACKGROUND AND AIM: Indian patients with oral squamous cell carcinoma (OSCC) are etiologically associated with the use of tobacco and alcohol; yet, a proportion of tumors that may harbor human papillomavirus (HPV) infections cannot be neglected. The following meta-analysis was conducted to address the association of p16(INK4a) and HPV DNA with OSCC. In addition, the study also provides the updated prevalence of HPV-induced OSCC. MATERIALS AND METHODS: Literature survey was performed using databases such as PubMed with the help of the following keywords - "HPV infection," "oral squamous cell carcinoma," "p16(INK4a)," "HPV DNA," "E6," "E7," "L1," "L2" and "LCR...
January 2017: Journal of Oral and Maxillofacial Pathology: JOMFP
https://www.readbyqxmd.com/read/28472822/human-papillomavirus-association-is-the-most-important-predictor-for-surgically-treated-patients-with-oropharyngeal-cancer
#9
Steffen Wagner, Claus Wittekindt, Shachi Jenny Sharma, Nora Wuerdemann, Theresa Jüttner, Miriam Reuschenbach, Elena-Sophie Prigge, Magnus von Knebel Doeberitz, Stefan Gattenlöhner, Ernst Burkhardt, Jörn Pons-Kühnemann, Jens Peter Klussmann
BACKGROUND: Upfront surgery is a valuable treatment option for oropharyngeal squamous cell carcinoma (OPSCC) and risk stratification is emerging for treatment de-escalation in human papillomavirus (HPV)-related OPSCC. Available prognostic models are either based on selected, mainly non-surgically treated cohorts. Therefore, we investigated unselected OPSCC treated with predominantly upfront surgery. METHODS: All patients diagnosed with OPSCC and treated with curative intent between 2000 and 2009 (n=359) were included...
May 4, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28470939/expression-of-p16-ink4a-in-mixed-squamous-cell-and-glandular-papilloma-of-the-lung
#10
Ryo Miyoshi, Toshi Menju, Akihiko Yoshizawa, Hiroshi Date
Mixed squamous cell and glandular papilloma (mixed papilloma) of the lung is an extremely rare neoplasm, with only 21 cases reported in the English literature. Although the expression of p16(Ink4a) has been analyzed in only two cases of mixed papilloma, they were negative for p16(Ink4a) . Therefore, the significance of p16(Ink4a) overexpression in mixed papilloma remains unclear. This is the first case of mixed papilloma with positive p16(Ink4a) expression in a 72-year-old male smoker. The 20 mm sized tumor was histologically diagnosed as mixed papilloma following right upper lobectomy...
May 3, 2017: Pathology International
https://www.readbyqxmd.com/read/28468038/-sorting-role-of-p16-ink4a-ki-67-double-immunostaining-in-the-cervical-cytology-specimens-of-ascus-and-lsil-cases
#11
J Yu, H T Zhu, J J Zhao, J Z Su, Y D Xia
Objective: To investigate the sorting effect of p16(INK4a)/Ki-67 double immunostaining method in patients with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) cytology results. Methods: Four-hundred and twenty cases collected during April 2014 to February 2015 of cervical cytology of ASCUS (n=318) and LSIL (n=102) were selected, and residual liquid-based cytology specimens were used for p16(INK4a)/Ki-67 double immunostaining. The sensitivity and specificity of the detection of cervical precancerous lesions and cervical cancer were calculated, and the results were compared with high risk HPV...
May 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28436958/local-clearance-of-senescent-cells-attenuates-the-development-of-post-traumatic-osteoarthritis-and-creates-a-pro-regenerative-environment
#12
Ok Hee Jeon, Chaekyu Kim, Remi-Martin Laberge, Marco Demaria, Sona Rathod, Alain P Vasserot, Jae Wook Chung, Do Hun Kim, Yan Poon, Nathaniel David, Darren J Baker, Jan M van Deursen, Judith Campisi, Jennifer H Elisseeff
Senescent cells (SnCs) accumulate in many vertebrate tissues with age and contribute to age-related pathologies, presumably through their secretion of factors contributing to the senescence-associated secretory phenotype (SASP). Removal of SnCs delays several pathologies and increases healthy lifespan. Aging and trauma are risk factors for the development of osteoarthritis (OA), a chronic disease characterized by degeneration of articular cartilage leading to pain and physical disability. Senescent chondrocytes are found in cartilage tissue isolated from patients undergoing joint replacement surgery, yet their role in disease pathogenesis is unknown...
