Alcohol use disorder(AUD)represents a major public health issue which affects millions of people globally and consist a chronic relapsing condition associated with substantial morbidity and mortality.The gut microbiom...Alcohol use disorder(AUD)represents a major public health issue which affects millions of people globally and consist a chronic relapsing condition associated with substantial morbidity and mortality.The gut microbiome plays a crucial role in maintaining overall health and has emerged as a significant contributor to the pathophysiology of various psychiatric disorders.Recent evidence suggests that the gut microbiome is intimately linked to the development and progression of AUD,with alcohol consumption directly impacting its composition and function.This review article aims to explore the intricate relationship between the gut microbiome and AUD,focusing on the implications for mental health outcomes and potential therapeutic strategies.We discuss the bidirectional communication between the gut microbiome and the brain,highlighting the role of microbiotaderived metabolites in neuroinflammation,neurotransmission,and mood regulation.Furthermore,we examine the influence of AUD-related factors,such as alcohol-induced gut dysbiosis and increased intestinal permeability,on mental health outcomes.Finally,we explore emerging therapeutic avenues targeting the gut microbiome in the management of AUD,including prebiotics,probiotics,and fecal microbiota transplantation.Understanding the complex interplay between the gut microbiome and AUD holds promise for developing novel interventions that could improve mental health outcomes in individuals with AUD.展开更多
Functional gastrointestinal disorders(FGID) are heterogeneous disorders with a variety of clinical manifestations, primarily defined by signs and symptoms rather than a definite underlying cause. Their pathophysiology...Functional gastrointestinal disorders(FGID) are heterogeneous disorders with a variety of clinical manifestations, primarily defined by signs and symptoms rather than a definite underlying cause. Their pathophysiology remains obscure and, although it is expected to differ according to the specific FGID, disruptions in the brain-gut axis are now thought to be a common denominator in their pathogenesis. The hormone ghrelin is an important component of this axis,exerting a wide repertoire of physiological actions, including regulation of gastrointestinal motility and protection of mucosal tissue. Ghrelin's gene shows genetic polymorphism, while its protein product undergoes complex regulation and metabolism in the human body. Numerous studies have studied ghrelin's relation to the emergence of FGIDs, its potential value as an index of disease severity and as a predictive marker for symptom relief during attempted treatment. Despite the mixed results currently available in scientific literature, the plethora of statistically significant findings shows that disruptions in ghrelin genetics and expression are plausibly related to FGID pathogenesis. The aim of this paper is to review current literature studying these associations, in an effort to uncover certain patterns of alterations in both genetics and expression, which could delineate its true contribution to FGID emergence, either as a causative agent or as a pathogenetic intermediate.展开更多
Irritable bowel syndrome(IBS)is a functional disorder characterized by abdominal pain,discomfort and bloating.The pathophysiology of IBS is poorly understood,but the presence of psychosocial basis is now known.There i...Irritable bowel syndrome(IBS)is a functional disorder characterized by abdominal pain,discomfort and bloating.The pathophysiology of IBS is poorly understood,but the presence of psychosocial basis is now known.There is an increasing number of publications supporting the role of genetics in IBS.Most of the variations are found in genes associated with the brain-gut axis,revealing the strong correlation of brain-gut axis and IBS.miRNAs,which play critical roles in physiological processes,are not well studied in IBS.However,so far there is found an involvement of alterations in miRNA expression or sequence,in IBS symptoms.IBS phenotype is affected by epigenetic alteration and environment.Changes in DNA and histone methylation are observed in patients who suffered childhood trauma or abuse,resulting in altered gene expression,such as the glucocorticoid receptor gene.Finally,diet is another factor associated with IBS,which may contribute to symptom onset.Certain foods may affect on bacterial metabolism and epigenetic modifications,predisposing to IBS.展开更多
AIM: The significance of preoperative serum IL-6, TNFα and CRP levels in the progression of colorectal cancer (CRC) has not been fully elucidated. Our intention was to investigate their role and identify their progno...AIM: The significance of preoperative serum IL-6, TNFα and CRP levels in the progression of colorectal cancer (CRC) has not been fully elucidated. Our intention was to investigate their role and identify their prognostic significance. METHODS: The IL-6, TNFa and CRP levels were measured in 74 CRC patients and the relationships between their elevations and both the clinicopathological factors and prognosis of patients were investigated. Serum concentrations of human IL-6 and TNFα were determined by enzyme-linked immunosorbent assay (ELISA). CRP was measured by an immunoturbinometric method. RESULTS: Median IL-6, TNFα and CRP levels were significantly higher in CRC patients than in normal controls. High levels of serum IL-6, TNFα and CRP were correlated with larger tumor size. Furthermore, high IL-6 and high CRP levels were associated with reduced overall survival. CONCLUSION: Serum IL-6, TNFα and CRP levels definitely increase in CRC patients. Pre-operative serum elevation of IL-6 and CRP was thus found to be predictor of the prognosis of CRC patients. The clinical value of TNFα in CRC needs to be further investigated.展开更多
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 comp...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'sesophagus 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.展开更多
