Interactions between circRNAs and miR-141 in Cancer: From Pathogenesis to Diagnosis and Therapy.

The function of non-coding RNAs (ncRNAs) in the pathogenesis and development of cancer is indisputable. Molecular mechanisms underlying carcinogenesis involve the aberrant expression of ncRNAs, including circular RNAs (circRNAs), and microRNAs (miRNAs). CircRNAs are a class of single-stranded, covalently closed RNAs responsible for maintaining cellular homeostasis through their diverse functions. As a part of the competing endogenous RNA (ceRNAs) network, they play a central role in the regulation of accessibility of miRNAs to their mRNA targets. The interplay between these molecular players is based on the primary role of circRNAs that act as miRNAs sponges, and the circRNA/miRNA imbalance plays a central role in different pathologies including cancer. Herein, we present the latest state of knowledge about interactions between circRNAs and miR-141, a well-known member of the miR-200 family, in malignant transformation, with emphasis on the biological role of circRNA/miR-141/mRNA networks as a future target for novel anti-cancer therapies.

The Role of Sirtuin 6 in the Deacetylation of Histone Proteins as a Factor in the Progression of Neoplastic Disease.

SIRT6 is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, predominantly located in the nucleus, that is involved in the processes of histone modification, DNA repair, cell cycle regulation, and apoptosis. Disturbances in SIRT6 expression levels have been observed in the development and progression of various types of cancer. Therefore, it is important to better understand the role of SIRT6 in biochemical pathways and assign it specific biological functions. This review aims to summarize the role of SIRT6 in carcinogenesis and tumor development. A better understanding of the factors influencing SIRT6 expression and its biological role in carcinogenesis may help to develop novel anti-cancer therapeutic strategies. Moreover, we discuss the anti-cancer effects and mechanism of action of small molecule SIRT6 modulators (both activators and inhibitors) in different types of cancer.

Dexmedetomidine Increases MMP-12 and MBP Concentrations after Coronary Artery Bypass Graft Surgery with Extracorporeal Circulation Anaesthesia without Impacting Cognitive Function: A Randomised Control Trial.

Postoperative neurological deficits remain a concern for patients undergoing cardiac surgeries. Even minor injuries can lead to neurocognitive decline (i.e., postoperative cognitive dysfunction). Dexmedetomidine may be beneficial given its reported neuroprotective effect. We aimed to investigate the effects of dexmedetomidine on brain injury during cardiac surgery anaesthesia. This prospective observational study analysed data for 46 patients who underwent coronary artery bypass graft surgery with extracorporeal circulation between August 2018 and March 2019. The patients were divided into two groups: control (CON) with typical anaesthesia and dexmedetomidine (DEX) with dexmedetomidine infusion. Concentrations of the biomarkers matrix metalloproteinase-12 (MMP-12) and myelin basic protein (MBP) were measured preoperatively and at 24 and 72 h postoperatively. Cognitive evaluations were performed preoperatively, at discharge, and 3 months after discharge using Addenbrooke's Cognitive Examination version III (ACE-III). The primary endpoint was the ACE-III score at discharge. Increased MMP-12 and MBP concentrations were observed in the DEX group 24 and 72 h postoperatively. No significant differences in ACE-III scores were observed between the groups at discharge; however, the values were increased when compared with initial values after 3 months (p = 0.000). The current results indicate that the administration of dexmedetomidine as an adjuvant to anaesthesia can increase MMP-12 and MBP levels without effects on neurocognitive outcomes at discharge and 3 months postoperatively.

Inter-component immunohistochemical assessment of proliferative markers in uterine carcinosarcoma.

