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p16 ink4a

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https://www.readbyqxmd.com/read/27893710/muc1-c-activates-bmi1-in-human-cancer-cells
#1
M Hiraki, T Maeda, A Bouillez, M Alam, A Tagde, K Hinohara, Y Suzuki, T Markert, M Miyo, K Komura, R Ahmad, H Rajabi, D Kufe
B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) is a component of the polycomb repressive complex 1 (PRC1) complex that is overexpressed in breast and other cancers, and promotes self-renewal of cancer stem-like cells. The oncogenic mucin 1 (MUC1) C-terminal (MUC1-C) subunit is similarly overexpressed in human carcinoma cells and has been linked to their self-renewal. There is no known relationship between MUC1-C and BMI1 in cancer. The present studies demonstrate that MUC1-C drives BMI1 transcription by a MYC-dependent mechanism in breast and other cancer cells...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27889388/cellular-aging-contributes-to-failure-of-cold-induced-beige-adipocyte-formation-in-old-mice-and-humans
#2
Daniel C Berry, Yuwei Jiang, Robert W Arpke, Elizabeth L Close, Aki Uchida, David Reading, Eric D Berglund, Michael Kyba, Jonathan M Graff
Cold temperatures induce progenitor cells within white adipose tissue to form beige adipocytes that burn energy and generate heat; this is a potential anti-diabesity therapy. However, the potential to form cold-induced beige adipocytes declines with age. This creates a clinical roadblock to potential therapeutic use in older individuals, who constitute a large percentage of the obesity epidemic. Here we show that aging murine and human beige progenitor cells display a cellular aging, senescence-like phenotype that accounts for their age-dependent failure...
November 21, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27865368/effect-of-hpv-on-head-and-neck-cancer-patient-survival-by-region-and-tumor-site-a-comparison-of-1362-cases-across-three-continents
#3
Gypsyamber D'Souza, Devasena Anantharaman, Tarik Gheit, Behnoush Abedi-Ardekani, Daniel C Beachler, David I Conway, Andrew F Olshan, Victor Wunsch-Filho, Tatiana N Toporcov, Wolfgang Ahrens, Kathy Wisniewski, Franco Merletti, Stefania Boccia, Eloiza H Tajara, Jose P Zevallos, José Eduardo Levi, Mark C Weissler, Sylvia Wright, Ghislaine Scelo, Angela L Mazul, Massimo Tommasino, Paul Brennan, Gabriella Cadoni
OBJECTIVES: To explore whether HPV-related biomarkers predict oropharyngeal squamous cell cancer (OPSCC) survival similarly across different global regions, and to explore their prognostic utility among non-oropharyngeal (non-OP) head and neck cancers. METHODS: Data from 1362 head and neck SCC (HNSCC) diagnosed 2002-2011 was used from epidemiologic studies in: Brazil (GENCAPO study, n=388), U.S. (CHANCE study, n=472), and Europe (ARCAGE study, n=502). Tumors were centrally tested for p16(INK4a) and HPV16 DNA (by PCR)...
November 2016: Oral Oncology
https://www.readbyqxmd.com/read/27861555/p16ink4a-expression-and-immunologic-aging-in-chronic-hiv-infection
#4
Susan Pereira Ribeiro, Jeffrey M Milush, Edecio Cunha-Neto, Esper G Kallas, Jorge Kalil, Luiz Felipe D Passero, Peter W Hunt, Steven G Deeks, Douglas F Nixon, Devi SenGupta
Chronic HIV infection is characterized by increased immune activation and immunosenescence. p16 INK4a (p16) is a member of the cyclin-dependent kinase antagonist family that inhibits cellular proliferation, and its protein expression increases during normal chronological aging. However, some infectious diseases can increase the expression of this anti-proliferative protein, potentially accelerating immunological aging and dysfunction. In order to investigate the immunological aging in HIV patients, p16 protein expression was evaluated by flow cytometry, in T cell subsets in a cohort of chronically HIV-infected patients on and off ART as well as age-matched healthy controls...
2016: PloS One
https://www.readbyqxmd.com/read/27859428/low-p16-ink4a-expression-in-early-passage-human-prostate-basal-epithelial-cells-enables-immortalization-by-telomerase-expression-alone
#5
Mindy Kim Graham, Lorenzo Principessa, Lizamma Antony, Alan K Meeker, John T Isaacs
BACKGROUND: There are two principal senescence barriers that must be overcome to successfully immortalize primary human epithelial cells in culture, stress-induced senescence, and replicative senescence. The p16(INK4a) /retinoblastoma protein (p16/Rb) pathway mediates stress-induced senescence, and is generally upregulated by primary epithelial cells in response to the artificial conditions from tissue culture. Replicative senescence is associated with telomere loss. Following each round of cell division, telomeres progressively shorten...
