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Objective The LRG, HMGB1, MMP3 and ANXA1 proteins have been implicated in different inflammatory pathways in ulcerative colitis (UC), but their role as specific biomarkers of both endoscopic and histological activity has yet to be elucidated. In the present study, we aimed to evaluate the LRG1, HMGB1, MMP3 and ANXA1 as potential serum biomarkers for UC endoscopic and histological activity. Methods This cross-sectional study included UC patients under 5-ASA, and healthy controls (HC) undergoing colonoscopy. Blood and biopsy samples were obtained and endoscopic Mayo sub-score (Ms) was recorded for the UC patients. Intramucosal calprotectin as a marker of histologic activity was evaluated in all biopsy samples and serum LRG1, HMGB1, MMP3 and ANXA1 levels were measured in the blood samples. Results The HCs ANXA1 level was lower compared to that of the UC group [P = 0.00, area under the curve (AUC) = 0.881] and so was the HCs MMP3 level compared to that of patients (P = 0.00, AUC = 0.835). The HCs ANXA1 levels were also lower compared to these of the independent Ms groups, even to the Ms = 0 (P = 0.00, AUC = 0.913). UC endoscopic activity was associated with MMP3 levels (r = 0.54, P = 0.000) but not with ANXA1, LRG1 and HMGB1 levels CONCLUSION: Serum ANXA1 is a potential diagnostic biomarker of UC and serum MMP3 is a potential biomarker of UC endoscopic and histological activity.

ObjectiveTo assess CYP2D6 genotype prevalence in chronic pain patients treated with tramadol or codeine.DesignProspective cohort study.SettingGeneral hospital, pain management unit.SubjectsPatients with chronic pain, treated with codeine or tramadol.MethodsPatients’ pain was assessed at baseline (numeric rating scale [NRS]; 0–10). Prescription of codeine or tramadol was selected randomly. The assessment of patients’ response to the drug in terms of pain relief and adverse effects was performed after 24 hours. Reduction of pain intensity of >50% or an NRS ResultsSeventy-six consecutive patients were studied (20 males, 56 females), aged 21–85 years. Thirty-four received tramadol and 42 codeine. The main genotypes of CYP2D6 identified were the wt/wt (35.5%), the *4/wt (17.1%), and the *6/wt (10.5%). Adverse effects were common, especially in carriers of *9/*9, *5/*5, *5/*4, and *10/*10, as well as in variants including the 4 allele (*4/*1 [38.4%] and *4/*4 [42.8%]).ConclusionsGenotyping can facilitate personalized pain management with opioids, as specific alleles are related to decreased efficacy and adverse effects.

Background Canine inflammatory bowel disease (IBD) is a group of chronic gastrointestinal (GI) disorders of still largely unknown etiology. Canine IBD diagnosis is time-consuming and costly as other diseases with similar signs should be initially excluded. In human IBD microRNA (miR) expression changes have been reported in GI mucosa and blood. Thus, there is a possibility that miRs may provide insight into disease pathogenesis, diagnosis and even treatment of canine IBD. The aim of this study was to determine the colonic mucosal and serum relative expression of a miRs panel in dogs with large intestinal IBD and healthy control dogs. Results Compared to healthy control dogs, dogs with large intestinal IBD showed significantly increased relative expression of miR-16, miR-21, miR-122 and miR-147 in the colonic mucosa and serum, while the relative expression of miR-185, miR-192 and miR-223 was significantly decreased. Relative expression of miR-146a was significantly increased only in the serum of dogs with large intestinal IBD. Furthermore, serum miR-192 and miR-223 relative expression correlated to disease activity and endoscopic score, respectively. Conclusion Our data suggest the existence of dysregulated miRs expression patterns in canine IBD and support the potential future use of serum miRs as useful noninvasive biomarkers.

Background-aim Intravenously administered biologicals are associated with a huge pressure to Infusion Units and increased cost. We aimed to assess the impact of switching infliximab to golimumab in ulcerative colitis (UC) patients in deep remission. Patients and method: In a prospective, single-centre pilot study UC patients on infliximab mono-therapy for = 2 years, whowere in deep remission, consented to switch to golimumab and were followed for 1 year with clinical assessment, serum and faecal biomarkers, work productivity, satisfaction with treatment and quality of life parameters. Endoscopic remission was assessed by colonoscopy at 1 year. Patients fulfilling the same inclusion criteria, who did not consent to switch to golimumab and continued to receive infliximab mono-therapy, for the same period, served as controls. Patients and methods In a prospective, single-centre pilot study UC patients on infliximab mono-therapy for ≥ 2 years, who were in deep remission, consented to switch to golimumab and were followed for 1 year with clinical assessment, serum and faecal biomarkers, work productivity, satisfaction with treatment and quality of life parameters. Endoscopic remission was assessed by colonoscopy at 1 year. Patients fulfilling the same inclusion criteria, who did not consent to switch to golimumab and continued to receive infliximab mono-therapy, for the same period, served as controls. Results Between October 2015 and October 2017, 20 patients were recruited; however one patient stopped therapy because of pregnancy. All 19 patients who were switched to golimumab were still in clinical, biomarker and endoscopic remission at 1 year and maintained excellent quality of life without any complications. In the control group, 18 of 19 patients were also in deep remission, since only one patient had a flare which was managed with IFX dose intensification. During a median 3 years extension treatment with golimumab only 2 patients experienced a flare of colitis. Conclusions This pilot study indicates that switching from in-fliximab to golimumab in UC patients in deep remission does not compromise treatment effectiveness or the course of disease; golimumab offers a valid alternative to intravenous infliximab infusions during the COVID-19 pandemic.

Background: MicroRNAs have been linked to angiogenesis and could prove to be valuable future therapeutic targets in ischemic cardiovascular diseases.Methods: Ten-week-old male C57Bl/6 mice were subjected to left femoral artery ligation and were treated with microRNA-126 mimic at a dose of 5 mg/kg (Group A, n = 10) or 5 mg/kg microRNA mimic negative control (Group B, n = 10) on days 1, 3, and 7. Laser Doppler imaging was performed to verify successful ligation on day 0 and to evaluate differences in the ischemic-to-normal (I/N) hind limb perfusion ratio on day 28. Muscle tissue expression of microRNA-126 and vascular endothelial growth factor (VEGF) was determined via PCR.Results: Following microRNA-126 mimic administration in Group A subjects, we noted a stepwise increase in I/N hind limb perfusion ratio (Day 0: 0.364 ± 0.032 vs. Day 8: 0.788 ± 0.049 vs. Day 28: 0.750 ± 0.039, p = 0.001). In Group B a stepwise increase in I/N hind limb perfusion ratio was observed (Day 0: 0.272 ± 0.057 vs. Day 8: 0.382 ± 0.020 vs. Day 28: 0.542 ± 0.028, p = 0.074). Muscle tissue expression of microRNA-126 in the ischemic hind limb of Group A was 350-fold lower compared to the ischemic hind limb of Group B (p < 0.001). A higher expression (14.2-fold) of VEGF in the ischemic hind limb of microRNA-126-treated mice compared to that of control group was detected (p < 0.001). A statistically significant negative correlation was noted between microRNA-126 and VEGF tissue expression levels in the ischemic limbs of the entire study population.Conclusion: MicroRNA-126 delivery in the ischemic hind limb of mice improved vascular perfusion with VEGF upregulation.

