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Mohamed Bassiouni, Aurélie Dos Santos, Hasan X Avci, Hubert Löwenheim, Marcus Müller
The mature mammalian organ of Corti does not regenerate spontaneously after injury, mainly due to the absence of cell proliferation and the depletion of otic progenitors with age. The polycomb gene B lymphoma Mo-MLV insertion region 1 homolog (Bmi1) promotes proliferation and cell cycle progression in several stem cell populations. The cell cycle inhibitor p16ink4a has been previously identified as a downstream target of Bmi1. In this study, we show that Bmi1 is expressed in the developing inner ear. In the organ of Corti, Bmi1 expression is temporally regulated during embryonic and postnatal development...
2016: PloS One
Samuel B Pattle, Natasa Utjesanovic, Athena Togo, Lucy Wells, Brendan Conn, Hannah Monaghan, Elizabeth Junor, Ingolfur Johannessen, Kate Cuschieri, Simon Talbot
Squamous cell carcinomas of the hypopharynx (HPSCC) and oropharynx (OPSCC) have markedly different patient outcomes. Differences in HPV prevalence between these two patient groups may account for some of this difference, but other molecular markers of prognosis or pathological phenotype have not been established. Copy number gain of oncogenes is a well-established molecular change contributing to HNSCC development. Quantitative PCR was used to explore copy number gains of specific genes (3q - PIK3CA, TP63; 11q13...
October 17, 2016: Genes, Chromosomes & Cancer
Zhen Wang, Rong-Hui Xia, Dong-Xia Ye, Jiang Li
OBJECTIVES: To investigate the clinicopathological characteristics, human papillomavirus (HPV) infection, p53 expression, and TP53 mutations in oropharyngeal squamous cell carcinoma (OPSCC) and determine their utility as prognostic predictors in a primarily eastern Chinese population. METHODS: The HPV infection status was tested via p16INK4A immunohistochemistry and validated using PCR, reverse blot hybridization and in situ hybridization (ISH) in 188 OPSCC samples...
2016: PloS One
Carolin Götz, Enken Drecoll, Melanie Straub, Oliver Bissinger, Klaus-Dietrich Wolff, Andreas Kolk
BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) are often divided by their aetiology. Noxae associated collectives are compared with the human papilloma virus (HPV)-associated group, whereas different localisations of oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinomas are mostly discussed as one single group. Our aim was to show that classification by aetiology is not appropriate for OSCC. RESULTS: HPV DNA was detected by PCR in 7 (3.47%) patients, and we identified 12 (5...
October 6, 2016: Oncotarget
Elena Piegari, Rosa Russo, Donato Cappetta, Grazia Esposito, Konrad Urbanek, Carmela Dell'Aversana, Lucia Altucci, Liberato Berrino, Francesco Rossi, Antonella De Angelis
New strategies to prevent and early detect the cardiotoxic effects of the anticancer drug doxorubicin (DOXO) are required. MicroRNAs emerged as potential diagnostic, therapeutic and prognostic approaches in cardiovascular diseases. MiR-34a has a role in cardiac dysfunction and ageing and is involved in several cellular processes associated with DOXO cardiotoxicity. Our in vitro and in vivo results indicated that after DOXO exposure the levels of miR-34a are enhanced in cardiac cells, including Cardiac Progenitor Cells (CPCs)...
September 20, 2016: Oncotarget
Garren M Low, David S Thylur, Vicky N Yamamoto, Uttam K Sinha
Much of the current literature regarding the molecular pathophysiology of human papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC) has focused on the virus's effect on cell cycle modulation and cell proliferation. A second mechanism of pathogenicity employed by HPV, dysregulation of cellular DNA repair processes, has been more sparsely studied. The purpose of this review is to describe current understanding about the effect of HPV on DNA repair in HNSCC, taking cues from cervical cancer literature...
October 2016: Oral Oncology
Ya-di Han, Xue-Bin Wang, Ning-Hua Cui, Shuai Zhang, Chen Wang, Fang Zheng
To assess the associations of P16INK4a methylation status with low-grade squamous intra-epithelial lesion (LSIL), high-grade squamous intra-epithelial lesion (HSIL), cervical cancer (CC) and their clinicopathological features, a meta-analysis with 29 eligible studies was conducted. Pooled odds ratios (ORs) with their 95% confidence intervals (CIs) were estimated to assess the strength of the associations. Heterogeneity, sensitivity of pooled results and publication bias were also evaluated. Overall, there was an increasing trend of P16INK4a hypermethylation rates among LSIL (21...
