Background： Increased level of serum macrophage inhibitory cytokine- 1 （MIC- 1 ）, a member oftransfonning growth thctor-β superfamily, was found in patients with epithelial tumors. This study aimed to evaluate whe...Background： Increased level of serum macrophage inhibitory cytokine- 1 （MIC- 1 ）, a member oftransfonning growth thctor-β superfamily, was found in patients with epithelial tumors. This study aimed to evaluate whether serum level of MIC-I can be a candidate diagnostic and prognostic indicator for early-stage nonsmall cell lung cancer （NSCLC）. Methods： A prospective study enrolled 152 patients with Stage I-II NSCLC, who were followed up after surgical resection. Forty-eight patients with benign pulmonary disease （BPD） and 105 healthy controls were also included in the study. Serum M IC- 1 levels were measured using an enzyme-linked immunosorbent assay, and the association with clinical and prognostic features was analyzed. Results： In patients with NSCLC, serum protein levels of M IC-I were significantly increased compared with healthy controls and BPD patients （all P 〈 0.001 ）. A threshold of 1000 pg/ml ofM IC-1 was found in patients with early-stage （Stage 1 and II） NSCLC, with sensitivity and specificity of 70.4% and 99.0%, respectively. The serum levels ofMIC- ] were associated with age （P = 0.001 ）, gender （P = 0.030）, and T stage （P = 0.022）. Serum MIC-1 threshold of 1465 pg/ml was found in patients with poor early outcome, with sensitivity and specificity of 72.2% and 66.1%, respectively. The overall 3-year survival rate of NSCLC patients with high serum levels of MIC-1 （〉I 465 pg/ml） was lower than that of NSCLC patients with low serum MIC-1 levels （77.6% vs. 94.8%）. Multivariate Cox regression survival analysis showed that a high serum level ofMIC- 1 was an independent risk factor lbr reduced overall survival （hazard ratio - 3.37, 95% confidential interval： 1.09-10.42, P = 0.035）. Conclusion： The present study suggested that serum M1C-I may be a potential diagnostic and prognostic biomarker ~cbr patients with early-stage NSCLC.展开更多
Background:Recent studies have indicated that a high-fat diet(HFD)and/or HFD-induced obesity may influence prostate cancer(PCa)progression,but the role of HFD in PCa microenvironment is unclear.This study aimed to del...Background:Recent studies have indicated that a high-fat diet(HFD)and/or HFD-induced obesity may influence prostate cancer(PCa)progression,but the role of HFD in PCa microenvironment is unclear.This study aimed to delineate the molecular mechanisms of PCa progression underHFDmilieus and define the stromal microenvironment focusing on macrophage inhibitory cytokine-1(MIC-1)activation.Methods:We investigated the effects of HFD on PCa stromal microenvironment and MIC-1 signaling activation using PC-3M-luc-C6 PCa model mice fed with HFD or control diet.Further,we explored the effect of periprostatic adipocytes derived from primary PCa patients on activation and cytokine secretion of prostate stromal fibroblasts.Expression patterns and roles of MIC-1 signaling on human PCa stroma activation and progression were also investigated.Results:HFD stimulated PCa cell growth and invasion as a result of upregulated MIC-1 signaling and subsequently increased the secretion of interleukin(IL)-8 and IL-6 from prostate stromal fibroblasts in PC-3M-luc-C6 PCa mousemodel.In addition,periprostatic adipocytes directly stimulatedMIC-1 production from PC-3 cells and IL-8 secretion in prostate stromal fibroblasts through the upregulation of adipose lipolysis and free fatty acid release.The increased serum MIC-1 was significantly correlated with human PCa stroma activation,high serum IL-8,IL-6,and lipase activity,advanced PCa progression,and high body mass index of the patients.Glial-derived neurotrophic factor receptor α-like(GFRAL),a specific receptor of MIC-1,was highly expressed in both cytoplasm and membrane of PCa cells and surrounding stromal fibroblasts,and the expression levelwas decreased by androgen deprivation therapy and chemotherapy.Conclusion:HFD-mediated activation of the PCa stromal microenvironment through metabolically upregulated MIC-1 signaling by increased available free fatty acids may be a critical mechanism of HFD and/or obesity-induced PCa progression.展开更多
