Vascular endothelial growth factor (VEGF, namely VEGF-A) is an angiogenic polypeptide and VEGF-C is a lymphangiogenic polypeptide that has been implicated in cancer growth, invasion and metastasis. Several cytokines a...Vascular endothelial growth factor (VEGF, namely VEGF-A) is an angiogenic polypeptide and VEGF-C is a lymphangiogenic polypeptide that has been implicated in cancer growth, invasion and metastasis. Several cytokines and growth factors play an important part in cancer progression. These cytokines and growth factors are the principal mediators of cancer cells-stromal cell interaction , which is critical for invasion of cancer cells to the surrounding tissues and metastatic dissemination to distant organs. In this study, we studied VEGF-A, C expression in cultured human pancreatic cancer cell lines and whether the presence of VEGF-A, C in the cell lines is regulated by cytokines interleukin-lct (EL-1α), and interleukin-6 (IL-6). METHODS: We used Northern blot and Western blot methods to analyze expression of the gene and protein of VEGF-A, C in all 6 tested cell lines (ASPC-1, CAPAN-1, MIA-PaCa-2, PANC-1, COLO-357 and T3M4) respectively. To analyze what is the regulator for this VEGF-A, C expression in pancreatic cancer,we used the reverse transcription -polymerase chain reaction (RT-PCR) method to analyze VEGF-A, C expression in cultured human pancreatic cancer cell lines (CAPAN-1 and COLO-357) under the stimulation with IL-1α (10μg/L) or IL-6 (100 μg/L). RESULTS:Northern blot analysis revealed the presence of the 4.1-kb VEGF-A mRNA transcript and 2.4-kb VEGF-C mRNA transcript in all 6 tested cell lines. Immunoblotting with highly specific anti-VEGF-A, anti-VEGF-C antibody revealed the presence of a molecular weight of 43-kDa VEGF-A protein and 55-kDa VEGF-C protein in all the cell lines. RT-PCR analysis revealed the levels of the VEGF-A and VEGF-C gene were 1-2 fold and a 1-fold increase in the COLO-357 cell line by stimulation with IL-la, however, no effect was found in the CAPAN-1 cell line. The levels of the VEGF-A and VEGF-C gene were 2-5 fold and a 1-fold increase in the CAPAN-1 cell line by stimulation with IL-6, but, no effect was found in the COLO-357 cell line. CONCLUSION:These findings suggested that the expression of VEGF-A, C and their regulation by IL-1α, IL-6 in pancreatic cancer contributes to the lymphatic and distant metastasis and the disease progression.展开更多
Pigment epithelium-derived factor （PEDF） is an antiangiogenic factor which is effective in tumour inhibition in a variety of tumours and has not yet been studied in bladder tumour before. In this study the expressio...Pigment epithelium-derived factor （PEDF） is an antiangiogenic factor which is effective in tumour inhibition in a variety of tumours and has not yet been studied in bladder tumour before. In this study the expression of PEDF, interleukin-1α （IL-1α） and -8 （IL-8） in bladder tumours was investigated. Immunohistochemistry was performed on 64 bladder tumour and 23 normal uroepithelium samples. Expression change of the factors was compared with clinicopathological parameters. Correlations between PEDF, IL-1α and IL-8 were analyzed. None of the factors was in relation to gender, tumour occurrence, and size or onset pattern. PEDF （P=0.014） and IL-1α （P=0.049） expression was down-regulated with grade progression. PEDF expression was lower in normal uroepithelium than in papillary urothelial neoplasm of low malignant potential （PUNLMP） （P=0.000） and carcinoma （P=0.009） whilst IL-1α （P=0.000 and P=0.000 respectively） and IL-8 （P=0.000 and P=0.023 respectively） expression was higher in the same grouping. PEDF expression had a negative correlation with IL-8 in PUNLMP （P=0.049, r=-0.578） as well as in tumour grouping （P=0.033, r=-0.276）. Deranged expressional change of PEDF, IL-1α and IL-8 could be in relation to loss of differentiation from normal uroepithelium to papillary lesion and eventually to carcinoma.展开更多