September 22, 2016: Oncotarget
Hai Ha Thi Pham, Yeong-Ae Seong, Chul-Woong Oh, Gun-Do Kim
Cyperus amuricus (C. amuricus) is one of the most common herbs in Oriental folk medicine for exerting astringent, diuretic, wound healing and other intestinal problems. However, little is known about the molecular mechanism of C. amuricus on anticancer activity. In the present study, the underlying mechanism of the anticancer effect of C. amuricus were elucidated. The methyl alcohol extract from the whole plant of C. amuricus exhibited cytotoxicity against Hep3B cells, but not against A549 and HaCaT cells...
September 20, 2016: International Journal of Oncology
Junlei Chang, Yiming Li, Yu Huang, Karen S L Lam, Ruby L C Hoo, Wing Tak Wong, Kenneth K Y Cheng, Yiqun Wang, Paul M Vanhoutte, Aimin Xu
No abstract text is available yet for this article.
October 2016: Diabetes
Xiyue Xiao, Fucheng Cai, Xun Niu, Hao Shi, Yi Zhong
BACKGROUND: Ovarian cancer is the primary cause of death in women diagnosed with gynecological malignancies worldwide. Absence of early symptoms prevents prompt diagnosis or successful therapeutic intervention. P16INK4a is a well-known tumor suppressor gene (TSG). Aberrant methylation of TSG promoter is an important epigenetic silencing mechanism leading to ovarian cancer progression. Studies have reported differences in methylation frequencies of the p16INK4a promoter between ovarian cancer and the corresponding control group...
2016: PloS One
Tara J Wu, Karen Smith-McCune, Miriam Reuschenbach, Magnus von Knebel Doeberitz, May Maloba, Megan J Huchko
OBJECTIVE: A biomarker with increased specificity for cervical dysplasia compared with human papillomavirus (HPV) testing would be an attractive option for cervical cancer screening among HIV-infected women in resource-limited settings. p16(INK4a) has been explored as a biomarker for screening in general populations. DESIGN: A 2-year cross-sectional study. SETTING: 2 large HIV primary care clinics in western Kenya. PARTICIPANTS: 1054 HIV-infected women in western Kenya undergoing cervical cancer screening as part of routine HIV care from October 2010 to November 2012...
September 13, 2016: BMJ Open
Angela L Mazul, James M Taylor, Kimon Divaris, Mark C Weissler, Paul Brennan, Devasena Anantharaman, Behnoush Abedi-Ardekani, Andrew F Olshan, Jose P Zevallos
BACKGROUND: Indicators of poor oral health, including smoking, have been associated with increased risk of head and neck squamous cell carcinoma, especially oropharyngeal squamous cell carcinoma (OPSCC), yet few studies have examined whether this association is modified by human papillomavirus (HPV) status. METHODS: Data from interviews and tumor HPV status from a large population-based case-control study, the Carolina Head and Neck Cancer Study (CHANCE), were used to estimate the association between oral health indicators and smoking among 102 HPV-positive patients and 145 HPV-negative patients with OPSCC and 1396 controls...
August 29, 2016: Cancer
Y P Wong, S H Abdul Raub, A Z H Mohd Dali, F Kassim, V Visvalingam, Z Zakaria, M A Kamaluddin, S Noor Akmal
Human papillomavirus (HPV) is a necessary cause of cervical cancer and its precursors. Increased expression of high-risk hrHPV viral oncogenes in abnormal cells might increase the expression of p16INK4a. We aimed to determine the role of p16INK4a in detecting hrHPV-transformed epithelial cells in liquid-based cervical cytology, and compared the results with hrHPV DNA testing by realtime polymerase chain reaction (RT-PCR). Fifty-seven cytological samples were tested for p16INK4a immunomarker and hrHPV DNA. Test performance of both tests was determined by comparing sensitivity, specificity and predictive values using available histological follow-up data as gold standard...
August 2016: Malaysian Journal of Pathology
Fan Lin, Mark C de Gooijer, Diana Hanekamp, Gayathri Chandrasekaran, Levi Buil, Nishita Thota, Rolf W Sparidans, Jos H Beijnen, Thomas Wurdinger, Olaf van Tellingen
PURPOSE: The PI3K-AKT-mTOR signaling pathway is frequently activated in glioblastoma (GBM) and offers several drugable targets. However, clinical efficacy of PI3K/mTOR inhibitors in GBM has not yet been demonstrated. Insufficient drug delivery may limit the efficacy of PI3K/mTOR inhibitors against GBM. The presence of the efflux transporters ABCB1/Abcb1 (P-glycoprotein, MDR1) and ABCG2/Abcg2 (BCRP) at the blood-brain barrier (BBB) restricts the brain penetration of many drugs. EXPERIMENTAL DESIGN: We used in vitro drug transport assays and performed pharmacokinetic/pharmacodynamic studies in wildtype and ABC-transporter knockout mice...