AIM: Crohn's disease(CD)and ulcerative colitis(UC)are multifactorial diseases with a significant genetic background.Apart from CARD15/NOD2 gene, evidence is accumulating that molecules related to the innate immune...AIM: Crohn's disease(CD)and ulcerative colitis(UC)are multifactorial diseases with a significant genetic background.Apart from CARD15/NOD2 gene, evidence is accumulating that molecules related to the innate immune response such as CD14 or Toll-like receptor 4 (TLR4), are involved in their pathogenesis. In further exploring the genetic background of these diseases, we investigated the variations in the CARD15/NOD2 gene (Arg702Trp,Gly908Arg and Leu1007fsinsC), and polymorphisms in the TLR4 gene (Asp299Gly and Thr399Ile) as well as in the promoter of the CD14 gene (T/C at position -159) in Greek patients with CD and UC.METHODS: DNA was obtained from 120 patients with CD,85 with UC and 100 healthy individuals. Genotyping was performed by allele specific PCR or by PCR-RFLP analysis.RESULTS: The 299Gly allele frequency of the TLR4 gene and the T allele and TT genotype frequendes of the CD14 promoter were significantly higher in CD patients only compared to healthy individuals (P = 0.026＜0.05; P = 0.0048＜0.01 and P= 0.047＜0.05 respectively). Concerning the NOD2/CARD15mutations the overall presence in CD patients was significantly higher than that in UC patients or in controls.Additionally, 51.67% of the CD patients were carriers of a TLR4 and/or CD14 polymorphic allele and at least one variant of the NOD2/CARD15, compared to 27% of the UC patients. It should be pointed out that both frequencies significantly increased as compared with the 10% frequency of multiple carriers found in healthy controls. A possible interaction of the NOD2/CARD15 with TLR4 and especially CD14, increased the risk of developing inflammatory bowel disease (IBD).CONCLUSION: Our results indicate that co-existence of a mutation in either the TLR4 or CD14 gene, and in NOD2/CARD15is associated with an increased susceptibility to developing CD compared to UC, and to developing either CD or UC compared to healthy individuals.展开更多
AIM: To validate novel single nucleotide polymorphisms (SNPs) in Greek patients with Crohn's disease (CD).METHODS: A total of 120 patients with CD, 85 patients with UC, and 100 unrelated healthy controls were geno...AIM: To validate novel single nucleotide polymorphisms (SNPs) in Greek patients with Crohn's disease (CD).METHODS: A total of 120 patients with CD, 85 patients with UC, and 100 unrelated healthy controls were genotyped. Genotyping was performed by allele-specific PCR or by PCR-RFLP analysis.RESULTS: Our results showed that the 1672T and -207C alleles were obviously over-represented in CD patients only (P＜0.01 and P＜0.05, respectively) compared to the control population. The G113A polymorphism was completely absent in our studied population. The odds ratio for the carriage of the TC haplotype was 2.21 for CD patients as compared with controls. Additionally, the frequency of the TC haplotype was increased in patients with ileocolitis or colitis, and was mainly associated with the fibrostenotic phenotype of the disease. Furthermore, when the TC haplotype was compared jointly with the carriage of at least one mutation of the NOD2/CARD15 gene, there was an increased risk for CD, but not for UC, compared to controls. Regarding the location of the disease, the concomitant presence of the TC haplotype and NOD2/CARD15 mutations was mainly associated with ileocolitis or ileitis. CONCLUSION: Collectively, our results suggest that the 1672T variant of the OCTN1 gene and the -207C variant of the OCTN2 gene represent risk factors for CD in the Greek population.展开更多
AIM： To investigate the association between common single nucleotide polymorphisms （SNPs） in inflammatory response-related genes such as interleukin （IL）-6, IL-8, tumor necrosis factor α （TNFα）, peroxisome pr...AIM： To investigate the association between common single nucleotide polymorphisms （SNPs） in inflammatory response-related genes such as interleukin （IL）-6, IL-8, tumor necrosis factor α （TNFα）, peroxisome proliferators-activated receptor γ （PPARγ）, intercellular adhesion molecule-1 （ICAM-1） and the risk of colorectal cancer （CRC） in a group of Greek patients. METHODS： The study group consisted of 222 CRC patients and 200 healthy controls. Genotyping was performed using allele-specific PCR of PRC-RFLP and the results were confirmed by sequencing. We studied the association of SNPs in the IL-6 （-174G 〉 C）, IL-8 （-251T 〉 A）, TNFα （-308G 〉 A）, ICAM-1 （R241G and K469E）, and PPARγ （Pro12Ala） genes and the risk of CRC. RESULTS： The IL-6 -174G, R241 and K469 alleles of ICAM-1 were associated with increased risk of CRC （OR = 1.77, 95% CI： 1.34-2.34; OR = 1.83, 95% CI： 1.23-2.72; and OR = 1.35, 95% CI： 1.03-1.77 respectively）. The IL-8 and TNFα polymorphisms had no effect. Whereas the PPARγ Pro12 genotype was associated with increased risk of disease （OR = 1.78, 95% CI： 1.25-2.49）. CONCLUSION： The association between common SNPs in immunologic response-related genes and CRC is reported in the present study. Apart from shedding light on the mechanisms of malignancy initiation and progression, SNPs may improve appropriate screening for sub-populations at risk.展开更多
AIM: To assess whether the polymorphisms of NOD2/ CARD15 , autophagy-related 16-like 1 (ATG16L1 ), and interleukin-23 receptor (IL23R ) genes play a more critical role in the susceptibility of childhood-onset than in ...AIM: To assess whether the polymorphisms of NOD2/ CARD15 , autophagy-related 16-like 1 (ATG16L1 ), and interleukin-23 receptor (IL23R ) genes play a more critical role in the susceptibility of childhood-onset than in adult-onset Crohn’s disease (CD). METHODS: Polymorphisms R702W, G908R, and 3020insC of NOD2/CARD15 ; rs2241880 A/G of ATG16L1 , and rs11209026 (R381Q) of IL23R gene were assessed in 110 childhood-onset CD, 364 adult-onset CD, and 539 healthy individuals. Analysis of polymorphisms R702W, G908R, and 3020insC of NOD2/CARD15 genotyping was performed by allele specific polymerase chain reaction (PCR) or by PCR-restriction fragment length polymor-phism analysis. The polymorphisms rs2241880 A/G of the ATG16L1 , and rs11209026 (R381Q) of the IL23R gene in the children’s cohort were genotyped by PCR and melting curve analysis whereas adult group genotyping was performed using the Affymetrix Genome-Wide Human SNP Array 5.0 (500K). RESULTS: The 3020insC allele in NOD2/CARD15 was significantly higher in childhood than in adult-onset CD (P = 0.0067). Association with at least 1 NOD2/CARD15 variant was specific for ileal disease (with or without co- lonic involvement). Even if the frequency of G allele of the rs2241880 ATG16L1 polymorphism was increased in both paediatric and adult CD patients compared to con- trols (P = 0.017 and P = 0.001, respectively), no difference was observed between the childhood and the adult cohort. The rare Q allele of IL23R rs11209026 polymorphism was underrepresented in both paediatric and adult CD cases (P = 0.0018 and P = 0.04, respectively) and no difference was observed between the childhood and the adult cohort. The presence of the rs2241880 ATG16L1 and rs11209026 IL23R polymorphisms did not influence disease phenotype. CONCLUSION: Polymorphism 3020insC in NOD2/ CARD15 occurs statistically significantly more often in patients with childhood-onset CD than in patients with adult-onset CD. The ATG16L1 and IL23R variants are associated with susceptibility to CD, but not earlyonset disease.展开更多