April 24, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28431961/ionizing-radiation-induces-long-term-senescence-in-endothelial-cells-through-mitochondrial-respiratory-complex-ii-dysfunction-and-superoxide-generation
#13
Audrey Lafargue, Charlotte Degorre, Isabelle Corre, Marie-Clotilde Alves-Guerra, Marie-Hélène Gaugler, François Vallette, Claire Pecqueur, François Paris
Ionizing radiation causes oxidative stress, leading to acute and late cellular responses. We previously demonstrated that irradiation of non-proliferating endothelial cells, as observed in normal tissues, induces early apoptosis, which can be inhibited by pretreatment with Sphingosine-1-Phosphate. We now propose to better characterize the long-term radiation response of endothelial cells by studying the molecular pathways associated with senescence and its link with acute apoptosis. First, senescence was validated in irradiated quiescent microvascular HMVEC-L in a dose- and time-dependent manner by SA β-galactosidase staining, p16(Ink4a) and p21(Waf1) expression, pro-inflammatory IL-8 secretion and DNA damage response activation...
April 19, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28418604/loss-of-ink4a-arf-gene-enhances-ultraviolet-radiation-induced-cutaneous-tumor-development
#14
Israr Ahmad, Purushotham Guroji, Amanda H DeBrot, Padma P Manapragada, Santosh K Katiyar, Craig A Elmets, Nabiha Yusuf
The CDKN2A locus encodes for tumor suppressor genes p16(INK)(4a) and p14(Arf) which are frequently inactivated in human skin tumors. The purpose of this study was to determine the relationship between loss of INK4a/Arf activity and inflammation in the development of ultraviolet (UV) radiation-induced skin tumors. Panels of INK4a/Arf(-/-) mice and wild type (WT) mice were treated with a single dose of UVB (200 mJ/cm(2) ). For long-term studies, these mice were irradiated with UVB (200 mJ/cm(2) ) three times weekly for 30 weeks...
April 18, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28410532/role-of-p16-ink4a-and-bmi-1-in-oxidative-stress-induced-premature-senescence-in-human-dental-pulp-stem-cells
#15
Cristina Mas-Bargues, José Viña-Almunia, Marta Inglés, Jorge Sanz-Ros, Juan Gambini, José Santiago Ibáñez-Cabellos, José Luis García-Giménez, José Viña, Consuelo Borrás
Human dental pulp stem cells (hDPSCs) are a source for cell therapy. Before implantation, an in vitro expansion step is necessary, with the inconvenience that hDPSCs undergo senescence following a certain number of passages, loosing their stemness properties. Long-term in vitro culture of hDPSCs at 21% (ambient oxygen tension) compared with 3-6% oxygen tension (physiological oxygen tension) caused an oxidative stress-related premature senescence, as evidenced by increased β-galactosidase activity and increased lysil oxidase expression, which is mediated by p16(INK4a) pathway...
April 7, 2017: Redox Biology
https://www.readbyqxmd.com/read/28408139/the-anti-inflammatory-effect-of-melatonin-in-sh-sy5y-neuroblastoma-cells-exposed-to-sublethal-dose-of-hydrogen-peroxide
#16
Chutikorn Nopparat, Varunya Chantadul, Kannika Permpoonputtana, Piyarat Govitrapong
Brain inflammaging is considered as one of the underlying factors of neurodegenerative diseases. The present study aimed to investigate the effects of melatonin, an endogenous indoleamine mainly synthesized by the pineal gland, on hydrogen peroxide (H2O2)-induced inflammaging state in SH-SY5Y cells. Our data showed that p21(Cip1) and p16(INK4a), cell cycle arrest markers, and the number of senescence-associated β-galactosidase (SA-βgal) staining increased significantly in H2O2-treated cells. Melatonin treatment could reverse this effect...
