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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.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).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).RDW, RPR and RLR values turned out to be significantly higher in ALC and MAFLD groups compared to controls (ALC: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.

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=0,839forcutoff<0.17%); in NAFLD group, it was MPV (AUC=0,808forcutoff<7.9 fl). PCT in ALC and MPV in NAFLD can be perceived as potential diagnostic markers.

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.

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.

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.

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.

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.

Various laboratory parameters are commonly used to assess the efficacy of biological treatment (BT). The aim of our study was to assess the correlation between platelet (PLT) indices: (mean platelet volume (MPV), plateletcrit (PCT), platelet distribution width (PDW)), C-reactive protein (CRP) and endoscopic picture in the course of infliximab induction regimen in ulcerative colitis (UC) patients. The study enrolled 46 patients with UC – 32 men and 16 women. They were administered infliximab (standard induction therapy). Laboratory tests (CRP and PLT indices) and colonoscopy were performed in all patients during the induction regimen – at 0, 2, and 6 weeks and in follow-up six weeks after the completion of induction therapy. The study revealed a statistically significant decrease in CRP and PLT, and an increase in MPV, together with improvement of endoscopic picture (p

Introduction. Efficacy of biological treatment (BT) is a key issue among inflammatory bowel disease (IBD) patients. Laboratory markers and endoscopic procedures are basic diagnostic tools in the assessment of response to biological agents in the course of Crohn’s disease (CD) and ulcerative colitis (UC). Aim. The aim of our investigation was to assess the correlation between laboratory parameters and endoscopic picture in the course of BT in patients with IBD – CD and UC–treated with biological agents. Material and methods. The total number of 71 patients were enrolled in the study, 25 with CD and 46 with UC. When it comes to 15 patients with CD, they were treated with infliximab (IFX) and 10 patients with adalimumab (ADA) – one year of therapy. Patients with UC were administered IFX – induction therapy. Laboratory tests (C-reactive protein (CRP) and platelet (PLT) count) and colonoscopy were performed in all patients before and during BT. Results. BT improved endoscopic picture (SES-CD, MAYO) in all patients. BT lowered CRP (p Discussion. BT revolutionized a natural history of IBD and its efficacy was approved worldwide. Nevertheless, biological agents do not lead to a full remission of the disease in all patients. Because of this reason, laboratory parameters and endoscopic picture must be carefully monitored during BT to achieve the best outcome in IBD patients. Conclusion. Full clinical and endoscopic remission of IBD was not achieved, although BT lowered CRP level, PLT count and improved endoscopic picture of patients enrolled into our study.

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

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.HER1 and EGFRvIII variants in meningiomas and glioblastomas were evaluated at the RNA level.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.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.

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.

Artykuł opisuje pięć etymologii nienaukowych toponimu Oliwa. Mają one następujące wykładnie onomastyczne: 1) ‘miejsce, w którym księciu pomorskiemu Subisławowi lub Samborowi przyśnili się Matka Boska z Dzieciątkiem w koronie drzewa oliwkowego lub anioł z gałązką oliwną albo cysters z gałązką oliwną ułożoną na krzyż, i na pamiątkę tego snu wzniesiono tu klasztor’, 2) ‘miejscowość z klasztorem, którego patronką jest Święta Oliwa’, 3) ‘miejsce, w którym naród wybrany wędrujący przez Kaszuby stanowiące ziemię obiecaną miał jeszcze oliwę’, 4) ‘miejsce zawarcia pokoju oliwskiego’, 5) ‘miejsce, w którym jest katedra wyglądająca jak ulana’. Pełnią one funkcję objaśniającą i prestiżotwórczą.

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.

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

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.

