AIM： To evaluate the role of genetic factors in the pathogenesis of Crohn＇s disease （CD） and ulcerative colitis （UC）, we investigated the single nucleotide polymorphisms （SNPs） of NOD2/CARD15 （R702W, Gg08R an...AIM： To evaluate the role of genetic factors in the pathogenesis of Crohn＇s disease （CD） and ulcerative colitis （UC）, we investigated the single nucleotide polymorphisms （SNPs） of NOD2/CARD15 （R702W, Gg08R and L1007finsC）, and Toll-like receptor 4 （TLR4） genes （D299G and T399I） in a selected inflammatory bowel disease （IBD） population coming from Southern Italy. METHODS： Allele and genotype frequencies of NOD2/ CARD15 （R702W, Gg08R and L1007finsC） and TLR4 （D299G and T399I） SNPs were examined in 133 CD patients, in 45 UC patients, and in 103 healthy controls. A genotype-phenotype correlation was performed. RESULTS： NOD2/CARD15 R702W mutation was significantly more frequent in CD （9.8%） than in controls （2.4%, P = 0.001） and in UC （2.3%, P = 0.03）. No significant difference was found between UC patients and control group （P 〉 0.05）. In CD and UC patients, no significant association with G908R variant was found. L1007finsC SNP showed an association with CD （9.8%） compared with controls （2.9%, P = 0.002） and UC patients （2.3%, P = 0.01）. Moreover, in CD patients, G908R and L1007finsC mutations were significantly associated with different phenotypes compared to CD wild-type patients. No association of IBD with the TLR4 SNPs was found in either cohort （allele frequencies： D299G-controls 3.9%, CD 3.7%, UC 3.4%, P 〉 0.05; T399I-controls 2.9%, CD 3.0%, UC 3.4%, P 〉 0.05）. CONCLUSION： These findings confirm that, in our IBD patients selected from Southern Italy, the NOD2/ CARD15, but not TLR4 SNPs, are associated with increased risk of CD.展开更多
AIM： To evaluate the predictive value of hepatocyte proliferation and hepatic angiogenesis for the occurrence of Hepatocellular carcinoma （HCC） in hepatitis C virus （HCV） cirrhotic patients.METHODS： One hundred-...AIM： To evaluate the predictive value of hepatocyte proliferation and hepatic angiogenesis for the occurrence of Hepatocellular carcinoma （HCC） in hepatitis C virus （HCV） cirrhotic patients.METHODS： One hundred-five patients （69 males, 36 females; age range, 51-90 year; median 66 year） with biopsy proven HCV cirrhosis were prospectively monitored for HCC occurrence for a median time of 64 too. Angiogenesis was assessed by using microvessel density （MVD）, hepatocyte turnover by MIB1 and PCNA indexes at inclusion in liver biopsies.RESULTS： Forty six patients （43.8%） developed HCC after a median time of 55 （6-120） mo while 59 （56.2%） did not. Patients were divided into two groups according to the median value of each index. The difference between patients with low （median MVD = 3; range 0-20） and high （median MVD = 7; range 1-24） MVD was statist（caUy s（gn（ficant （χ^2= 22.06; P 〈 0.0001） wh（ch was not the case for MIB1 or PCNA （MIB-I： χ^2 = 1.41; P = 0.2351; PCNA： χ^2 = 1.27; P = 0.2589）. The median MVD was higher in patients who developed HCC than in those who did not. HOe-free interval was significantly longer in patients with the MVD ≤ 4 （P = 0.0006）. No relationship was found between MIB1 or PCNA and MVD （MIB-1 r^2 = 0.00007116, P = 0.9281; PCNA： P =0.001950; P = 0.6692）. MVD only was able to predict the occurrence of HCC in these patients. Among other known risk factors for HCC, only male sex was statistically associated with an increased risk. CONCLUSION： Liver angiogenesis has a role for in HCV- related liver carcinogenesis and for defining patients at higher risk.展开更多
AIM: To investigate the behaviour of total plasma homocysteine (tHcy) and its most common genetic determinant defect, the methylenetetrahydrofolate reductase C677T (C677TMTHFR) polymorphism in patients with early stag...AIM: To investigate the behaviour of total plasma homocysteine (tHcy) and its most common genetic determinant defect, the methylenetetrahydrofolate reductase C677T (C677TMTHFR) polymorphism in patients with early stage colorectal carcinoma. METHODS: tHcy was quantified by Abbott IMx immunoassay; screening for C677TMTHFR substitution was performed by PCR and restriction analysis. RESULTS: The frequency of the C/T and T/T genotypes of the C677TMTHFR gene polymorphism did not differ between the groups. The mean tHcy was statistically higher in cancer patients than in control subjects carrying the same C/C or C/T genotype, whereas there was no difference in the T/T homozygous carriers of the two groups. tHcy was significantly higher in the T/T homozygous carriers than in C/C and C/T genotype carriers. CONCLUSION: The statistically significant increase of tHcy observed in C/C and C/T genotype carriers among our cancer patients is related to substrate consumption dependent on the tumor cell proliferation rate, whereas the tHcy increase observed in T/T genotype carriers of both groups probably depends on the enzymatic deficit of the homocysteine conversion to methionine and/or on the folate deficiency.展开更多