Objectives： To investigate the mechanism of Liuwei Dihuang Pill （六味地黄丸, LDP） in treating postmenopausal osteoporosis （PMOP） with Shen （Kidney） yin deficiency. Methods： In this study, 205 cases of PMOP wer...Objectives： To investigate the mechanism of Liuwei Dihuang Pill （六味地黄丸, LDP） in treating postmenopausal osteoporosis （PMOP） with Shen （Kidney） yin deficiency. Methods： In this study, 205 cases of PMOP were divided into the PMOP Shen-yin deficiency group （Group A）, PMOP Shen-yang deficiency group （Group B）, PMOP without Shen deficiency group （Group C）, and control group （Group N）. Real-time polymerase chain reaction （RT-PCR） and Western blot techniques were used to observe the effects of LDP treatment on the cardiotrophin-like cytokine factor 1 （CLCF1）, ankyrin repeat and SOCS box containing 1 （ASB1）, and proldneticin 2 （PROK2） genes and the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway. Results： The mRNA （P〈0.05） and protein （P〈0.01） expression levels of the CLCF1 gone in Group A were significantly lower than the corresponding levels in Group N. After LDP treatment for 3 months, the mRNA expression levels of the CLCF1 gone were obviously up-regulated （P〈0.01）. After 6-month treatment, the expression levels of CLCF1 mRNA and protein were significantly up-regulated （both P〈0.01）, and the average bone density of the top femur had significantly increased （P〈0.05）. In vitro, CLCF1 overexpression resulted in a significant increase in the total protein and phosphorylated protein levels of JAK2 and STAT3. Conclusions： The CLCF1 gone is an important gone associated with PMOP Shen-yin deficiency and the therapeutic effects of LDP may be mediated by up-regulation of CLCF1 gone expression and activation of the JAK/STAT signaling pathway.展开更多
目的观察慢性乙型肝炎患者(CHB)CISH、SOCS1和SOCS3 m RNA及CD4+T淋巴细胞亚群相关细胞因子的表达,探讨CISH、SOCS1和SOCS3在慢性乙型肝炎病毒(HBV)感染中的作用。方法选取慢性乙型肝炎患者(CHB)31例,乙肝携带者(As C)18例,正常健康者1...目的观察慢性乙型肝炎患者(CHB)CISH、SOCS1和SOCS3 m RNA及CD4+T淋巴细胞亚群相关细胞因子的表达,探讨CISH、SOCS1和SOCS3在慢性乙型肝炎病毒(HBV)感染中的作用。方法选取慢性乙型肝炎患者(CHB)31例,乙肝携带者(As C)18例,正常健康者18例作为对照,采用实时荧光定量PCR的方法检测外周血单个核细胞(PBMC)中CISH、SOCS1和SOCS3 m RNA的表达,ELISA法检测PBMC上清中IL-2、IL-4、IFN-γ、IL-10、IL-17A和TGF-β细胞因子的表达水平,并分析其相关性。结果CHB组患者CISH m RNA表达高于健康对照组(P<0.01),CHB组SOCS3 m RNA表达显著高于健康对照组(P<0.01),较As C组高(P<0.05),SOCS1 m RNA表达量在各组间比较无明显差异(P>0.05);CHB组IL-4的表达量高于As C组,CHB组IFN-γ/IL-4的比值低于健康对照组,As C组IL-4和TGF-β的表达量均高于健康对照组,差异均有统计学意义(P<0.05),CHB组IL-4、IL-17A和TGF-β的表达量均显著高于健康对照组,差异有显著统计学意义(P<0.01);CHB组患者SOCS1 m RNA表达量与CISH m RNA表达量和SOCS3 m RNA表达量之间均存在显著性关联(P=0.004,P=0.002),SOCS3 m RNA表达量与IFN-γ水平之间存在相关性(P=0.037)。结论 CISH和SOCS3基因可能参与慢性乙型肝炎疾病的发生发展,并与CD4+T淋巴细胞亚群变化之间存在一定的相关性。展开更多
背景与目的:细胞因子信号抑制因子(suppressor of cytokine signaling1,SOCS1)在肿瘤免疫负反馈调节中起重要作用,下调其表达可以有效增强机体的抗肿瘤免疫反应。本研究应用RNA干扰(RNA interference,RNAi)技术下调SOCS1基因表达联合OK-...背景与目的:细胞因子信号抑制因子(suppressor of cytokine signaling1,SOCS1)在肿瘤免疫负反馈调节中起重要作用,下调其表达可以有效增强机体的抗肿瘤免疫反应。本研究应用RNA干扰(RNA interference,RNAi)技术下调SOCS1基因表达联合OK-432刺激成熟的树突细胞(dendritic cell,DC)体外诱导特异性抗肿瘤作用,初步探讨其作用机制。方法:利用特异性小干扰RNA(siRNA)下调DC中SOCS1的表达,同时用肝癌HepG2细胞裂解物负载DC,OK-432刺激DC成熟,观察DC的形态特征,流式细胞仪检测刺激前后DC的表型变化,奥马蓝(AlamarBlue)法检测成熟DC对自身淋巴细胞的激活和增殖作用,LDH法检测其对HepG2、EC109细胞和K562细胞的杀伤作用。结果:DC体外诱导培养成功,设计的siRNA片段能有效下调iDC中SOCS1的表达,OK-432刺激DC成熟,CD80、CD83、CD86、HLA-DR等DC表面抗原明显表达上调,而负载肝癌抗原对DC表型无明显影响;SOCS1的下调可以促进DC成熟,负载肝癌抗原的DC能有效刺激自体淋巴细胞增殖,T细胞增殖率为(110.7±22.2)%,同时产生针对HepG2细胞的特异性杀伤作用,特异性细胞毒T淋巴细胞活性为(54.0±13.2)%。而针对EC109细胞和K562细胞的杀伤率仅为(10.0±30.7)%和(14.5±15.5)%。结论:RNAi下调SOCS1表达,OK432刺激负载肝癌全细胞抗原的成熟DC可以产生高效而特异性的抗肝癌的免疫应答。展开更多
基金grants from the National Natural Science Foundation of China，National High-tech R&D Program (863Program)，Capital Characteristic clinic projects
