In the present study, we investigated the dynamic expression of fibroblast growth factor 8 and Sonic Hedgehog signaling pathway related factors in the process of in vitro hippocampal neural stem/progenitor cell differ...In the present study, we investigated the dynamic expression of fibroblast growth factor 8 and Sonic Hedgehog signaling pathway related factors in the process of in vitro hippocampal neural stem/progenitor cell differentiation from embryonic Sprague-Dawley rats or embryonic Kunming species mice, using fluorescent quantitative reverse transcription-PCR and western blot analyses. Results demonstrated that the dynamic expression of fibroblast growth factor 8 was similar to fibroblast growth factor receptor 1 expression but not to other fibroblast growth factor receptors. Enzyme-linked immunosorbent assay demonstrated that fibroblast growth factor 8 and Sonic Hedgehog signaling pathway protein factors were secreted by neural cells into the intercellular niche. Our experimental findings indicate that fibroblast growth factor 8 and Sonic Hedgehog expression may be related to the differentiation of neural stem/progenitor cells.展开更多
目的 通过给予外源性SHH激动剂或抑制剂从而激活或抑制SHH信号通路,观察其在兔急性心肌梗死(AMI)模型中对血管生成的影响。方法 通过用丝线结扎新西兰大白兔左冠状动脉前降支来构建兔急性心肌梗死模型。将兔随机分为对照组(假手术组)、...目的 通过给予外源性SHH激动剂或抑制剂从而激活或抑制SHH信号通路,观察其在兔急性心肌梗死(AMI)模型中对血管生成的影响。方法 通过用丝线结扎新西兰大白兔左冠状动脉前降支来构建兔急性心肌梗死模型。将兔随机分为对照组(假手术组)、模型组(结扎左前降支急性心肌梗死模型)、激动剂组(结扎左前降支,通过使用Purmorphamine激活SHH通路)、抑制剂组(结扎左前降支,通过使用Cyclopamine抑制SHH通路),术后24 h处死动物并留取静脉血液及心肌组织。采用ELISA方法检测动物模型术后24 h血清中血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF),使用免疫组化检测各组心肌组织中VEGF、bFGF蛋白的表达,实时荧光定量PCR(RT-PCP)检测各组心肌组织Hedgehog通路SHH、SMO、Gli-1 mRNA表达情况。结果 与对照组相比,急性心肌梗死模型组用ELISA方法测得的血清中VEGF、bFGF均升高(228.03±9.62pg/mL vs 306.59±12.42pg/mL,78.25±8.35pg/mL vs 141.80±5.58pg/mL),差异有统计学意义(P<0.05),与模型组相比,激动剂组VEGF、bFGF水平升高(306.59±12.42pg/mL vs 374.68±17.52pg/mL,141.80±5.58pg/mL vs 167.00±9.57pg/mL),抑制剂组VEGF、bFGF水平降低(306.59±12.42pg/mL vs 266.12±13.69pg/mL,141.80±5.58pg/mL vs 106.53±7.23pg/mL),差异有统计学意义(P<0.05);与对照组比较,模型组兔梗死心肌组织中VEGF、bFGF蛋白表达升高(0.0951±0.0080 vs 0.1732±0.0068,0.0636±0.0047 vs 0.1921±0.0063),差异有统计学意义(P<0.05),与模型组比较,激动剂组的心肌组织中VEGF、bFGF表达升高(0.1732±0.0068 vs 0.1963±0.0127,0.1921±0.0063 vs 0.2320±0.0120),抑制剂组的VEGF、bFGF表达减少(0.1732±0.0068 vs 0.1472±0.0416,0.1921±0.0063 vs 0.1645±0.0048),差异有统计学意义(P<0.05);与对照组相比,模型组SHH、SMO、Gli-1基因表达水平显著升高(1±0.058 vs 1.376±0.171,1±0.067 vs 1.202±0.877,1±0.105 vs 1.028±0.083),差异有统计学意义(P<0.05),与模型组相比,激动剂组SHH、SMO、Gli-1基因表达水平显著增高(1.376±0.171 vs 2.165±0.267,1.202±0.877 vs 1.990±0.152,1.028±0.083 vs 1.619±0.174),抑制剂组SHH、SMO、Gli-1基因表达显著下降(1.376±0.171 vs 0.911±0.15,1.202±0.877 vs 0.536±0.389,1.028±0.083 vs 0.583±0.053),差异有统计学意义(P<0.05)。结论 激活SHH信号通路,血管生成因子的表达相应增加,从而促进心肌梗死后血管生成,提示SHH信号通路激活与AMI血管再生有关。展开更多
For patients with metastatic or locally advanced eyelid and periocular carcinoma not amenable to surgical excision, targeted therapies have shown efficacy with better tolerability compared to cytotoxic chemotherapy. O...For patients with metastatic or locally advanced eyelid and periocular carcinoma not amenable to surgical excision, targeted therapies have shown efficacy with better tolerability compared to cytotoxic chemotherapy. Overexpression of epithelial growth factor receptor was found in squamous cell carcinomas. Vismodegib targets the mutation in the hedgehog pathway identified in basal cell carcinoma and basal cell nevus syndrome. Targeted therapies provide a novel and potentially effective treatment alternative for patients with eyelid carcinoma not amendable for surgery, including those with metastatic, locally advanced disease, advanced age, and significant comorbidities. High cost, need for long-term treatment, and toxicity are relative limitations.展开更多
