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p16ink4a

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https://www.readbyqxmd.com/read/28627675/distinctive-crypt-shape-in-a-sessile-serrated-adenoma-polyp-distribution-of-ki67-p16ink4a-wnt5a-positive-cells-and-intraepithelial-lymphocytes
#1
Kenji Hisamatsu, Kei Noguchi, Hiroyuki Tomita, Aoi Muto, Natsumi Yamada, Kazuhiro Kobayashi, Akihiro Hirata, Tomohiro Kanayama, Ayumi Niwa, Kazuhisa Ishida, Takayuki Nakashima, Yuichiro Hatano, Natsuko Suzui, Tatsuhiko Miyazaki, Akira Hara
Serrated lesions in the colorectum are currently predominantly classified as hyperplastic polyps (HPs), sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs) according to their morphology. However, the histological morphology and the molecular changes in the serrated lesions are still unclear. We performed immunohistochemistry for Ki67, p16INK4a, and WNT5A in human HPs (n=22), SSA/Ps (n=41), and TSAs (n=19). The distribution of Ki67 and p16INK4a positive cells in TSAs was different from that in HPs and SSA/Ps...
June 15, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28592523/germline-cdkn2a-p16ink4a-mutations-contribute-to-genetic-determinism-of-sarcoma
#2
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
#3
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/28577549/whole-exome-sequencing-of-an-asbestos-induced-wild-type-murine-model-of-malignant-mesothelioma
#4
Sophie Sneddon, Ann-Marie Patch, Ian M Dick, Stephen Kazakoff, John V Pearson, Nicola Waddell, Richard J N Allcock, Robert A Holt, Bruce W S Robinson, Jenette Creaney
BACKGROUND: Malignant mesothelioma (MM) is an aggressive cancer of the pleural and peritoneal cavities caused by exposure to asbestos. Asbestos-induced mesotheliomas in wild-type mice have been used extensively as a preclinical model because they are phenotypically identical to their human counterpart. However, it is not known if the genetic lesions in these mice tumours are similar to in the human disease, a prerequisite for any new preclinical studies that target genetic abnormalities...
June 2, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28574130/hpv-related-vulvar-diseases-and-perspectives-of-p16ink4a-immunochemistry-a-review-of-the-literature
#5
Angela Carrone, Lucia Riganelli, Delia Savone, Assunta Casorelli, Lucia Merlino, Francesco Pecorini, Irene Pecorella, Pasquale Mancino, Maria Grazia Piccioni, Pierluigi Benedetti Panici
INTRODUCTION: Two different types of vulvar intraepithelial neoplasia (VIN), HPV-related and HPV-unrelated, should be considered as two separate entities with different management options. The incidence of HPV-related VIN is increasing worldwide and is implicated in carcinogenesis. Our objective is to investigate the use of p16INK4a immunostaining or p16INK4a/p53 double staining for the detection of HPV-related disease to overcome the problem that histological criteria often have significant overlap...
May 26, 2017: Tumori
https://www.readbyqxmd.com/read/28521315/p16-ki-67-immunocytochemistry-in-gynecological-cytology-limitations-in-practice
#6
Peter Ziemke
OBJECTIVE: Immunochemical detection of the protein p16INK4a in cervical cytology is used in combination with Ki-67. Cells positive for both proteins are certain to have been transformed by high-risk HPV. p16/Ki-67 immunocytochemistry provides a significant improvement in specificity over cytology and HPV DNA testing. However, p16/Ki-67 immunocytochemistry also has its limitations. STUDY DESIGN: The research is based on the follow-up of 1,131 patients for whom p16/Ki-67 immunocytochemistry was performed with cytology...