November 8, 2016: Prostate
https://www.readbyqxmd.com/read/27859245/diagnostic-accuracy-of-p16-ink4a-immunohistochemistry-in-oropharyngeal-squamous-cell-carcinomas-a-systematic-review-and-meta-analysis
#6
Elena-Sophie Prigge, Marc Arbyn, Magnus von Knebel Doeberitz, Miriam Reuschenbach
The accurate diagnosis of human papillomavirus (HPV) causality in oropharyngeal squamous cell carcinomas (OPSCC) is likely to influence therapeutic decisions in affected patients in the near future. We conducted a systematic review and meta-analysis to determine the diagnostic accuracy of p16(INK4a) immunohistochemistry (IHC) to identify HPV-induced OPSCC. We identified all studies that performed p16(INK4a) IHC (index test) and HPV E6/E7 mRNA detection using an amplification-based method (gold standard to indicate a transforming relevance of HPV) in OPSCC...
November 14, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27844328/molecular-profiling-of-thymoma-and-thymic-carcinoma-genetic-differences-and-potential-novel-therapeutic-targets
#7
Franz Enkner, Bettina Pichlhöfer, Alexandru Teodor Zaharie, Milica Krunic, Tina Maria Holper, Stefan Janik, Bernhard Moser, Karin Schlangen, Barbara Neudert, Karin Walter, Brigitte Migschitz, Leonhard Müllauer
Thymoma and thymic carcinoma are thymic epithelial tumors (TETs). We performed a molecular profiling to investigate the pathogenesis of TETs and identify novel targets for therapy. We analyzed 37 thymomas (18 type A, 19 type B3) and 35 thymic carcinomas. The sequencing of 50 genes detected nonsynonymous mutations in 16 carcinomas affecting ALK, ATM, CDKN2A, ERBB4, FGFR3, KIT, NRAS and TP53. Only two B3 thymomas had a mutation in noncoding regions of the SMARCB1 and STK11 gene respectively. Three type A thymomas harbored a nonsynonymous HRAS mutation...
November 14, 2016: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/27831553/reed-sternberg-cells-in-hodgkin-s-lymphoma-present-features-of-cellular-senescence
#8
J Gopas, E Stern, U Zurgil, J Ozer, A Ben-Ari, G Shubinsky, A Braiman, R Sinay, J Ezratty, V Dronov, S Balachandran, D Benharroch, E Livneh
Hodgkin's Lymphoma (HL) is one of the most prevailing malignancies in young adults. Reed-Sternberg (RS) cells in HL have distinctive large cell morphology, are characteristic of the disease and their presence is essential for diagnosis. Enlarged cells are one of the hallmarks of senescence, but whether RS cells are senescent has not been previously investigated. Here we show that RS cells have characteristics of senescent cells; RS cells in HL biopsies specifically express the senescence markers and cell cycle inhibitors p21(Cip1) and p16(INK4a) and are negative for the proliferation marker Ki-67, suggesting that these cells have ceased to proliferate...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27812879/senescence-like-phenotypes-in-human-nevi
#9
Andrew Joselow, Darren Lynn, Tamara Terzian, Neil F Box
Cellular senescence is an irreversible arrest of cell proliferation at the G1 stage of the cell cycle in which cells become refractory to growth stimuli. Senescence is a critical and potent defense mechanism that mammalian cells use to suppress tumors. While there are many ways to induce a senescence response, oncogene-induced senescence (OIS) remains the key to inhibiting progression of cells that have acquired oncogenic mutations. In primary cells in culture, OIS induces a set of measurable phenotypic and behavioral changes, in addition to cell cycle exit...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27803052/cancer-associated-fibroblasts-regulate-keratinocyte-cell-cell-adhesion-via-tgf-%C3%A3-dependent-pathways-in-genotype-specific-oral-cancer
#10
N Cirillo, Y Hassona, A Celentano, K P Lim, S Manchella, E K Parkinson, S S Prime
The inter-relationship between malignant epithelium and the underlying stroma is recognised as being of fundamental importance in tumour development and progression. In the present study, we used cancer associated fibroblasts (CAFs) derived from genetically unstable oral squamous cell carcinomas (GU-OSCC), tumours that are characterised by the loss of genes such as TP53 and p16(INK4A) and with extensive LOH, together with CAFs from their more genetically stable counterparts that have wild type TP53 and p16(INK4A) and minimal LOH (GS-OSCC)...