In the scientific literature, a selected number of reports have investigated the impact of proliferative activity on the development and progression of uterine carcinosarcomas (UC). The aim of the present retrospective study was to compare the immunohistochemical proliferation markers [Ki67, proliferating cell nuclear antigen (PCNA), minichromosome maintenance complex component 3 (MCM3), and topoisomerase IIα (topoIIα)] assessment in both components of UC. A total of 30 paraffin-embedded slides of UCs, obtained from patients who underwent surgery between January 1, 2006, and December 31, 2020, were analyzed. Medical records and clinicopathological data of patients were reviewed. Formalin-fixed, paraffin-embedded tissue sections were immunostained with monoclonal antibodies against Ki67, PCNA, MCM3 and topoIIα. Ki67-positive nuclear immunoreactivity was reported in 20 (67%) and 16 (53%) UC carcinomatous and sarcomatous components, respectively. In the epithelial component, Ki67 positive staining was related to the International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.025), and histological grade (G1 vs. G2/G3, P=0.031). Nuclear PCNA reactivity was observed in 18 (60%) and 16 (53%) carcinomatous and sarcomatous components, respectively. Notably, all four cases with omental metastases were PCNA-positive, and a relationship between staining pattern and the existence of metastases was of significant value (P=0.018). MCM3-positive nuclear staining was found nearly twice as high in the carcinomatous (n=19; 63%), compared with the sarcomatous (n=11; 37%) component, respectively, and MCM3 expression in the epithelial component was related to clinical stage (P=0.030), and the existence of omental metastasis (P=0.012). In addition, out of the 30 UCs, 17 (57%) and 13 (43%) showed topoIIα positivity in the carcinomatous and sarcomatous UC components, respectively. A significant relationship between protein immunoreactivity and FIGO stage (P=0.049), and omental metastasis (P=0.026) was revealed to exist. However, no significant differences between expression of proliferation markers and clinicopathological features in the sarcomatous UC component were identified. Finally, a significant correlation between each protein immunohistochemical staining was demonstrated, particularly in the sarcomatous UC component. Collectively, a combined analysis of Ki67, PCNA, MCM3, and topoIIα may provide more detailed information of cell-cycle alterations determining the heterogeneity of uterine carcinosarcomas.

Red blood cell distribution width derivatives in alcohol-related liver cirrhosis and metabolic-associated fatty liver disease.

BACKGROUND: Looking for undiscovered blood markers of liver fibrosis and steatosis still remains an issue worth exploring. There are still plenty of unresolved issues related to the actual role of hematological indices as potential markers of liver function. AIM: To study red blood cell distribution width (RDW), RDW-to-platelet ratio (RPR) and RDW-to-lymphocyte ratio (RLR) in alcohol-related liver cirrhosis (ALC) and metabolic-associated fatty liver disease (MAFLD). METHODS: The study group was composed of 302 people: 142 patients with ALC and 92 with MAFLD; 68 persons were included as controls. RDW, RPR and RLR were measured in each person. Indirect and direct parameters of liver fibrosis were also assessed [aspartate transaminase to alkaline transaminase ratio, aspartate transaminase to platelet ratio index (APRI), fibrosis-4 (FIB-4), gamma-glutamyl transpeptidase to platelet ratio (GPR), procollagen I carboxyterminal propeptide, procollagen III aminoterminal propeptide, transforming growth factor-α, platelet-derived growth factor AB, laminin]. MELD score in ALC patients and non-alcoholic fatty liver disease (NAFLD) fibrosis score together with BARD score were obtained in the MAFLD group. The achieved results were compared to controls. Then a correlation between assessed markers was done. Diagnostic value of each investigated parameter and its suggested cut-off in the research group were evaluated with area under the curve (AUC). RESULTS: RDW, RPR and RLR values turned out to be significantly higher in ALC and MAFLD groups compared to controls (ALC: P < 0.0001; NAFLD: P < 0.05, P < 0.0001 and P < 0.0001, respectively). RPR correlated positively with MELD score (P < 0.01) and indirect indices of liver fibrosis (FIB-4 and GPR; P < 0.0001) in ALC patients; negative correlations were found between PDGF-AB and both: RDW and RPR (P < 0.01 and P < 0.0001, respectively). RPR correlated positively with NAFLD fibrosis score and APRI (P < 0.0001) in the MAFLD group; a positive relationship was observed between RDW and FIB-4, too (P < 0.05). AUC values and suggested cut-offs for RDW, RPR and RLR in ALC patients were: 0.912 (> 14.2%), 0.965 (> 0.075) and 0.914 (> 8.684), respectively. AUC values and suggested cut-offs for RDW, RPR and RLR in MAFLD patients were: 0.606 (> 12.8%), 0.724 (> 0.047) and 0.691 (> 6.25), respectively. CONCLUSION: RDW with its derivatives appear to be valuable diagnostic markers in patients with ALC. They can also be associated with a deterioration of liver function in this group.

