Objective: To investigate the association of Graves’ disease and Graves’ ophthalmopathy with the C/T transition polymorphism at position –318 of promoter and the A/G transition polymorphism at position 49 of exon 1...Objective: To investigate the association of Graves’ disease and Graves’ ophthalmopathy with the C/T transition polymorphism at position –318 of promoter and the A/G transition polymorphism at position 49 of exon 1 within cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene. Methods: Thirty-three patients with ophthalmopathy of Graves’ disease, fifty-six Graves’ patients without ophthalmopathy and sixty normal subjects as control were involved in the present case-control study. The polymorphisms were evaluated by polymerase chain reaction fragment length polymorphism (PCR-RFLP). Com-parisons were made of gene frequencies and allele frequencies between the groups. Results: The gene frequencies of CT and allele frequencies of T were much higher in Graves’ patients with ophthalmopathy than that in the group without ophthalmopathy (P=0.020, P=0.019). The gene frequencies of GG and allele frequencies of G in patients with Graves’ disease were significantly increased as compared with control group (P=0.008, P=0.007). The data suggest that smokers with Graves’ disease seemed to be more predisposed to ophthalmopathy than non-smokers (P=0.018). Conclusion: Our results suggest that an allele of T at position –318 of promoter is associated with genetic susceptibility to Graves’ ophthalmopathy while an allele of G at position 49 of exon 1 is associated with genetic susceptibility to Graves’ disease instead. Smoking is believed to be a major risk factor for ophthalmo-pathy.展开更多
AIM： To assess the three polymorphJsm regions within cytotoxic T-lymphocyte antigen 4 （CTLA-4） gene, a C/T base exchange in the promoter region-318 （CTLA-4 -318C/T）, an A/G substitution in the exon 1 position 49 ...AIM： To assess the three polymorphJsm regions within cytotoxic T-lymphocyte antigen 4 （CTLA-4） gene, a C/T base exchange in the promoter region-318 （CTLA-4 -318C/T）, an A/G substitution in the exon 1 position 49 （CTLA-4 49A/G）, a T/C substitution in 1172 （CTLA-4 -1172T/C） in patients with chronic hepatitis B. METHODS： Fifty-one patients with chronic hepatitis B virus infection and 150 healthy subjects were recruited sequentially as they presented to the hepatic clinic. Classification of chronic hepatitis B virus （HBV）-infected patients was as asymptomatic carrier state （26 patients） and chronic hepatitis B （25 patients）. Genomic DNA was isolated from anti-coagulated peripheral blood Bully coat using Miller＇s salting-out method. The presence of the CTLA-4 gene polymorphisms was determined using polymerase chain reaction amplification refractory mutation system （ARMS）. RESULTS： We observed a significant association between -318 genotypes frequency （T＋C-, T＋C＋, T-C＋） and susceptibility to chronic hepatitis B （P=0.012, OR=0.49, 95%CI： 0.206-1.162）. However, we did not observe a significant association for ＋49 genotype frequency （T＋C＋, T＋C- T-C＋） and -1172 genotype frequency （C＋T＋, T＋C- C＋T-） and state of disease. CONCLUSION： Our results suggest that CTLA-4 gene polymorphisms may partially be involved in the susceptibility to chronic hepatitis B.展开更多
Objective： Previous studies have investigated the role of cytotoxic T-lymphocyte antigen-4 （CTLA-4） and tumor necrosis factor-alpha （TNF-a） in carcinogenesis of osteosarcoma, but their results were inconsistent. ...Objective： Previous studies have investigated the role of cytotoxic T-lymphocyte antigen-4 （CTLA-4） and tumor necrosis factor-alpha （TNF-a） in carcinogenesis of osteosarcoma, but their results were inconsistent. We aimed to clarify the associations between CTLA-4, TNF-a polymorphism and osteosarcoma risk by using meta-analysis. Methods： We searched relevant studies without language restriction in PubMed, EMbase, Cochrane Library, Google Scholar databases, Chinese National Knowledge Infrastructure （CNKI） and conference