Clock genes create a complicated molecular time-keeping system consisting of multiple positive and negative feedback loops at transcriptional and translational levels. This circadian system coordinates and regulates m...Clock genes create a complicated molecular time-keeping system consisting of multiple positive and negative feedback loops at transcriptional and translational levels. This circadian system coordinates and regulates multiple cellular procedures implicated in cancer development such as metabolism, cell cycle and DNA damage response. Recent data support that molecules such as CLOCK1, BMAL1 and PER and CRY proteins have various effects on c-Myc/p21 and Wnt/β-catenin pathways and influence multiple steps of DNA damage response playing a critical role in the preservation of genomic integrity in normal and cancer cells. Notably, all these events have already been related to the development and progression of colorectal cancer (CRC). Recent data highlight critical correlations between clock genes’ expression and pathogenesis, progression, aggressiveness and prognosis of CRC. Increased expression of positive regulators of this circadian system such as BMAL1 has been related to decrease overall survival while decreased expression of negative regulators such as PER2 and PER3 is connected with poorer differentiation, increased aggressiveness and worse prognosis. The implications of these molecules in DNA repair systems explain their involvement in the development of CRC but at the same time provide us with novel targets for modern therapeutic approaches for patients with advanced CRC.展开更多
Idiopathic inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), are multifactorial diseases that are manifested after disruption of a genetic predisposed individual and its in...Idiopathic inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), are multifactorial diseases that are manifested after disruption of a genetic predisposed individual and its intestinal microflora through an environmental stimulus. Urbanization and industrialization are associated with IBD. Epidemiological data, clinical observations and family/immigrants studies indicate the significance of environmental influence in the development of IBD. Some environmental factors have a different effect on the subtypes of IBD. Smoking and appendectomy is negatively associated with UC, but they are aggravating factors for CD. A westernized high fat diet, full of refined carbohydrates is strongly associated with the development of IBD, contrary to a high in fruit, vegetables and polyunsaturated fatty acid-3 diet that is protective against these diseases. High intake of nonsteroidal antiinflammatory drug and oral contraceptive pills as well as the inadequacy of vitamin D leads to an increased risk for IBD and a more malignant course of disease. Moreover, other factors such as air pollution, psychological factors, sleep disturbances and exercise influence the development and the course of IBD. Epigenetic mechanism like DNA methylation, histone modification and altered expression of miRNAS could explain the connection between genes and environmental factors in triggering the development of IBD.展开更多
Inflammatory bowel diseases(IBD)include a spectrum of chronic inflammatory disorders of the gastrointestinal tract whose pathogenesis is yet to be elucidated.The intestinal microbiome has been studied as a causal comp...Inflammatory bowel diseases(IBD)include a spectrum of chronic inflammatory disorders of the gastrointestinal tract whose pathogenesis is yet to be elucidated.The intestinal microbiome has been studied as a causal component,with certain microbiotic alterations having been observed in subtypes of IBD.Physical exercise is a modulator of the intestinal microbiome,causing shifts in its composition that are partially corrective of those observed in IBD;furthermore,physical exercise may be beneficial in patients with certain IBD subtypes.This review studies the effects of physical exercise on the human gut microbiome while investigating pathophysiologic mechanisms that could explain physical activity’s clinical effects on patients with IBD.展开更多
Treatment of inflammatory bowel disease has significantly improved since the introduction of biological agents, such as infliximab, adalimumab, certolizumab pegol, and golimumab. The Food and Drug Administration has c...Treatment of inflammatory bowel disease has significantly improved since the introduction of biological agents, such as infliximab, adalimumab, certolizumab pegol, and golimumab. The Food and Drug Administration has classified these factors in category B, which means that they do not demonstrate a fetal risk. However, during pregnancy fetuses are exposed to high anti-tumor necrosis factor(TNF) levels that are measurable in their plasma after birth. Since antibodies can transfer through the placenta at the end of the second and during the third trimesters, it is important to know the safety profile of these drugs, particularly for the fetus, and whether maintaining relapse of the disease compensates for the potential risks of fetal exposure. The limited data available for the anti-TNF drugs to date have not demonstrated any significant adverse outcomes in the pregnant women who continued their therapy from conception to the first trimester of gestation. However, data suggest that antiTNFs should be discontinued during the third trimester, as they may affect the immunological system of the newborn baby. Each decision should be individualized, based on the distinct characteristics of the patient and her disease. Considering all the above, there is a need for more clinical studies regarding the effect of antiTNF therapeutic agents on pregnancy outcomes.展开更多
The emergence of coronavirus disease-2019 induced by a newly identified bcoronavirus, namely severe acute respiratory syndrome coronavirus 2(SARSCoV-2) has constituted a public health emergency. Even though it was con...The emergence of coronavirus disease-2019 induced by a newly identified bcoronavirus, namely severe acute respiratory syndrome coronavirus 2(SARSCoV-2) has constituted a public health emergency. Even though it was considered a zoonotic disease, the virus has also spread among humans via respiratory secretions. The expression and distribution of angiotensin converting enzyme type 2(ACE2) in various human organs might also show other possible infection routes. High ACE2 ribonucleic acid expression has been identified in the gastrointestinal tract(GI) indicating its importance as a possible infection pathway of SARS-CoV-2. ACE2 induces viral entry into the host and most importantly has been found to be associated with the function of the gut. Its deficiency has been implicated in several pathologies such as colorectal inflammation. The renin-angiotensin system(RAS) is an essential regulatory cascade operating both at a local tissue level and at the systemic or circulatory level. The RAS may be important in the pathogenesis of chronic liver disease and is associated with the up-regulation of ACE2. Thus, the aim of this review is firstly, the analysis of some important general and genome characteristics of SARS-CoV-2 and secondly, and most importantly, to focus on the utility of ACE2 receptors in both SARS-CoV-2 replication and pathogenesis, especially in the GI tract.展开更多