Colorectal cancer is the fourth cause of cancer-related death. Drug toxicity and resistance remain concerns of major importance. miR-100 and miR-218 are micro-RNAs that regulate cellular proliferation, differentiation and apoptosis acting as oncogenes and tumour suppressors; their functions and have been linked with toxicity development and drug resistance. We investigated the correlation between rs11134527 miR-218 and rs1834306 miR-100 polymorphisms and irinotecan-based regimens with regard to drug efficacy and toxicity. A total of 105 mCRC patients receiving irinotecan-based regimens were included in our study and assessed in terms of toxicity development and response to treatment. Rs11134527 miR-218 and rs1834306 miR-100 polymorphism genotyping in the peripheral blood was performed with PCR-RFLP. Neither rs11134527 miR-218 nor rs1834306 miR-100 are associated with toxicity risk to treatment regimens. GA/AA genotypes of rs11134527 and CT/TT genotypes of rs1834306 were associated with a significantly reduced time-to-progression (TTP) and overall survival (OS). GA/AA genotypes of rs11134527 miR-218 and CT/TT genotypes of rs1834306 miR-100 polymorphisms could serve as prognostic biomarkers of TTP and OS. Carriers of the A allele of the miR-218 rs11134527 and T allele of the miR-100 rs1834306 polymorphisms are more likely not to respond to irinotecan-based therapies. However, further studies in larger patient populations are required.

Background Colorectal cancer is the fourth cause of cancer related death. Drug resistance and toxicity remain major clinical issues. HOTAIR and MALAT1 are long non-coding RNAS that affect cellular proliferation, apoptosis and drug resistance; their up-regulation has been linked with a poor prognosis. Objective Investigation of the association between rs4759314 HOTAIR and rs3200401 MALAT1 polymorphisms and irinotecan-based chemotherapy in terms of drug efficacy and toxicity. Methods Samples from 98 patients receiving different regimens of irinotecan-based therapy were included. Efficacy and toxicity were evaluated. KRAS mutation, rs3200401 HOTAIR and rs4759314 MALAT1 polymorphisms genotyping in the tumors and peripheral blood respectively were performed with PCR. Results Neither rs3200401 MALAT1 nor rs4759314 HOTAIR polymorphism are associated with response to treatment regimens. Rs4759314 was also not associated with increased toxicity in patients receiving irinotecan-based regimens. CT genotype of rs3200401 was associated with significantly reduced overall survival. An association between KRAS mutation and AG/GG genotypes in the rs4759314 was detected. Conclusions CT genotype of rs3200401 MALAT1 polymorphism could serve as a toxicity biomarker. Carriers of the G allele of the rs4759314 HOTAIR are more likely to be carriers of KRAS mutations too. However, further studies in larger patient populations are required.

OBJECTIVES The aim of this was the assessment of the prognostic role of the rs4938723 C > T polymorphism of the miR-34 in triple negative breast cancer patients. METHODS Therefore formalin fixed paraffin embedded tissue samples from 114 triple negative breast cancer patients and blood samples from 124 healthy donors were genotyped and subsequently extensive statistical analysis was performed in order to investigate the clinical value of this polymorphism in triple negative breast cancer. RESULTS Our statistical analysis disclosed that the majority of patients harboring ductal breast carcinoma (69.4%) have the TC or CC genotypes (P = .020). Moreover the survival of the patients was significantly correlated with the occurrence of the TC or CC alleles (P

To investigate possible associations of single-nucleotide polymorphisms (SNPs) from five genes with branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). A total of 69 patients with retinal vein occlusion-RVO (24 with BRVO and 45 with CRVO), and 82 controls, were enrolled in this study. All subjects were screened for hypertension, diabetes mellitus, hyperlipidemia, glaucoma, anticoagulant medication, smoking status and history of stroke. The genotyping of AGTR1-A1166C, adiponectin + 276 G/T, MMP2-1306C/T, Gpla/lla-C807T/G873A and VKORC1-G1639A polymorphisms was performed using restriction fragment length polymorphism or allele-specific polymerase chain reaction. The percentage of the AGTR1-A1166C C allele carriers and Gpla/lla-C807T/G873A T/A carriers was significantly higher in the CRVO patients than in the controls (P = 0.00001 and P = 0.0004, respectively). At the multiple logistic regression analysis, the AGTR1-A1166C C allele carrier status and the Gpla/lla-C807T/G873A T/A allele carrier status were found to be associated with an increased risk of CRVO. Moreover, adiponectin + 276 G/T T allele carriers had a significantly increased risk of RVO in subjects ≥ 75 years old. There was no significant difference between the BRVO patients and controls concerning the genotype or the allele frequency distributions of these SNPs. The genotype distributions or allelic frequencies of the other evaluated polymorphisms did not significantly differ between the patients with RVO and the control subjects. AGTR1 A1166C and Gpla/lla C807T/G873A polymorphisms are likely to be risk factors for CRVO. Adiponectin + 276 G/T SNP is likely to predispose to RVO in older subjects.

Aim: The purpose of this study is to evaluate the role of MET T1010I and MET rs40239 as potential risk factor and/or prognostic markers in patients with triple-negative breast cancer (TNBC). Methods: 114 samples of DNA from paraffin-embedded breast normal tissues of patients with TNBC and 124 samples of healthy controls were collected and analyzed for MET T1010I and MET rs40239 polymorphisms. Results: MET T1010I CT genotype was associated with increased risk of TNBC in both univariate and multivariate analysis. The status of rs40239 was not associated with a higher risk for TNBC at either the univariate or the multivariate analysis. None of the examined polymorphisms was associated with overall survival at the univariate or multivariate Cox regression analysis (adjusted HR=1.35, 95% CI: 0.31–5.97 for MET T1010I CT/TT vs CC; adjusted HR=1.78, 95% CI: 0.73–4.35 for rs40239 AG/GG vs AA). Conclusion: Our case–control study suggests that MET T1010I seems to be a risk factor for TNBC in the Caucasian Greek population, in contrast with MET rs40239, where no correlation was found.

Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values

BACKGROUND Infliximab trough levels (IFX-TLs) and antibodies to infliximab (ATIs) have been suggested as useful markers for the optimization of treatment in inflammatory bowel disease (IBD). We aimed to estimate the patterns over time of IFX-TLs and ATIs in IBD patients on maintenance treatment with IFX. METHODS Two different measurements of IFX-TLs and ATIs were performed (ELISA; Eagle BioSciences) at a 10-month interval using serum samples of consecutive patients on maintenance treatment with IFX. Certain biomarkers [hemoglobin, erythrocyte sedimentation rate, C-reactive protein (CRP), platelets, albumin] measured at the same time as well as clinical disease activity and quality of life were assessed. RESULTS Among a total of 86 IBD patients under maintenance treatment with IFX, 64 [49 Crohn's disease, 15 ulcerative colitis (UC), 42 men, mean age 44.2±15.2 years, 41 in combination therapy with immunomodulator, six in intensified dose], with two available measurements of IFX-TLs and ATIs (A and B), were included in the study. The median levels of IF-TLs were 5.07 (interquartiles range: 1.60-12.73) μg/ml in measurement A and 4.68 (1.19-7.83) μg/ml in measurement B (P

Although pancreatic ductal adenocarcinoma (PDAC) survival is poor, there are differences in patients’ response to the treatments. Detection of predictive biomarkers explaining these differences is of the utmost importance. In a recent study two genetic markers (CD44-rs353630 and CHI3L2-rs684559) were reported to be associated with survival after PDAC resection. We attempted to replicate the associations in 1856 PDAC patients (685 resected with stage I/II) from the PANcreatic Disease ReseArch (PANDoRA) consortium. We also analysed the combined effect of the two genotypes in order to compare our results with what was previously reported. Additional stratified analyses considering TNM stage of the disease and whether the patients received surgery were also performed. We observed no statistically significant associations, except for the heterozygous carriers of CD44-rs353630, who were associated with worse OS (HR = 5.01; 95% CI 1.58–15.88; p = 0.006) among patients with stage I disease. This association is in the opposite direction of those reported previously, suggesting that data obtained in such small subgroups are hardly replicable and should be considered cautiously. The two polymorphisms combined did not show any statistically significant association. Our results suggest that the effect of CD44-rs353630 and CHI3L2-rs684559 cannot be generalized to all PDAC patients.

Irritable bowel syndrome (IBS) is a functional gut brain gastrointestinal (GI) disorder, typically accompanied by constipation or diarrhea, usually without any organic evidence. The prevalence of IBS is rather high of about 10-15% (10, 1 % according to Rome III and 4, 1% according to Rome IV, Enck P. et al 2016, Sperber A.D. et al 2020, Black C.J. et al 2020) in the working population. Quality of life in patients with IBS is reduced and therefore a major obstacle to the normal physical and social wellbeing. In intensified clinical research worldwide new pathogenic mechanisms of IBS are suggested, including intestinal dysbiois one of the critical contributing factors to onset or further development of IBS. Intestinal microbiome represents a real ecosystem of microorganisms and human GI tract lining cells. The diversity and composition of the GI microbiome may differ significantly inter- and intra-individually, depending on sex, age or physiological conditions (pregnancy, disease, etc). Intestinal microbiome composition frequently changes in association with IBS symptoms, and the purpose of this study was to investigate if there is a clear relationship in microbial composition and relative abundance of microbial taxa in feces of persons diagnosed with IBS. Fecal microbiota profiling was done in a group of nine clinically confirmed IBS patients and 6 corresponding healthy controls, based on species specific 16s RNA gene. No statistically significant differences in Alpha and Beta diversity indices were found.

Glaucoma is a progressive optic neuropathy resulting from retinal ganglion cells death; it represents one of the leading causes of irreversible blindness worldwide. Although, primary open angle glaucoma (POAG) is the most common type of the disease, the pathogenesis of POAG and the genetic factors contributing to disease development remain poorly understood. The aim of this study was to investigate whether the polymorphisms rs76481776 in miR182 gene and rs3217992 in cyclin-dependent kinase inhibitor-2B (CDKN2B) gene are risk factors for POAG in a series of patients of Greek origin. A case-control study was conducted including 120 patients with POAG and 113 unaffected healthy controls of Greek origin, surveyed for polymorphisms with potential correlation to POAG. DNA from each individual was tested for the miR182 rs76481776 and CDKN2B rs3217992 polymorphisms. Regarding the miR182 rs76481776 polymorphism, the T allele occurred with significantly higher frequency in POAG patients compared to controls (OR: 2.62, 95% CI: 1.56–4.39; p = 0.0002). The CDKN2B rs3217992 A allele frequency was found significantly increased in POAG patients compared to healthy individuals (OR: 1.72, 95% CI: 1.18–2.49; p = 0.005). Therefore, both rs76481776 polymorphism in miR182 gene and rs3217992 polymorphism in CDKN2B gene seem to be associated with the development of POAG in a Greek population. The carriers of the T allele of rs76481776 in miR182 and the carriers of the A allele of rs3217992 in CDKN2B have an increased risk of developing POAG.

To investigate the possible association of the matrix metalloproteinase 2 (MMP2)-1306C/T polymorphism with the risk of ischemic retinal vein occlusion (iRVO).A total of 69 patients with RVO were enrolled in this study (43 with non-iRVO and 26 with iRVO). All subjects were screened for hypertension, diabetes mellitus, hyperlipidemia, history of stroke, anticoagulant medication, smoking status and glaucoma. The genotyping of MMP2-1306C/T polymorphism was performed using PCR-RFLP-based methods.MMP2-1306C/T T allele carriers (CT+TT) were statistically significant associated with a higher risk of iRVO compared to CC genotype in the overall RVO group (odds ratio = 3.91, p = 0.015, 95% confidence interval:1.30-11.79). Analysis, following stratification by age revealed that T allele carriers had a statistically significant increased risk of iRVO compared to C allele carriers only in RVO patients75 years old.Our results demonstrated that MMP2-1306C/T polymorphism is a likely predisposing factor for iRVO in patients75 years old. This is the first study attempting association of a gene polymorphism with the prevalence of iRVO.