The present study showed that, interleukin-1α (IL-1α) stimulateal cultured bovine cerebral microvascular endothelial cells (BCMEC) releasing growth factor which promoted bovine cerebral microvascular smooth muscle c...The present study showed that, interleukin-1α (IL-1α) stimulateal cultured bovine cerebral microvascular endothelial cells (BCMEC) releasing growth factor which promoted bovine cerebral microvascular smooth muscle cells (BCMSMC) proliferation in a dose-dependent manner. The mitogenic activity in conditioned medium of BCMEC stimulated by IL-1α was neutralized significantly by the antibody to platelet-derived growth factor (PDGF). Imperatorin (Imp), iso-Imperatorin (iso Imp) and 6-(α,α-phenylacetylpiperazinyl)phenyl-5-methyl-4,5-dihydro-3 (2H)-pyridazinone (PMDP) did not affect the releasing of PDGF from IL-1α stimulated BCMEC, but inhibited the promotion of PDGF on the proliferation of BCMSMC. We concluded that the promotion of IL-1α on the proliferation of BCMSMC should be mediated by some growth factors, such as PDGF.展开更多
Interleukin-1α (IL-1α) is a proinflammatory cytokine that has also been found to act as a paracrine mediator involved in the regulation of testicular functions. The present review provides an overview of the role of...Interleukin-1α (IL-1α) is a proinflammatory cytokine that has also been found to act as a paracrine mediator involved in the regulation of testicular functions. The present review provides an overview of the role of IL 1α in testicular physiology. Bioactive IL-1α isolated from adult rat testis was found to consist of three distinct immunoreactive protein species with apparent sizes of 45, 24 and 19 kDa. These isoforms showed bioactivity in a thymocyte proliferation and steroidogenesis assays with different biopotencies. The background of the molecular heterogeneity and processing, secretion and regulation of the isoforms of testicular IL-1α are discussed. All three isoforms have been found to be secreted into the testis tubular lumen and interstitial space. We have provided evidence that IL-1α is a paracrine factor that may be of importance in, e.g., the regulation of Leydig cell steroidogenesis. Pathophysiologically, testicular IL-1α may contribute to testicular relapse of acute lymphocytic leukemia in boys.展开更多
Objectives: The aim of this study was to investigate the effect of orthodontic loading on the expression of interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α) in compressed gingiva. Materials and Methods: ...Objectives: The aim of this study was to investigate the effect of orthodontic loading on the expression of interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α) in compressed gingiva. Materials and Methods: Twenty-four male Wistar rats were used with four rats as controls at day 0. In ten rats, corticotomy was performed on either left or right side and the re-maining side was served as control, and killed at 7 and 14 days. In the remaining ten rats, maxillary right and left first molars were moved orthodontically with a constant force of 20 g;appliance and appliance in conjunction with cortictomy (appliance-corticotomy) were sequentially alternated between left and right sides and euthanized at 7 and 14 days. Real time polymerase chain reactions of compressed gingiva excised from the euthanized rats was performed to measure mRNA expressions of IL-1α and TNF-α. Results: There were no significant differences in the expression of IL-1α between all the groups. On the other hand, TNF-α from the pressure side in the ap- pliance group and the appliance in conjunction with corticotomy group showed significant increase on the 7th day compared to that of either control or corticotomy group. Conclusions: Orthodontic loading induced the elevation of TNF-α in compressed展开更多
The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multi...The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.展开更多
目的探究纤维蛋白原样蛋白1(fibrinogen-like protein 1,FGL1)和膜联蛋白A11(annexin A11,ANXA11)对肺癌手术患者效用评估价值及与预后的相关性。方法将本院2020年1月至2023年12月接诊的98例肺癌患者纳入肺癌组,另选取98例健康人作为对...目的探究纤维蛋白原样蛋白1(fibrinogen-like protein 1,FGL1)和膜联蛋白A11(annexin A11,ANXA11)对肺癌手术患者效用评估价值及与预后的相关性。方法将本院2020年1月至2023年12月接诊的98例肺癌患者纳入肺癌组,另选取98例健康人作为对照组。受试者入院后分别于空腹状态下采取6 mL肘静脉血,采用ELISA法检测血清ANXA11水平,采用实时荧光定量PCR技术检测ANXA11表达水平。根据术后1个月肿瘤标志物变化、影像学表现和免疫功能指标变化情况分为治疗有效组(n=68)和无效组(n=30)。患者出院后均行12~36个月的随访,根据患者预后情况分为预后良好组(n=63)和预后不良组(n=35)。对比对照组和肺癌组/有效组和无效组/预后FGL1、ANXA11表达差异;ROC分析FGL1、ANXA11单一及联合检测对肺癌手术患者临床效用评估价值;Spearman分析FGL1、ANXA11表达与预后的关系。结果肺癌组FGL1和ANXA11表达水平明显高于对照组(均P<0.05);无效组FGL1和ANXA11表达水平明显高于有效组(均P<0.05);ROC结果显示FGL1、ANXA11单独及联合检测对肺癌手术患者效用评估的曲线线下面积分别为0.928,并且联合检测具有较高的特异性(95.59%)以及敏感度(90.00%),诊断价值显著高于单独检测ROC曲线线下面积(均P<0.05);预后不良组FGL1和ANXA11表达水平明显高于预后良好组(均P<0.05);Spearman相关性结果显示FGL1、ANXA11与肺癌手术患者预后呈显著正相关(r=0.771、0.793,均P<0.05)。结论肺癌患者的FGL1与ANXA11表达水平高于健康人,治疗无效者高于有效者,预后不良者高于良好者,二者单独及联合检测对患者手术治疗效用评估均有价值,且其与预后相关性显著。展开更多
基金This work was supported by a grant from the Chinese Ministry of Education, China (JWSL 2002247).