An Insight into miR-1290: An Oncogenic miRNA with Diagnostic Potential.

For more than two decades, the view of the roles of non-coding RNAs (ncRNAs) has been radically changing. These RNA molecules that are transcribed from our genome do not have the capacity to encode proteins, but are critical regulators of gene expression at different levels. Our knowledge is constantly enriched by new reports revealing the role of these new molecular players in the development of many pathological conditions, including cancer. One of the ncRNA classes includes short RNA molecules called microRNAs (miRNAs), which are involved in the post-transcriptional control of gene expression affecting various cellular processes. The aberrant expression of miRNAs with oncogenic and tumor-suppressive function is associated with cancer initiation, promotion, malignant transformation, progression and metastasis. Oncogenic miRNAs, also known as oncomirs, mediate the downregulation of tumor-suppressor genes and their expression is upregulated in cancer. Nowadays, miRNAs show promising application in diagnosis, prediction, disease monitoring and therapy response. Our review presents a current view of the oncogenic role of miR-1290 with emphasis on its properties as a cancer biomarker in clinical medicine.

Deacetylation of Transcription Factors in Carcinogenesis.

Reversible Nε-lysine acetylation/deacetylation is one of the most common post-translational modifications (PTM) of histones and non-histone proteins that is regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). This epigenetic process is highly involved in carcinogenesis, affecting histone and non-histone proteins' properties and their biological functions. Some of the transcription factors, including tumor suppressors and oncoproteins, undergo this modification altering different cell signaling pathways. HDACs deacetylate their targets, which leads to either the upregulation or downregulation of proteins involved in the regulation of cell cycle and apoptosis, ultimately influencing tumor growth, invasion, and drug resistance. Therefore, epigenetic modifications are of great clinical importance and may constitute a new therapeutic target in cancer treatment. This review is aimed to present the significance of HDACs in carcinogenesis through their influence on functions of transcription factors, and therefore regulation of different signaling pathways, cancer progression, and metastasis.

Plateletcrit and Mean Platelet Volume in the Evaluation of Alcoholic Liver Cirrhosis and Nonalcoholic Fatty Liver Disease Patients.

Platelet (PLT) indices have been proposed as potential markers in the assessment of liver fibrosis and exacerbation of liver failure. The aim of our study was to verify mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) in alcohol-related liver cirrhosis (ALC) and nonalcoholic fatty liver disease (NAFLD) patients. One hundred forty-two patients with ALC, 92 with NAFLD, and 68 in control group were enrolled in this study. Hematological indices (MPV, PCT, and PDW) and serological (indirect and direct) markers of liver fibrosis (AAR, APRI, FIB-4, GPR, PICP, PIIINP, TGF-α, PDGF-AB, laminin) were measured in each participant. MELD score in ALC patients and NAFLD fibrosis score (NFS) together with BARD score in the NAFLD group were also obtained. Results were compared between research and control groups. Then, a correlation between evaluated indices was performed in study groups. Receiver operating characteristic curves (ROCs) and area under the curve (AUC) values were applied to assess the diagnostic accuracy of measured indices. Significant increase in PDW and decrease in PCT in comparison to controls were noted in examined ALC (60.4% vs. 51.2% and 0.1% vs. 0.21%, respectively, p < 0.0001) and NAFLD (54.75% vs. 51.2% and 0.19 vs. 0.21%, respectively, p < 0.01) patients. Decreased level of MPV was observed in NAFLD group (7.85 fl vs. 8.90 fl, p < 0.0001). Additionally, PCT correlated with NFS (p < 0.0001). Evaluated PLT indices correlated with MELD score (MPV and PDW, p < 0.001; PCT, p < 0.05). They correlated with indirect and direct markers of liver fibrosis in the whole research group, too. PCT was the parameter with the greatest diagnostic accuracy in ALC patients (AUC = 0,839 for cutoff < 0.17%); in NAFLD group, it was MPV (AUC = 0,808 for cutoff < 7.9 fl). PCT in ALC and MPV in NAFLD can be perceived as potential diagnostic markers.