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

[b]Introduction and objectives. [/b]The vertical orientation of the body in the upright standing position is maintained by keeping the body’s centre of gravity (COG) upright, above the base of support, by a dynamic interplay of visual, vestibular, and somatosensory control systems. The objectives of this study were: to compare the postural control strategy between people with and without low back pain (LBP), to estimate the influence of the stretching therapy on the postural control strategy, and to discover the relationship between the restriction of spine mobility and occurrence of some ergonomic factors. [b]Materials and methods.[/b] The study consisted of 32 patients with LBP and 25 healthy controls. Postural characteristics of the subjects were measured with the use of a computerized force platform. The software programme filters and measures COG sway velocity in different conditions. Additional measurements and tests were conducted in patients after stretching therapy. Based on survey research, all individuals were selected and evaluated from the aspect of ergonomics. [b]Results[/b]. The results of the COG sway velocity vary under the testing conditions. From the aspect of ergonomic attitude and influence of the rehabilitation, results varied in the groups. [b]Conclusions[/b]. Ergonomic factors are often accompanied by the appearance of LBP. The restrictions within the musculoskeletal system cause disorders in muscle synergies, which is expressed by an increase in the angular velocity of the COG. In patients with chronic back pain syndrome, selected stretching therapy techniques improves the range of motion of the spine and reduces pain.

Uterine leiomyosarcomas (LMS) are rare tumors typically presenting rapid growth and unfavorable outcome. Nowadays the results of uterine LMS treatment do not meet expectations. Angiogenesis is one of processes investigated to be target for future treatment. The aim of the research was to assess microvessels density (MVD) in tumor samples collected from 50 patients with histological confirmed uterine leiomyosarcoma and to investigate statistical relations between MVD, patients survival, and FIGO stage of tumor. The assessment was carried out using immunohistochemistry methods with anti-CD34 antibody. No significant difference in MVD between FIGO stages was observed. Furthermore, contrary to many other malignancies, we found no significant relation between MVD and patients overall and 2-year survival. Results obtained in the study suggest that processes on vascular mimicry and mesenchymal to epithelial transition (MET) may play important role in development of LMS. No statistical relation between MVD and survival leads to conclusion that not only angiogenesis but other mechanisms as well should be taken into consideration in planning future research.

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: 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&ndash, 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 &ndash, 108C/T promotor region was determined by polymerase chain reaction-restriction fragments length polymorphism (PCR&ndash, 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 = &ndash, 0.264, p = 0.026) and between the premature coronary heart disease in family history and PON1 activity (R = &ndash, 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.

Carcinosarcomas (CSs) are composed of two separate histological components and are rare neoplasms of the female genital tract. Therefore, CS pathogenesis has not yet been fully elucidated. In the present study, immunohistochemical techniques were used to determine the role of p53 and Ki-67 overexpression in female genital tract CSs. The study group was comprised of 36 patients with CSs originating from the uterus (n=31), cervix (n=3) and ovary (n=2), as well as 3 metastatic tissues. p53 was overexpressed in the epithelial component of 23 out of 36 (64%) tumors, and in the mesenchymal component of 20 out of 36 (56%) tumors. In both CS components, there was a significant correlation between p53 overexpression and patient age and ovarian metastases. Ki-67 overexpression was detected in the epithelial component in 15 out of 36 (42%) cases, and in the mesenchymal component in 13 out of 36 (36%) neoplasms. There was a significant correlation of p53 overexpression between the carcinomatous and sarcomatous components (R=0.884, P

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.

Objectives:Alterations of p53 pathway (p14ARF/MDM2/p53) play a crucial role in the development and progression of various human neoplasms, including endometrial carcinoma (EC). The aim of the current research was to examine the p14ARF expression pattern in primary ECs and corresponding metastatic lesions.Materials and Methods:We studied 47 primary ECs and corresponding metastatic lesions applying immunohistochemistry and investigated the relationship between p14ARF overexpression and clinicopathological variables of carcinoma as well as TP53 alterations.Results:Protein expression was predominantly nuclear, present in 32 (68%) of 47 primary cases and in 28 (60%) of 47 metastatic lesions. There were seven p14ARF-positive primary tumors showing negative reactivity in the metastatic lesions. On the other hand, 3 cases lacked protein immunoreactivity in the primary ECs but revealed weak nuclear staining in the corresponding metastases. A case of primary cervical adenocarcinoma metastasizing to the lymph nodes showed p14ARF expression both in the primary tumor and the corresponding metastases. A trend was found between the p14ARF expression in primary tumors and the presence of the neoplasms in the fallopian tube (P = 0.063), but none of the other clinicopathological variables of carcinoma was related to protein immunoreactivity in advanced-stage uterine neoplasms. The p14ARF expression in EC metastases was related to the presence of the primary tumor in the fallopian tube (P = 0.036). The p14ARF expression was not associated with unfavorable outcome both in the primary tumors (P = 0.302) and in the corresponding metastases (P = 0.217). There was also no relationship between the p14ARF expression pattern and TP53 pathway alterations.Conclusions:Altogether, the p14ARF protein is expressed in more than half of the primary ECs and metastatic lesions analyzed and is associated with the transtubal dissemination of the primary tumor. The pattern of the p14ARF expression is not associated with the alterations of other TP53 pathway members in advanced-stage human ECs.