文摘Vascular endothelial growth factor (VEGF, namely VEGF-A) is an angiogenic polypeptide and VEGF-C is a lymphangiogenic polypeptide that has been implicated in cancer growth, invasion and metastasis. Several cytokines and growth factors play an important part in cancer progression. These cytokines and growth factors are the principal mediators of cancer cells-stromal cell interaction , which is critical for invasion of cancer cells to the surrounding tissues and metastatic dissemination to distant organs. In this study, we studied VEGF-A, C expression in cultured human pancreatic cancer cell lines and whether the presence of VEGF-A, C in the cell lines is regulated by cytokines interleukin-lct (EL-1α), and interleukin-6 (IL-6). METHODS: We used Northern blot and Western blot methods to analyze expression of the gene and protein of VEGF-A, C in all 6 tested cell lines (ASPC-1, CAPAN-1, MIA-PaCa-2, PANC-1, COLO-357 and T3M4) respectively. To analyze what is the regulator for this VEGF-A, C expression in pancreatic cancer,we used the reverse transcription -polymerase chain reaction (RT-PCR) method to analyze VEGF-A, C expression in cultured human pancreatic cancer cell lines (CAPAN-1 and COLO-357) under the stimulation with IL-1α (10μg/L) or IL-6 (100 μg/L). RESULTS:Northern blot analysis revealed the presence of the 4.1-kb VEGF-A mRNA transcript and 2.4-kb VEGF-C mRNA transcript in all 6 tested cell lines. Immunoblotting with highly specific anti-VEGF-A, anti-VEGF-C antibody revealed the presence of a molecular weight of 43-kDa VEGF-A protein and 55-kDa VEGF-C protein in all the cell lines. RT-PCR analysis revealed the levels of the VEGF-A and VEGF-C gene were 1-2 fold and a 1-fold increase in the COLO-357 cell line by stimulation with IL-la, however, no effect was found in the CAPAN-1 cell line. The levels of the VEGF-A and VEGF-C gene were 2-5 fold and a 1-fold increase in the CAPAN-1 cell line by stimulation with IL-6, but, no effect was found in the COLO-357 cell line. CONCLUSION:These findings suggested that the expression of VEGF-A, C and their regulation by IL-1α, IL-6 in pancreatic cancer contributes to the lymphatic and distant metastasis and the disease progression.
基金sponsored in part by Science and Technology Commission of Shanghai Municipality, China (No. 07ZR14018)
文摘Pigment epithelium-derived factor （PEDF） is an antiangiogenic factor which is effective in tumour inhibition in a variety of tumours and has not yet been studied in bladder tumour before. In this study the expression of PEDF, interleukin-1α （IL-1α） and -8 （IL-8） in bladder tumours was investigated. Immunohistochemistry was performed on 64 bladder tumour and 23 normal uroepithelium samples. Expression change of the factors was compared with clinicopathological parameters. Correlations between PEDF, IL-1α and IL-8 were analyzed. None of the factors was in relation to gender, tumour occurrence, and size or onset pattern. PEDF （P=0.014） and IL-1α （P=0.049） expression was down-regulated with grade progression. PEDF expression was lower in normal uroepithelium than in papillary urothelial neoplasm of low malignant potential （PUNLMP） （P=0.000） and carcinoma （P=0.009） whilst IL-1α （P=0.000 and P=0.000 respectively） and IL-8 （P=0.000 and P=0.023 respectively） expression was higher in the same grouping. PEDF expression had a negative correlation with IL-8 in PUNLMP （P=0.049, r=-0.578） as well as in tumour grouping （P=0.033, r=-0.276）. Deranged expressional change of PEDF, IL-1α and IL-8 could be in relation to loss of differentiation from normal uroepithelium to papillary lesion and eventually to carcinoma.
文摘The present study showed that, interleukin-1α (IL-1α) stimulateal cultured bovine cerebral microvascular endothelial cells (BCMEC) releasing growth factor which promoted bovine cerebral microvascular smooth muscle cells (BCMSMC) proliferation in a dose-dependent manner. The mitogenic activity in conditioned medium of BCMEC stimulated by IL-1α was neutralized significantly by the antibody to platelet-derived growth factor (PDGF). Imperatorin (Imp), iso-Imperatorin (iso Imp) and 6-(α,α-phenylacetylpiperazinyl)phenyl-5-methyl-4,5-dihydro-3 (2H)-pyridazinone (PMDP) did not affect the releasing of PDGF from IL-1α stimulated BCMEC, but inhibited the promotion of PDGF on the proliferation of BCMSMC. We concluded that the promotion of IL-1α on the proliferation of BCMSMC should be mediated by some growth factors, such as PDGF.