CD44, in its standard form as well in its isoforms, is a cell surface adhesion glycoprotein which occurs in a widevariety of non-neoplastic and neoplastic ceils. CD44 has been considered to be implicated in tumoral gr...CD44, in its standard form as well in its isoforms, is a cell surface adhesion glycoprotein which occurs in a widevariety of non-neoplastic and neoplastic ceils. CD44 has been considered to be implicated in tumoral growth andin metastatic potential. We studied the immunohistochemical expression of CD44 standard in 30 oligodendrogliomas(19 primary lesions and 11 recurrences) in order to verify its possible prognostic role. Twelve primary oligoden-展开更多
AIM： To analyze the prevalence of the two commonest thrombophilic mutations, factor V Leiden and prothrombin G20210A, in patients with gastric cancer. METHODS： One hundred and twenty-one patients with primary gastri...AIM： To analyze the prevalence of the two commonest thrombophilic mutations, factor V Leiden and prothrombin G20210A, in patients with gastric cancer. METHODS： One hundred and twenty-one patients with primary gastric carcinoma and 130 healthy subjects, comparable for age and sex, were investigated. Factor V Leiden was detected by using polymerase chain reaction and restriction enzyme digestion, and prothrombin G20210A gene mutation by allele-specific PCR. RESULTS： Among the 121 cancer patients, factor V Leiden was found in 4 cases （GA genotype： 3.3%） and prothrombin G20210A in 10 cases （GA genotype： 8.3%）. Of the 130 control subjects, factor V Leiden was detected in 6 cases （GA genotype： 4.6%） and prothrombin G20210A in 8 cases （GA genotype： 6.1%）. No double heterozygous carriers of both mutations were found in either group. The prevalence of both factor V Leiden and prothrombin G20210A variant was not statistically different between the cancer patients and the healthy subjects. CONCLUSION： Our study suggests that, in gastric cancer, the risk factors of thrombophilic cancer state are on acquired rather than on a genetic basis and that prothrombin G20210A does not seem to be a cofactor in gastric cancer pathogenesis.展开更多
文摘AIM： To evaluate the role of genetic factors in the pathogenesis of Crohn＇s disease （CD） and ulcerative colitis （UC）, we investigated the single nucleotide polymorphisms （SNPs） of NOD2/CARD15 （R702W, Gg08R and L1007finsC）, and Toll-like receptor 4 （TLR4） genes （D299G and T399I） in a selected inflammatory bowel disease （IBD） population coming from Southern Italy. METHODS： Allele and genotype frequencies of NOD2/ CARD15 （R702W, Gg08R and L1007finsC） and TLR4 （D299G and T399I） SNPs were examined in 133 CD patients, in 45 UC patients, and in 103 healthy controls. A genotype-phenotype correlation was performed. RESULTS： NOD2/CARD15 R702W mutation was significantly more frequent in CD （9.8%） than in controls （2.4%, P = 0.001） and in UC （2.3%, P = 0.03）. No significant difference was found between UC patients and control group （P 〉 0.05）. In CD and UC patients, no significant association with G908R variant was found. L1007finsC SNP showed an association with CD （9.8%） compared with controls （2.9%, P = 0.002） and UC patients （2.3%, P = 0.01）. Moreover, in CD patients, G908R and L1007finsC mutations were significantly associated with different phenotypes compared to CD wild-type patients. No association of IBD with the TLR4 SNPs was found in either cohort （allele frequencies： D299G-controls 3.9%, CD 3.7%, UC 3.4%, P 〉 0.05; T399I-controls 2.9%, CD 3.0%, UC 3.4%, P 〉 0.05）. CONCLUSION： These findings confirm that, in our IBD patients selected from Southern Italy, the NOD2/ CARD15, but not TLR4 SNPs, are associated with increased risk of CD.
基金Supported by Grants from the Italian Ministry of University, Scientific and Technological Research (MIUR, Progetto Nazionale cofinanziato COFIN No. 2002067115)the University of Florence to R. M.
