Objective: To investigate whether nitric oxide synthase (NOS) is expressed in T-cell-dependent liver injury initiated by concanavalin A (ConA) in Kunming mice and study the possible effect of nitric oxide(NO) on liver...Objective: To investigate whether nitric oxide synthase (NOS) is expressed in T-cell-dependent liver injury initiated by concanavalin A (ConA) in Kunming mice and study the possible effect of nitric oxide(NO) on liver injury models. Methods: Liver injury in Kunming mice was induced by administration of ConA through tail vein. Expression of NOS in the liver was detected by NADPH diaphorase staining method. The possible effect of NO on liver injury models was obtained by L-NAME injection to suppress synthesis of NO. Results: NOS has a strong expression in hepatocytes after ConA injection, especially in those close to the central vein, while only a weak expression was found in the epithelial cells in control group. Liver injury became more serious when NO synthesis was inhibited by L-NAME, accompanied by great malondialdehyde(MDA) increase in serum and severe intrahepatic vascular thrombosis. Conclusion: NOS markedly expressed in ConA-induced liver injury, which may subsequently promote nitric oxide synthesis. Increasement of nitric oxide has a protective effect on ConA-induced liver injury.展开更多
Objective:Foxp3,the main regulator of Treg (regulatory T) cells, is down-regulated in breast carcinoma and other cancers. The rs2294021 Foxp3 polymorphism contributes to Foxp3 down-regulation, thereby weakens its tumo...Objective:Foxp3,the main regulator of Treg (regulatory T) cells, is down-regulated in breast carcinoma and other cancers. The rs2294021 Foxp3 polymorphism contributes to Foxp3 down-regulation, thereby weakens its tumor suppressing activity. The aim of our study was to evaluate the potential influence of Foxp3 polymorphism on breast cancer, we conducted a case-control study in Han Chinese women. Methods: Foxp3 genotyping was conducted in 677 breast carcinoma patients and 828 age-frequency matched cancer-free controls. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Experiment data was analyzed using Chi-square test and SPSS software. Results: The T/C genotype was found to be significantly associated with increased risk of breast carcinoma occurrence (OR = 1.462; 95% CI 1.165-1.833, P = 0.001) compared with the T/T or C/C (OR 1.143; 95% CI 0.838-1.559, P = 0.397) genotype. The increased risk for breast carcinoma related to heterozygous genotype was more pronounced in subjects over 50 years (OR 1.631; 95% CI 1.116-2.383, P = 0.011). No significant association was found between the polymorphism and the ER/PR status, metastasis or tumor stage of breast cancer. Conclusion: Our findings suggest that rs2294021 Foxp3 polymorphism may be a potential contributor for development of breast carcinoma in Han Chinese women.展开更多
Objective： Our group has previously observed that in patients with small-cell lung cancers （SCLCs）, the expression of a tumor antigen, glioma big potassium （gBK） ion channel, is higher at the time of death than w...Objective： Our group has previously observed that in patients with small-cell lung cancers （SCLCs）, the expression of a tumor antigen, glioma big potassium （gBK） ion channel, is higher at the time of death than when the cancer is first treated by surgical resection. This study aimed to determine whether this dichotomy was common in other potential lung tumor antigens by examining the same patient samples using our more extensive profile analysis of tumor-antigen precursor protein （TAPP）. We then tested the hypothesis that therapeutic intervention may inadvertently cause this increased gBK production. Methods： SCLC samples （eight surgical resections and three autopsy samples） and three control lungs were examined by quantitative real-time polymerase chain reaction for 42 potential TAPPs that represent potential T-cell-mediated immunological targets. Results： Twenty-two TAPP mRNAs displayed the same profile as gBK, i.e., more mRNAs were expressed at autopsy than in their surgical counterparts. B-cyclin and mouse double minute 2, human homolog of PS3-binding protein were elevated in both autopsy and surgical specimens above the normal-lung controls. When HTB119 cells were incubated with doxorubicin, gBK was strongly induced, as confirmed by intracellular flow cytometry with a gBK-specific antibody. Conclusion： Our findings suggested that more immunological targets became available as the tumor responded to chemotherapy and proceeded toward its terminal stages.展开更多
Diversity in the T cell receptor(TCR) repertoire provides a miniature defense ability for the T cell immune system that may be related to tumor initiation and progression. Understanding the T cell immune status of leu...Diversity in the T cell receptor(TCR) repertoire provides a miniature defense ability for the T cell immune system that may be related to tumor initiation and progression. Understanding the T cell immune status of leukemia patients is critical for establishing specific immunotherapies. Previous studies have reported abnormal TCR repertoires and clonally expanded TCR V? T cells in chronic myeloid leukemia in chronic phase(CP-CML). In this study, we investigated the distribution and clonality of the TCR V? repertoire in 4 cases with imatinib-resistant CML in blast crisis(BC-CML) with abelson murine leukemia viral oncogene homolog 1(ABL1) kinase domain mutations(KDMs). Examination of TCR V? expression and clonality was performed by reverse transcription-polymerase chain reaction(RT-PCR) and Gene Scan analysis. Significantly skewed TCR V? repertoires were observed in BC-CML patients with different KDMs, and 4 to 8 oligoclonally expanded TCR V? subfamilies could be identified in each sample. Intriguingly, a relatively highly expanded V?9 clone with the same length as complementarity-determining region 3(CDR3)(139 bp) was found in all three CML patients in lymphoid blast crisis(LBC-CML) who had different KDMs, but the clone was not detected in the only CML patient in myeloid blast crisis(MBC-CML). In conclusion, restricted TCR V? repertoire expression and decreased clone complexity was a general phenomenon observed in the BC-CML patients with different KDMs, indicating the T-cell immunodeficiency of these patients. In addition, clonally expanded V?9 T cell clones may indicate a specific immune response to leukemia-associated antigens in LBC-CML patients.展开更多
文摘Objective: To investigate whether nitric oxide synthase (NOS) is expressed in T-cell-dependent liver injury initiated by concanavalin A (ConA) in Kunming mice and study the possible effect of nitric oxide(NO) on liver injury models. Methods: Liver injury in Kunming mice was induced by administration of ConA through tail vein. Expression of NOS in the liver was detected by NADPH diaphorase staining method. The possible effect of NO on liver injury models was obtained by L-NAME injection to suppress synthesis of NO. Results: NOS has a strong expression in hepatocytes after ConA injection, especially in those close to the central vein, while only a weak expression was found in the epithelial cells in control group. Liver injury became more serious when NO synthesis was inhibited by L-NAME, accompanied by great malondialdehyde(MDA) increase in serum and severe intrahepatic vascular thrombosis. Conclusion: NOS markedly expressed in ConA-induced liver injury, which may subsequently promote nitric oxide synthesis. Increasement of nitric oxide has a protective effect on ConA-induced liver injury.