文摘Background： Increased level of serum macrophage inhibitory cytokine- 1 （MIC- 1 ）, a member oftransfonning growth thctor-β superfamily, was found in patients with epithelial tumors. This study aimed to evaluate whether serum level of MIC-I can be a candidate diagnostic and prognostic indicator for early-stage nonsmall cell lung cancer （NSCLC）. Methods： A prospective study enrolled 152 patients with Stage I-II NSCLC, who were followed up after surgical resection. Forty-eight patients with benign pulmonary disease （BPD） and 105 healthy controls were also included in the study. Serum M IC- 1 levels were measured using an enzyme-linked immunosorbent assay, and the association with clinical and prognostic features was analyzed. Results： In patients with NSCLC, serum protein levels of M IC-I were significantly increased compared with healthy controls and BPD patients （all P 〈 0.001 ）. A threshold of 1000 pg/ml ofM IC-1 was found in patients with early-stage （Stage 1 and II） NSCLC, with sensitivity and specificity of 70.4% and 99.0%, respectively. The serum levels ofMIC- ] were associated with age （P = 0.001 ）, gender （P = 0.030）, and T stage （P = 0.022）. Serum MIC-1 threshold of 1465 pg/ml was found in patients with poor early outcome, with sensitivity and specificity of 72.2% and 66.1%, respectively. The overall 3-year survival rate of NSCLC patients with high serum levels of MIC-1 （〉I 465 pg/ml） was lower than that of NSCLC patients with low serum MIC-1 levels （77.6% vs. 94.8%）. Multivariate Cox regression survival analysis showed that a high serum level ofMIC- 1 was an independent risk factor lbr reduced overall survival （hazard ratio - 3.37, 95% confidential interval： 1.09-10.42, P = 0.035）. Conclusion： The present study suggested that serum M1C-I may be a potential diagnostic and prognostic biomarker ~cbr patients with early-stage NSCLC.
基金This work was supported by the Japan Society for the Pro-motion of Science(JSPS,Grant No.:16H02679,16K10992,19K09663)AMED-CREST,Japan Agency for Medical Research and Development(AMED).
文摘Background:Recent studies have indicated that a high-fat diet(HFD)and/or HFD-induced obesity may influence prostate cancer(PCa)progression,but the role of HFD in PCa microenvironment is unclear.This study aimed to delineate the molecular mechanisms of PCa progression underHFDmilieus and define the stromal microenvironment focusing on macrophage inhibitory cytokine-1(MIC-1)activation.Methods:We investigated the effects of HFD on PCa stromal microenvironment and MIC-1 signaling activation using PC-3M-luc-C6 PCa model mice fed with HFD or control diet.Further,we explored the effect of periprostatic adipocytes derived from primary PCa patients on activation and cytokine secretion of prostate stromal fibroblasts.Expression patterns and roles of MIC-1 signaling on human PCa stroma activation and progression were also investigated.Results:HFD stimulated PCa cell growth and invasion as a result of upregulated MIC-1 signaling and subsequently increased the secretion of interleukin(IL)-8 and IL-6 from prostate stromal fibroblasts in PC-3M-luc-C6 PCa mousemodel.In addition,periprostatic adipocytes directly stimulatedMIC-1 production from PC-3 cells and IL-8 secretion in prostate stromal fibroblasts through the upregulation of adipose lipolysis and free fatty acid release.The increased serum MIC-1 was significantly correlated with human PCa stroma activation,high serum IL-8,IL-6,and lipase activity,advanced PCa progression,and high body mass index of the patients.Glial-derived neurotrophic factor receptor α-like(GFRAL),a specific receptor of MIC-1,was highly expressed in both cytoplasm and membrane of PCa cells and surrounding stromal fibroblasts,and the expression levelwas decreased by androgen deprivation therapy and chemotherapy.Conclusion:HFD-mediated activation of the PCa stromal microenvironment through metabolically upregulated MIC-1 signaling by increased available free fatty acids may be a critical mechanism of HFD and/or obesity-induced PCa progression.