literature in humans published prior to March 2013. The strengths of the associations between genetic variants and osteosarcoma risk were estimated by odds ratio （OR） with 95% confidence interval （95% CI）. Results： A total of seven studies with 1,198 osteosarcoma patients and 1,493 controls were selected. Four studies were eligible for CTLA-4 （1,003 osteosarcoma and 1,162 controls）, and three studies for TNF-a （195 osteosarcoma and 331 controls）. Pooled results showed that rs231775 polymorphism of CTLA-4 was associated with osteosarcoma risk （GG vs. AA： OR=1.63, 95% CI=1.24-2.13; GG ＋ GA vs. AA： OR=1.56, 95% CI=1.21-2.01; AA ＋ GA vs. GG： OR=0.83, 95% CI=0.71-0.97; G vs. A： OR=1.21, 95% CI=1.08-1.36）. No significant heterogeneity was observed across the studies. No significant associations were found between rs5742909 polymorphism of CTLA-4 or rs1800629 polymorphism of TNF-a and osteosarcoma risk. Conclusions： These results suggest that the rs231775 polymorphism of CTLA-4 may play an important role in carcinogenesis of osteosarcoma.展开更多
T cell activation following alloantigen recognition plays a critical role in the development of the rejection in all solid organ, tissue and cell transplantation. A recombinant molecule, cytotoxic T lymphocyte antigen...T cell activation following alloantigen recognition plays a critical role in the development of the rejection in all solid organ, tissue and cell transplantation. A recombinant molecule, cytotoxic T lymphocyte antigen 4 antibody （CTLA-4Ig）, is known to induce to T-cell into ＂anergy＂ by blocking the costimulatory B7-CD28 interaction. Either systemic or localized administration of CTLA-Ig has been shown to prolong allograft survival and induce donor-specific tolerance in some transplant models. In this study, we characterized the expression and immunosuppressive effectiveness of adenoviral-mediated CTLA-4Ig gene transfer. We demonstrated transduction of the allografts with AdCTLA-4Ig resulted in localized expression, permanent graft survival and stable donor-specific tolerance. In addition, by performing simultaneous dual-organ through a local expression of CTLA-4Ig via adenoviral-mediated transplantation, we targeted on immunosuppression gene transfer into pancreatic allografts.展开更多
In recent years,with the extensive application of immunotherapy in clinical practice,it has achieved encouraging therapeutic effects.While enhancing clinical efficacy,however,it can also cause autoimmune damage,trigge...In recent years,with the extensive application of immunotherapy in clinical practice,it has achieved encouraging therapeutic effects.While enhancing clinical efficacy,however,it can also cause autoimmune damage,triggering immunerelated adverse events(irAEs).Reports of immunotherapy-induced gastritis have been increasing annually,but due to its atypical clinical symptoms,early diagnosis poses a certain challenge.Furthermore,it can lead to severe complications such as gastric bleeding,elevating the risk of adverse outcomes for solid tumor patients if immunotherapy is interrupted.Therefore,gaining a thorough understanding of the pathogenesis,clinical manifestations,diagnostic criteria,and treatment of immune-related gastritis is of utmost importance for early identification,diagnosis,and treatment.Additionally,the treatment of immune-related gastritis should be personalized according to the specific condition of each patient.For patients with grade 2-3 irAEs,restarting immune checkpoint inhibitors(ICIs)therapy may be considered when symptoms subside to grade 0-1.When restarting ICIs therapy,it is often recommended to use different types of ICIs.For grade 4 irAEs,permanent discontinuation of the medication is necessary.展开更多