2017: Acta Cytologica
https://www.readbyqxmd.com/read/28515351/local-immune-response-depends-on-p16ink4a-status-of-primary-tumor-in-vulvar-squamous-cell-carcinoma
#7
Jacek J Sznurkowski, Anton Żawrocki, Wojciech Biernat
BACKGROUND: The p16Ink4a is not a surrogate marker for high-risk human papilloma virus (HPV) genotypes but indicates better prognosis in vulvar squamous cell carcinoma patients. Our recent study confirmed substantial mismatch between p16Ink4a and high-risk HPV-status as well as revealed that p16Ink4a-overexpression itself is an independent prognostic factor for vulvar cancer. AIM: To determine significance of the tumor infiltrating immune cells and p16Ink4a-status for better outcome of patients with vulvar cancer...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28502129/diagnostic-role-of-rassf1a-and-p16ink4a-promoter-gene-hypermethylation-in-serum-dna-of-lung-cancer-patients-clinicopathological-significance
#8
Wafaa T El-Sherif, Sohair K Sayed, Sherif H Galal, Hoda A Makhlouf, Alaa T Hassan, Hosam A Yousef
The most common inactivation mechanism of tumor suppressor genes, RASSF1A and p16INK4a, in lung cancer is hypermethylation. We detected the methylation status of RASSF1A and p16INK4a in serum of lung cancer patients using methylation-specific PCR and analyzed their clinicopathological significance. Each of RASSF1A and p16INK4a hypermethylation was detected in 31.1% cancer patients but not in benign lung lesion patients. Hypermethylation was preferentially observed in small cell lung cancer (SCLC) for RASSF1A (50%), but not for p16INK4a...
June 2016: Egyptian Journal of Immunology
https://www.readbyqxmd.com/read/28453456/the-synergic-effect-of-hpv-infection-and-epigenetic-anomaly-of-the-p16-gene-in-the-development-of-cervical-cancer
#9
Arif Ahmad, Mohammad Raish, Mohammad Shahid, Swaraj Batra, Vineeta Batra, Syed Akhtar Husain
BACKGROUND: Cervical cancer is the most common cancer in Indian women. Infection with a high-risk human papillomavirus (HR-HPV) is the greatest risk factor for developing cervical cancer. The genetic and epigenetic changes in the tumor suppressor p16 gene is play an important role in the development of cervical cancer. OBJECTIVE: To evaluate the expression and promoter methylation of p16 gene in HR-HPV infected squamous cell carcinoma of the uterine cervix. METHODS: To find out p16INK4a expression and methylation status 105 squamous cell carcinoma of the uterine cervix were investigated by using immunohistochemistry and Methylation Specific PCR techniques...
April 14, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28440978/methylation-status-of-p16ink4a-in-human-papillomavirus-associated-cancer-of-oral-cavity-and-oropharynx-in-northeastern-thailand
#10
Piyawut Swangphon, Chamsai Pientong, Ati Burassakarn, Patravoot Vatanasapt, Pilaiwan Kleebkaow, Natcha Patarapadungkit, Thanabut Treebupachatsakul, Supannee Promthet, Bunkerd Kongyingyoes, Tipaya Ekalaksananan
Background: Over-expression of p16INK4a protein is a biomarker for human papillomavirus (HPV)-associated cervical cancer. However, absence of p16INK4a protein expression in HPV-associated cancer of the oral cavity and oropharynx has been reported. Among a number of possible reasons for this is methylation, which is frequently noted in the promoter region of p16INK4a and is associated with silencing of the gene and disease severity. Methods: We investigated the relationships between p16INK4a protein expression, HPV infection and methylation status of the p16INK4a promoter in cancers of the oral cavity and oropharynx...
March 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28440912/performance-of-in-silico-tools-for-the-evaluation-of-p16ink4a-cdkn2a-variants-in-cagi
#11
Marco Carraro, Giovanni Minervini, Manuel Giollo, Yana Bromberg, Emidio Capriotti, Rita Casadio, Roland Dunbrack, Lisa Elefanti, Pietro Fariselli, Carlo Ferrari, Julian Gough, Panagiotis Katsonis, Emanuela Leonardi, Olivier Lichtarge, Chiara Menin, Pier Luigi Martelli, Abhishek Niroula, Lipika R Pal, Susanna Repo, Maria Chiara Scaini, Mauno Vihinen, Qiong Wei, Qifang Xu, Yuedong Yang, Yizhou Yin, Jan Zaucha, Huiying Zhao, Yaoqi Zhou, Steven E Brenner, John Moult, Silvio C E Tosatto
Correct phenotypic interpretation of variants of unknown significance for cancer-associated genes is a diagnostic challenge as genetic screenings gain in popularity in the next-generation sequencing era. The Critical Assessment of Genome Interpretation (CAGI) experiment aims to test and define the state of the art of genotype-phenotype interpretation. Here, we present the assessment of the CAGI p16INK4a challenge. Participants were asked to predict the effect on cellular proliferation of 10 variants for the p16INK4a tumor suppressor, a cyclin-dependent kinase inhibitor encoded by the CDKN2A gene...
