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https://www.readbyqxmd.com/read/28736821/testing-for-high-risk-hpv-in-cervical-and-tonsillar-paraffin-embedded-tissue-using-a-cartridge-based-assay
#1
Elina Virtanen, Pekka Laurila, Jaana Hagström, Pekka Nieminen, Eeva Auvinen
This study evaluates the suitability of Xpert HPV (Cepheid, Sunnyvale, CA, USA) test for cervical and tonsillar formalin-fixed paraffin-embedded (FFPE) tissue samples as compared to the tests currently used in diagnostics. Cervical biopsies and liquid cytology (LC) samples were collected from 48 women attending colposcopy. Biopsies were processed for histology and tested for hrHPV using Xpert HPV. LC samples were tested using Xpert and Hybrid Capture 2 (HC2; Qiagen, Hilden, Germany) tests. Also 29 archived tonsillar carcinoma samples were tested using Xpert, and the results were compared with histology and immunohistochemical p16INK4a (p16) staining...
July 24, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28711940/clinical-significance-of-p16ink4a-and-p14arf-promoter-methylation-in-renal-cell-carcinoma-a-meta-analysis
#2
Yu Ren, Li Xiao, Guobin Weng, Bingyi Shi
The inactivation of p16INK4A and p14ARF via promoter methylation has been investigated in various cancers. However, the clinical effects of p16INK4A and p14ARF promoter methylation on renal cell carcinoma (RCC) remain to be clarified. The pooled data were calculated and summarized. Finally, an investigation of 14 eligible studies with 1231 RCC patients and 689 control patients was performed. Methylated p16INK4A and p14ARF were observed to be significantly higher in RCC than in control subjects without malignancies (OR = 2...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28706164/clinicopathological-significance-of-the-p16-hypermethylation-in-multiple-myeloma-a-systematic-review-and-meta-analysis
#3
Huiqing Yu, Liejun Yang, Yunfeng Fu, Meng Gao, Ling Tian
It is well known that the loss of function of the p16INK4A gene is mainly caused by the hypermethylation of the p16 gene; however, whether or not the inactivation is associated with the clinical significance of multiple myeloma (MM) remains elusive. A meta-analysis was conducted to quantitatively determine the role of the p16 hypermethylation in the clinical significance of MM. We demonstrated that MM patients show much higher hypermethylation rates on the p16 gene in bone marrow compared to normal individuals, as well as monoclonal gammopathy of undetermined significance (MGUS)...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28701722/asxl1-deficiency-in-embryonic-fibroblasts-leads-to-cellular-senescence-via-impairment-of-the-akt-e2f-pathway-and-ezh2-inactivation
#4
Hye Sook Youn, Tae-Yoon Kim, Ui-Hyun Park, Seung-Tae Moon, So-Jung An, Yong-Kyu Lee, Jin-Taek Hwang, Eun-Joo Kim, Soo-Jong Um
Although ASXL1 mutations are frequently found in human diseases, including myeloid leukemia, the cell proliferation-associated function of ASXL1 is largely unknown. Here, we explored the molecular mechanism underlying the growth defect found in Asxl1-deficient mouse embryonic fibroblasts (MEFs). We found that Asxl1, through amino acids 371 to 655, interacts with the kinase domain of AKT1. In Asxl1-null MEFs, IGF-1 was unable to induce AKT1 phosphorylation and activation; p27Kip1, which forms a ternary complex with ASXL1 and AKT1, therefore remained unphosphorylated...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28682291/cellular-senescence-what-why-and-how
#5
Matthew J Regulski
Cellular senescence is a process that results from a variety of stresses and leads to a state of irreversible growth arrest. Senescent cells accumulate during aging and have been implicated in promoting a variety of age-related diseases. Cellular senescence may play an important role in tumor suppression, wound healing, and protection against tissue fibrosis; however, accumulating evidence that senescent cells may have harmful effects in vivo and may contribute to tissue remodeling, organismal aging, and many age-related diseases also exists...