AIM： To study the association between Crohn＇s disease （CD）, Mycobacterium avium subspecies paratubercuolsis （MAP）, and genetic factors by examining the role of natural resistance-associated macrophage protein 1 ...AIM： To study the association between Crohn＇s disease （CD）, Mycobacterium avium subspecies paratubercuolsis （MAP）, and genetic factors by examining the role of natural resistance-associated macrophage protein 1 （NRAMP1） gene polymorphisms （now SLCllA1） in Sardinian patients with CD and controls. METHODS： Thirty-seven CD patients and 34 controls with no inflammatory bowel disease （IBD） were recruited at the University of Sassari after giving written consent. Six SCL11A1 polymorphisms previously reported to be the most significantly associated with IBD were searched. M, pafatubefculosis was identified by IS900 PCR and sequencing. Logistic regression was used to calculate odds ratios （OR） for the associations among CD, presence of MAP, and 6 loci described above.＇ RESULTS： For the first time, a strong association was observed between polymorphisms at NRAMP1 locus 823C/T and CD. While CD was strongly associated with both NRAMP1 and MAP, NRAMP1 polymorphisms and MAP themselves were not correlated. CONCLUSION： Combined with previous work on the NOD2/CARD15 gene, it is clear that the interplay of genetic, infectious, and immunologic factors in the etiology of CD is complex.展开更多
Colorectal cancer(CRC) is one of the most prevalent malignancies in the world. CRC-associated morbidity and mortality is continuously increasing, in part due to a lack of early detection. The existing screening tools ...Colorectal cancer(CRC) is one of the most prevalent malignancies in the world. CRC-associated morbidity and mortality is continuously increasing, in part due to a lack of early detection. The existing screening tools such as colonoscopy, are invasive and yet high cost, affecting the willingness of patients to participate in screening programs. In recent years, evidence is accumulating that the interaction of aberrant genetic and epigenetic modifications is the cornerstone for the CRC development and progression by alternating the function of tumor suppressor genes, DNA repair genes and oncogenes of colonic cells. Apart from the understanding of the underlying mechanism(s) of carcinogenesis, the aforementioned interaction has also allowed identification of clinical biomarkers, especially epigenetic, for the early detection and prognosis of cancer patients. One of the ways to detect these epigenetic biomarkers is the cell-free circulating DNA(circ DNA), a blood-based cancer diagnostic test, mainly focusing in the molecular alterations found in tumor cells, such as DNA mutations and DNA methylation.In this brief review, we epitomize the current knowledge on the research in circ DNA biomarkers-mainly focusing on DNA methylation-as potential blood-based tests for early detection of colorectal cancer and the challenges for validation and globally implementation of this emergent technology.展开更多
AIM:To detect of colorectal cancer(CRC) circulating tumour cells(CTCs) surface antigens,we present an assay incorporating cadmium selenide quantum dots(QDs) in these paper.METHODS:The principle of the assay is the imm...AIM:To detect of colorectal cancer(CRC) circulating tumour cells(CTCs) surface antigens,we present an assay incorporating cadmium selenide quantum dots(QDs) in these paper.METHODS:The principle of the assay is the immunomagnetic separation of CTCs from body fluids in conjunction with QDs,using specific antibody biomarkers:epithelial cell adhesion molecule antibody,and monoclonal cytokeratin 19 antibody.The detection signal was acquired from the fluorescence signal of QDs.For the evaluation of the performance,the method under study was used to isolate the human colon adenocarcinoma cell line(DLD-1) and CTCs from CRC patients' peripheral blood.RESULTS:The minimum detection limit of the assay was defined to 10 DLD-1 CRC cells/mL as fluorescence was measured with a spectrofluorometer.Fluorescenceactivated cell sorting analysis and Real Time RT-PCR,they both have also been used to evaluate the performance of the described method.In conclusion,we developed a simple,sensitive,efficient and of lower cost(than the existing ones) method for the detection of CRC CTCs in human samples.We have accomplished these results by using magnetic bead isolation and subsequent QD fluorescence detection.CONCLUSION:The method described here can be easily adjusted for any other protein target of either the CTC or the host.展开更多
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 pati...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 standardclinical, 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 HarveyBradshaw 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 nonresponders. 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 antiTNF 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.展开更多
AIM.:To evaluate the association between the interleukin 1β(IL-1β) polymorphisms and the pancreatic neuroendocrine tumor(pN ET) development.METHODS.:A case-control study was conducted analyzing IL-1β polymorphisms ...AIM.:To evaluate the association between the interleukin 1β(IL-1β) polymorphisms and the pancreatic neuroendocrine tumor(pN ET) development.METHODS.:A case-control study was conducted analyzing IL-1β polymorphisms using germline DNA collected in a population-based case-control study of pancreatic cancer(51 pN ET cases,85 pancreatic ductal adenocarcinoma cases,19 intraductal papillary mucinous neoplasm and 98 healthy controls).RESULTS.:The distribution of genotypes for the-511C/T polymorphism in the pN ET patient groups showed significant difference compared to the control group.It is known that the carriers of the IL-1β-511 T allele have increased concentrations of IL-1β.The-511 CT and TT high-expression genotypes were over-represented in pN ET patients.CONCLUSION.:The findings of this study suggested a possible role of IL-1β-511 C/T genotypes in the pathogenesis of pN ETs since the presence of the IL-1β-511 CT and TT genotypes and the T allele was associated with an increased risk of pN ET only.展开更多
