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Relation between common polymorphisms in genes related to inflammatory response and colorectal cancer

World Journal of Gastroenterology 2006年第31期12卷 5037-5043页

作者： George Theodoropoulos Ioannis Papaconstantinou Evangelos Felekouras Nikolaos Nikiteas petros karakitsos Dimitris Panoussopoulos Andreas Ch Lazaris Efstratios Patsouris John Bramis Maria Gazouli 1st Propaideutic Surgical DepartmentHippocration University Hospital School of MedicineUniversity of AthensGreece 1st Surgical DepartmentLaikon University Hospital University of AthensGreece Department of PathologySchool of Medicine University of AthensGreece 2nd Propaideutic Surgical DepartmentLaikon University Hospital University of AthensGreece Department of CytopathologyUniversity General Hospital "Artikon" University of AthensGreece Department of BiologySchool of Medicine University of AthensGreece

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.

关键词： Colorectal cancer Inflammation Single nucleotide polymorphisms

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Integrating TYMS, KRAS and BRAF testing in patients with metastatic colorectal cancer

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World Journal of Gastroenterology 2017年第32期23卷 5913-5924页

作者： Anastasios Ntavatzikos Aris Spathis Paul Patapis Nikolaos Machairas George Peros Stefanos Konstantoudakis Danai Leventakou Ioannis G Panayiotides petros karakitsos Anna Koumarianou Hematology-Oncology Unit 4^th Department of Internal MedicineMedical SchoolNational and Kapodistrian University of Athens“ATTIKON”University Hospital Department of Cytopathology National and Kapodistrian University of AthensMedical School“ATTIKON”University Hospital 3^rd Department of Surgery Medical SchoolNational and Kapodistrian University of Athens“ATTIKON”University Hospital Department of Surgery Medical SchoolNational and Kapodistrian University of AthensEvgenideio Therapeutirio S.A.“I AGIA TRIAS”11528 AthensGreece 2^nd Department of Pathology University of AthensMedical School“ATTIKON”University Hospital

AIM To investigate the impact of thymidylate synthase(TYMS), KRAS and BRAF in the survival of metastatic colorectal cancer(m CRC) patients treated with chemotherapy. METHODS Clinical data were collected retrospectively from records of consecutive patients with m CRC treated with fluoropyrimidine-based chemotherapy from 1/2005 to 1/2007. Formalin-fixed paraffin-embedded tissues were retrieved for analysis. TYMS genotypes were identified with restriction fragment analysis PCR, while KRAS and BRAF mutation status was evaluated using real-time PCR assays. TYMS gene polymorphisms of each of the 3' untranslated region(UTR) and 5'UTR were classified into three groups according to the probability they have for high, medium and low TYMS expression(and similar levels of risk) based on evidence from previous studies. Univariate and multivariate survival analyses were *** The analysis recovered 89 patients with m CRC(46.1% de novo metastatic disease and 53.9% relapsed). Of these, 46 patients(51.7%) had colon cancer and 43(48.3%) rectal cancer as primary. All patients were treated with fluoropyrimidine-based chemotherapy(5FU or capecitabine) as single-agent or in combination with irinotecan or/and oxaliplatin or/and bevacizumab. With a median follow-up time of 14.8 mo(range 0-119.8), 85 patients(95.5%) experienced disease progression, and 63 deaths(70.8%) were recorded. The 3-year and 5-year OS rate was 25.4% and 7.7% while the 3-year progression-free survival rate was 7.1%. Multivariate analysis of TYMS polymorphisms, KRAS and BRAF with clinicopathological parameters indicated that TYMS 3'UTR polymorphisms are associated with risk for disease progression and death(P < 0.05 and P < 0.03 respectively). When compared to tumors without any del allele(genotypes ins/ins and ins/loss of heterozygosity(LOH) linked with high TYMS expression) tumors with del/del genotype(low expression group) and tumors with ins/del or del/LOH(intermediate expression group) have lower risk

关键词： Thymidylate synthase Polymorphisms m CRC Loss of heterozygosity Survival Chemotherapy KRAS BRAF TYMS

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Cytopathologic diagnosis of fine needle aspiration biopsies of thyroid nodules

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World Journal of Clinical Cases 2016年第2期4卷 38-48页

作者： Evangelos P Misiakos Niki Margari Christos Meristoudis Nickolas Machairas Dimitrios Schizas Konstantinos Petropoulos Aris Spathis petros karakitsos Anastasios Machairas 3rd Department of Surgery Attikon University Hospital University of Athens School of Medicine Department of Cytopathology Attikon University HospitalUniversity of Athens School of Medicine 2nd Department of Propedeutic Surgery Laiko HospitalUniversity of Athens School of Medicine

Fine-needle aspiration(FNA) cytology is an important diagnostic tool in patients with thyroid *** systems have been proposed for the cyropathologic diagnosis of the thyroid *** cases with indeterminate cytological findings still remain a matter of *** this review we analyze all literature regarding Thyroid Cytopathology Reporting systems trying to identify the most suitable methodology to use in clinical practice for the preoperative diagnosis of thyroid nodules.A review of the English literature was conducted,and data were analyzed and summarized and integrated from the authors' *** main purpose of thyroid FNA is to identify patients with higher risk for malignancy,and to prevent unnecessary surgeries for benign *** Bethesda System for Reporting Thyroid Cytopathology is the most widely used system for the diagnosis of thyroid FNA *** system also contains guidelines for the diagnosis and treatment of indeterminate or suspicious for malignancy *** conclusion,patients who require repeated FNAs for indeterminate diagnoses will be resolved by repeat FNA in a percentage of 72%-80%.

