AIM To establish the relationship of protein tyrosine phosphatase non-receptor type 2 and 22(PTPN2/22) polymorphisms and mycobacterial infections in Crohn's disease(CD). METHODS All 133 subjects' blood samples...AIM To establish the relationship of protein tyrosine phosphatase non-receptor type 2 and 22(PTPN2/22) polymorphisms and mycobacterial infections in Crohn's disease(CD). METHODS All 133 subjects' blood samples were genotyped for nine single nucleotide polymorphisms(SNPs) in PTPN2/22 using TaqMan^(?) genotyping, while the effect of the SNPs on PTPN2/22 and IFN-γ gene expression was determined using RT-PCR. Detection of Mycobacterium avium subspecies paratuberculosis(MAP) IS900 gene was done by nPCR after DNA extraction from the isolated leukocytes of each subjects' blood samples. T-cells isolated from the patient samples were tested for response to phytohematoagglutonin(PHA) mitogen or mycobacterial antigens by Brd U proliferation assays for T-cell activity. RESULTS Out of the nine SNPs examined, subjects with either heterozygous(TC)/minor(CC) alleles in PTPN2:rs478582 occurred in 83% of CD subjects compared to 61% healthy controls(P-values < 0.05; OR = 3.03). Subjects with either heterozygous(GA)/minor(AA) alleles in PTPN22:rs2476601 occurred in 16% of CD compared to 6% healthy controls(OR = 2.7). Gene expression in PTPN2/22 in CD subjects was significantly decreased by 2 folds compared to healthy controls(P-values < 0.05). IFN-γ expression levels were found to be significantly increased by approxiately 2 folds in subjects when either heterozygous or minor alleles in PTPN2:rs478582 and/or PTPN22:rs2476601 were found(P-values < 0.05). MAP DNA was detected in 61% of CD compared to only 8% of healthy controls(P-values < 0.05, OR = 17.52), where subjects with either heterozygous or minor alleles in PTPN2:rs478582 and/or PTPN22:rs2476601 had more MAPbacteremia presence than subjects without SNPs did. T h e average T-cell proliferation in CD treated with PHA or mycobacteria antigens was, respectively, 1.3 folds and 1.5 folds higher than healthy controls without any significant SNP. CONCLUSION The data suggests that SNPs in PTPN2/22 affect the negative regulation of the immune response in CD patients, thus leading to an increase in inflammation/apoptosis and susceptibility of mycobacteria.展开更多
非受体型蛋白酪氨酸磷酸酶2(protein tyrosine phosphatase non-receptor type 2,PTPN2)是一种蛋白酪氨酸磷酸酶(the counterbalance of protein tyrosine phosphatases,PTPs),是一种有前景的肿瘤免疫治疗靶点。PTPN2表达和活性的增加...非受体型蛋白酪氨酸磷酸酶2(protein tyrosine phosphatase non-receptor type 2,PTPN2)是一种蛋白酪氨酸磷酸酶(the counterbalance of protein tyrosine phosphatases,PTPs),是一种有前景的肿瘤免疫治疗靶点。PTPN2表达和活性的增加与恶性肿瘤疾病进展和免疫反应的降低相关,并在肿瘤生长、分化、代谢、免疫应答等方面发挥重要作用。PTPN2在人类头颈部恶性肿瘤中异常表达并与头颈部恶性肿瘤不良预后相关,因此PTPN2有望成为头颈部恶性肿瘤诊断和预后预测的标志物及治疗靶点,对头颈部恶性肿瘤的临床诊断及治疗具有临床意义。本文主要就PTPN2在头颈部恶性肿瘤中的作用机制及免疫治疗研究进展作一综述,旨在为头颈部恶性肿瘤诊断、评估患者临床预后以及免疫治疗相关研究提供参考。展开更多
BACKGROUND Multiple genetic risk factors for Crohn’s disease(CD)have been identified.However,these observations are not consistent across different populations.The protein tyrosine phosphate non-receptor type 2(PTPN2...BACKGROUND Multiple genetic risk factors for Crohn’s disease(CD)have been identified.However,these observations are not consistent across different populations.The protein tyrosine phosphate non-receptor type 2(PTPN2)gene plays a role in various aspects of host defense including epithelial barrier function,autophagy,and innate and adaptive immune response.Two common polymorphisms in the PTPN2 gene(rs2542151 and rs7234029)have been associated with risk of CD in Western countries.AIM To evaluate the association of PTPN2 gene polymorphisms with risk of CD in Indian population.METHODS We conducted a prospective case-control study.Patients with CD were recruited,and their clinical and investigation details were noted.Controls were patients without organic gastrointestinal disease or other comorbid illnesses.Two common polymorphisms in the PTPN2 gene(rs2542151 and rs7234029)were assessed.DNA was extracted from peripheral blood samples of cases and controls and target DNA was amplified using specific sets of primers.The amplified fragments were digested with restriction enzymes and the