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https://www.readbyqxmd.com/read/28630279/obesity-and-p16-ink4a-down-regulation-activate-breast-adipocytes-and-promote-their-pro-tumorigenicity
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28573642/aberrant-gene-promoter-methylation-of-e-cadherin-p16-ink4a-p14-arf-and-mgmt-in-epstein-barr-virus-associated-oral-squamous-cell-carcinomas
#10
Ati Burassakarn, Chamsai Pientong, Nuchsupha Sunthamala, Jureeporn Chuerduangphui, Patravoot Vatanasapt, Natcha Patarapadungkit, Bunkerd Kongyingyoes, Tipaya Ekalaksananan
The etiology of oral carcinogenesis appears to be multifactorial. There is emerging evidence of the presence of Epstein-Barr virus (EBV) in epithelial oral squamous cell carcinoma (OSCC), but an association of EBV with oral carcinogenesis has not yet been established. Although epigenetic alterations, such as aberrant DNA methylation, are known to contribute to the pathogenesis of oral cancer, the relationship of such alterations with EBV infection is little known. This study aimed to investigate the association between EBV infection and promoter methylation patterns of tumor-associated genes in OSCC tissues...
July 2017: Medical Oncology
https://www.readbyqxmd.com/read/28566925/p16-ink4a-expression-in-porokeratosis
#11
Miki Uryu, Masutaka Furue
No abstract text is available yet for this article.
June 2017: Annals of Dermatology
https://www.readbyqxmd.com/read/28561270/barriers-to-generating-pdx-models-of-hpv-related-head-and-neck-cancer
#12
Nicole D Facompre, Varun Sahu, Kathleen T Montone, Kayla M Harmeyer, Hiroshi Nakagawa, Anil K Rustgi, Gregory S Weinstein, Phyllis A Gimotty, Devraj Basu
OBJECTIVES/HYPOTHESIS: Delineate factors impacting the creation and use of patient-derived xenografts (PDXs) of human papilloma virus-related (HPV+) head and neck squamous cell carcinomas (HNSCCs). STUDY DESIGN: Laboratory-based translational study. METHODS: Fifty-one surgically resected HNSCCs, including 31 HPV + cancers, were implanted into NOD/SCID/IL-2Rγ(-/-) (NSG) mice using standardized methodology. Clinical and pathologic factors were tested for association with engraftment...
May 31, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28554573/clinical-significance-of-ck7-hpv-l1-and-koilocytosis-for-patients-with-cervical-low-grade-squamous-intraepithelial-lesions-a-retrospective-analysis
#13
Lanqing Cao, Ping-Li Sun, Min Yao, Shifan Chen, Hongwen Gao
Most cervical low-grade squamous intraepithelial lesions (LSILs) do not progress to high-grade squamous intraepithelial lesions (HSILs); however, reliable biomarkers that predict LSIL progression are lacking. We investigated the association of cytokeratin 7 (CK7), human papillomavirus-L1 capsid protein (HPV-L1), and koilocytosis with clinical outcomes of patients with LSIL. CK7, HPV-L1, Ki67, and p16-INK4A expression was determined in 72 cervical LSIL and 28 HSIL biopsy samples; koilocytosis was evaluated by reviewing biopsy slides...
May 26, 2017: Human Pathology
https://www.readbyqxmd.com/read/28553357/human-adipose-derived-stem-cells-exhibit-enhanced-proliferative-capacity-and-retain-multipotency-longer-than-donor-matched-bone-marrow-mesenchymal-stem-cells-during-expansion-in-vitro
#14
Kimberley L Burrow, Judith A Hoyland, Stephen M Richardson
Bone marrow-derived mesenchymal stem cells (MSCs) and adipose-derived multipotent/mesenchymal stem cells (ASCs) have been proposed as the ideal cell types for a range of musculoskeletal tissue engineering and regenerative medicine therapies. However, extensive in vitro expansion is required to generate sufficient cells for clinical application and previous studies have demonstrated differences in the proliferative capacity and the impact of expansion on differentiation capacity of both MSCs and ASCs. Significantly, these studies routinely use cells from different donors, making direct comparisons difficult...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28549747/increased-dipeptidyl-peptidase-4-accelerates-diet-related-vascular-aging-and-atherosclerosis-in-apoe-deficient-mice-under-chronic-stress
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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: (i) p16-mRNA assay and (ii) digital analysis of sections stained for p16 protein. The primary analysis considered 232 high-risk human papilloma virus positive (HPV+) samples from diagnostic cervical specimens...
May 16, 2017: International Journal of Cancer. Journal International du Cancer
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