April 10, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28405521/human-papilloma-virus-load-and-pd-1-pd-l1-cd8-and-foxp3-in-anal-cancer-patients-treated-with-chemoradiotherapy-rationale-for-immunotherapy
#17
Panagiotis Balermpas, Daniel Martin, Ulrike Wieland, Margret Rave-Fränk, Klaus Strebhardt, Claus Rödel, Emmanouil Fokas, Franz Rödel
We examined the prognostic role of immune markers programmed cell death protein-1 (PD-1) and its ligand (PD-L1), CD8(+) tumor-infiltrating lymphocytes (TILs), FOXP3+ Tregs and phosphorylated Caspase-8 (T273) in patients with anal squamous cell cancer (ASCC) treated with standard chemoradiotherapy (CRT). The baseline immunohistochemical expression of immune markers was correlated with clinicopathologic characteristics, and cumulative incidence of local failure, disease-free survival (DFS) and overall survival (OS) in 150 patients, also in the context of human papilloma virus 16 (HPV16) DNA load and p16(INK4a) expression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28403538/human-papillomavirus-epstein-barr-virus-and-methylation-status-of-p16-ink4a-in-penile-cancer
#18
Larissa Alves Afonso, Fernanda Nahoum Carestiato, Antonio Augusto Ornellas, Paulo Ornellas, Willker Menezes Rocha, Thaissa Isaias Cordeiro, Daniela Ceperuelo Lisboa, Gilda Brown Alves, Silvia Maria Baeta Cavalcanti
Little is known about penile carcinogenesis. The aim of this study was to evaluate the prevalence of HPV and EBV, and the methylation status of p16(ink4a) in penile cancer samples, and to contribute to the understanding of the mechanisms responsible for penile cancer development. HPV DNA was detected in 63.6% of 122 cases, with HPV16 being the most prevalent type. EBV DNA was detected in 47.7%, with EBV-1 being the most prevalent type. HPV/EBV co-infections were found in 27.3% of the cases. Hypermethylation in p16(ink4a) was detected in 64...
April 12, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28395715/-subcellular-re-distribution-of-f-actin-in-mcf7-cells-upon-inducible-expression-of-cdkn2a-p16-ink4a
#19
Jianqing Liang, Manna Wang, Zhengrong Zhang, Long Yuan, You Zheng, Hongyan Huang, Qiang Sun, Jufang Wang, Xiaoning Wang
Objective To investigate the effect of CDKN2A/p16(INK4a), a cyclin-dependent kinase inhibitor, on cell morphology and cytoskeleton in MCF7 breast cancer cells by tetracycline operon (Tet-on) inducible gene expression system. Methods MCF7 cells, genetically null for p16(INK4a) expression, were sequentially infected with two viruses of Tet-on systems to make MCF7-pTet-on-p16(INK4a) cells, which were induced to express p16NK4a by doxycycline (Dox) treatment. Cell growth was evaluated by cell counting. To observe the effect of p16(INK4a) on cell adhesion and cytoskeleton, intercellular adhesion and intracellular F-actin were examined by fluorescent staining with anti-E-cadherin antibody and phalloidin, respectively...
April 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28387325/hpv-negative-penile-squamous-cell-carcinoma-disruptive-mutations-in-the-tp53-gene-are-common
#20
Karl Kashofer, Elke Winter, Iris Halbwedl, Andrea Thueringer, Marisa Kreiner, Stefan Sauer, Sigrid Regauer
The majority of penile squamous cell carcinomas is caused by transforming human papilloma virus (HPV) infection. The etiology of HPV-negative cancers is unclear, but TP53 mutations have been implicated. Archival tissues of 108 invasive squamous cell carcinoma from a single pathology institution in a low-incidence area were analyzed for HPV-DNA and p16(ink4a) overexpression and for TP53 mutations by ion torrent next-generation sequencing. Library preparation failed in 32/108 squamous cell carcinomas. Institutional review board approval was obtained...
April 7, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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