Epidermal Growth Factor Receptor and its Oncogenic EGFRvIII Variant in Benign and Malignant Brain Tumors.

BACKGROUND/AIM: Tumorigenesis and cancer progression might be driven by abnormal activation of growth factor receptors. Importantly, molecular changes in EGFR-dependent signaling is one of the most common characteristics of brain tumors. PATIENTS AND METHODS: HER1 and EGFRvIII variants in meningiomas and glioblastomas were evaluated at the RNA level. RESULTS: EGFRvIII was found in 18.6% of glioblastomas (GBM), whereas 25% of EGFRvIII positive tumors express wild-type EGFR as well. HER1 was over-expressed in benign meningiomas compared to glioblastomas, whereas HER1 expression in meningiomas differed significantly between sub-types of meningiomas. EGFRvIII and HER1 where positively correlated in glioblastomas. Yet, the patient overall survival did not differ between high- and low-HER1 expressing glioblastomas or between EGFRvIII positive and negative GBMs. CONCLUSION: HER1 may be considered as an independent factor for classification of benign meningiomas. The mRNA levels of HER1 or EGFRvIII should not be used as independent prognostic factors for patients with gliomas.

Serum miR-210-3p can be used to differentiate between patients with pancreatic ductal adenocarcinoma and chronic pancreatitis.

Patients with chronic pancreatitis (CP) are at risk of developing pancreatic ductal adenocarcinoma (PDAC). To the best of our knowledge, there are no suitable non-invasive biomarkers for differentiation between CP and PDAC; however, potential molecular candidates include circulating miRNAs due to ease of extraction, their stability and tissue specificity. Therefore, the aim of the present study was to identify potential serum marker(s) that may be used for differentiating between CP and PDAC. In total, 77 patients were enrolled in the present study; 34 patients with CP, 26 patients with PDAC and a control group of 17 healthy individuals. Expression of miR-10b-5p, miR-106b-5p, miR-210-3p and miR-216a-5p in serum was determined by reverse transcription-quantitative PCR. Serum miRNA expression levels in patients with CP, PDAC and in the control group were compared. Routine biochemical blood parameters were determined and correlation analysis of these parameters with miRNA expression was performed. Expression of miR-210-3p was increased in the sera of patients with PDAC compared with the CP patients (P=0.015) and with the control group (P<0.001). MiR-106b-5p (P=0.056) and miR-10b-5p (P=0.080) were not significantly upregulated in patients with PDAC compared with those with CP. Analysis of miRNA expression in relation to laboratory blood parameters showed positive correlations between miR-210-3p with alkaline phosphatase (r=0.605; P=0.022) and with γ-glutamyltranspeptidase (r=0.529; P=0.029) in PDAC. The novel finding of the present study was that miR-10b-5p was positively correlated with C-reactive protein (r=0.429; P=0.047) in patients with PDAC and with carbohydrate antigen 19-9 (r=0.483; P=0.005) in CP. Based on the preliminary data obtained in the present study, it was concluded that miR-210-3p may be used as a non-invasive biomarker that can be used to distinguish between patients with PDAC and CP.

Elevated miRNA Inversely Correlates with E-cadherin Gene Expression in Tissue Biopsies from Crohn Disease Patients in contrast to Ulcerative Colitis Patients.