文摘Interleukin-1α (IL-1α) is a proinflammatory cytokine that has also been found to act as a paracrine mediator involved in the regulation of testicular functions. The present review provides an overview of the role of IL 1α in testicular physiology. Bioactive IL-1α isolated from adult rat testis was found to consist of three distinct immunoreactive protein species with apparent sizes of 45, 24 and 19 kDa. These isoforms showed bioactivity in a thymocyte proliferation and steroidogenesis assays with different biopotencies. The background of the molecular heterogeneity and processing, secretion and regulation of the isoforms of testicular IL-1α are discussed. All three isoforms have been found to be secreted into the testis tubular lumen and interstitial space. We have provided evidence that IL-1α is a paracrine factor that may be of importance in, e.g., the regulation of Leydig cell steroidogenesis. Pathophysiologically, testicular IL-1α may contribute to testicular relapse of acute lymphocytic leukemia in boys.
文摘Objectives: The aim of this study was to investigate the effect of orthodontic loading on the expression of interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α) in compressed gingiva. Materials and Methods: Twenty-four male Wistar rats were used with four rats as controls at day 0. In ten rats, corticotomy was performed on either left or right side and the re-maining side was served as control, and killed at 7 and 14 days. In the remaining ten rats, maxillary right and left first molars were moved orthodontically with a constant force of 20 g;appliance and appliance in conjunction with cortictomy (appliance-corticotomy) were sequentially alternated between left and right sides and euthanized at 7 and 14 days. Real time polymerase chain reactions of compressed gingiva excised from the euthanized rats was performed to measure mRNA expressions of IL-1α and TNF-α. Results: There were no significant differences in the expression of IL-1α between all the groups. On the other hand, TNF-α from the pressure side in the ap- pliance group and the appliance in conjunction with corticotomy group showed significant increase on the 7th day compared to that of either control or corticotomy group. Conclusions: Orthodontic loading induced the elevation of TNF-α in compressed
基金supported by the National Natural Science Foundational of China(Key Program),No.U24A20692(to CJZ)the National Natural Science Foundational of China,Nos.82101414(to MLJ),82371355(to CJZ)+4 种基金the National Natural Science Foundational of China for Excellent Young Scholars,No.82022019(to CJZ)Sichuan Special Fund for Distinguished Young Scholars,No.24NSFJQ0052(to CJZ)The Innovation and Entrepreneurial Team of Sichuan Tianfu Emei Program,No.CZ2024018(to CJZ)Funding for Distinguished Young Scholars of Sichuan Provincial People’s Hospital,No.30420230005(to CJZ)Funding for Distinguished Young Scholars of University of Electronic Science and Technology of China,No.A1098531023601381(to CJZ)。
文摘The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.
文摘目的探究纤维蛋白原样蛋白1(fibrinogen-like protein 1,FGL1)和膜联蛋白A11(annexin A11,ANXA11)对肺癌手术患者效用评估价值及与预后的相关性。方法将本院2020年1月至2023年12月接诊的98例肺癌患者纳入肺癌组,另选取98例健康人作为对照组。受试者入院后分别于空腹状态下采取6 mL肘静脉血,采用ELISA法检测血清ANXA11水平,采用实时荧光定量PCR技术检测ANXA11表达水平。根据术后1个月肿瘤标志物变化、影像学表现和免疫功能指标变化情况分为治疗有效组(n=68)和无效组(n=30)。患者出院后均行12~36个月的随访,根据患者预后情况分为预后良好组(n=63)和预后不良组(n=35)。对比对照组和肺癌组/有效组和无效组/预后FGL1、ANXA11表达差异;ROC分析FGL1、ANXA11单一及联合检测对肺癌手术患者临床效用评估价值;Spearman分析FGL1、ANXA11表达与预后的关系。结果肺癌组FGL1和ANXA11表达水平明显高于对照组(均P<0.05);无效组FGL1和ANXA11表达水平明显高于有效组(均P<0.05);ROC结果显示FGL1、ANXA11单独及联合检测对肺癌手术患者效用评估的曲线线下面积分别为0.928,并且联合检测具有较高的特异性(95.59%)以及敏感度(90.00%),诊断价值显著高于单独检测ROC曲线线下面积(均P<0.05);预后不良组FGL1和ANXA11表达水平明显高于预后良好组(均P<0.05);Spearman相关性结果显示FGL1、ANXA11与肺癌手术患者预后呈显著正相关(r=0.771、0.793,均P<0.05)。结论肺癌患者的FGL1与ANXA11表达水平高于健康人,治疗无效者高于有效者,预后不良者高于良好者,二者单独及联合检测对患者手术治疗效用评估均有价值,且其与预后相关性显著。