Liver is unique in its capacity to regenerate in response to injury or tissue loss. Hepatocytes and other liver cells are able to proliferate and repopulate the liver. However, when this response is impaired, the cont...Liver is unique in its capacity to regenerate in response to injury or tissue loss. Hepatocytes and other liver cells are able to proliferate and repopulate the liver. However, when this response is impaired, the contribution of hepatic progenitors becomes very relevant. Here, we present an update of recent studies on growth factors and cytokine-driven intracellular pathways that govern liver stem/pro-genitor cell expansion and differentiation, and the rel-evance of these signals in liver development, regeneration and carcinogenesis. Tyrosine kinase receptor signaling, in particular, c-Met, epidermal growth factor receptors or fibroblast growth factor receptors, contribute to prolifera-tion, survival and differentiation of liver stem/progenitor cells. Different evidence suggests a dual role for the trans-forming growth factor (TGF)-β signaling pathway in liver stemness and differentiation. On the one hand, TGF-βmediates progression of differentiation from a progenitor stage, but on the other hand, it contributes to the expan-sion of liver stem cells. Hedgehog family ligands are nec-essary to promote hepatoblast proliferation but need to be shut off to permit subsequent hepatoblast differentiation. In the same line, the Wnt family and β-catenin/T-cell fac-tor pathway is clearly involved in the maintenance of liver stemness phenotype, and its repression is necessary for liver differentiation during development. Collectively, data indicate that liver stem/progenitor cells follow their own rules and regulations. The same signals that are essential for their activation, expansion and differentiation are good candidates to contribute, under adequate conditions, to the paradigm of transformation from a pro-regenerative to a pro-tumorigenic role. From a clinical perspective, this is a fundamental issue for liver stem/progenitor cell-based therapies.展开更多
基金supported by the National Natural Science Foundation of China,No.81070614the Key Project of the Natural Science Foundation of Hubei Province of China,No.2008CDA044the Natural Science Foundation of Hubei University of Medicine,No.2011QDZR-2
文摘In the present study, we investigated the dynamic expression of fibroblast growth factor 8 and Sonic Hedgehog signaling pathway related factors in the process of in vitro hippocampal neural stem/progenitor cell differentiation from embryonic Sprague-Dawley rats or embryonic Kunming species mice, using fluorescent quantitative reverse transcription-PCR and western blot analyses. Results demonstrated that the dynamic expression of fibroblast growth factor 8 was similar to fibroblast growth factor receptor 1 expression but not to other fibroblast growth factor receptors. Enzyme-linked immunosorbent assay demonstrated that fibroblast growth factor 8 and Sonic Hedgehog signaling pathway protein factors were secreted by neural cells into the intercellular niche. Our experimental findings indicate that fibroblast growth factor 8 and Sonic Hedgehog expression may be related to the differentiation of neural stem/progenitor cells.