Inflammatory bowel disease (IBD) comprises ulcerative colitis (UC) and Crohn disease (CD). Similar symptoms, but different treatment procedures for both diseases require precise diagnosis. MicroRNAs (miRNAs) are major posttranscriptional players that regulate the expression of genes during the inflammation and thus could be appropriate biomarkers for differentiation between UC and CD. For this purpose, we analyzed the expression of miR-21-3p, miR-31-3p, miR-125b-1-3p, miR-146a-3p, miR-155-5p, and E-cadherin (CDH1) genes associated with IBD, in 67 tissue samples: 28 inflamed mucosa samples (n = 16 UC, n = 12 CD), 28 adjacent normal colonic mucosa (n = 16 UC, n = 12 CD), and 11 normal mucosa from healthy patients using reverse transcription real-time RT-PCR. We found all analyzed miRNAs were significantly overexpressed in UC tissue as compared to adjacent normal tissue of patients with UC, as well as to normal mucosa from healthy controls. Four miRNAs (except miR-125b-1-3p) were significantly upregulated in CD lesions as compared to adjacent normal tissue of patients with CD, and four miRNAs, except miR-146a-3p, were significantly higher in CD samples compared to normal mucosa from healthy individuals. In the CD group, we found an inverse correlation between miR-155-5p or miR-146a-3p expressions and CDH1expression in inflamed mucosa. This type of correlation was also detected for miR-213p in adjacent normal tissue and CDH1 in inflamed mucosa, as well as between miR-155-5p and CDH1 in adjacent normal tissue. Elevated miRNA expression is characteristic for IBD-mediated inflammation process and inversely correlated with CDH1 gene expression, which suggest involvement of epithelial to mesenchymal transition (EMT) in IBD development.

Towards an evaluation of alcoholic liver cirrhosis and nonalcoholic fatty liver disease patients with hematological scales.

BACKGROUND: Seeking potentially novel blood markers of liver fibrosis and steatosis is constantly of crucial importance. Despite a growing number of studies in this field of hepatology, a certain role of hematological indices in the course of liver disorders has not been fully elucidated, yet. AIM: To evaluate a diagnostic accuracy of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and mean platelet volume-to-platelet-ratio (MPR) in the course of alcoholic liver cirrhosis (ALC) and nonalcoholic fatty liver disease (NAFLD). METHODS: One hundred forty-two patients with ALC, 92 with NAFLD and 68 persons in control group were enrolled in the study. Hematological indices (NLR, PLR and MPR), indirect and direct markers of liver fibrosis (aspartate transaminase to alkaline transaminase ratio, aspartate transaminase to platelet ratio index, fibrosis-4, gamma-glutamyl transpeptidase to platelet ratio, procollagen I carboxyterminal propeptide, procollagen III aminoterminal propeptide, transforming growth factor-α, platelet-derived growth factor AB, laminin) were measured in each person. Model for end-stage liver disease (MELD) score in ALC group and NAFLD fibrosis score together with BARD score were calculated in NAFLD patients. Receiver operating characteristic (ROC) curves and area under the curve (AUC) values were applied to assess the sensitivity and specificity of examined markers and to evaluate proposed cut-offs of measured indices in the course of ALC and NAFLD. RESULTS: MPR and NLR values in ALC patients were significantly higher in comparison to control group; PLR level was significantly lower. MPR and PLR correlated with assessed indirect and direct markers of liver fibrosis. MPR, NLR and PLR correlated with MELD score. NLR level in NAFLD patients was significantly higher in comparison to controls. MPR correlated with indirect markers of liver fibrosis and NAFLD fibrosis score. AUC values and proposed cut-offs for NLR, PLR and MPR in ALC patients were: 0.821 (> 2.227), 0.675 (< 70.445) and 0.929 (> 0.048), respectively. AUC values and proposed cut-offs for NLR, PLR and MPR in NAFLD group were: 0.725 (> 2.034), 0.528 (> 97.101) and 0.547 (> 0.038), respectively. CONCLUSION: Hematological markers are inseparably connected with serological indices of liver fibrosis in ALC and NAFLD patients. MPR and NLR turned out to be the most powerful parameters in ALC patients.