Loss of heterozygosity (LOH) is implicated in the initiation and progression of various human neoplasia, and is observed in both early or in advanced-stage human cancers. The current study was aimed at investigating the frequency of LOH TP53 in human endometrial carcinoma (EC) metastases. LOH was analyzed using 3 intragenic polymorphisms in 38 primary ECs and corresponding metastatic lesions. Allelic loss at intron 1 was detected in 14 out of 38 (37%) primary carcinomas and in 11 out of 38 (29%) metastatic lesions. LOH at intron 1 in primary and metastatic tumors was concomitantly noted in 8 out of 38 (21%) cases. LOH at intron 4 was seen in 46% (17 out of 37) primary ECs and in 35% (13 out of 37) metastatic lesions. LOH at intron 4 in primary tumor/metastasis was concomitantly demonstrated in 27% (10 out of 33) cases. Allelic loss at exon 4 was detected in 5 out of 33 (15%) primary ECs and in one out of 33 (3%) corresponding metastases. Coexistence of LOH TP53 in primary ECs with metastases at intron 1 and intron 4 was observed in three out of 33 (9%) cases. Correlation between allelic loss at intron 1 in primary ECs and corresponding metastases was found (R = 0.475, p = 0.003). Moreover, there was correlation between LOH at intron 1 in metastastic ECs and allelic imbalance at intron 4 in primary uterine tumors (R = 0.416, p = 0.01). There was a relationship between LOH at intron 4 in primary ECs and corresponding metastatic lesions (R = 0.457, p = 0.004). LOH TP53 at intron 4 correlated with the presence of the neoplasm in the uterine cervix (R = 0.319, p = 0.049), and with the non-endometrioid type of primary tumor (R = 0.371, p = 0.024). There was a significant correlation between exon 4 LOH and patient age (less or equal to 50 years and above this age; R = -0.375, p = 0.032). p53 overexpression was present in thirteen out of 38 (34%) cases, both in primary ECs and in metastatic lesions. Overexpression of p53 was higher in non-endometrioid ECs (three out of 5; 60%) than in endometrioid-type uterine tumors (ten out of 33; 30.3%; p = 0.315). p53 overexpression correlated with the presence of cancer in the lumen of fallopian tube(s) (R = 0.032, p = 0.046), and with allelic loss at intron 1 in primary ECs (R = 0.599, p = 0.0001). In conclusion, LOH occurs not only in primary uterine tumors but also in corresponding metastases, with the higher incidence being reported at intron 4 of the TP53. A significant link existed between LOH TP53 at intron 1 and p53 overexpression in primary ECs, but not in the corresponding metastatic lesions.

Background Well-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. Methods Available 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. Results The 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. Conclusions The 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 material The online version of this article (doi:10.1186/s12885-015-1242-9) contains supplementary material, which is available to authorized users.