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder with an increasing prevalence. GERD develops when the reflux of stomach contents causes troublesome typical and atypical symptoms and/or complications. Several risk factors of GERD have been identified and evaluated over the years, including a considerable amount of genetic factors. Multiple mechanisms are involved in the pathogenesis of GERD including: (1) motor abnormalities, such as impaired lower esophageal sphincter (LES) resting tone, transient LES relaxations, impaired esophageal acid clearance and delayed gastric emptying; and (2) anatomical factors, such as hiatal hernia and obesity. Genetic contribution seems to play a major role in GERD and GERD- related disorders development such Barrett's esophagus and esophageal adenocarcinoma. Twin and family studies have revealed an about 31% heritability of the disease. Numerous single-nucleotide polymorphisms in various genes like FOXF1, MHC, CCND1, anti-inflammatory cytokine and DNA repair genes have been strongly associated with increased GERD risk. GERD, Barrett's esophagus and esophageal adenocarcinoma share several genetic loci. Despite GERD polygenic basis, specific genetic loci such as rs10419226 on chromosome 19, rs2687201 on chromosome 3, rs10852151 on chromosome 15 and rs520525 on the paired related homeobox 1 gene have been mentioned as potential risk factors. Further investigation on the risk genes may elucidate their exact function and role and demonstrate new therapeutic approaches to this increasingly common disease.

AIM To investigate the correlation between rs2910164, rs11 614913, rs113054794, and rs188519172 polymorphisms and response to anti-TNF treatment in patients with Crohn’s disease (CD). METHODS One hundred seven patients with CD based on standard clinical, endoscopic, radiological, and pathological criteria were included in the study. They all received infliximab or adalimumab intravenously or subcutaneously at standard induction doses as per international guidelines. Clinical and biochemical response was assessed using the Harvey-Bradshaw index and CRP levels respectively. Endoscopic response was evaluated by ileocolonoscopy at week 12-20 of therapy. The changes in endoscopic appearance compared to baseline were classified into four categories, and patients were classified as responders and non-responders. Whole peripheral blood was extracted and genotyping was performed by PCR. RESULTS One hundred and seven patients were included in the study. Seventy two (67.3%) patients were classified as complete responders, 22 (20.5%) as partial while 13 (12.1%) were primary non-responders. No correlation was detected between response to anti-TNF agents and patients’ characteristics such as gender, age and disease duration while clinical and biochemical indexes used were associated with endoscopic response. Concerning prevalence of rs2910164, rs11614913, and rs188519172 polymorphisms of miR-146, miR-196a and miR-224 respectively no statistically important difference was found between complete, partial, and non-responders to anti-TNF treatment. Actually CC genotype of rs2910164 was not detected in any patient. Regarding rs113054794 of miR-221, normal CC genotype was the only one detected in all studied patients, suggesting this polymorphism is highly rare in the studied population. CONCLUSION No correlation is detected between studied polymorphisms and patients’ response to anti-TNF treatment. Polymorphism rs113054794 is not detected in our population.

Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (ORhomozygous = 1.19, 95% CI 1.02-1.38, p = 0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (ORheterozygous = 0.51, 95% CI 0.39-0.67, p = 1.10 × 10-6 ) and MORC4-rs 12837024 (ORhomozygous = 2.07 (1.55-2.77, ptrend = 0.7 × 10-11 ). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants.

Colorectal cancer is the third and second, respectively, most common form of cancer in the male and female populations, according to new cases reported at the global level. The aim of this study was to contribute to the understanding of the role of the inhibitor of growth gene - 2 (ING2-mRNA) protein in colorectal cancer, raising its potential to the prognostic level. The research sample consisted of 60 patients (60% men, mean age 73.2 ± 11.1 years) who underwent surgery for colorectal cancer during the period 2008-2013 in the Asklipieio Voulas General Hospital. Samples from tumor tissue mucosal were compared with normal ones and the levels of ING2-mRNA were defined quantitively through Real Time Polymerase Chain Reaction (RT-PCR). Finally, these levels were correlated with the correspond pathological image and characteristics of each patient, using the SPPS V.20 program for statistical process. After Total RNA was extracted, the primers used were listed as follows: ING2 (sense: 5’-GCAGGCAGCGGACCAGTGAA-3’, antisense: 5’-CCTGCTTGGCCTTGGAGCGT-3’), GAPDH (sense: 5’-GAAATCCCATCACCATCTTCCAGG-3’, antisense: 5’-GAGCCCCAGCCTTCTCCATG-3’). The results of the study confirmed the marginal correlation already documented between negative expression of ING2-mRNA and stage 2a of the TNM staging of colorectal cancer. These results lead to the conclusion that the level of this specific mRNA can be prognostic of clinical outcome. Further research is needed, both to corroborate this correlation and to elucidate the mechanism of ING2 action in colorectal cancer.

A key factor protecting from oxidative stress in gestational diabetes mellitus (GDM) and in type 2 diabetes (T2D) is paraoxonase-1 (PON1). Inconclusive and limited data exist regarding the effect of a coding polymorphism (Q192R) of the PON1 gene in conferring susceptibility to both states. In the present study, we investigated the association between the PON1 gene and the risk for GDM in the Greek population and assessed for the first time its transcriptional efficiency. We studied 185 women with GDM and 104 non-diabetic controls for the PON1 polymorphism. For PON1 mRNA expression, peripheral leucocytes were harvested from 20 GDM and 20 control women, harboring different genotypes for the polymorphism, using real-time quantitative PCR. The RR genotype and the R allele of the PON1 Q192R polymorphism were significantly associated with an increased risk for GDM (p = 0.012 and p 0.0001, respectively). Furthermore, there was no statistical correlation between the individual metabolic parameters tested and the three genotypes. Finally, the expression levels of PON1 mRNA in GDM patients did not exhibit any statistical difference compared with normal controls (p = 0.138). These data independently document that the Q192R polymorphism is closely associated with GDM susceptibility, while the PON1 gene expression is not impaired in GDM.

AIM Our aim was to perform a comparison study of the mutation rate of V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), and v-Raf murine sarcoma viral oncogene homolog-B (BRAF) genes between blood-based cell-free DNA (cfDNA), and tissue sample biopsies in individuals undergoing screening colonoscopy. MATERIALS AND METHODS All specimens were collected from January 2015 to January 2016. A total of 92 blood samples and colonic biopsy specimens were collected from healthy individuals with no polyps undergoing screening colonoscopy (group A, n=35), patients with colorectal cancer (group B, n=27), and patients with neoplastic intestinal polyps (group C, n=30). Peripheral blood was collected from each patient and a focal tissue biopsy was conducted. RESULTS We only found a limited statistically significant difference (p=0.046) in the mutation analysis for codon 12 of the KRAS gene when we compared tissue biopsies from patients in group B to those from group C. In the blood samples, only the rate of mutation in codon 12 of the KRAS gene in samples of group B was significantly higher than that in group A (p=0.013). CONCLUSION Blood cfDNA may be a promising tool in CRC screening as it may discriminate patients with CRC compared to healthy individuals and those with colonic polyps, even though it does not appear useful in predicting the presence of colonic polyps.