April 25, 2017: Human Mutation
https://www.readbyqxmd.com/read/28440512/astemizole-protects-against-human-umbilical-vein-endothelial-cell-injury-induced-by-hydrogen-peroxide-via-the-p53-signaling-pathway
#12
Jia-Nan Tian, Xiao-Dong Shi, Xiao-Kun Wang, Shuang Wang, Jing-Xue Xu, Chun-Xiao Yang
Astemizole has gained attention as an antineoplastic drug that targets important ion channels. The present study aimed to investigate the protective effects of astemizole against hydrogen peroxide (H2O2)‑induced oxidative damage to human umbilical vein endothelial cells (HUVECs). HUVECs were pretreated with astemizole (0.5 and 1 µM) for 12 h, then exposed to H2O2 (200 µM) for 12 h. Cell viability was measured using the MTT assay. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH‑Px), reactive oxygen species (ROS) and apoptotic percentage were determined...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28426830/correction-p16ink4a-expression-and-immunologic-aging-in-chronic-hiv-infection
#13
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
[This corrects the article DOI: 10.1371/journal.pone.0166759.].
2017: PloS One
https://www.readbyqxmd.com/read/28425986/p16ink4a-upregulation-mediated-by-tbk1-induces-retinal-ganglion-cell-senescence-in-ischemic-injury
#14
L U Li, Yin Zhao, Hong Zhang
Glaucoma is a leading cause of irreversible blindness worldwide that is characterized by progressive retinal ganglion cell (RGC) death. However, RGC senescence as a phase before RGC death, and the mechanism of RGC senescence remains unclear. Here, we demonstrate that TANK-binding protein 1 (TBK1) is upregulated in acute IOP elevation-induced ischemic retinas mouse model. Moreover, pre-treatment with the TBK1 inhibitor BX-795 reduced p16INK4a (p16) expression and RGC senescence. Upregulation of TBK1 via plasmid transfection increased Akt phosphorylation at Ser473 and Bmi1 phosphorylation...
April 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28418845/preclinical-development-of-g1t38-a-novel-potent-and-selective-inhibitor-of-cyclin-dependent-kinases-4-6-for-use-as-an-oral-antineoplastic-in-patients-with-cdk4-6-sensitive-tumors
#15
John E Bisi, Jessica A Sorrentino, Jamie L Jordan, David D Darr, Patrick J Roberts, Francis X Tavares, Jay C Strum
Inhibition of the p16INK4a/cyclin D/CDK4/6/RB pathway is an effective therapeutic strategy for the treatment of estrogen receptor positive (ER+) breast cancer. Although efficacious, current treatment regimens require a dosing holiday due to severe neutropenia potentially leading to an increased risk of infections, as well as tumor regrowth and emergence of drug resistance. Therefore, a next generation CDK4/6 inhibitor that can inhibit proliferation of CDK4/6-dependent tumors while minimizing neutropenia could reduce both the need for treatment holidays and the risk of inducing drug resistance...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412731/c-terminal-binding-protein-2-promotes-cell-proliferation-and-migration-in-breast-cancer-via-suppression-of-p16ink4a
#16
Xiaojing Yang, Yi Sun, Hongling Li, Yuhui Shao, Depeng Zhao, Weiwei Yu, Jie Fu
C-terminal binding protein-2 (CtBP2) enhances cancer proliferation and metastasis. The role and mechanism of CtBP2 in breast cancer remains to be elucidated. Western blot and immunochemistry were employed to evaluate the level of CtBP2 and p16INK4A in breast cancer. Genetic manipulation was used to study the expression of p16INK4A and its downstream genes regulated by CtBP2. Functional assays, including colony formation, wound healing, transwell invasion, anchorage-independent growth assay and a xenograft tumor model were used to determine the oncogenic role of CtBP2 in breast cancer progression...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28403025/p16ink4a-cytokeratin-7-and-ki-67-as-potential-markers-for-low-grade-cervical-intraepithelial-neoplasia-progression