EMulate Therapeutics has developed a system for emulating the effects of solvated molecules via their magnetic field recordings. Recordings of magnetic field emissions of select small inhibitor RNAs (siRNAs;murine tar...EMulate Therapeutics has developed a system for emulating the effects of solvated molecules via their magnetic field recordings. Recordings of magnetic field emissions of select small inhibitor RNAs (siRNAs;murine targeting CTLA-4 and murine targeting PD-1) were tested on C57Bl/6 mice implanted subcutaneously with the GL261 murine tumor cell line. A signal composed of concatenated recordings of siRNA molecules targeting the murine CTLA-4 and PD-1 receptors (labeled A2) was used in immune competent C57Bl/6 mice. The mice were flank implanted with the murine glioblastoma cell line GL261. Mice were exposed to the signal continuously (24 hours a day) until tumor volumes reached the designated volume limit. Tumors were excised and analyzed via PAGE/Western blot for the expression of CTLA-4, PD-1, Ki67, Caspase 3, CD4 and CD8. Terminal blood draws were used for CBCs. We report the down regulation of the checkpoint inhibitors CTLA-4 in the exposed mice. Significant tumor volume reduction was observed in mice exposed to the siRNA signal compared to control mice;no adverse events were recorded. Cell blood counts (CBC) and protein expression patterns were observed to correlate with the expected function of protein expression inhibition of the targets.展开更多
文摘Objective: To investigate the association of Graves’ disease and Graves’ ophthalmopathy with the C/T transition polymorphism at position –318 of promoter and the A/G transition polymorphism at position 49 of exon 1 within cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene. Methods: Thirty-three patients with ophthalmopathy of Graves’ disease, fifty-six Graves’ patients without ophthalmopathy and sixty normal subjects as control were involved in the present case-control study. The polymorphisms were evaluated by polymerase chain reaction fragment length polymorphism (PCR-RFLP). Com-parisons were made of gene frequencies and allele frequencies between the groups. Results: The gene frequencies of CT and allele frequencies of T were much higher in Graves’ patients with ophthalmopathy than that in the group without ophthalmopathy (P=0.020, P=0.019). The gene frequencies of GG and allele frequencies of G in patients with Graves’ disease were significantly increased as compared with control group (P=0.008, P=0.007). The data suggest that smokers with Graves’ disease seemed to be more predisposed to ophthalmopathy than non-smokers (P=0.018). Conclusion: Our results suggest that an allele of T at position –318 of promoter is associated with genetic susceptibility to Graves’ ophthalmopathy while an allele of G at position 49 of exon 1 is associated with genetic susceptibility to Graves’ disease instead. Smoking is believed to be a major risk factor for ophthalmo-pathy.
文摘AIM： To assess the three polymorphJsm regions within cytotoxic T-lymphocyte antigen 4 （CTLA-4） gene, a C/T base exchange in the promoter region-318 （CTLA-4 -318C/T）, an A/G substitution in the exon 1 position 49 （CTLA-4 49A/G）, a T/C substitution in 1172 （CTLA-4 -1172T/C） in patients with chronic hepatitis B. METHODS： Fifty-one patients with chronic hepatitis B virus infection and 150 healthy subjects were recruited sequentially as they presented to the hepatic clinic. Classification of chronic hepatitis B virus （HBV）-infected patients was as asymptomatic carrier state （26 patients） and chronic hepatitis B （25 patients）. Genomic DNA was isolated from anti-coagulated peripheral blood Bully coat using Miller＇s salting-out method. The presence of the CTLA-4 gene polymorphisms was determined using polymerase chain reaction amplification refractory mutation system （ARMS）. RESULTS： We observed a significant association between -318 genotypes frequency （T＋C-, T＋C＋, T-C＋） and susceptibility to chronic hepatitis B （P=0.012, OR=0.49, 95%CI： 0.206-1.162）. However, we did not observe a significant association for ＋49 genotype frequency （T＋C＋, T＋C- T-C＋） and -1172 genotype frequency （C＋T＋, T＋C- C＋T-） and state of disease. CONCLUSION： Our results suggest that CTLA-4 gene polymorphisms may partially be involved in the susceptibility to chronic hepatitis B.