BackgroundMost cases of pancreatic ductal adenocarcinoma (PDAC) are asymptomatic in early stages, and the disease is typically diagnosed in advanced phases, resulting in very high mortality. Tools to identify individuals at high risk of developing PDAC would be useful to improve chances of early detection.ObjectiveWe generated a polygenic risk score (PRS) for PDAC risk prediction, combining the effect of known risk SNPs, and carried out an exploratory analysis of a multifactorial score.MethodsWe tested the associations of the individual known risk SNPs on up to 2851 PDAC cases and 4810 controls of European origin from the PANcreatic Disease ReseArch (PANDoRA) consortium. Thirty risk SNPs were included in a PRS, which was computed on the subset of subjects that had 100% call rate, consisting of 839 cases and 2040 controls in PANDoRA and 6420 cases and 4889 controls from the previously published Pancreatic Cancer Cohort Consortium I–III and Pancreatic Cancer Case-Control Consortium genome-wide association studies. Additional exploratory multifactorial scores were constructed by complementing the genetic score with smoking and diabetes.ResultsThe scores were associated with increased PDAC risk and reached high statistical significance (OR=2.70, 95% CI 1.99 to 3.68, p=2.54×10−10 highest vs lowest quintile of the weighted PRS, and OR=14.37, 95% CI 5.57 to 37.09, p=3.64×10−8, highest vs lowest quintile of the weighted multifactorial score).ConclusionWe found a highly significant association between a PRS and PDAC risk, which explains more than individual SNPs and is a step forward in the direction of the construction of a tool for risk stratification in the population.

Background Remote ischemic post-conditioning attenuates ischemia-reperfusion injury in patients with STEMI. However, its biochemical mechanisms, including micro-RNA expression, and effects on cardiac remodeling have not been defined. Methods We examined 80 patients with STEMI and 20 healthy controls. All patients had been evaluated by cardiac echocardiography. The conditioning protocol utilised a single ischemic stimulus by brachial cuff inflation of both arms at 200mmHg for 5 minutes, while 20 patients underwent a sham conditioning procedure by way of cuff inflation omission after its placement. Blood samples were taken before and after the conditioning protocol; thus, the expression of microRNA-144,-150,-499 (cardioprotective action), -21, and -208 (remodeling stimuli) was quantified at baseline and after the ischemic conditioning procedure, by polymerase chain reaction. Additionally, cardiac remodeling was evaluated by repeat echocardiography after a 2-year follow-up period, in 40 patients. Results Our conditioning protocol resulted in a statistically significant increase in miR-144,-150, -499, -21, and -208 expression (55.9 vs 7.4/U6sn, p Conclusion Remote ischemic conditioning may prevent adverse myocardial remodelling within 2 years of the index ischemic event, likely by up-regulation of cardio-protective microRNAs expression.

Early onset pancreatic cancer (EOPC) is a rare disease with a very high mortality rate. Almost nothing is known on the genetic susceptibility of EOPC, therefore we performed a genome-wide association study (GWAS) to identify novel genetic variants specific for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) at younger ages. In the first phase, conducted on 821 cases with age of onset ≤60 years, of whom 198 with age of onset ≤50, and 3227 controls from PanScan I-II, we observed four SNPs (rs7155613, rs2328991, rs4891017 and rs12610094) showing an association with EOPC risk (P < 1x10-4 ). We replicated these SNPs in the PANcreatic Disease ReseArch (PANDoRA) consortium and used additional in silico data from PanScan III and PanC4. Among these four variants rs2328991 was significant in an independent set of 855 cases with age of onset ≤60 years, of whom 265 with age of onset≤50, and 4142 controls from the PANDoRA consortium while in the in silico data we observed no statistically significant association. However, the resulting meta-analysis supported the association (P = 1.15x10-4 ). In conclusion we propose a novel variant rs2328991 to be involved in EOPC risk. Even though it was not possible to find a mechanistic link between the variant and the function, the association is supported by a solid statistical significance obtained in the largest study on EOPC genetics present so far in the literature. This article is protected by copyright. All rights reserved.

Tinnitus is the perception of sound in the absence of any external stimulus. Oxidative stress is possibly involved in its pathogenesis and a variety of antioxidant compounds have been studied as potential treatment approaches. The objective of the present study was to assess the effects of antioxidant supplementation in tinnitus patients. This is a randomized, double-blind, placebo-controlled clinical trial. Patients (N = 70) were randomly allocated to antioxidant supplementation (N = 35) or to placebo (N = 35) for a total of 3 months. Demographic, anthropometric, clinical, and nutritional data were collected. Serum total antioxidant capacity (TAC), oxidized LDL (oxLDL), and superoxide dismutase (SOD), tinnitus loudness, frequency, and minimum masking level (MML), and scores in Tinnitus Handicap Inventory questionnaire (THI), Tinnitus Functional Index (TFI), and Visual Analogue Scale (VAS) were evaluated at baseline and follow-up. Tinnitus loudness and MML significantly decreased from baseline to post measure (p &lt, 0.001) only in the antioxidant group, the overall change being significantly different between the two groups post-intervention (p &lt, 0.001). THI and VAS decreased only in the antioxidant group. Differences in changes in serum TAC, SOD, and oxLDL post-intervention were insignificant. In conclusion, antioxidant therapy seems to reduce the subjective discomfort and tinnitus intensity in tinnitus patients.

Introduction/Objective: Irritable bowel syndrome (IBS) is a bowel disorder characterized by pain accompanying defecation or altered bowel habits, divided into diarrhea-predominant, constipation-predominant, and alternating subtypes, whose pathogenesis is considered to include disordered bowel motility. The hormone ghrelin is a growth hormone secretagogue which furthermore affects gastrointestinal motility. We study the association between its genetic polymorphisms and the risk for IBS. Methods: IBS patients meeting the Rome III criteria and controls similar in age and gender were recruited. Whole blood samples were used for genotyping via polymerase chain reaction and restriction fragment length polymorphism for the polymorphisms rs34911341, rs696217, and rs2075356. Results: Participants included 142 patients and 209 controls. The rs696217 GG genotype frequency was higher in patients (78.87%) compared to controls (55.5%). The rs696217 GT genotype was significantly less frequent among patients than in controls (OR 0.31, 95% CI 0.19–0.52), as was the T allele (OR 0.43, 95% CI 0.28–0.66). No significant differences in genotype distribution were found for the rs34911341 and rs2075356 polymorphisms between patients and controls. The genotype frequencies did not significantly differ between IBS subtype groups for any of the polymorphisms studied. Conclusions: The GG and GT genotypes of the rs696217 polymorphism, as well as the G-allele, demonstrate significant association with IBS susceptibility, while the T allele appears to bear a protective effect. Ghrelin’s polymorphisms are plausibly involved in IBS pathogenesis, but do not correlate with any distinct IBS subtype.