关键词： Thyroid Cytopathology Nodule Papillary cancer Fine needle Biopsy

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Promoter Methylation, BRAF Mutation Analysis and Topoisomerase IIa Expression for the Detection of Endometrial Carcinoma in Liquid Based Cytology Samples

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Journal of Cancer Therapy 2013年第5期4卷 19-27页

作者： Aris Spathis Vasileios Sioulas Evaggelia Aga Dionissios Aninos Christine Kottaridi Emmanouil Terzakis Charalambos Chrelias petros karakitsos 2nd Department of Gynecology St. Savvas Anticancer-Oncologic Hospital Athens Greece. 3rd Department of Obstetrics and Gynecology School of Medicine University General Hospital “ATTIKON” National and Kapodistrian University of Athens Athens Greece Department of Cytopathology School of Medicine University General Hospital “ATTIKON” National and Kapodistrian University of Athens Athens Greece

Cancer of the corpus uteri remains the most common gynecological related cancer in developed countries. Cytology, after the induction of liquid based cytology, has reemerged as a possible first line non-interventional diagnostic procedure with promising results. Apart from slide preparation for cytology diagnosis, LBC allows the application of elaborate molecular tests on the residual material. Samples from 74 symptomatic women were collected in ThinPrep?PreservCyt medium, from witch immunocytochemical and molecular tests were performed. Final diagnosis of 39 endometrioid carcinomas, 20 non-endometrioid carcinomas and 15 non-malignant was set after hysterectomy. Topoisomerase IIa expression was common (42%) in both types of cancer. Promoter methylation analysis revealed that hMLH1 is commonly methylated in cancers (52.7%), CDKN2A and MGMT less often (27.1%) and RARB rarely methylated (8.4%). BRAF activating mutation V600E was a rare event (8.4%) only found in low grade endometrioid carcinomas. Topoisomerase IIa expression correlated with BRAF mutations, hMLH1 and to lesser extent with CDKN2A methylation. Almost none of the biomarkers were positive in cytological negative or hyperplastic without atypia samples. Detection of methylation in any gene displayed sensitivity, specificity, PPV and NPV similar to cytology of cancer. However, inclusion of cytology diagnosis of hyperlasias with atypia increased sensitivity and NPV of cytology outperforming methylation of any gene. Further evaluation of the panel of promoter methylation, especially in cytology diagnoses of hyperplasia with or without atypia should be evaluated since initial results are promising. Even though methylation of MGMT and RARB are rare events, some patients could be benefit from specific chemotherapeutics that target either of them or the more frequently expressed topoisomerase IIa.

关键词： Endometrial Cancer Promoter Methylation Topoisomerase IIa BRAF Liquid Based Cytology

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Increased levels of circulating platelet-derived microparticles in psoriasis:Possible implications for the associated cardiovascular risk

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World Journal of Cardiology 2016年第11期8卷 667-675页

作者： Evangelia Papadavid Konstantina Diamanti Aris Spathis Maria Varoudi Ioanna Andreadou Kostas Gravanis Kostas Theodoropoulos petros karakitsos John Lekakis Dimitrios Rigopoulos Ignatios Ikonomidis 2~(nd) Department of Dermatology and Venereology University of Athens Medical SchoolAttikon Hospital Department of Cytopathology University of Athens Medical SchoolAttikon Hospital 2~(nd) Department of Cardiology University of Athens Medical SchoolAttikon Hospital Department of Pharmaceutical Chemistry University of Athens School of Pharmacy

AIM To evaluate platelet activation markers in psoriasis patients, compared to controls, and investigate their association with the inflammatory burden of *** Forty psoriatic patients without cardiovascular disease,and 12 healthy controls were subjected to measurement of baseline platelet CD62 P, CD63 and CD42 b expression, platelet-leukocyte complexes, i.e., platelet-monocyte complexes(PMC), platelet-neutrophil complexes(PNC) and platelet-lymphocyte complexes, and concentrations of platelet-derived microparticles(PMPs) using flow cytometry. Both larger-size(0.5-0.9 μm) and smallersize(< 0.5 μm) PMPs were determined. Serum interleukin(IL)-12 and IL-17 levels were also measured by enzyme-linked immunosorbent assay. The severity of psoriasis was evaluated by the Psoriasis Area Severity Index(PASI).RESULTS PMP concentrations were significantly higher in psoriasis patients than controls [mean±standard error of mean(SEM): 22±5/μL vs 11±6/μL; P=0.018), for both smaller-size(10±2/μL vs 4±2/μL; P=0.033) and larger-size(12±3/μL vs 6±4/μL; P=0.014) PMPs. Platelet CD62 P, CD63 and CD42 b expression and circulating PMC and PNC were similar between the two groups. Lower circulating PLC were observed in psoriasis patients compared to controls(mean±SEM: 16%±3% vs 23%±6%; P=0.047). Larger-size PMPs were related with IL-12 levels(P<0.001) and smaller-size PMPs with both IL-12 and IL-17 levels(P<0.001). Total PMPs also correlated with IL-12(P<0.001). CD63 expression was positively correlated with both IL-12 and IL-17(P<0.05). Increased PASI score was associated with increased levels of larger-size PMPs(r=0.45; P=0.011) and increased CD63 expression(r=0.47; P<0.01).CONCLUSION PMPs, known to be predictive of cardiovascular outcomes, are increased in psoriasis patients, and associated with high inflammatory disease burden. Enhanced platelet activation may be the missing link leading to cardiovascular events in psoriatic patients.

关键词： Psoriasis Atherosclerosis Inflammation Platelet activation Platelet-derived microparticles

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