文摘Objective:Foxp3,the main regulator of Treg (regulatory T) cells, is down-regulated in breast carcinoma and other cancers. The rs2294021 Foxp3 polymorphism contributes to Foxp3 down-regulation, thereby weakens its tumor suppressing activity. The aim of our study was to evaluate the potential influence of Foxp3 polymorphism on breast cancer, we conducted a case-control study in Han Chinese women. Methods: Foxp3 genotyping was conducted in 677 breast carcinoma patients and 828 age-frequency matched cancer-free controls. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Experiment data was analyzed using Chi-square test and SPSS software. Results: The T/C genotype was found to be significantly associated with increased risk of breast carcinoma occurrence (OR = 1.462; 95% CI 1.165-1.833, P = 0.001) compared with the T/T or C/C (OR 1.143; 95% CI 0.838-1.559, P = 0.397) genotype. The increased risk for breast carcinoma related to heterozygous genotype was more pronounced in subjects over 50 years (OR 1.631; 95% CI 1.116-2.383, P = 0.011). No significant association was found between the polymorphism and the ER/PR status, metastasis or tumor stage of breast cancer. Conclusion: Our findings suggest that rs2294021 Foxp3 polymorphism may be a potential contributor for development of breast carcinoma in Han Chinese women.
文摘Objective： Our group has previously observed that in patients with small-cell lung cancers （SCLCs）, the expression of a tumor antigen, glioma big potassium （gBK） ion channel, is higher at the time of death than when the cancer is first treated by surgical resection. This study aimed to determine whether this dichotomy was common in other potential lung tumor antigens by examining the same patient samples using our more extensive profile analysis of tumor-antigen precursor protein （TAPP）. We then tested the hypothesis that therapeutic intervention may inadvertently cause this increased gBK production. Methods： SCLC samples （eight surgical resections and three autopsy samples） and three control lungs were examined by quantitative real-time polymerase chain reaction for 42 potential TAPPs that represent potential T-cell-mediated immunological targets. Results： Twenty-two TAPP mRNAs displayed the same profile as gBK, i.e., more mRNAs were expressed at autopsy than in their surgical counterparts. B-cyclin and mouse double minute 2, human homolog of PS3-binding protein were elevated in both autopsy and surgical specimens above the normal-lung controls. When HTB119 cells were incubated with doxorubicin, gBK was strongly induced, as confirmed by intracellular flow cytometry with a gBK-specific antibody. Conclusion： Our findings suggested that more immunological targets became available as the tumor responded to chemotherapy and proceeded toward its terminal stages.
基金supported by the National Natural Science Foundation of China(81270604U1301226+7 种基金81400109)the China Postdoctoral Science Foundation(2013M540685)the Guangdong Natural Science Foundation(S2013040016151S2013020012863)the Foundation for High-level Talents in Higher Education of GuangdongChina([2013]246-54)the Guangzhou Science and Technology Project Foundation(201510010211)Jinan University’s Scientific Research Creativeness Cultivation Project for Outstanding Undergraduates Recommended for Postgraduate Study
文摘Diversity in the T cell receptor(TCR) repertoire provides a miniature defense ability for the T cell immune system that may be related to tumor initiation and progression. Understanding the T cell immune status of leukemia patients is critical for establishing specific immunotherapies. Previous studies have reported abnormal TCR repertoires and clonally expanded TCR V? T cells in chronic myeloid leukemia in chronic phase(CP-CML). In this study, we investigated the distribution and clonality of the TCR V? repertoire in 4 cases with imatinib-resistant CML in blast crisis(BC-CML) with abelson murine leukemia viral oncogene homolog 1(ABL1) kinase domain mutations(KDMs). Examination of TCR V? expression and clonality was performed by reverse transcription-polymerase chain reaction(RT-PCR) and Gene Scan analysis. Significantly skewed TCR V? repertoires were observed in BC-CML patients with different KDMs, and 4 to 8 oligoclonally expanded TCR V? subfamilies could be identified in each sample. Intriguingly, a relatively highly expanded V?9 clone with the same length as complementarity-determining region 3(CDR3)(139 bp) was found in all three CML patients in lymphoid blast crisis(LBC-CML) who had different KDMs, but the clone was not detected in the only CML patient in myeloid blast crisis(MBC-CML). In conclusion, restricted TCR V? repertoire expression and decreased clone complexity was a general phenomenon observed in the BC-CML patients with different KDMs, indicating the T-cell immunodeficiency of these patients. In addition, clonally expanded V?9 T cell clones may indicate a specific immune response to leukemia-associated antigens in LBC-CML patients.