基金supported by National Natural Science Foundation(No.81260315)Foundation of the Education Department of Guangxi Province,China(No.201010LX375)the Foundation of the Nature Science Fund,Guangxi Province,China(No.2012GXNSFBA053121)
文摘Objective： Previous studies have investigated the role of cytotoxic T-lymphocyte antigen-4 （CTLA-4） and tumor necrosis factor-alpha （TNF-a） in carcinogenesis of osteosarcoma, but their results were inconsistent. We aimed to clarify the associations between CTLA-4, TNF-a polymorphism and osteosarcoma risk by using meta-analysis. Methods： We searched relevant studies without language restriction in PubMed, EMbase, Cochrane Library, Google Scholar databases, Chinese National Knowledge Infrastructure （CNKI） and conference literature in humans published prior to March 2013. The strengths of the associations between genetic variants and osteosarcoma risk were estimated by odds ratio （OR） with 95% confidence interval （95% CI）. Results： A total of seven studies with 1,198 osteosarcoma patients and 1,493 controls were selected. Four studies were eligible for CTLA-4 （1,003 osteosarcoma and 1,162 controls）, and three studies for TNF-a （195 osteosarcoma and 331 controls）. Pooled results showed that rs231775 polymorphism of CTLA-4 was associated with osteosarcoma risk （GG vs. AA： OR=1.63, 95% CI=1.24-2.13; GG ＋ GA vs. AA： OR=1.56, 95% CI=1.21-2.01; AA ＋ GA vs. GG： OR=0.83, 95% CI=0.71-0.97; G vs. A： OR=1.21, 95% CI=1.08-1.36）. No significant heterogeneity was observed across the studies. No significant associations were found between rs5742909 polymorphism of CTLA-4 or rs1800629 polymorphism of TNF-a and osteosarcoma risk. Conclusions： These results suggest that the rs231775 polymorphism of CTLA-4 may play an important role in carcinogenesis of osteosarcoma.
文摘T cell activation following alloantigen recognition plays a critical role in the development of the rejection in all solid organ, tissue and cell transplantation. A recombinant molecule, cytotoxic T lymphocyte antigen 4 antibody （CTLA-4Ig）, is known to induce to T-cell into ＂anergy＂ by blocking the costimulatory B7-CD28 interaction. Either systemic or localized administration of CTLA-Ig has been shown to prolong allograft survival and induce donor-specific tolerance in some transplant models. In this study, we characterized the expression and immunosuppressive effectiveness of adenoviral-mediated CTLA-4Ig gene transfer. We demonstrated transduction of the allografts with AdCTLA-4Ig resulted in localized expression, permanent graft survival and stable donor-specific tolerance. In addition, by performing simultaneous dual-organ through a local expression of CTLA-4Ig via adenoviral-mediated transplantation, we targeted on immunosuppression gene transfer into pancreatic allografts.
文摘In recent years,with the extensive application of immunotherapy in clinical practice,it has achieved encouraging therapeutic effects.While enhancing clinical efficacy,however,it can also cause autoimmune damage,triggering immunerelated adverse events(irAEs).Reports of immunotherapy-induced gastritis have been increasing annually,but due to its atypical clinical symptoms,early diagnosis poses a certain challenge.Furthermore,it can lead to severe complications such as gastric bleeding,elevating the risk of adverse outcomes for solid tumor patients if immunotherapy is interrupted.Therefore,gaining a thorough understanding of the pathogenesis,clinical manifestations,diagnostic criteria,and treatment of immune-related gastritis is of utmost importance for early identification,diagnosis,and treatment.Additionally,the treatment of immune-related gastritis should be personalized according to the specific condition of each patient.For patients with grade 2-3 irAEs,restarting immune checkpoint inhibitors(ICIs)therapy may be considered when symptoms subside to grade 0-1.When restarting ICIs therapy,it is often recommended to use different types of ICIs.For grade 4 irAEs,permanent discontinuation of the medication is necessary.
文摘EMulate Therapeutics has developed a system for emulating the effects of solvated molecules via their magnetic field recordings. Recordings of magnetic field emissions of select small inhibitor RNAs (siRNAs;murine targeting CTLA-4 and murine targeting PD-1) were tested on C57Bl/6 mice implanted subcutaneously with the GL261 murine tumor cell line. A signal composed of concatenated recordings of siRNA molecules targeting the murine CTLA-4 and PD-1 receptors (labeled A2) was used in immune competent C57Bl/6 mice. The mice were flank implanted with the murine glioblastoma cell line GL261. Mice were exposed to the signal continuously (24 hours a day) until tumor volumes reached the designated volume limit. Tumors were excised and analyzed via PAGE/Western blot for the expression of CTLA-4, PD-1, Ki67, Caspase 3, CD4 and CD8. Terminal blood draws were used for CBCs. We report the down regulation of the checkpoint inhibitors CTLA-4 in the exposed mice. Significant tumor volume reduction was observed in mice exposed to the siRNA signal compared to control mice;no adverse events were recorded. Cell blood counts (CBC) and protein expression patterns were observed to correlate with the expected function of protein expression inhibition of the targets.
