Acetylation and deacetylation are posttranslational modifications (PTMs) which affect the regulation of chromatin structure and its remodeling. Acetylation of histone 3 at lysine placed on position 18 (H3K18Ac) plays an important role in driving progression of many types of cancer, including breast, colon, lung, hepatocellular, pancreatic, prostate, and thyroid cancer. The aim of this review is to analyze and discuss the newest findings regarding the role of H3K18Ac and acetylation of other histones in carcinogenesis. We summarize the level of H3K18Ac in different cancer cell lines and analyze its association with patients’ outcomes, including overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS). Finally, we describe future perspectives of cancer therapeutic strategies based on H3K18 modifications.
BackgroundWell-organised quality-controlled screening can substantially reduce the burden of cervical cancer (CC). European guidelines (EuG) for quality assurance in CC screening provide guidance on all aspects of an organised screening programme. Organised CC screening in Poland was introduced in 2007. The purpose of our study was to analyse: (i) adherence of the programme to EuG; (ii) programme process and performance indicators; (iii) impact of the programme on the incidence of and mortality from CC.MethodsAvailable data on the policy, structure and functioning of the Polish programme were compared with the major points of the EuG. Data on the process, and available performance indicators were drawn from the screening database and other National Health Fund (NHF) systems. Joinpoint regression was used to assess changes in CC incidence and mortality trends.ResultsThe Polish programme adheres partially to EuG in terms of policy and organisation. Only a limited set of performance indicators can be calculated due to screening database incompleteness or lack of linkage between existing databases. The screening database does not include opportunistic smears collected within NHF-reimbursed or private care. The organised programme coverage rate fluctuated from 21% to 27% between 2007-2013. In 2012 the coverage reached 35% after combining both organised and opportunistic smears reimbursed by the NHF. In 2012 the number of smears reimbursed by NHF was 60% higher in opportunistic than in organised screening with significant overlap. Data from the private sector are not recorded. Depending on years, 30-50% of women referred for colposcopy/biopsy because of abnormal Pap smears were managed within the programme. The age-standardised CC incidence and mortality dropped linearly between 1999 and 2011 without evidence of a period effect.ConclusionsThe Polish organised cervical screening programme is only partially adherent to evidence-based EuG. Its implementation has not influenced the burden of CC in the country so far. Changes with special focus on increasing coverage, development of information systems and assessment of quality are required to increase programme adherence to EuG and to measure its effectiveness. Our findings may be useful to improve the Polish programme and those implemented or planned in other countries.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1242-9) contains supplementary material, which is available to authorized users.
Aside from existing opportunistic screening, an organised screening programme (OSP) for cervical cancer (CC) was implemented in 2006/2007 in Poland. We applied joinpoint regression and age-period-cohort model to look for the impact of the OSP on CC incidence/mortality trends. Decline of age-standardised incidence rates (ASIRs) in the screening-age group (25-59 years) accelerated from -2.2% (95% CI -2.7 to -1.7%) between 1993 and 2008 to -6.1% (95% CI -7.7 to -4.4%) annually after 2008. In women aged 60+ years, ASIRs declined from 1986 until 2005 [annual percent change (APC) = -2.6%, 95% CI -2.9 to -2.4%] and stabilised thereafter. Decline of age-standardised mortality rates (ASMRs) in the screening-age group accelerated from -1.3% (95% CI -1.5 to -1.1%) between 1980 and 2005 to -4.7% (95% CI -5.6 to -3.8%) annually after 2005. In women aged 60+ ASMR declined between 1991 and 2004 (APC = -2.9%, 95% CI -3.5 to -2.3%) and stabilised thereafter. Relative risks of CC diagnosis and death were 0.63 (95% CI 0.62-0.65) and 0.61 (95% CI 0.59-0.63), respectively, for the most recent period compared to the reference around 1982. Implementation of the OSP possibly accelerated downward trends in the burden of CC in Polish women under the age of 60, but recent stabilisation of trends in older women requires actions.
Background/Aim: Ovarian cancer is the most frequent cause of death in women among gynecological cancers in Poland. MMP-2 and MMP-9 are frequently dysregulated in cancers and they are considered as potential biomarkers. Our goal was to assess the associations between MMP-2 and MMP-9 mRNA expression, clinicopathological parameters and patients' response to chemotherapy. Materials and Methods: We evaluated MMP-2 and MMP-9 mRNA expression in epithelial ovarian cancer (EOC) tissues from 44 untreated patients, four ovarian cancer cell lines, and human skin fibroblasts (HSF). The expression of both MMPs was estimated using qPCR. Results: MMP-2 expression was significantly higher (p=0.020) in EOCs sensitive to chemotherapy compared to resistant and refractory tumors. The highest MMP-2 expression was found in HSF and MMP-9 expression was the highest in EOCs (p<0.001). The expression of neither MMP was significantly associated with patients' overall survival (OS). Conclusion: MMP-2 may be engaged in early stages of ovarian carcinogenesis. MMP-2 expression in EOCs may discriminate patients with a favorable response to first line chemotherapy.
In order to evaluate the role of K-ras gene point mutations in the progression of endometrial carcinoma, we applied the polymerase chain reaction/restriction-fragment-length polymorphism technique to 57 tumours surgically removed from women of Polish origin. We assessed the relationship between K-ras gene activation and clinicopathological features as well as patients' outcome. Mutational activation in codon 12 of the K-ras gene was detected in 8 out of 57 (14%) endometrial carcinomas, while in codon 13 of the K-ras gene no point mutations were noted. A correlation between the histological type of the tumour and codon 12 K-ras gene mutation was noted (P < 0.05; Fisher exact test). K-ras gene mutation was not related to the patients' age, surgical stage, histological grade or to the depth of myometrial invasion. A trend towards a poorer prognosis was noted during the follow-up of patients whose tumours had shown K-ras codon 12 point mutations, but the difference was not significant (P = 0.06; log-rank test). Our data indicate that point mutations in codon 12 of the K-ras gene are a rare event in human endometrial carcinomas. The lack of correlation between K-ras point mutations and clinicopathological features (except histological type) supports the hypothesis of a random activation of the K-ras gene in human neoplastic endometrium.
The molecular bases of miR-182 deregulation in epithelial ovarian cancers (EOCs) remain unknown and its diagnostic or prognostic role in EOCs is still unclear. We performed miR-182 expression analysis using a microarray approach and real-time PCR (qPCR). We also used array comparative genomic hybridization and methylated DNA immunoprecipitation to study copy number changes and methylation aberrations within coding locus/promoter sequences of miR-182 in EOC tissues, respectively. We have found that miR-182 expression is significantly increased in EOC (P < 0.00001) and that higher miR-182 expression in EOC is linked with significantly shorter overall survival (P = 0.026). The methylation of miR-182 promoter was significantly associated with lower miR-182 expression in EOC tissues (P = 0.045). miR-182 over-expression is connected with copy number (CN) gains of this miRNA coding sequences in EOC (P = 0.002), and the number of PRDM5 copies is significantly and inversely correlated with miR-182 expression evaluated by qPCR (R = -0.615, P = 0.009). We conclude that the aberrant miR-182 expression in EOC may be due to CN gains within its coding locus. The miR-182 promoter is rarely methylated in EOC, and its methylation status is associated with lower miR-182 expression. Deletion of the PRDM5 locus may play a supportive role in miR-182 overexpression in EOC. miR-182 is an unfavorable prognostic factor in EOC. © 2016 Wiley Periodicals, Inc.
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