Colorectal cancer(CRC),one of the most common cancers of the world,is actually a spectrum of several subtypes,with different molecular profiles,clinicopathological characteristics and possibly separate pathways of pro...Colorectal cancer(CRC),one of the most common cancers of the world,is actually a spectrum of several subtypes,with different molecular profiles,clinicopathological characteristics and possibly separate pathways of progression.It is estimated that in approximately 25-35 of cases,a familial component exists,so they are classified as familial CRC(fCRC).However the known hereditary CRC syndromes justify only up to 5.The rest are attributed to some inherited genetic predisposition passed to offspring through lowpenetrance genes,which in the proper environmental setting can bring on tumorigenesis.Furthermore,part of the familial clustering may be attributed to chance.Because of the complexity regarding the etiology of CRC,the clinician is sometimes faced with obscure patient data,and cannot be sure if they are dealing with fCRC or sporadic CRC.The elucidation of what is going on with the as yet "undefined" portion of CRC will aid not only in the diagnosis,classification and treatment of CRC,but more importantly in the proper adjustment of the screening guidelines and in genetic counselling of patients.展开更多
文摘Alcohol use disorder(AUD)represents a major public health issue which affects millions of people globally and consist a chronic relapsing condition associated with substantial morbidity and mortality.The gut microbiome plays a crucial role in maintaining overall health and has emerged as a significant contributor to the pathophysiology of various psychiatric disorders.Recent evidence suggests that the gut microbiome is intimately linked to the development and progression of AUD,with alcohol consumption directly impacting its composition and function.This review article aims to explore the intricate relationship between the gut microbiome and AUD,focusing on the implications for mental health outcomes and potential therapeutic strategies.We discuss the bidirectional communication between the gut microbiome and the brain,highlighting the role of microbiotaderived metabolites in neuroinflammation,neurotransmission,and mood regulation.Furthermore,we examine the influence of AUD-related factors,such as alcohol-induced gut dysbiosis and increased intestinal permeability,on mental health outcomes.Finally,we explore emerging therapeutic avenues targeting the gut microbiome in the management of AUD,including prebiotics,probiotics,and fecal microbiota transplantation.Understanding the complex interplay between the gut microbiome and AUD holds promise for developing novel interventions that could improve mental health outcomes in individuals with AUD.
文摘Functional gastrointestinal disorders(FGID) are heterogeneous disorders with a variety of clinical manifestations, primarily defined by signs and symptoms rather than a definite underlying cause. Their pathophysiology remains obscure and, although it is expected to differ according to the specific FGID, disruptions in the brain-gut axis are now thought to be a common denominator in their pathogenesis. The hormone ghrelin is an important component of this axis,exerting a wide repertoire of physiological actions, including regulation of gastrointestinal motility and protection of mucosal tissue. Ghrelin's gene shows genetic polymorphism, while its protein product undergoes complex regulation and metabolism in the human body. Numerous studies have studied ghrelin's relation to the emergence of FGIDs, its potential value as an index of disease severity and as a predictive marker for symptom relief during attempted treatment. Despite the mixed results currently available in scientific literature, the plethora of statistically significant findings shows that disruptions in ghrelin genetics and expression are plausibly related to FGID pathogenesis. The aim of this paper is to review current literature studying these associations, in an effort to uncover certain patterns of alterations in both genetics and expression, which could delineate its true contribution to FGID emergence, either as a causative agent or as a pathogenetic intermediate.
文摘Irritable bowel syndrome(IBS)is a functional disorder characterized by abdominal pain,discomfort and bloating.The pathophysiology of IBS is poorly understood,but the presence of psychosocial basis is now known.There is an increasing number of publications supporting the role of genetics in IBS.Most of the variations are found in genes associated with the brain-gut axis,revealing the strong correlation of brain-gut axis and IBS.miRNAs,which play critical roles in physiological processes,are not well studied in IBS.However,so far there is found an involvement of alterations in miRNA expression or sequence,in IBS symptoms.IBS phenotype is affected by epigenetic alteration and environment.Changes in DNA and histone methylation are observed in patients who suffered childhood trauma or abuse,resulting in altered gene expression,such as the glucocorticoid receptor gene.Finally,diet is another factor associated with IBS,which may contribute to symptom onset.Certain foods may affect on bacterial metabolism and epigenetic modifications,predisposing to IBS.
文摘AIM: The significance of preoperative serum IL-6, TNFα and CRP levels in the progression of colorectal cancer (CRC) has not been fully elucidated. Our intention was to investigate their role and identify their prognostic significance. METHODS: The IL-6, TNFa and CRP levels were measured in 74 CRC patients and the relationships between their elevations and both the clinicopathological factors and prognosis of patients were investigated. Serum concentrations of human IL-6 and TNFα were determined by enzyme-linked immunosorbent assay (ELISA). CRP was measured by an immunoturbinometric method. RESULTS: Median IL-6, TNFα and CRP levels were significantly higher in CRC patients than in normal controls. High levels of serum IL-6, TNFα and CRP were correlated with larger tumor size. Furthermore, high IL-6 and high CRP levels were associated with reduced overall survival. CONCLUSION: Serum IL-6, TNFα and CRP levels definitely increase in CRC patients. Pre-operative serum elevation of IL-6 and CRP was thus found to be predictor of the prognosis of CRC patients. The clinical value of TNFα in CRC needs to be further investigated.
文摘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'sesophagus 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.