Aim The incidence of various single- nucleotide polymorphisms with reported malignant potential in esophageal cancer tissues has only sparsely been investigated in the west, as of today. The aim of our study was to investigate the contribution of four lncRNAs’ polymorphisms HOTAIR rs920778, LINC00951 rs11752942, POLR2E rs3787016 and HULC rs7763881c in esophageal carcinoma susceptibility. Background & Methods Formalin-Fixed Paraffin-Embedded (FFPE) tissue specimens from 95 consecutive patients operated for esophageal or gastro-esophageal junction carcinoma between 01/03/2014- 01/03/2019 were retrieved and processed. Clinical data concerning patients’ demographics, histopathological parameters, surgical, and oncological outcomes were also retrospectively collected from our prospective database. DNA findings concerning rs920778, rs11752942, rs3787016 and rs7763881 of the above mentioned population were compared with 121 healthy controls. Results Sixty-seven patients underwent Ivor Lewis or McKeown esophagectomy for either squamous cell esophageal carcinoma (n= 5) or adenocarcinoma of esophagus or gastroesophageal junction Siewert I or II (n= 62). Twenty-eight additional patients were subjected to total gastrectomy for gastroesophageal junction adenocarcinoma Siewert III. Neither HOTAIR rs920778 nor LINC00951 rs11752942 nor HULC rs7763881 polymorphism was found more frequently in esophageal cancer specimens in comparison to healthy subjects. On the contrary, the presence of C allele, as well as CC/TT genotypes of POLR2E rs3787016 were found more often in the control population, and when found in esophageal cancerous tissues it was associated with earlier stages of the disease, as well as with minor lymph node involvement and lesser metastatic potential. Conclusion The presence of POLR2E rs3787016 seems to be less common in esophageal cancer patients than healthy controls and is also associated with early stage disease. The clinical implications of this finding need to be clarified with further studies with larger sample size.

MicroRNAs (miRNAs) have been found to play an important role in breast cancer, functioning either as potential oncogenes or tumor suppressor genes, but their role in the prognosis of patients remains unclear. The aim of the present review study is to highlight recent preclinical and clinical studies performed on both circulating and tissue-specific miRNAs and their potential role as prognostic markers in breast cancer. We systematically searched the PubMed database to explore the prognostic value of miRNAs in breast cancer. After performing the literature search and review, 117 eligible studies were identified. We found that 110 aberrantly expressed miRNAs have been associated with prognosis in breast cancer. In conclusion, the collective data presented in this review indicate that miRNAs could serve as novel prognostic tools in breast cancer, while the clinical application of these findings has yet to be verified.

Background/Aim: Almost 15% of patients with sporadic primary hyperparathyroidism (sPHPT) present with multiple gland disease (MGD). The aim of this study was to investigate the potential role of two polymorphisms of the hsa-miR-30e, in sPHPT tumorigenesis. Patients and Methods: One-hundred twenty sPHPT patients, 77 presenting a single adenoma and 43 with MGD, and 54 healthy controls were genotyped. The SNPs were identified using the allele-specific PCR methodology, while the hsa-miR-30e expression was analyzed by real-time quantitative reverse transcriptase PCR. Results: Hsa-miR-30e expression was found to be significantly higher in patients with MGD compared to patients with single adenomas (p=0.0019), but no differences were found regarding specific genotype carriers. The genotype frequencies for ss178077483 and rs7556088 were significantly different between patients and healthy controls. Conclusion: Although the polymorphisms cannot be used as biomarkers for the differential diagnosis of MGD, hsa-miR-30e expression could potentially serve as a biomarker for this purpose.

Purpose: The purpose of this study was to investigate the potential association between rhegmatogenous retinal detachment (RRD) and BAX and BCL2 polymorphisms. Methods: This is a case control study of 99 patients with RRD and 120 healthy control subjects of Greek origin, surveyed for BAX and BCL2 polymorphisms (rs2279115 and rs4645878) and a potential correlation to RRD. Results: The rs4645878 AA genotype was found to be significantly associated with RRD (p = 0.003; OR: 6.89, 95% CI: 1.76-26.93), while the rs2279115 CC genotype as well as the C allele was not found in patients with RRD. Conclusions: This is the first study evaluating the potential relationship between BCL2 and BAX gene polymorphisms and RRD in a Greek population, showing a significant association between BAX rs4645878 polymorphism and RRD susceptibility. This finding suggests that an apoptotic mechanism is implicated in the pathogenesis of RRD.

Anti-platelet drugs are necessary in treating patients with coronary artery disease, ischemic stroke and peripheral arterial disease. However, despite the use of adequate anti-platelet therapy, some patients will experience a recurrent atherothrombotic vascular event. These patients are characterized as low-or non-responders to therapy. Individual responsiveness to anti-platelet therapy as the use of clopidogrel and/or aspirin varies widely among patients. Such an individual variability is mainly determined by environmental and genetic factors. In this review, we focused on the underlying genetic mechanisms that might influence response to anti-platelet drugs. © 2016 Bentham Science Publishers.

To investigate DNA methylation changes in peripheral blood from patients with gestational diabetes mellitus (GDM) and preeclampsia (PE) due to poorly treated GDM. Eighteen pregnant women participated in the study: 6 with GDM, 6 with PE, and 6 healthy controls. The promoter methylation status of genes was profiled using the Human Inflammatory Response and Autoimmunity EpiTect Methyl II Signature PCR Array profiles. The results were validated with quantitative real-time polymerase chain reaction (qRT-PCR). Fewer inflammation-related genes were significantly hypomethylated in PE cases compared to healthy subjects than in GDM cases. Some of the examined genes show different methylation patterns between GDM and PE. The epigenetic changes observed in this study indicate that GDM and PE exhibit specific DNA methylation profiles, with possible clinical applications.