November 1, 2016: Carcinogenesis
https://www.readbyqxmd.com/read/27794120/bmp-smad-id-promotes-reprogramming-to-pluripotency-by-inhibiting-p16-ink4a-dependent-senescence
#11
Yohei Hayashi, Edward C Hsiao, Salma Sami, Mariselle Lancero, Christopher R Schlieve, Trieu Nguyen, Koyori Yano, Ayako Nagahashi, Makoto Ikeya, Yoshihisa Matsumoto, Ken Nishimura, Aya Fukuda, Koji Hisatake, Kiichiro Tomoda, Isao Asaka, Junya Toguchida, Bruce R Conklin, Shinya Yamanaka
Fibrodysplasia ossificans progressiva (FOP) patients carry a missense mutation in ACVR1 [617G > A (R206H)] that leads to hyperactivation of BMP-SMAD signaling. Contrary to a previous study, here we show that FOP fibroblasts showed an increased efficiency of induced pluripotent stem cell (iPSC) generation. This positive effect was attenuated by inhibitors of BMP-SMAD signaling (Dorsomorphin or LDN1931890) or transducing inhibitory SMADs (SMAD6 or SMAD7). In normal fibroblasts, the efficiency of iPSC generation was enhanced by transducing mutant ACVR1 (617G > A) or SMAD1 or adding BMP4 protein at early times during the reprogramming...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27763519/segmental-aging-underlies-the-development-of-a-parkinson-phenotype-in-the-as-agu-rat
#12
Sohair M Khojah, Anthony P Payne, Dagmara McGuinness, Paul G Shiels
There is a paucity of information on the molecular biology of aging processes in the brain. We have used biomarkers of aging (SA β-Gal, p16(Ink4a), Sirt5, Sirt6, and Sirt7) to demonstrate the presence of an accelerated aging phenotype across different brain regions in the AS/AGU rat, a spontaneous Parkinsonian mutant of PKCγ derived from a parental AS strain. P16(INK4a) expression was significantly higher in AS/AGU animals compared to age-matched AS controls (p < 0.001) and displayed segmental expression across various brain regions...
October 17, 2016: Cells
https://www.readbyqxmd.com/read/27752926/ccn2-induces-cellular-senescence-in-fibroblasts
#13
Joon-Ii Jun, Lester F Lau
The expression of Ccn2 (CTGF) has been linked to fibrosis in many tissues and pathologies, although its activities in fibroblastic cells and precise mechanism of action in fibrogenesis are still controversial. Here, we showed that CCN2 can induce cellular senescence in fibroblasts both in vitro and in vivo, whereupon senescent cells express an anti-fibrotic "senescence-associated secretory phenotype" (SASP) that includes upregulation of matrix metalloproteinases and downregulation of collagen. Mechanistically, CCN2 induces fibroblast senescence through integrin α6β1-mediated accumulation of reactive oxygen species, leading to activation of p53 and induction of p16(INK4a)...
October 18, 2016: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/27752126/activated-factor-x-induces-endothelial-cell-senescence-through-igfbp-5
#14
Fumihiro Sanada, Yoshiaki Taniyama, Jun Muratsu, Rei Otsu, Masaaki Iwabayashi, Miguel Carracedo, Hiromi Rakugi, Ryuichi Morishita
Uncontrolled coagulation contributes to the pathophysiology of several chronic inflammatory diseases. In these conditions, senescent cells are often observed and is involved in the generation of inflammation. The coincidence of hyper-coagulation, cell senescence, and inflammation suggests the existence of a common underlying mechanism. Recent evidence indicates that activated coagulation factor X (FXa) plays a role in the processes beyond blood coagulation. This non-hematologic function entails the mediation of inflammation and tissue remodeling...
October 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27751621/prognostic-significance-of-p16-in-squamous-cell-carcinoma-of-the-larynx-and-hypopharynx
#15
Jessica Meshman, Pin-Chieh Wang, Robert Chin, Maie St John, Elliot Abemayor, Sunita Bhuta, Allen M Chen
PURPOSE: To evaluate the prognostic significance of p16 expression among patients with squamous cell carcinoma of the larynx (LSCC) and hypopharynx (HSCC). METHODS: The medical records of all patients with locally advanced, non-metastatic LSCC/HSCC were reviewed. p16(INK4A) (p16) protein expression was evaluated on pathological specimens by immunohistochemistry (IHC), and the Kaplan-Meier method was used to estimate overall survival (OS) and locoregional control (LRC)...
September 28, 2016: American Journal of Otolaryngology
https://www.readbyqxmd.com/read/27743340/%C3%AE-tocotrienol-prevents-cell-cycle-arrest-in-aged-human-fibroblast-cells-through-p16-ink4a-pathway
#16
Azalina Zainuddin, Kien-Hui Chua, Jen-Kit Tan, Faizul Jaafar, Suzana Makpol
Human diploid fibroblasts (HDFs) proliferation in culture has been used as a model of aging at the cellular level. Growth arrest is one of the most important mechanisms responsible for replicative senescence. Recent researches have been focusing on the function of vitamin E in modulating cellular signaling and gene expression. Therefore, the aim of this study was to elucidate the effect of palm γ-tocotrienol (vitamin E) in modulating cellular aging through p16(INK4a) pathway in HDF cells. Primary culture of senescent HDFs was incubated with 70 μM of palm γ-tocotrienol for 24 hours...