presence of polymorphism was detected by restriction fragment length polymorphism.The frequency of alleles was determined.The frequencies of genotypes and alleles were compared between cases and controls to look for significant differences.RESULTS A total of 108 patients with CD(mean age 37.5±12.7 years,females 42.6%)and 100 controls(mean age 39.9±13.5 years,females 37%)were recruited.For the single nucleotide polymorphism(SNP)rs7234029,the overall frequency of G variant genotype(AG or GG)was noted to be significantly lower in the cases compared to controls(35.2%vs 50%,P=0.05).For the SNP rs2542151,the overall frequency of G variant genotype(GT or GG)was noted to be similar in cases compared to controls(43.6%vs 47%,P=0.73).There were no significant differences in minor allele(G)frequency for both polymorphisms between the cases and controls.Both the SNPs had no significant association with age of onset of illness,gender,disease location,disease behaviour,perianal disease,or extraintestinal manifestations of CD.CONCLUSION Unlike observation form the West,polymorphisms in the PTPN2 gene(rs7234029 and rs2542151)are not associated with an increased risk of developing CD in Indian patients.展开更多
PTPN11,which encodes tyrosine phosphatase Shp2,is a critical gene mediating cellular responses to hormones and cytokines.Against original prediction as tumor suppressor for tyrosine phosphatases,PTPN11 was first ident...PTPN11,which encodes tyrosine phosphatase Shp2,is a critical gene mediating cellular responses to hormones and cytokines.Against original prediction as tumor suppressor for tyrosine phosphatases,PTPN11 was first identified as a proto-oncogene because activating mutations of this gene are associated with leukemogenesis.However,most recent experimental data suggest PTPN11/Shp2 acting as a tumor suppressor in hepatocarcinogenesis.This review focuses on the tumor-promoting or suppressing roles of the gene PTPN11/Shp2 in different cell types.展开更多
基金Supported by the Florida Legislative Grant and the Crohn’s Disease Grant Funded by the State of Florida(in part)
文摘AIM To establish the relationship of protein tyrosine phosphatase non-receptor type 2 and 22(PTPN2/22) polymorphisms and mycobacterial infections in Crohn's disease(CD). METHODS All 133 subjects' blood samples were genotyped for nine single nucleotide polymorphisms(SNPs) in PTPN2/22 using TaqMan^(?) genotyping, while the effect of the SNPs on PTPN2/22 and IFN-γ gene expression was determined using RT-PCR. Detection of Mycobacterium avium subspecies paratuberculosis(MAP) IS900 gene was done by nPCR after DNA extraction from the isolated leukocytes of each subjects' blood samples. T-cells isolated from the patient samples were tested for response to phytohematoagglutonin(PHA) mitogen or mycobacterial antigens by Brd U proliferation assays for T-cell activity. RESULTS Out of the nine SNPs examined, subjects with either heterozygous(TC)/minor(CC) alleles in PTPN2:rs478582 occurred in 83% of CD subjects compared to 61% healthy controls(P-values < 0.05; OR = 3.03). Subjects with either heterozygous(GA)/minor(AA) alleles in PTPN22:rs2476601 occurred in 16% of CD compared to 6% healthy controls(OR = 2.7). Gene expression in PTPN2/22 in CD subjects was significantly decreased by 2 folds compared to healthy controls(P-values < 0.05). IFN-γ expression levels were found to be significantly increased by approxiately 2 folds in subjects when either heterozygous or minor alleles in PTPN2:rs478582 and/or PTPN22:rs2476601 were found(P-values < 0.05). MAP DNA was detected in 61% of CD compared to only 8% of healthy controls(P-values < 0.05, OR = 17.52), where subjects with either heterozygous or minor alleles in PTPN2:rs478582 and/or PTPN22:rs2476601 had more MAPbacteremia presence than subjects without SNPs did. T h e average T-cell proliferation in CD treated with PHA or mycobacteria antigens was, respectively, 1.3 folds and 1.5 folds higher than healthy controls without any significant SNP. CONCLUSION The data suggests that SNPs in PTPN2/22 affect the negative regulation of the immune response in CD patients, thus leading to an increase in inflammation/apoptosis and susceptibility of mycobacteria.