Cyclin A is a cell-cycle regulatory gene and its overexpression promotes tumor cell growth. Y-Box-binding protein 1 (YB1) is a transcription/translation factor involved in tumor growth, invasion, and drug resistance. We investigated whether an association exists between protein products of these genes in epithelial ovarian cancer (EOC) specimens and clinicopathological parameters, patient response and EOC sensitivity to platinum-based first-line chemotherapy.Cyclin A and YB1 expression were analyzed by immunohistochemistry in 54 human primary EOC tissues. Immunolabeling of both proteins was graded according to their staining intensity (scale 0-3) and the proportion of immunostained cancer cells (scale 0-4) to obtain a staining index (SI; value=0-12).Significantly higher cyclin A immunostaining (SI≥4) in EOC specimens was discovered in patients with advanced (International Federation of Gynaecology and Obstetrics (FIGO) III and IV, p=0.003), poorly differentiated (G3, p0.001) tumors, and tumors of those with residual disease1 cm (p=0.001). YB1 immunostaining was significantly higher in EOCs from patients with suboptimal debulking (p=0.025). Over-expression of cyclin A (SI≥9) in EOCs was significantly linked with poorer patient response (p=0.001) and higher resistance of tumors to platinum-based first-line chemotherapy (p=0.007), while immunolabeling of YB1 in EOCs was not significantly associated with either of these variables (p0.05). Cyclin A expression was significantly and positively correlated with that of YB1 (R=0.588, p0.001).Increased cyclin A expression in EOC is related to a more aggressive tumor behavior and predicts the response of patients to first-line platinum-based chemotherapy.

We examined loss of heterozygosity (LOH) at the TP53 gene in primary human endometrial carcinomas (EC), and investigated the relationship between allelic loss, p53 protein overexpression, pRb-1 pathway alterations and MIB-1 proliferative activity. Applying the non-isotopic PCR-RFLP/VNTR-silver staining techniques, we investigated TP53 LOH in 46 tumors at four polymorphic loci. Out of 42 informative carcinomas, LOH was found in 19% of the cases studied. In general, there was no significant relationship between LOH and the clinical and pathological variables of cancer, including patient age, clinical stage, histological grade or depth of myometrial invasion. Interestingly, none of 7 tumors associated with hyperplasia revealed allelic imbalance, whereas 8 of 27 (30%) tumors without hyperplasia exhibited LOH (p = 0.312; Fisher’s exact test). Overexpression of nuclear p53 was not correlated with allelic loss at TP53 (p = 0.336, Fisher’s exact test). It is worth pointing out that p53 immunoreactivity was significantly related to proliferative activity of cancer (R = 0.42, p = 0.0037; Spearman’s rank correlation test). A tendency towards a poorer outcome was reported in EC patients displaying TP53 LOH during short-time follow-up (p = 0.093; log-rank test). None of the tumors simultaneously showed LOH at TP53 and RB1 genes(R = –0.211, p = 0.16; Spearman’s rank correlation test). p16INK4A alterations (LOH and gene deletion) occurred concomitantly, with 3 tumors showing the TP53 allelic loss, whereas the cyclin D1/cdk4 complex was overexpressed in a case with TP53 LOH. Altogether, losses at TP53 were not associated with p53 nuclear overexpression, but may affect a subset of EC patients characterized by an unfavorable prognosis at short-time follow-up. Allelic loss at TP53 seems to arise independently of LOH at the RB1 gene in carcinomas of the uterine corpus in humans. Disruptions at p16INK4A and/or cdk4/cyclin D1 concomitantly occurring with TP53 LOH may participate in the development of a subset of endometrioid-type ECs.

The aim of this paper is to describe the prospective 10-year follow-up study of prognostic value of p53 protein accumulation in cancer cells in relation to the localisation of tumour in colorectum. Methods : The p53 protein accumulation has been assessed immunohistochemically in tumour tissue samples obtained from 80 selected sporadic colorectal cancer patients. Results : p53 protein accumulation was detected more often in rectum than in colon tumours. Lower survival rates were observed in patients with p53 protein accumulation in cancer cells independent of primary tumour site. Significantly lower cumulative survival rate was detected in the group of patients with left-sided colon cancer. The p53 protein accumulation was an independent prognostic factor in the left-sided colon tumours. Conclusions : The right-sided colon tumours may be developed in p53-independent manner and p53 protein accumulation in cancer cells has prognostic value only in the left-sided colorectal tumours.