基金Supported by the EU Project "Sacrohn" N. QLK2-CT-2000-00928.
文摘AIM: Crohn's disease(CD)and ulcerative colitis(UC)are multifactorial diseases with a significant genetic background.Apart from CARD15/NOD2 gene, evidence is accumulating that molecules related to the innate immune response such as CD14 or Toll-like receptor 4 (TLR4), are involved in their pathogenesis. In further exploring the genetic background of these diseases, we investigated the variations in the CARD15/NOD2 gene (Arg702Trp,Gly908Arg and Leu1007fsinsC), and polymorphisms in the TLR4 gene (Asp299Gly and Thr399Ile) as well as in the promoter of the CD14 gene (T/C at position -159) in Greek patients with CD and UC.METHODS: DNA was obtained from 120 patients with CD,85 with UC and 100 healthy individuals. Genotyping was performed by allele specific PCR or by PCR-RFLP analysis.RESULTS: The 299Gly allele frequency of the TLR4 gene and the T allele and TT genotype frequendes of the CD14 promoter were significantly higher in CD patients only compared to healthy individuals (P = 0.026＜0.05; P = 0.0048＜0.01 and P= 0.047＜0.05 respectively). Concerning the NOD2/CARD15mutations the overall presence in CD patients was significantly higher than that in UC patients or in controls.Additionally, 51.67% of the CD patients were carriers of a TLR4 and/or CD14 polymorphic allele and at least one variant of the NOD2/CARD15, compared to 27% of the UC patients. It should be pointed out that both frequencies significantly increased as compared with the 10% frequency of multiple carriers found in healthy controls. A possible interaction of the NOD2/CARD15 with TLR4 and especially CD14, increased the risk of developing inflammatory bowel disease (IBD).CONCLUSION: Our results indicate that co-existence of a mutation in either the TLR4 or CD14 gene, and in NOD2/CARD15is associated with an increased susceptibility to developing CD compared to UC, and to developing either CD or UC compared to healthy individuals.
文摘AIM: To validate novel single nucleotide polymorphisms (SNPs) in Greek patients with Crohn's disease (CD).METHODS: A total of 120 patients with CD, 85 patients with UC, and 100 unrelated healthy controls were genotyped. Genotyping was performed by allele-specific PCR or by PCR-RFLP analysis.RESULTS: Our results showed that the 1672T and -207C alleles were obviously over-represented in CD patients only (P＜0.01 and P＜0.05, respectively) compared to the control population. The G113A polymorphism was completely absent in our studied population. The odds ratio for the carriage of the TC haplotype was 2.21 for CD patients as compared with controls. Additionally, the frequency of the TC haplotype was increased in patients with ileocolitis or colitis, and was mainly associated with the fibrostenotic phenotype of the disease. Furthermore, when the TC haplotype was compared jointly with the carriage of at least one mutation of the NOD2/CARD15 gene, there was an increased risk for CD, but not for UC, compared to controls. Regarding the location of the disease, the concomitant presence of the TC haplotype and NOD2/CARD15 mutations was mainly associated with ileocolitis or ileitis. CONCLUSION: Collectively, our results suggest that the 1672T variant of the OCTN1 gene and the -207C variant of the OCTN2 gene represent risk factors for CD in the Greek population.
文摘AIM： To investigate the association between common single nucleotide polymorphisms （SNPs） in inflammatory response-related genes such as interleukin （IL）-6, IL-8, tumor necrosis factor α （TNFα）, peroxisome proliferators-activated receptor γ （PPARγ）, intercellular adhesion molecule-1 （ICAM-1） and the risk of colorectal cancer （CRC） in a group of Greek patients. METHODS： The study group consisted of 222 CRC patients and 200 healthy controls. Genotyping was performed using allele-specific PCR of PRC-RFLP and the results were confirmed by sequencing. We studied the association of SNPs in the IL-6 （-174G 〉 C）, IL-8 （-251T 〉 A）, TNFα （-308G 〉 A）, ICAM-1 （R241G and K469E）, and PPARγ （Pro12Ala） genes and the risk of CRC. RESULTS： The IL-6 -174G, R241 and K469 alleles of ICAM-1 were associated with increased risk of CRC （OR = 1.77, 95% CI： 1.34-2.34; OR = 1.83, 95% CI： 1.23-2.72; and OR = 1.35, 95% CI： 1.03-1.77 respectively）. The IL-8 and TNFα polymorphisms had no effect. Whereas the PPARγ Pro12 genotype was associated with increased risk of disease （OR = 1.78, 95% CI： 1.25-2.49）. CONCLUSION： The association between common SNPs in immunologic response-related genes and CRC is reported in the present study. Apart from shedding light on the mechanisms of malignancy initiation and progression, SNPs may improve appropriate screening for sub-populations at risk.
文摘AIM: To assess whether the polymorphisms of NOD2/ CARD15 , autophagy-related 16-like 1 (ATG16L1 ), and interleukin-23 receptor (IL23R ) genes play a more critical role in the susceptibility of childhood-onset than in adult-onset Crohn’s disease (CD). METHODS: Polymorphisms R702W, G908R, and 3020insC of NOD2/CARD15 ; rs2241880 A/G of ATG16L1 , and rs11209026 (R381Q) of IL23R gene were assessed in 110 childhood-onset CD, 364 adult-onset CD, and 539 healthy individuals. Analysis of polymorphisms R702W, G908R, and 3020insC of NOD2/CARD15 genotyping was performed by allele specific polymerase chain reaction (PCR) or by PCR-restriction fragment length polymor-phism analysis. The polymorphisms rs2241880 A/G of the ATG16L1 , and rs11209026 (R381Q) of the IL23R gene in the children’s cohort were genotyped by PCR and melting curve analysis whereas adult group genotyping was performed using the Affymetrix Genome-Wide Human SNP Array 5.0 (500K). RESULTS: The 3020insC allele in NOD2/CARD15 was significantly higher in childhood than in adult-onset CD (P = 0.0067). Association with at least 1 NOD2/CARD15 variant was specific for ileal disease (with or without co- lonic involvement). Even if the frequency of G allele of the rs2241880 ATG16L1 polymorphism was increased in both paediatric and adult CD patients compared to con- trols (P = 0.017 and P = 0.001, respectively), no difference was observed between the childhood and the adult cohort. The rare Q allele of IL23R rs11209026 polymorphism was underrepresented in both paediatric and adult CD cases (P = 0.0018 and P = 0.04, respectively) and no difference was observed between the childhood and the adult cohort. The presence of the rs2241880 ATG16L1 and rs11209026 IL23R polymorphisms did not influence disease phenotype. CONCLUSION: Polymorphism 3020insC in NOD2/ CARD15 occurs statistically significantly more often in patients with childhood-onset CD than in patients with adult-onset CD. The ATG16L1 and IL23R variants are associated with susceptibility to CD, but not earlyonset disease.