August 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
K J Senthil Kumar, M Gokila Vani, Jeng-Leun Mau, Chin-Chung Lin, Fang-Hua Chu, Chia-Cheng Wei, Vivian Hsiu-Chuan Liao, Sheng-Yang Wang
The present study revealed the anti-aging properties of antcin M (ANM) and elucidated the molecular mechanism underlying the effects. We found that exposure of human normal dermal fibroblasts (HNDFs) to high-glucose (HG, 30 mM) for 3 days, accelerated G0/G1 phase arrest and senescence. Indeed, co-treatment with ANM (10 µM) significantly attenuated HG-induced growth arrest and promoted cell proliferation. Further molecular analysis revealed that ANM blocked the HG-induced reduction in G1-S transition regulatory proteins such as cyclin D, cyclin E, CDK4, CDK6, CDK2 and protein retinoblastoma (pRb)...
August 11, 2016: Oncotarget
MinJeong Kim, Kui Young Park, Mi-Kyung Lee, Taewon Jin, Seong Jun Seo
Recent studies have revealed that adiponectin can suppress cellular inflammatory signaling pathways. This study aimed to elucidate the effect of adiponectin on the unregulated production of hBD2 in UVB-induced premature senescent keratinocytes. We constructed an in vitro model of premature senescent keratinocytes through repeated exposure to low energy UVB. After repeated low energy UVB exposure, there was significant generation of reactive oxygen species (ROS) and induction of senescence-associated markers, including senescence associated beta-galactosidase activity and expression of p16INK4a and histone H2AX...
2016: PloS One
Olaf Reich, Sigrid Regauer
The WHO defines thin high-grade squamous intraepithelial lesions (HSIL) as a high-grade intraepithelial lesion of the cervix that is usually ≤9 cells thick. These lesions usually develop in early metaplastic squamous epithelium without anteceding low-grade squamous intraepithelial lesions (LSIL). The prevalence of thin HSIL is not well documented. We evaluated different characteristics of thin HSIL at time of treatment. We studied 25 formalin-fixed and paraffin-embedded conization specimens processed as step-serial sections...
August 10, 2016: International Journal of Gynecological Pathology
Anna Manawapat-Klopfer, Louise T Thomsen, Peter Martus, Christian Munk, Rainer Russ, Hans Gmuender, Kirsten Frederiksen, Juliane Haedicke-Jarboui, Frank Stubenrauch, Susanne K Kjaer, Thomas Iftner
Women persistently infected with human papillomavirus (HPV) type 16 are at high risk for development of cervical intraepithelial neoplasia grade 3 or cervical cancer (CIN3+). We aimed to identify biomarkers for progression to CIN3+ in women with persistent HPV16 infection. In this prospective study, 11,088 women aged 20-29 years were enrolled during 1991-1993, and re-invited for a second visit two years later. Cervical cytology samples obtained at both visits were tested for HPV DNA by Hybrid Capture 2 (HC2), and HC2-positive samples were genotyped by INNO-LiPA...
2016: American Journal of Cancer Research
Jian-Jie Zhao, Shuai Hao, Ling-Li Wang, Chun-Yan Hu, Shu Zhang, Ling-Ji Guo, Gang Zhang, Bo Gao, Yan Jiang, Wu-Guo Tian, Dong-Lin Luo
OBJECTIVE: To investigate the effect of antisense non-coding RNA in the INK4 locus (ANRIL) on invasion and metastasis of thyroid cancer (TC). RESULTS: ANRIL expression was significantly up-regulated in TC tissues and cells (P < 0.001), and ANRIL expression was significantly different regarding histological grade and LNM (both P < 0.01). The siRNA-mediated ANRIL silencing inhibits proliferation, invasion, and metastasis of TPC-1 and SW579 cells, and lung metastasis, which can be reversed by TGF-β1 siRNA...
August 5, 2016: Oncotarget
Itziar Vergara, Francisco Rivas-Ruiz, Kalliopi Vrotsou, Eugenio Contreras-Fernández, Teresa Téllez-Santana, Mónica Machón, Ana Isabel Díez Ruiz, Yolanda de Mesa Berenguer, Andoni Bueno, Jazmina Núñez, M Carmen Saucedo Figueredo, Alonso Montiel-Luque, M Antonia Nava Del Val, Raúl Quirós-López, Estefanía Carrasco, Gabor Abellan
BACKGROUND: In the last few years several indices and tools, aimed at identifying frail subjects in various care settings have been developed. However, to date none of them has been incorporated into usual practice in the primary care setting. The purposes of this study are: 1) to evaluate the predictive capacity of the Tilburg Frailty Indicator (TFI), the Gérontopôle Frailty Screening Tool (GFST) and the KoS model together with two biomarker levels (SOX2 and p16INK4a) for adverse events related to frailty; 2) to determine differences in the use of healthcare services according to frailty...
2016: BMC Health Services Research
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