H3K18Ac as a Marker of Cancer Progression and Potential Target of Anti-Cancer Therapy.

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.

MMP-2 mRNA Expression in Ovarian Cancer Tissues Predicts Patients' Response to Platinum-Taxane Chemotherapy.

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.

Paraoxonase 1 Activity, Polymorphism and Atherosclerosis Risk Factors in Patients Undergoing Coronary Artery Surgery.

BACKGROUND: Paraoxonase1 (PON1), an enzyme connected to high density lipoproteins (HDL) particles, plays an important role in protecting arteries against atherosclerosis. The serum activity and concentration of PON1 depends on several genetic polymorphisms as well as environmental factors. MATERIALS AND METHODS: Investigated population consisted of 71 patients aged 43⁻76 years with confirmed coronary heart disease (CHD). Established risk factors of CHD such as hypertension, elevated total cholesterol and LDL cholesterol (LDL-C), low HDL cholesterol (HDL-C), diabetes mellitus, obesity, smoking and premature CHD in family history were assessed. PON1 genotype for ⁻108C/T promotor region was determined by polymerase chain reaction-restriction fragments length polymorphism (PCR⁻RFLP) method. Paraoxonase activity towards paraoxon and arylesterase activity towards phenyl acetate were measured spectrophotometrically. RESULTS: Significant correlations between diabetes mellitus and paraoxonase activity (R = ⁻0.264, p = 0.026) and between the premature coronary heart disease in family history and PON1 activity (R = ⁻0.293, p = 0.013) were found. In multivariate analysis, PON1 paraoxonase activity was independently of confounding factors associated with diabetes (OR = 0.985; p = 0.024) and premature CHD in family history (OR = 0.983; p = 0.027). PON1 activity towards aryl acetate positively correlated with HDL-C level (R = 0.255, p = 0.032). In patients treated with statins, PON1 paraoxonase activity was significantly (p = 0.033) higher than in patients without treatment. CONCLUSIONS: In diabetic patients with CHD, paraoxonase activity is lower than in normoglycemic patients despite similar lipid profiles. Diabetes and positive family history in patients with overt CHD are associated with the serum PON1 activity, which might be an additional factor helpful in evaluating cardiovascular risk in this group of patients.

Trends in cervical cancer incidence and mortality in Poland: is there an impact of the introduction of the organised screening?

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.

Dynamic changes of paraoxonase 1 activity towards paroxon and phenyl acetate during coronary artery surgery.

BACKGROUND: Serum paraoxonase 1 (PON1), an enzyme associated with high - density lipoproteins (HDL) particles, inhibits the oxidation of serum lipoproteins and cell membranes. PON1 activity is lower in patients with atherosclerosis and in inflammatory diseases. The systemic inflammatory response provoked during cardiopulmonary bypass grafting may contribute to the development of postoperative complications. The aim of the present study was to estimate the dynamic changes in paraoxonase 1 (PON1) activity towards paraoxon and phenyl acetate during and after coronary artery surgery. METHODS: Twenty six patients with coronary heart disease undergoing coronary artery bypass grafting (CABG) were enrolled into the study. Venous blood samples were obtained preoperatively, after aortic clumping, after the end of operation, at 6, 18, 30 and 48 h after operation. Paraoxonase activity was measured spectrophotometrically in 50 mM glycine/NaOH buffer (pH 10.5) containing 1.0 mM paraoxon, and 1.0 mM CaCl2. Arylesterase activity was measured in 20 mM TrisCl buffer (pH 8.0) containing 1 mM phenyl acetate and 1 mM CaCl2. RESULTS: PON1 activity toward paraoxon and phenyl acetate significantly decreased after aorta cross clumping and increased directly after operation. PON1 activity towards paraoxon in preoperative period and PON1 activity towards phenyl acetate in seventh stage of experiment tended to inversely correlate with the occurrence of postoperative complications. CONCLUSION: The paraoxonase 1 plasma activity is markedly reduced during CABG surgery.