Background The measurement of infliximab trough levels (IFX-TLs) has been suggested as an important biomarker for the optimisation of treatment in patients with inflammatory bowel disease (IBD). We have previously reported that IFX-TLs of patients under maintenance treatment with IFX show decreasing patterns associated with an increasing pattern of CRP levels1. We aimed to study the clinical impact of this observation by recording the treatment changes that became necessary during a three year follow-up. Methods Consecutive asymptomatic patients on maintenance treatment with IFX were included. Two different measurements of IFX-TLs were made (ELISA, Eagle BioSciences) with a ten-month interval using serum samples drained before IFX infusion. After the second measurement patients were followed up for three years and all treatment modifications including IFX intensification, change of biologic agent or IBD-related surgical intervention were assessed. Results Among a total of 86 IBD patients under maintenance treatment with IFX, 64 [49 CD, 15 UC, 42 men, mean age 44.2 ± 15.2 years, 41 in combination therapy with immunomodulator, 6 in intensified dose], with 2 available measurements of IFX-TLs (A and B) were included in the study. Median levels of IF-TLs were 5.07 (IQR 1.60–12.73) μg/ml in measurement A and 4.68 (1.19–7.83) μg/ml in measurement B (p < 0.0001). Treatment was intensified in 8 patients after measurement A. Patients with stable IFX dose showed a significant reduction in median IFX-TLs from 5.65 to 3.8 μg/ml (p < 0.0001). Moreover, CRP levels were significantly increased in measurement B compared with measurement A [0.33 (03–4.4) mg/dl vs. 0.31 (0.3–3.8) mg/dl, p = 0.02]. During a 3 year follow-up, 22 (34%) patients needed treatment optimisation (6 IFX intensification, 7 change of agent, 6 surgery, 3 change of agent plus surgery). In three patients IFX was stopped for safety reasons. Fifty-eight hospitalisations in 19 patients were also recorded. The decrease of IFX-TLs between the two measurements was significantly more in patients with treatment optimisation compared with patients without treatment optimisation (p = 0.03). Conclusion IBD patients who are on maintenance treatment with infliximab showing decreasing patterns of IFX-TLs often need treatment optimisation during the follow-up due to clinical or endoscopic activity. These results probably suggest the importance of the proactive therapeutic drug monitoring and early treatment optimisation in these patients References

Background/aims Gastroesophageal reflux disease (GERD) represents a common condition having a substantial impact on the patients' quality of life, as well as the health system. According to many studies, the BARX1 and ADAMTS17 genes have been suggested as genetic risk loci for the development of GERD and its complications. The purpose of this study is to investigate the potential association between GERD and BARX1 and ADAMTS17 polymorphisms. Methods The present is a prospective cohort study of 160 GERD patients and 180 healthy control subjects of Greek origin, examined for BARX1 and ADAMTS17 polymorphisms (rs11789015 and rs4965272) and a potential correlation to GERD. Results The rs11789015 AG and GG genotypes were found to be significantly associated with GERD (P= 0.032; OR, 1.65; 95% CI, 1.062.57 and P= 0.033; OR, 3.00; 95% CI, 1.15-7.82, respectively), as well as the G allele (P= 0.007; OR, 1.60; 95% CI, 1.14- 2.24). Concerning the rs4965272, only the GG genotype was significantly associated with GERD (P= 0.035; OR, 3.42; 95% CI, 1.06-11.05). Conclusions This is a study investigating the potential correlation between BARX1 and ADAMTS17 polymorphisms and the development of GERD, showing a considerable association between both polymorphisms and the disease. This finding suggests that esophageal differentiation or altered regulation on microfibrils in the cell environment could be implicated as possible mechanisms in the pathogenesis of GERD.

Aim The purpose of this study is to evaluate the role of pre-miR34a rs72631823 as potential risk factor and/or prognostic marker in patients with triple negative breast cancer. Methods 114 samples of DNA from paraffin embedded breast normal tissues of patients with triple negative breast cancer and 124 samples of healthy controls were collected and analyzed for pre-miR34a rs72631823 polymorphism. Results Pre-miR34a rs72631823 A allele was associated with increased TNBC risk both in univariate and multivariate analysis. The number of pre-miR34a rs72631823 AA subjects was very small and the association did not reach significance (p = 0.176, Fisher's exact test). The examined polymorphism was not associated with overall survival at the univariate or multivariate Cox regression analysis (adjusted HR = 1.60, 95%CI: 0.64-3.96 for miR34 rs72631823 GA/AA vs. GG). Conclusion Our case-control study suggests that pre-miR34a rs72631823 A allele is associated with increased triple negative breast cancer risk.

Pancreatic neuroendocrine neoplasms (pNEN) account for less than 5% of all pancreatic neoplasms and genetic association studies on susceptibility to the disease are limited. We sought to identify possible overlap of genetic susceptibility loci between pancreatic ductal adenocarcinoma (PDAC) and pNEN; therefore, PDAC susceptibility variants (n = 23) from Caucasian genome-wide association studies (GWAS) were genotyped in 369 pNEN cases and 3277 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium to evaluate the odds associated with pNEN risk, disease onset and tumor characteristics. Main effect analyses showed four PDAC susceptibility variants-rs9854771, rs1561927, rs9543325 and rs10919791 to be associated with pNEN risk. Subsequently, only associations with rs9543325, rs10919791 and rs1561927 were noteworthy with false positive report probability (FPRP) tests. Stratified analyses considering age at onset (50-year threshold), showed rs2736098, rs16986825 and rs9854771 to be associated with risk of developing pNEN at a younger age. Stratified analyses also showed some single nucleotide polymorphisms to be associated with different degrees of tumor grade, metastatic potential and functionality. Our results identify known GWAS PDAC susceptibility loci, which may also be involved in sporadic pNEN etiology and suggest that some genetic mechanisms governing pathogenesis of these two entities may be similar, with few of these loci being more influential in younger cases or tumor subtypes.

Background Bevacizumab, an angiogenesis inhibitor is used in regimens for metastatic colorectal cancer (CRC). A minority of cancer cells with characteristics of cancer stem cells (CSC) may be responsible for progression and development of chemotherapy resistance in this disease. CD133 is a well-known CSC marker and is associated with angiogenesis, poor prognosis and resistance to chemotherapy. Objective The purpose of our study was to evaluate the association between the rs3130 and rs2286455 polymorphisms of the CD133 gene and the response, toxicity, and overall survival of patients with CRC on bevacizumab-based treatment. Methods Forty-three patients receiving bevacizumab, irinotecan and capecitabine and 15 patients receiving bevacizumab, irinotecan and 5-FU were included. Efficacy and toxicity were evaluated. KRAS mutation analysis and rs3130 and rs2286455 polymorphisms genotyping in the tumors and peripheral blood respectively were performed with PCR-RFLP. Results No association between KRAS mutated alleles and response was found. The rs3130 CC genotype was associated with reduced toxicity of treatments (p= 0.0017), and with lower overall survival on bevacizumab (p= 0.002). Conclusions The CC genotype of rs3130 polymorphism in the CD133 gene can predict poorer overall survival in patients with metastatic CRC on bevacizumab which cannot be attributed to increased treatment toxicity.