文摘非受体型蛋白酪氨酸磷酸酶2(protein tyrosine phosphatase non-receptor type 2,PTPN2)是一种蛋白酪氨酸磷酸酶(the counterbalance of protein tyrosine phosphatases,PTPs),是一种有前景的肿瘤免疫治疗靶点。PTPN2表达和活性的增加与恶性肿瘤疾病进展和免疫反应的降低相关,并在肿瘤生长、分化、代谢、免疫应答等方面发挥重要作用。PTPN2在人类头颈部恶性肿瘤中异常表达并与头颈部恶性肿瘤不良预后相关,因此PTPN2有望成为头颈部恶性肿瘤诊断和预后预测的标志物及治疗靶点,对头颈部恶性肿瘤的临床诊断及治疗具有临床意义。本文主要就PTPN2在头颈部恶性肿瘤中的作用机制及免疫治疗研究进展作一综述,旨在为头颈部恶性肿瘤诊断、评估患者临床预后以及免疫治疗相关研究提供参考。
基金Supported by the CMC Vellore FLUID grant,No.10360.
文摘BACKGROUND Multiple genetic risk factors for Crohn’s disease(CD)have been identified.However,these observations are not consistent across different populations.The protein tyrosine phosphate non-receptor type 2(PTPN2)gene plays a role in various aspects of host defense including epithelial barrier function,autophagy,and innate and adaptive immune response.Two common polymorphisms in the PTPN2 gene(rs2542151 and rs7234029)have been associated with risk of CD in Western countries.AIM To evaluate the association of PTPN2 gene polymorphisms with risk of CD in Indian population.METHODS We conducted a prospective case-control study.Patients with CD were recruited,and their clinical and investigation details were noted.Controls were patients without organic gastrointestinal disease or other comorbid illnesses.Two common polymorphisms in the PTPN2 gene(rs2542151 and rs7234029)were assessed.DNA was extracted from peripheral blood samples of cases and controls and target DNA was amplified using specific sets of primers.The amplified fragments were digested with restriction enzymes and the presence of polymorphism was detected by restriction fragment length polymorphism.The frequency of alleles was determined.The frequencies of genotypes and alleles were compared between cases and controls to look for significant differences.RESULTS A total of 108 patients with CD(mean age 37.5±12.7 years,females 42.6%)and 100 controls(mean age 39.9±13.5 years,females 37%)were recruited.For the single nucleotide polymorphism(SNP)rs7234029,the overall frequency of G variant genotype(AG or GG)was noted to be significantly lower in the cases compared to controls(35.2%vs 50%,P=0.05).For the SNP rs2542151,the overall frequency of G variant genotype(GT or GG)was noted to be similar in cases compared to controls(43.6%vs 47%,P=0.73).There were no significant differences in minor allele(G)frequency for both polymorphisms between the cases and controls.Both the SNPs had no significant association with age of onset of illness,gender,disease location,disease behaviour,perianal disease,or extraintestinal manifestations of CD.CONCLUSION Unlike observation form the West,polymorphisms in the PTPN2 gene(rs7234029 and rs2542151)are not associated with an increased risk of developing CD in Indian patients.
基金funded by NIH grants R01DK075916 and R01HL096125supported by Chinese National Key Project(2012ZX10002-009,011,013)+2 种基金National Natural Science Foundation of China(Grant Nos.30921006,30900770)Key Basic Science Foundation of Shanghai(10JC1418500)Project of the State Key Laboratory of Shanghai Jiaotong University(91-10-02).
文摘PTPN11,which encodes tyrosine phosphatase Shp2,is a critical gene mediating cellular responses to hormones and cytokines.Against original prediction as tumor suppressor for tyrosine phosphatases,PTPN11 was first identified as a proto-oncogene because activating mutations of this gene are associated with leukemogenesis.However,most recent experimental data suggest PTPN11/Shp2 acting as a tumor suppressor in hepatocarcinogenesis.This review focuses on the tumor-promoting or suppressing roles of the gene PTPN11/Shp2 in different cell types.