文摘AIM： To evaluate the predictive value of hepatocyte proliferation and hepatic angiogenesis for the occurrence of Hepatocellular carcinoma （HCC） in hepatitis C virus （HCV） cirrhotic patients.METHODS： One hundred-five patients （69 males, 36 females; age range, 51-90 year; median 66 year） with biopsy proven HCV cirrhosis were prospectively monitored for HCC occurrence for a median time of 64 too. Angiogenesis was assessed by using microvessel density （MVD）, hepatocyte turnover by MIB1 and PCNA indexes at inclusion in liver biopsies.RESULTS： Forty six patients （43.8%） developed HCC after a median time of 55 （6-120） mo while 59 （56.2%） did not. Patients were divided into two groups according to the median value of each index. The difference between patients with low （median MVD = 3; range 0-20） and high （median MVD = 7; range 1-24） MVD was statist（caUy s（gn（ficant （χ^2= 22.06; P 〈 0.0001） wh（ch was not the case for MIB1 or PCNA （MIB-I： χ^2 = 1.41; P = 0.2351; PCNA： χ^2 = 1.27; P = 0.2589）. The median MVD was higher in patients who developed HCC than in those who did not. HOe-free interval was significantly longer in patients with the MVD ≤ 4 （P = 0.0006）. No relationship was found between MIB1 or PCNA and MVD （MIB-1 r^2 = 0.00007116, P = 0.9281; PCNA： P =0.001950; P = 0.6692）. MVD only was able to predict the occurrence of HCC in these patients. Among other known risk factors for HCC, only male sex was statistically associated with an increased risk. CONCLUSION： Liver angiogenesis has a role for in HCV- related liver carcinogenesis and for defining patients at higher risk.
基金Supported by a research grant from the University of Siena (PAR)
文摘AIM: To investigate the behaviour of total plasma homocysteine (tHcy) and its most common genetic determinant defect, the methylenetetrahydrofolate reductase C677T (C677TMTHFR) polymorphism in patients with early stage colorectal carcinoma. METHODS: tHcy was quantified by Abbott IMx immunoassay; screening for C677TMTHFR substitution was performed by PCR and restriction analysis. RESULTS: The frequency of the C/T and T/T genotypes of the C677TMTHFR gene polymorphism did not differ between the groups. The mean tHcy was statistically higher in cancer patients than in control subjects carrying the same C/C or C/T genotype, whereas there was no difference in the T/T homozygous carriers of the two groups. tHcy was significantly higher in the T/T homozygous carriers than in C/C and C/T genotype carriers. CONCLUSION: The statistically significant increase of tHcy observed in C/C and C/T genotype carriers among our cancer patients is related to substrate consumption dependent on the tumor cell proliferation rate, whereas the tHcy increase observed in T/T genotype carriers of both groups probably depends on the enzymatic deficit of the homocysteine conversion to methionine and/or on the folate deficiency.
文摘CD44, in its standard form as well in its isoforms, is a cell surface adhesion glycoprotein which occurs in a widevariety of non-neoplastic and neoplastic ceils. CD44 has been considered to be implicated in tumoral growth andin metastatic potential. We studied the immunohistochemical expression of CD44 standard in 30 oligodendrogliomas(19 primary lesions and 11 recurrences) in order to verify its possible prognostic role. Twelve primary oligoden-
基金Supported by a Research Grant from the University of Siena (PAR)
文摘AIM： To analyze the prevalence of the two commonest thrombophilic mutations, factor V Leiden and prothrombin G20210A, in patients with gastric cancer. METHODS： One hundred and twenty-one patients with primary gastric carcinoma and 130 healthy subjects, comparable for age and sex, were investigated. Factor V Leiden was detected by using polymerase chain reaction and restriction enzyme digestion, and prothrombin G20210A gene mutation by allele-specific PCR. RESULTS： Among the 121 cancer patients, factor V Leiden was found in 4 cases （GA genotype： 3.3%） and prothrombin G20210A in 10 cases （GA genotype： 8.3%）. Of the 130 control subjects, factor V Leiden was detected in 6 cases （GA genotype： 4.6%） and prothrombin G20210A in 8 cases （GA genotype： 6.1%）. No double heterozygous carriers of both mutations were found in either group. The prevalence of both factor V Leiden and prothrombin G20210A variant was not statistically different between the cancer patients and the healthy subjects. CONCLUSION： Our study suggests that, in gastric cancer, the risk factors of thrombophilic cancer state are on acquired rather than on a genetic basis and that prothrombin G20210A does not seem to be a cofactor in gastric cancer pathogenesis.