June 2017: Wounds: a Compendium of Clinical Research and Practice
https://www.readbyqxmd.com/read/28658942/cellular-senescence-biomarker-p16ink4a-cell-burden-in-thigh-adipose-is-associated-with-poor-physical-function-in-older-women
#6
Jamie N Justice, Heather Gregory, Tamar Tchkonia, Nathan K LeBrasseur, James L Kirkland, Stephen B Kritchevsky, Barbara J Nicklas
Background: Ample evidence implicates cellular senescence as a contributor to frailty and functional decline in rodents, but considerable effort remains to translate these findings to human aging. Methods: We quantified senescence biomarker p16INK4a-expressing cells in thigh adipose tissue obtained from older women previously enrolled in a 5-month resistance training intervention, with or without caloric restriction (RT±CR, n=11 baseline, 8 pre-post-intervention pairs)...
June 27, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28658331/evaluation-of-telomerase-htert-ki67-and-p16ink4a-expressions-in-low-and-high-grade-cervical-intraepithelial-lesions
#7
Ana Paula Szezepaniak Goulart, Manoel Afonso Guimarães Gonçalves, Vinicius Duval DA-Silva
Objective : to study the association between the histological grading of cervical intraepithelial neoplasia (CIN I, CIN II and CIN III) and the immunohistochemical expression for p16ink4a, hTert and Ki67, as well as to evaluate the relationship of these markers with the risk of recurrence after surgical treatment. Methods : we studied a historical cohort of 94 women with intraepithelial lesions CIN I (low grade), CIN II and CIN III (high grades) submitted to conization or electrosurgical excision of the transformation zone...
March 2017: Revista do Colégio Brasileiro de Cirurgiões
https://www.readbyqxmd.com/read/28652169/oncogene-induced-senescence-and-its-evasion-in-a-mouse-model-of-thyroid-neoplasia
#8
Roberto Bellelli, Donata Vitagliano, Giorgia Federico, Pina Marotta, Anna Tamburrino, Paolo Salerno, Orlando Paciello, Serenella Papparella, Jeffrey A Knauf, James A Fagin, Samuel Refetoff, Giancarlo Troncone, Massimo Santoro
Here we describe a conditional doxycycline-dependent mouse model of RET/PTC3 (NCOA4-RET) oncogene-induced thyroid tumorigenesis. In these mice, after 10 days of doxycycline (dox) administration, RET/PTC3 expression induced mitogen activated protein kinase (MAPK) stimulation and a proliferative response which resulted in the formation of hyperplastic thyroid lesions. This was followed, after 2 months, by growth arrest accompanied by typical features of oncogene-induced senescence (OIS), including upregulation of p16INK4A and p21CIP, positivity at the Sudan black B, activation of the DNA damage response (DDR) markers γH2AX and pChk2 T68, and induction of p53 and p19ARF...
June 23, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28646455/human-nucleus-pulposus-intervertebral-disc-cells-becoming-senescent-using-different-treatments-exhibit-a-similar-transcriptional-profile-of-catabolic-and-inflammatory-genes
#9
Sotiris-Spyros Vamvakas, Eleni Mavrogonatou, Dimitris Kletsas
PURPOSE: Chronic low back pain has been associated with intervertebral disc (IVD) degeneration, which is characterized by the accumulation of extracellular matrix (ECM)-degrading proteases and inflammatory molecules in the degenerate tissue. IVD degeneration could be the outcome of natural organismal ageing and/or of the exposure of the disc to cumulative stressful environmental stimuli and is accompanied by an increased population of senescent cells in the tissue. On the other hand, senescent cells are known to secrete proteolytic enzymes and inflammatory molecules, which can contribute to ECM catabolism...
June 23, 2017: European Spine Journal
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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...
July 11, 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
#17
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
#18
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...
July 4, 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
#19
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
#20
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
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