文摘Clock genes create a complicated molecular time-keeping system consisting of multiple positive and negative feedback loops at transcriptional and translational levels. This circadian system coordinates and regulates multiple cellular procedures implicated in cancer development such as metabolism, cell cycle and DNA damage response. Recent data support that molecules such as CLOCK1, BMAL1 and PER and CRY proteins have various effects on c-Myc/p21 and Wnt/β-catenin pathways and influence multiple steps of DNA damage response playing a critical role in the preservation of genomic integrity in normal and cancer cells. Notably, all these events have already been related to the development and progression of colorectal cancer (CRC). Recent data highlight critical correlations between clock genes’ expression and pathogenesis, progression, aggressiveness and prognosis of CRC. Increased expression of positive regulators of this circadian system such as BMAL1 has been related to decrease overall survival while decreased expression of negative regulators such as PER2 and PER3 is connected with poorer differentiation, increased aggressiveness and worse prognosis. The implications of these molecules in DNA repair systems explain their involvement in the development of CRC but at the same time provide us with novel targets for modern therapeutic approaches for patients with advanced CRC.
基金Supported by The Hellenic State Scholarships Foundation to Legaki E
文摘Idiopathic inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), are multifactorial diseases that are manifested after disruption of a genetic predisposed individual and its intestinal microflora through an environmental stimulus. Urbanization and industrialization are associated with IBD. Epidemiological data, clinical observations and family/immigrants studies indicate the significance of environmental influence in the development of IBD. Some environmental factors have a different effect on the subtypes of IBD. Smoking and appendectomy is negatively associated with UC, but they are aggravating factors for CD. A westernized high fat diet, full of refined carbohydrates is strongly associated with the development of IBD, contrary to a high in fruit, vegetables and polyunsaturated fatty acid-3 diet that is protective against these diseases. High intake of nonsteroidal antiinflammatory drug and oral contraceptive pills as well as the inadequacy of vitamin D leads to an increased risk for IBD and a more malignant course of disease. Moreover, other factors such as air pollution, psychological factors, sleep disturbances and exercise influence the development and the course of IBD. Epigenetic mechanism like DNA methylation, histone modification and altered expression of miRNAS could explain the connection between genes and environmental factors in triggering the development of IBD.
文摘Inflammatory bowel diseases(IBD)include a spectrum of chronic inflammatory disorders of the gastrointestinal tract whose pathogenesis is yet to be elucidated.The intestinal microbiome has been studied as a causal component,with certain microbiotic alterations having been observed in subtypes of IBD.Physical exercise is a modulator of the intestinal microbiome,causing shifts in its composition that are partially corrective of those observed in IBD;furthermore,physical exercise may be beneficial in patients with certain IBD subtypes.This review studies the effects of physical exercise on the human gut microbiome while investigating pathophysiologic mechanisms that could explain physical activity’s clinical effects on patients with IBD.
文摘Treatment of inflammatory bowel disease has significantly improved since the introduction of biological agents, such as infliximab, adalimumab, certolizumab pegol, and golimumab. The Food and Drug Administration has classified these factors in category B, which means that they do not demonstrate a fetal risk. However, during pregnancy fetuses are exposed to high anti-tumor necrosis factor(TNF) levels that are measurable in their plasma after birth. Since antibodies can transfer through the placenta at the end of the second and during the third trimesters, it is important to know the safety profile of these drugs, particularly for the fetus, and whether maintaining relapse of the disease compensates for the potential risks of fetal exposure. The limited data available for the anti-TNF drugs to date have not demonstrated any significant adverse outcomes in the pregnant women who continued their therapy from conception to the first trimester of gestation. However, data suggest that antiTNFs should be discontinued during the third trimester, as they may affect the immunological system of the newborn baby. Each decision should be individualized, based on the distinct characteristics of the patient and her disease. Considering all the above, there is a need for more clinical studies regarding the effect of antiTNF therapeutic agents on pregnancy outcomes.
文摘The emergence of coronavirus disease-2019 induced by a newly identified bcoronavirus, namely severe acute respiratory syndrome coronavirus 2(SARSCoV-2) has constituted a public health emergency. Even though it was considered a zoonotic disease, the virus has also spread among humans via respiratory secretions. The expression and distribution of angiotensin converting enzyme type 2(ACE2) in various human organs might also show other possible infection routes. High ACE2 ribonucleic acid expression has been identified in the gastrointestinal tract(GI) indicating its importance as a possible infection pathway of SARS-CoV-2. ACE2 induces viral entry into the host and most importantly has been found to be associated with the function of the gut. Its deficiency has been implicated in several pathologies such as colorectal inflammation. The renin-angiotensin system(RAS) is an essential regulatory cascade operating both at a local tissue level and at the systemic or circulatory level. The RAS may be important in the pathogenesis of chronic liver disease and is associated with the up-regulation of ACE2. Thus, the aim of this review is firstly, the analysis of some important general and genome characteristics of SARS-CoV-2 and secondly, and most importantly, to focus on the utility of ACE2 receptors in both SARS-CoV-2 replication and pathogenesis, especially in the GI tract.