#17
Larissa Bastos Eloy da Costa, Renata De Marchi Triglia, Liliana A Lucci De Angelo Andrade
OBJECTIVE: The aim of this study was to evaluate p16, cytokeratin 7 (CK7), and Ki-67 immunoexpressions in low-grade squamous intraepithelial lesion (LSIL), looking for differences among cases that progress to high-grade squamous intraepithelial lesion, maintain LSIL, or regress. MATERIALS AND METHODS: Sixty-six LSIL biopsies were studied. In the follow-up, a second biopsy showed 28.7% regression, 37.9% LSIL, and 33.4% progressed to high-grade squamous intraepithelial lesion...
April 11, 2017: Journal of Lower Genital Tract Disease
https://www.readbyqxmd.com/read/28391998/does-smoking-change-expression-patterns-of-the-tumor-suppressor-and-dna-repair-genes-in-the-prostate-gland
#18
Cetin Boran, Engin Kandirali, Serdar Yanik, Hilal Ahsen, Emre Ulukaradağ, Fahri Yilmaz
OBJECTIVES: Somatic mutations can be present in clonally expanded cell populations in nonmalignant tissues, which are detectable at tissue-level resolution. Some of the mutational changes may arise due to smoking. We aimed to find out changes in carcinogenic gene expressions related to smoking in nonmalignant prostate gland epithelia. MATERIALS AND METHODS: The patients who came to the Department of Urology at Abant Izzet Baysal University Medical Faculty from December 2006 to December 2009 for prostate biopsy were questioned for cigarette smoking...
April 6, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28361293/activation-of-liver-x-receptor-%C3%AE-protects-amyloid-%C3%AE-1-40-induced-inflammatory-and-senescent-responses-in-human-retinal-pigment-epithelial-cells
#19
Bingling Dai, Chunyan Lei, Ru Lin, Lifei Tao, Yue Bin, Hui Peng, Bo Lei
OBJECTIVE: To investigate whether activation of the liver X receptors (LXRs) inhibits amyloid β1-40 (Aβ1-40) induced inflammatory and senescent responses in human retinal pigment epithelial (RPE) cells. MATERIALS AND METHODS: Confluent cultures of human primary RPE and ARPE-19 cells pretreated with 5 μΜ of TO901317 (TO90), a synthetic agonist of LXR, or vehicle were incubated with 1 μΜ of Aβ1-40 or Aβ40-1. The optimum concentrations of Aβ1-40 and TO90 were determined by cell viability assay...
March 30, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28346462/wnt-tcf1-pathway-restricts-embryonic-stem-cell-cycle-through-activation-of-the-ink4-arf-locus
#20
Anchel De Jaime-Soguero, Francesco Aulicino, Gokhan Ertaylan, Anna Griego, Aniello Cerrato, Aravind Tallam, Antonio Del Sol, Maria Pia Cosma, Frederic Lluis
Understanding the mechanisms regulating cell cycle, proliferation and potency of pluripotent stem cells guarantees their safe use in the clinic. Embryonic stem cells (ESCs) present a fast cell cycle with a short G1 phase. This is due to the lack of expression of cell cycle inhibitors, which ultimately determines naïve pluripotency by holding back differentiation. The canonical Wnt/β-catenin pathway controls mESC pluripotency via the Wnt-effector Tcf3. However, if the activity of the Wnt/β-catenin controls the cell cycle of mESCs remains unknown...
March 2017: PLoS Genetics
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