Molecular bases of aberrant miR-182 expression in ovarian cancer.

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.

Reimbursed Costs of Management of Uterine Cervical Lesions in Poland--a Descriptive Analysis of Data from the National Health Fund and the Ministry of Health.

BACKGROUND: Despite implementation of organised screening programme in 2006/2007, cervical cancer (CC) incidence and mortality in Poland are still higher than the average in the European Union. CC and preceding cervical intraepithelial neoplasia (CIN) caused by human papillomaviruses (HPVs) can be prevented by vaccines which are reimbursed in around 20 European countries but not in Poland. CC and CIN can be also detected with the use of HPV tests which are not included in the Polish screening programme. Reimbursement for HPV vaccines and HPV testing requires cost-effectiveness analyses which include country-specific data on the burden and costs of management of cervical neoplasia. Therefore, we investigated the burden of cervical neoplasia and direct costs associated with its detection and management in Poland in 2012 reimbursed by the National Health Fund (NHF) - the only public healthcare insurance institution. We also report administrative costs of the organised screening programme covered by the Ministry of Health. METHODS: Data on the burden and reimbursed costs of organised and opportunistic screening as well as management of cervical neoplasia were drawn from the NHF databases. Numbers of women reported with CIN and CC were ascertained. RESULTS: In 2012, there were 765,266 and 1,288,358 reimbursed Pap smears collected within and outside the organised screening programme, respectively. Expenditures on medical and administrative procedures in organised screening reached PLN (Polish Zloty) 41,470,664 and 12,150,398 respectively. The number of women with particular diagnosis and reimbursement for the management of these lesions were as follows: glandular ectropion 208,033 and PLN 37,349,515; CIN1 10,521 and PLN 6,616,375; CIN2 5,812 and PLN 5,071,155; CIN3 6,487 and PLN 7,611,062; unspecified grade CIN 36,575 and PLN 12,352,034; and CC 33,482 and PLN 52,377,006, respectively. In women with ectropion and CIN the total number of local excision/ablative therapeutic procedures on the cervix reached 47,658 and the total number of hysterectomies was 1,321. CONCLUSION: In 2012, management of approximately 93 thousand women with HPV-related cervical lesions reimbursed in Poland amounted to PLN 84,027,632 which makes it a considerable public health problem. The number of women managed for glandular ectropion is considerable and related costs are high. Total reimbursement for detection, treatment and follow-up of all cervical lesions reaches at least PLN 137 million annually.

Cervical Cancer Histology, Staging and Survival before and after Implementation of Organised Cervical Screening Programme in Poland.

A population-based organised cervical cancer screening programme (OCCSP) was introduced in Poland in 2006. In this study we have aimed to analyse whether selected parameters related to invasive cervical cancer (ICC) of patients diagnosed in two distant gynaecological oncology centres changed after the first screening round of the programme run between 2006-2008. We have run a retrospective cross-sectional analysis of 189 women diagnosed with ICC between 2002-2005 (directly before introduction of the programme) and 165 patients diagnosed between 2009-2012 (just after the first screening round of the programme) and compared their age at diagnosis, histology, stage of tumours and overall survival (OS). Mean age of patients diagnosed in years 2002-2005 and 2009-2012 was 52.1 and 52.6 years respectively. Squamous cell carcinomas constituted 90.5% and 86.1% of tumours diagnosed in years 2002-2005 and 2009-2012 respectively and the rest of tumours had glandular and other histologies. 74.5% and 61.0% of women diagnosed in years 2002-2005 and 2009-2012 respectively had early ICC (FIGO-International Federation of Gynaecology and Obstetrics stages I-IIA) and the rest had advanced disease (FIGO IIB-IV). We have noticed no significant differences in mean age of patients, histology of tumours and OS of patients with ICC diagnosed before and after the first screening round of OCSSP in Poland. Advanced stages of ICC were more commonly diagnosed after the introduction of OCSSP. Changes only in some clinical parameters of patients with ICC were noticed before and after the first screening round of OCSSP in Poland but OS of patients remained the same.