Pancreatic cancer is the fourth leading cause of cancer death in the developed world. Both inherited high-penetrance mutations in BRCA2 (ref. 2), ATM, PALB2 (ref. 4), BRCA1 (ref. 5), STK11 (ref. 6), CDKN2A and mismatch-repair genes and low-penetrance loci are associated with increased risk. To identify new risk loci, we performed a genome-wide association study on 9,925 pancreatic cancer cases and 11,569 controls, including 4,164 newly genotyped cases and 3,792 controls in 9 studies from North America, Central Europe and Australia. We identified three newly associated regions: 17q25.1 (LINC00673, rs11655237, odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.19-1.34, P = 1.42 × 10(-14)), 7p13 (SUGCT, rs17688601, OR = 0.88, 95% CI = 0.84-0.92, P = 1.41 × 10(-8)) and 3q29 (TP63, rs9854771, OR = 0.89, 95% CI = 0.85-0.93, P = 2.35 × 10(-8)). We detected significant association at 2p13.3 (ETAA1, rs1486134, OR = 1.14, 95% CI = 1.09-1.19, P = 3.36 × 10(-9)), a region with previous suggestive evidence in Han Chinese. We replicated previously reported associations at 9q34.2 (ABO), 13q22.1 (KLF5), 5p15.33 (TERT and CLPTM1), 13q12.2 (PDX1), 1q32.1 (NR5A2), 7q32.3 (LINC-PINT), 16q23.1 (BCAR1) and 22q12.1 (ZNRF3). Our study identifies new loci associated with pancreatic cancer risk.

Primary hyperparathyroidism (pHPT) is a common endocrinopathy resulting from inappropriately high PTH secretion. It usually results from the presence of a single gland adenoma, multiple gland hyperplasia or rarely parathyroid carcinoma. All these conditions require different management, and it is important to be able to differentiate the underlined pathology, in order for the clinicians to provide the best therapeutic approach. Elucidation of the genetic background of each of these clinical entities would be of great interest. However, the molecular factors that control parathyroid tumorigenesis are poorly understood. There are data implicating the existence of specific genetic pathways involved in the emergence of parathyroid tumorigenesis. The main focus of the present study is to present the current optimal diagnostic and management protocols for pHPT as well as to review the literature regarding all molecular and genetic pathways that are to be involved in the pathophysiology of sporadic pHPT.

Choline deprivation is a recognized experimental approach to nonalcoholic steatohepatitis, while thioacetamide (TAA)-induced liver fibrosis resembles alcoholic liver fibrogenesis. In order to elucidate the effect of TAA on liver extracellular matrix composition under choline deprivation due to choline-deficient diet (CDD) administration, we evaluated the transcriptional and immunohistochemical (IHC) pattern of major hepatic matrix metalloproteinases (namely, MMP-2, -9) and their tissue inhibitors (TIMP-1, -2) in adult male albino Wistar rats at 30, 60 and 90 days. In the CDD+TAA group, IHC showed an early progressive increase in MMP-2 expression, while MMP-9 initially exhibited a significant increase followed by a gradual decrease; TIMP-1 and TIMP-2 IHC expressions showed gradual increase throughout the experiment. The MMPs-TIMPs regulation at the transcriptional level was found to be increased in all groups throughout the experiment. The increased MMP-2/TIMP-2 and suppressed MMP-9/TIMP-1 ratios in IHC and in real-time polymerase chain reaction (RT-PCR) seemed to correlate with the degree of liver fibrosis. These results support the important role of MMPs and TIMPs in controlling the hepatic pathogenesis and shed more light on the recently described experimental approach to liver disease (steatohepatitis) under the impact of two insults (TAA and CDD).

Objectives: Atherosclerosis is almost absent in intramyocardial coronary arteries, while epicardial coronary arteries may show extensive occlusive disease. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression has been implicated in atherogenesis. We aimed to investigate differences in arterial wall LOX-1 expression between human epicardial and intramyocardial coronary arteries. Methods: Epicardial and intramyocardial total artery wall specimens were obtained from 13 male patients (aged 61.9 ± 10.3 years) undergoing coronary artery bypass graft surgery due to 3-vessel coronary artery disease. LOX-1 expression was examined by reverse transcription-polymerase chain reaction. Results: LOX-1 expression was significantly higher in the arterial wall of epicardial coronary arteries compared to intramyocardial coronary arteries. The LOX-1/GAPDH ratio was 0.48 ± 0.07 vs. 0.35 ± 0.03 (p < 0.001). Conclusions: Our findings may partially explain the atheroprotective effect of the intramyocardial course since arterial wall LOX-1 expression was lower in intramyocardial arteries and higher in epicardial coronary arteries.

Background Recognizing resistance or susceptibility to the current standard cisplatin and paclitaxel treatment could improve therapeutic outcomes of metastatic or recurrent cervical cancer. Methods Forty-five tissue samples from patients participating in a phase II trial of cisplatin and ifosfamide, with or without paclitaxel were collected for retrograde analysis. Immunohistochemistry and genotyping was performed to test ERCC1, III β-tubulin, COX-2, CD4, CD8 and ERCC1 (C8092A and N118 N) and MDR1 (C3435T and G2677 T) gene polymorphisms, as possible predictive and prognostic markers. Results were statistically analyzed and correlated with patient characteristics and outcomes. Results Patients with higher levels of ERCC1 expression had shorter PFS and OS than patients with low ERCC1 expression (mPFS:5.1 vs 10.2 months, p = 0.027; mOS:10.5 vs. 21.4 months, p = 0.006). Patients with TT in the site of ERCC1 N118 N and GT in the site of MDR1 G2677 T polymorphisms had significantly longer PFS (p = 0.006 and p = 0.027 respectively). ERCC1 expression and the ERCC1 N118 N polymorphism remained independent predictors of PFS. Interestingly, high III beta tubulin expression was associated with chemotherapy resistance and fewer responses [5/20 (25%)] compared to lower III β-tubulin expression [15/23 (65.2%)] (p = 0.008). Finally, ΙΙΙ β-tubulin levels and chemotherapy regimen were independent predictors of response to treatment. Conclusions ERCC1 expression proved to be a significant prognostic factor for survival in our metastatic or recurrent cervical cancer population treated with cisplatin based chemotherapy. ERCC1 N118 N and MDR1 G2677 T polymorphism also proved of prognostic significance for disease progression, while overexpression of III β-tubulin was positively correlated with chemotherapy resistance.