Ovarian cancer is the second most common gynecological malignancy after cancer of the uterine corpus, and the fifth leading cause of cancer-related death among women. It has been discovered that cyclin I (CCNI) protein expression correlates with the proliferation of cancer cells and expression of angiogenesis-related proteins, such as vascular endothelial growth factor (VEGF) and VEGF receptor 2/kinase insert domain receptor (VEGFR2/KDR). We examined whether any association exists between mRNA expression of CCNI and KDR genes in epithelial ovarian cancer (EOC) tissues, clinicopathological parameters and patients' response to chemotherapy.Expression of CCNI and KDR genes was analyzed by quantitative real-time reverse transcription PCR in 40 human primary EOC tissues and four human ovarian cancer cell lines (TOV-112D, OV-90, OVCAR-3 and Caov-3).CCNI and KDR mRNA expression was detected in all EOC tissues and ovarian cancer cell lines. The mRNA levels of both genes were significantly higher in EOC than in ovarian cancer cell lines (p0.001). Neither CCNI nor KDR mRNA expression in EOC tissues was significantly associated with variables such as age, menopausal status, International Federation of Gynecology and Obstetrics (FIGO) stage, residual disease, patients' response to chemotherapy, tumor histology, grade or sensitivity to chemotherapy. However, we demonstrated a significant positive correlation between the mRNA expression of KDR and CCNI in EOC tissues (R=0.530, p0.001).Neither CCNI nor KDR mRNA expression predicts response of patients with EOC to platinum-based first-line chemotherapy. Cyclin I may be involved in angiogenesis in EOC, which needs further investigation.

Udostępnienie publikacji Wydawnictwa Uniwersytetu Łódzkiego finansowane w ramach projektu „Doskonałość naukowa kluczem do doskonałości kształcenia”. Projekt realizowany jest ze środków Europejskiego Funduszu Społecznego w ramach Programu Operacyjnego Wiedza Edukacja Rozwój; nr umowy: POWER.03.05.00-00-Z092/17-00.

To assess the clinico-prognostic relevance of the cell surface carbohydrate glycoprotein in normal and pathological conditions of human endometrium, Sialosyl-Tn (STn) antigen was immunohistochemically studied in normal (n = 10), hyperplastic (n = 18), and neoplastic (n = 60) endometrial lesions. There was no STn antigen reactivity in the proliferative endometrial slides, while weak staining was observed in all secretory endometria. STn expression was noted in 8/18 (44%) hyperplastic endometrial cases and in 40/60 (67%) endometrial carcinomas. Positive staining was observed throughout the cytoplasm of the glandular cancer cells, at the cell membranes, and in an intraluminar mucus. This antigen was mostly expressed heterogeneously as far as the distribution of positive cells is concerned. There was a statistically significant association between STn expression and the histological grading of cancer (p = 0.019). Advanced clinical stage (III-IV; p = 0.014) and infiltration of the myometrial wall (more than 1/2 of the myometrial wall; p = 0.004), but no STn immunoreactivity, were reported to be independent prognostic variables during follow-up. Our study shows that a) STn is not constantly expressed during the menstrual cycle, and is increased at the secretory phase of the cycle; b) Sialosyl-Tn reactivity decreases with the degree of tumor differentiation, but there was no relationship with other clinicopathological variables of cancer; c) this cell surface carbohydrate glycoprotein does not appear to predict the outcome of endometrial cancer patients.

The size, number, and enlargement of gaps as well as the process of gap formation were analyzed in a subalpine spruce forest in the Babia Gora massif, one of the highest in the western Carpathian Mountains. Openings in the forest canopy of up to one hundred square meters are typical structural elements of subalpine spruce forests. Gaps comprised 34% of the studied forest area of 14.4 ha. There were 38 gaps per ha, most of them