文摘AIM： To study the association between Crohn＇s disease （CD）, Mycobacterium avium subspecies paratubercuolsis （MAP）, and genetic factors by examining the role of natural resistance-associated macrophage protein 1 （NRAMP1） gene polymorphisms （now SLCllA1） in Sardinian patients with CD and controls. METHODS： Thirty-seven CD patients and 34 controls with no inflammatory bowel disease （IBD） were recruited at the University of Sassari after giving written consent. Six SCL11A1 polymorphisms previously reported to be the most significantly associated with IBD were searched. M, pafatubefculosis was identified by IS900 PCR and sequencing. Logistic regression was used to calculate odds ratios （OR） for the associations among CD, presence of MAP, and 6 loci described above.＇ RESULTS： For the first time, a strong association was observed between polymorphisms at NRAMP1 locus 823C/T and CD. While CD was strongly associated with both NRAMP1 and MAP, NRAMP1 polymorphisms and MAP themselves were not correlated. CONCLUSION： Combined with previous work on the NOD2/CARD15 gene, it is clear that the interplay of genetic, infectious, and immunologic factors in the etiology of CD is complex.
文摘Colorectal cancer(CRC) is one of the most prevalent malignancies in the world. CRC-associated morbidity and mortality is continuously increasing, in part due to a lack of early detection. The existing screening tools such as colonoscopy, are invasive and yet high cost, affecting the willingness of patients to participate in screening programs. In recent years, evidence is accumulating that the interaction of aberrant genetic and epigenetic modifications is the cornerstone for the CRC development and progression by alternating the function of tumor suppressor genes, DNA repair genes and oncogenes of colonic cells. Apart from the understanding of the underlying mechanism(s) of carcinogenesis, the aforementioned interaction has also allowed identification of clinical biomarkers, especially epigenetic, for the early detection and prognosis of cancer patients. One of the ways to detect these epigenetic biomarkers is the cell-free circulating DNA(circ DNA), a blood-based cancer diagnostic test, mainly focusing in the molecular alterations found in tumor cells, such as DNA mutations and DNA methylation.In this brief review, we epitomize the current knowledge on the research in circ DNA biomarkers-mainly focusing on DNA methylation-as potential blood-based tests for early detection of colorectal cancer and the challenges for validation and globally implementation of this emergent technology.
基金Supported by The John S Latsis Public Benefit FoundationThe Hellenic Society of Medical Oncology
文摘AIM:To detect of colorectal cancer(CRC) circulating tumour cells(CTCs) surface antigens,we present an assay incorporating cadmium selenide quantum dots(QDs) in these paper.METHODS:The principle of the assay is the immunomagnetic separation of CTCs from body fluids in conjunction with QDs,using specific antibody biomarkers:epithelial cell adhesion molecule antibody,and monoclonal cytokeratin 19 antibody.The detection signal was acquired from the fluorescence signal of QDs.For the evaluation of the performance,the method under study was used to isolate the human colon adenocarcinoma cell line(DLD-1) and CTCs from CRC patients' peripheral blood.RESULTS:The minimum detection limit of the assay was defined to 10 DLD-1 CRC cells/mL as fluorescence was measured with a spectrofluorometer.Fluorescenceactivated cell sorting analysis and Real Time RT-PCR,they both have also been used to evaluate the performance of the described method.In conclusion,we developed a simple,sensitive,efficient and of lower cost(than the existing ones) method for the detection of CRC CTCs in human samples.We have accomplished these results by using magnetic bead isolation and subsequent QD fluorescence detection.CONCLUSION:The method described here can be easily adjusted for any other protein target of either the CTC or the host.
文摘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 standardclinical, 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 HarveyBradshaw 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 nonresponders. 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 antiTNF 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.
基金Supported by Hellenic Society of Medical OncologyNo.5839/08--04--2015
文摘AIM.:To evaluate the association between the interleukin 1β(IL-1β) polymorphisms and the pancreatic neuroendocrine tumor(pN ET) development.METHODS.:A case-control study was conducted analyzing IL-1β polymorphisms using germline DNA collected in a population-based case-control study of pancreatic cancer(51 pN ET cases,85 pancreatic ductal adenocarcinoma cases,19 intraductal papillary mucinous neoplasm and 98 healthy controls).RESULTS.:The distribution of genotypes for the-511C/T polymorphism in the pN ET patient groups showed significant difference compared to the control group.It is known that the carriers of the IL-1β-511 T allele have increased concentrations of IL-1β.The-511 CT and TT high-expression genotypes were over-represented in pN ET patients.CONCLUSION.:The findings of this study suggested a possible role of IL-1β-511 C/T genotypes in the pathogenesis of pN ETs since the presence of the IL-1β-511 CT and TT genotypes and the T allele was associated with an increased risk of pN ET only.
文摘Colorectal cancer(CRC),one of the most common cancers of the world,is actually a spectrum of several subtypes,with different molecular profiles,clinicopathological characteristics and possibly separate pathways of progression.It is estimated that in approximately 25-35 of cases,a familial component exists,so they are classified as familial CRC(fCRC).However the known hereditary CRC syndromes justify only up to 5.The rest are attributed to some inherited genetic predisposition passed to offspring through lowpenetrance genes,which in the proper environmental setting can bring on tumorigenesis.Furthermore,part of the familial clustering may be attributed to chance.Because of the complexity regarding the etiology of CRC,the clinician is sometimes faced with obscure patient data,and cannot be sure if they are dealing with fCRC or sporadic CRC.The elucidation of what is going on with the as yet "undefined" portion of CRC will aid not only in the diagnosis,classification and treatment of CRC,but more importantly in the proper adjustment of the screening guidelines and in genetic counselling of patients.