基金Supported by National Natural Science Foundation of China(Nos.81173280,81302995,81403420)Fujian Medical Innovation project(No.2011-CX-30)+1 种基金Science and Technology Department of Fujian Province autonomous non-profit research institutes topics project(No.2011R1038-5)Fujian Academy of Traditional Chinese autonomous topics Project(No.2012fjzyyk-5)
文摘Objectives： To investigate the mechanism of Liuwei Dihuang Pill （六味地黄丸, LDP） in treating postmenopausal osteoporosis （PMOP） with Shen （Kidney） yin deficiency. Methods： In this study, 205 cases of PMOP were divided into the PMOP Shen-yin deficiency group （Group A）, PMOP Shen-yang deficiency group （Group B）, PMOP without Shen deficiency group （Group C）, and control group （Group N）. Real-time polymerase chain reaction （RT-PCR） and Western blot techniques were used to observe the effects of LDP treatment on the cardiotrophin-like cytokine factor 1 （CLCF1）, ankyrin repeat and SOCS box containing 1 （ASB1）, and proldneticin 2 （PROK2） genes and the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway. Results： The mRNA （P〈0.05） and protein （P〈0.01） expression levels of the CLCF1 gone in Group A were significantly lower than the corresponding levels in Group N. After LDP treatment for 3 months, the mRNA expression levels of the CLCF1 gone were obviously up-regulated （P〈0.01）. After 6-month treatment, the expression levels of CLCF1 mRNA and protein were significantly up-regulated （both P〈0.01）, and the average bone density of the top femur had significantly increased （P〈0.05）. In vitro, CLCF1 overexpression resulted in a significant increase in the total protein and phosphorylated protein levels of JAK2 and STAT3. Conclusions： The CLCF1 gone is an important gone associated with PMOP Shen-yin deficiency and the therapeutic effects of LDP may be mediated by up-regulation of CLCF1 gone expression and activation of the JAK/STAT signaling pathway.
文摘目的观察慢性乙型肝炎患者(CHB)CISH、SOCS1和SOCS3 m RNA及CD4+T淋巴细胞亚群相关细胞因子的表达,探讨CISH、SOCS1和SOCS3在慢性乙型肝炎病毒(HBV)感染中的作用。方法选取慢性乙型肝炎患者(CHB)31例,乙肝携带者(As C)18例,正常健康者18例作为对照,采用实时荧光定量PCR的方法检测外周血单个核细胞(PBMC)中CISH、SOCS1和SOCS3 m RNA的表达,ELISA法检测PBMC上清中IL-2、IL-4、IFN-γ、IL-10、IL-17A和TGF-β细胞因子的表达水平,并分析其相关性。结果CHB组患者CISH m RNA表达高于健康对照组(P<0.01),CHB组SOCS3 m RNA表达显著高于健康对照组(P<0.01),较As C组高(P<0.05),SOCS1 m RNA表达量在各组间比较无明显差异(P>0.05);CHB组IL-4的表达量高于As C组,CHB组IFN-γ/IL-4的比值低于健康对照组,As C组IL-4和TGF-β的表达量均高于健康对照组,差异均有统计学意义(P<0.05),CHB组IL-4、IL-17A和TGF-β的表达量均显著高于健康对照组,差异有显著统计学意义(P<0.01);CHB组患者SOCS1 m RNA表达量与CISH m RNA表达量和SOCS3 m RNA表达量之间均存在显著性关联(P=0.004,P=0.002),SOCS3 m RNA表达量与IFN-γ水平之间存在相关性(P=0.037)。结论 CISH和SOCS3基因可能参与慢性乙型肝炎疾病的发生发展,并与CD4+T淋巴细胞亚群变化之间存在一定的相关性。