October 14, 2016: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/27739458/senescence-mediated-by-p16-ink4a-impedes-reprogramming-of-human-corneal-endothelial-cells-into-neural-crest-progenitors
#17
Wen-Juan Lu, Scheffer C G Tseng, Shuangling Chen, Sean Tighe, Yuan Zhang, Xin Liu, Szu-Yu Chen, Chen-Wei Su, Ying-Ting Zhu
Human corneal endothelial cells (HCECs) have limited proliferative capacity due to "contact-inhibition" at G1 phase. Such contact-inhibition can be delayed from Day 21 to Day 42 by switching EGF-containing SHEM to LIF/bFGF-containing MESCM through transient activation of LIF-JAK1-STAT3 signaling that delays eventual nuclear translocation of p16(INK4a). Using the latter system, we have reported a novel tissue engineering technique by implementing 5 weekly knockdowns with p120 catenin (p120) and Kaiso siRNAs since Day 7 to achieve effective expansion of HCEC monolayers to a transplantable size with a normal HCEC density, through reprogramming of HCECs into neural crest progenitors by activating p120-Kaiso-RhoA-ROCK-canonical BMP signaling...
October 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27739439/usefulness-of-p16-ink4a-staining-for-managing-histological-high-grade-squamous-intraepithelial-cervical-lesions
#18
Ester Miralpeix, Jordi Genovés, Josep Maria Solé-Sedeño, Gemma Mancebo, Belen Lloveras, Beatriz Bellosillo, Francesc Alameda, Ramon Carreras
p16(INK4a) (p16) tumor-suppressor protein is a biomarker of human papillomavirus (HPV) oncogenic activity that has revealed a high rate of positivity in histological high-gade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 2 (HSIL/CIN2) lesions. However, there is a paucity of data regarding p16 status as a surrogate marker of HSIL/CIN2 evolution. The aim of this study was to evaluate the outcome of HSIL/CIN2 patients followed up without treatment for 12 months according to p16 immunohistochemical staining...
October 14, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27737960/swi-snf-regulates-a-transcriptional-program-that-induces-senescence-to-prevent-liver-cancer
#19
Luca Tordella, Sadaf Khan, Anja Hohmeyer, Ana Banito, Sabrina Klotz, Selina Raguz, Nadine Martin, Gopuraja Dhamarlingam, Thomas Carroll, José Mario González Meljem, Sumit Deswal, Juan Pedro Martínez-Barbera, Ramón García-Escudero, Johannes Zuber, Lars Zender, Jesús Gil
Oncogene-induced senescence (OIS) is a potent tumor suppressor mechanism. To identify senescence regulators relevant to cancer, we screened an shRNA library targeting genes deleted in hepatocellular carcinoma (HCC). Here, we describe how knockdown of the SWI/SNF component ARID1B prevents OIS and cooperates with RAS to induce liver tumors. ARID1B controls p16(INK4a) and p21(CIP1a) transcription but also regulates DNA damage, oxidative stress, and p53 induction, suggesting that SWI/SNF uses additional mechanisms to regulate senescence...
October 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27734200/increase-in-tumor-suppressor-arf-compensates-gene-dysregulation-in-in-vitro-aged-adipocytes
#20
Arif U Hasan, Koji Ohmori, Takeshi Hashimoto, Kazuyo Kamitori, Fuminori Yamaguchi, Kumi Konishi, Takahisa Noma, Junsuke Igarashi, Tetsuo Yamashita, Katsuya Hirano, Masaaki Tokuda, Tetsuo Minamino, Akira Nishiyama, Masakazu Kohno
Deterioration of adipocyte function due to increased oxidative stress predisposes patients to metabolic disorders in advanced age. However, the roles of tumor suppressors in such conditions remain largely unknown. Therefore, we aimed to address their dynamics in aged adipocytes using a long-term culture model. We compared 3T3-L1 adipocytes at 17-19 days (long-term) with those at 8-10 days (short-term) after initiation of adipogenic induction for mimicking 'aged' and 'young' adipocytes, respectively. H2O2 release and dihydroethidium (DHE) staining was increased, while superoxide dismutase (SOD) activity was reduced in long-term cultured adipocytes, which is suggestive of enhanced oxidative stress in this group...
October 12, 2016: Biogerontology
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