The aim of the work was to assess relationship between gene polymorphism of enzymes influencing dopaminergic-, serotoninergic, and noradrenergic transfer and cognitive functioning of paranoid schizophrenic inpatients (ICD-10).The following methods have been used in the study: The Test of Everyday Attention (TEA) and The Visual Object and Space Perception Battery (VOSP), psychiatric scales (SAPS, SANS, BDI) and techniques of genetic engineering (PCR reaction, RFLP and VNTR techniques). Subject groups included 100 schizophrenic patients (57 male) and 50 healthy controls (20 male).The results revealed positive correlation between polymorphism of Vall 58MetCOMT and cognitive deficits in schizophrenic patients. No statistically significant relationship was elicited between gene polymorphism of Val158Met COMT and VNTR MAO-A in promoter area and schizophrenia onset. Allelic polymorphism ofVall58Met OMT and VNTR MAO-A in promoter area did not differ between the subject groups. The patients with genotype Val/ Val of polymorphism Val 158MetCOMT showed major cognitive deficits.

Podoplanin is a transmembrane glycoprotein expressed in endothelial lymphatic cells. It was proven to be a predictive marker in a variety of cancers e.g. mesothelioma and head and neck squamous-cell carcinoma. Ovarian clear cell carcinoma (OCCC) is a rare and unique histopathologic subtype of epithelial ovarian cancer (EOC). The molecular basis of that phenomenon remains unknown.The aim of our study was to assess podoplanin expression on the protein level in OCCC.Immunohistochemistry was performed on paraffin-embedded tissues from 19 patients with diagnosed OCCC.Podoplanin expression was present (moderate or strong) in 52% of OCCC cases (10/19). Nine of eleven (81.2%) postmenopausal and one of eight (12.5%) premenopausal women were podoplanin positive. No differences in podoplanin expression were found in relation to clinical features of the tumorThe incidence of podoplanin expression is higher in ovarian clear cell adenocarcinoma in postmenopausal patients.

Alterations of p53 pathway (p14(ARF)/MDM2/p53) play a crucial role in the development and progression of various human neoplasms, including endometrial carcinoma (EC). The aim of the current research was to examine the p14(ARF) expression pattern in primary ECs and corresponding metastatic lesions.We studied 47 primary ECs and corresponding metastatic lesions applying immunohistochemistry and investigated the relationship between p14(ARF) overexpression and clinicopathological variables of carcinoma as well as TP53 alterations.Protein expression was predominantly nuclear, present in 32 (68%) of 47 primary cases and in 28 (60%) of 47 metastatic lesions. There were seven p14(ARF)-positive primary tumors showing negative reactivity in the metastatic lesions. On the other hand, 3 cases lacked protein immunoreactivity in the primary ECs but revealed weak nuclear staining in the corresponding metastases. A case of primary cervical adenocarcinoma metastasizing to the lymph nodes showed p14(ARF) expression both in the primary tumor and the corresponding metastases. A trend was found between the p14(ARF) expression in primary tumors and the presence of the neoplasms in the fallopian tube (P = 0.063), but none of the other clinicopathological variables of carcinoma was related to protein immunoreactivity in advanced-stage uterine neoplasms. The p14(ARF) expression in EC metastases was related to the presence of the primary tumor in the fallopian tube (P = 0.036). The p14(ARF) expression was not associated with unfavorable outcome both in the primary tumors (P = 0.302) and in the corresponding metastases (P = 0.217). There was also no relationship between the p14(ARF) expression pattern and TP53 pathway alterations.Altogether, the p14(ARF) protein is expressed in more than half of the primary ECs and metastatic lesions analyzed and is associated with the transtubal dissemination of the primary tumor. The pattern of the p14(ARF) expression is not associated with the alterations of other TP53 pathway members in advanced-stage human ECs.

mtDNA4977, the most common deletion of the mitochondrial DNA, has been detected in different types of human neoplasia. The aim of the current study was to determine the prevalence of mtDNA4977 deletion in primary human endometrial carcinomas (EC) as compared with matched control samples. Thirty-seven matched control tissues and EC samples were enrolled, and the 4977-bp mtDNA deletion was investigated using a PCR-based technique. Deletion of mtDNA4977 was detected in 32 out of 37 (84%) matched control samples and in 30 out of 37 (81%) ECs. A statistically significant correlation of mtDNA4977/wild-type mtDNA ratios was noted between normal and cancerous human endometrial tissues (R=0.844, p