文摘目的 通过给予外源性SHH激动剂或抑制剂从而激活或抑制SHH信号通路,观察其在兔急性心肌梗死(AMI)模型中对血管生成的影响。方法 通过用丝线结扎新西兰大白兔左冠状动脉前降支来构建兔急性心肌梗死模型。将兔随机分为对照组(假手术组)、模型组(结扎左前降支急性心肌梗死模型)、激动剂组(结扎左前降支,通过使用Purmorphamine激活SHH通路)、抑制剂组(结扎左前降支,通过使用Cyclopamine抑制SHH通路),术后24 h处死动物并留取静脉血液及心肌组织。采用ELISA方法检测动物模型术后24 h血清中血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF),使用免疫组化检测各组心肌组织中VEGF、bFGF蛋白的表达,实时荧光定量PCR(RT-PCP)检测各组心肌组织Hedgehog通路SHH、SMO、Gli-1 mRNA表达情况。结果 与对照组相比,急性心肌梗死模型组用ELISA方法测得的血清中VEGF、bFGF均升高(228.03±9.62pg/mL vs 306.59±12.42pg/mL,78.25±8.35pg/mL vs 141.80±5.58pg/mL),差异有统计学意义(P<0.05),与模型组相比,激动剂组VEGF、bFGF水平升高(306.59±12.42pg/mL vs 374.68±17.52pg/mL,141.80±5.58pg/mL vs 167.00±9.57pg/mL),抑制剂组VEGF、bFGF水平降低(306.59±12.42pg/mL vs 266.12±13.69pg/mL,141.80±5.58pg/mL vs 106.53±7.23pg/mL),差异有统计学意义(P<0.05);与对照组比较,模型组兔梗死心肌组织中VEGF、bFGF蛋白表达升高(0.0951±0.0080 vs 0.1732±0.0068,0.0636±0.0047 vs 0.1921±0.0063),差异有统计学意义(P<0.05),与模型组比较,激动剂组的心肌组织中VEGF、bFGF表达升高(0.1732±0.0068 vs 0.1963±0.0127,0.1921±0.0063 vs 0.2320±0.0120),抑制剂组的VEGF、bFGF表达减少(0.1732±0.0068 vs 0.1472±0.0416,0.1921±0.0063 vs 0.1645±0.0048),差异有统计学意义(P<0.05);与对照组相比,模型组SHH、SMO、Gli-1基因表达水平显著升高(1±0.058 vs 1.376±0.171,1±0.067 vs 1.202±0.877,1±0.105 vs 1.028±0.083),差异有统计学意义(P<0.05),与模型组相比,激动剂组SHH、SMO、Gli-1基因表达水平显著增高(1.376±0.171 vs 2.165±0.267,1.202±0.877 vs 1.990±0.152,1.028±0.083 vs 1.619±0.174),抑制剂组SHH、SMO、Gli-1基因表达显著下降(1.376±0.171 vs 0.911±0.15,1.202±0.877 vs 0.536±0.389,1.028±0.083 vs 0.583±0.053),差异有统计学意义(P<0.05)。结论 激活SHH信号通路,血管生成因子的表达相应增加,从而促进心肌梗死后血管生成,提示SHH信号通路激活与AMI血管再生有关。
文摘For patients with metastatic or locally advanced eyelid and periocular carcinoma not amenable to surgical excision, targeted therapies have shown efficacy with better tolerability compared to cytotoxic chemotherapy. Overexpression of epithelial growth factor receptor was found in squamous cell carcinomas. Vismodegib targets the mutation in the hedgehog pathway identified in basal cell carcinoma and basal cell nevus syndrome. Targeted therapies provide a novel and potentially effective treatment alternative for patients with eyelid carcinoma not amendable for surgery, including those with metastatic, locally advanced disease, advanced age, and significant comorbidities. High cost, need for long-term treatment, and toxicity are relative limitations.
基金Supported by Grants from the Ministerio de Ciencia e Innovación, MICINN, Spain (SAF2009-12477 to Sánchez A BFU2009-07219 and ISCIII-RTICC RD06/0020 to Fabregat I)+1 种基金AGAUR-Generalitat de Catalunya (2009SGR-312 to Fabregat I)UCM-BSCH (920359 to Sánchez A)
文摘Liver is unique in its capacity to regenerate in response to injury or tissue loss. Hepatocytes and other liver cells are able to proliferate and repopulate the liver. However, when this response is impaired, the contribution of hepatic progenitors becomes very relevant. Here, we present an update of recent studies on growth factors and cytokine-driven intracellular pathways that govern liver stem/pro-genitor cell expansion and differentiation, and the rel-evance of these signals in liver development, regeneration and carcinogenesis. Tyrosine kinase receptor signaling, in particular, c-Met, epidermal growth factor receptors or fibroblast growth factor receptors, contribute to prolifera-tion, survival and differentiation of liver stem/progenitor cells. Different evidence suggests a dual role for the trans-forming growth factor (TGF)-β signaling pathway in liver stemness and differentiation. On the one hand, TGF-βmediates progression of differentiation from a progenitor stage, but on the other hand, it contributes to the expan-sion of liver stem cells. Hedgehog family ligands are nec-essary to promote hepatoblast proliferation but need to be shut off to permit subsequent hepatoblast differentiation. In the same line, the Wnt family and β-catenin/T-cell fac-tor pathway is clearly involved in the maintenance of liver stemness phenotype, and its repression is necessary for liver differentiation during development. Collectively, data indicate that liver stem/progenitor cells follow their own rules and regulations. The same signals that are essential for their activation, expansion and differentiation are good candidates to contribute, under adequate conditions, to the paradigm of transformation from a pro-regenerative to a pro-tumorigenic role. From a clinical perspective, this is a fundamental issue for liver stem/progenitor cell-based therapies.
