AIM： To study the expression of Sonic hedgehog pathway-related molecules, Sonic hedgehog （Shh） and Glil in gastric carcinoma. METHODS： Expression of Shh in 56 gastric specimens including non-cancerous gastric tiss...AIM： To study the expression of Sonic hedgehog pathway-related molecules, Sonic hedgehog （Shh） and Glil in gastric carcinoma. METHODS： Expression of Shh in 56 gastric specimens including non-cancerous gastric tissues, gastric adenocarcinoma, gastric squamous cell carcinoma was detected by RT-PCR, in situ hybridization and immunohistochemistry. Expression of Glil was observed by in situ hybridization. RESULTS： The positive rate of Shh and Glil expression was 0.0%, 0.0% in non-cancerous gastric tissues while it was 66.7%, 57.8% respectively in gastric adenocarcinoma, and 100%, 100% respectively in gastric squamous cell carcinoma. There was a significant difference between the non-cancerous gastric tissues and gastric carcinoma （P 〈 0.05）. Elevated expression of Shh and Glil in gastric tubular adenocarcinoma was associated with poorly differentiated tumors while the expression was absent in gastric mucinous adenocarcinoma. CONCLUSION： The elevated expression of Shh and Glil in gastric adenocarcinoma and gastric squamous cell carcinoma shows the involvement of activated Shh signaling in the cellular proliferation of gastric carcinogenesis. It suggests Shh signaling gene may be a new and good target gene for gastric tumor diagnosis and therapy.展开更多
Baihui（DU20）-penetrating-Qubin（GB7） acupuncture can inhibit inflammatory reactions and activate signaling pathways related to proliferation after intracerebral hemorrhage.However,there is no research showing the r...Baihui（DU20）-penetrating-Qubin（GB7） acupuncture can inhibit inflammatory reactions and activate signaling pathways related to proliferation after intracerebral hemorrhage.However,there is no research showing the relationship between this treatment and cell apoptosis.Rat models of intracerebral hemorrhage were established by injecting 60 μL of autologous blood into the right side of the caudate-putamen.Six hours later,the needle traveled subcutaneously from the Baihui acupoint to Qubin acupoint.The needle was alternately rotated（180 ± 10 turns/min） manually along clockwise and counter-clockwise directions.Stimulation lasted for 7 days,and was performed three times each for 6 minutes with 6-minute intervals between stimulations.Rats intraperitoneally receiving Sonic hedgehog pathway activator,purmorphamine（1 mg/kg per day）,served as positive controls.Motor and sensory function were assessed using the Ludmila Belayev test.Extent of pathological changes were measured in the perihemorrhagic penumbra using hematoxylin-eosin staining.Apoptosis was examined by terminal deoxynucleotidyl transferase（Td T）-mediated d UTP nick end labeling assay.Expression of smoothened（Smo） and glioma-associated homolog 1（Gli1） was determined by western blot assay.Our results showed that Baihui-penetrating-Qubin acupuncture promoted recovery of motor and sensory function,reduced the apoptotic cell percentage in the perihemorrhagic penumbra,and up-regulated Smo and Gli1 expression.We conclude that Baihui-penetrating-Qubin acupuncture can mitigate hemorrhage and promote functional recovery of the brain in a rat model of intracerebral hemorrhage,possibly by activating the Sonic hedgehog pathway.展开更多
Pancreatic cancer, mostly pancreatic ductal adenocarcinoma （PDAC）, is a leading cause of cancer-related death in the US, with a dismal median survival of 6 months. Thus, there is an urgent unmet need to identify way...Pancreatic cancer, mostly pancreatic ductal adenocarcinoma （PDAC）, is a leading cause of cancer-related death in the US, with a dismal median survival of 6 months. Thus, there is an urgent unmet need to identify ways to diagnose and to treat this deadly cancer. Although a number of genetic changes have been identified in pancreatic cancer, their mechanisms of action in tumor development, progression and metastasis are not completely understood. Hedgehog signaling, which plays a major role in embryonic development and stem cell regulation, is known to be activated in pancreatic cancer; however, specific inhibitors targeting the smoothened molecule failed to improve the condition of pancreatic cancer patients in clinical trials. Furthermore, results regarding the role of Hh signaling in pancreatic cancer are controversial with some reporting tumor promoting activities whereas others tumor suppressive actions. In this review, we will summarize what we know about hedgehog signaling in pancreatic cancer, and try to explain the contradicting roles of hedgehog signaling as well as the reason（s） behind the failed clinical trials. In addition to the canonical hedgehog signaling, we will also discuss several non-canonical hedgehog signaling mechanisms.展开更多
[目的]探讨SRSF2/tGLI1轴调控Her2阳性乳腺癌侵袭的潜在机制。[方法]在TCGA和GEO数据集(GSE12276、GSE2034、GSE2603、GSE5327、GSE14020)中,分析SRSF2在正常组织和HER2阳性乳腺癌组织中的表达水平以及对无远处转移生存的影响。过表达...[目的]探讨SRSF2/tGLI1轴调控Her2阳性乳腺癌侵袭的潜在机制。[方法]在TCGA和GEO数据集(GSE12276、GSE2034、GSE2603、GSE5327、GSE14020)中,分析SRSF2在正常组织和HER2阳性乳腺癌组织中的表达水平以及对无远处转移生存的影响。过表达或敲低SRSF2或GLI1后,检测HER2阳性乳腺癌细胞SKBR-3、HCC1419、AU-565的侵袭细胞数。敲低SRSF2后分析GLI1的剪接形式,并且过表达GLI1不同剪接形式(fGLI1和tGLI1)后检测HER2阳性乳腺癌细胞的侵袭细胞数。[结果]在TCGA和GEO数据集中,与正常组织相比,HER2阳性乳腺癌组织中SRSF2的mRNA表达上升5倍(1.00±0.05 vs 5.74±0.37,P<0.05)。同时,SRSF2高表达的HER2阳性乳腺癌患者具有更短的无远处转移生存(P<0.05)。过表达SRSF2后,HER2阳性乳腺癌细胞的侵袭细胞数上升2倍(152.88±25.15个vs 376.47±32.31个,P<0.05)。敲低SRSF2后,HER2阳性乳腺癌细胞中fGLI1的mRNA表达上升,tGLI1的mRNA表达下降。过表达tGLI1后,HER2阳性乳腺癌细胞的侵袭细胞数上升3倍(147.43±21.99个vs 397.42±34.03个,P<0.05)。[结论]SRSF2通过选择性剪接将GLI1剪接成tGLI1的形式后,可促进HER2阳性乳腺癌的侵袭能力(152.88±25.15 vs 376.47±32.31,P<0.05)。展开更多
基金Supported by the Foundation of Shandong Province Bureau of Health, No. 2005JZ001
文摘AIM： To study the expression of Sonic hedgehog pathway-related molecules, Sonic hedgehog （Shh） and Glil in gastric carcinoma. METHODS： Expression of Shh in 56 gastric specimens including non-cancerous gastric tissues, gastric adenocarcinoma, gastric squamous cell carcinoma was detected by RT-PCR, in situ hybridization and immunohistochemistry. Expression of Glil was observed by in situ hybridization. RESULTS： The positive rate of Shh and Glil expression was 0.0%, 0.0% in non-cancerous gastric tissues while it was 66.7%, 57.8% respectively in gastric adenocarcinoma, and 100%, 100% respectively in gastric squamous cell carcinoma. There was a significant difference between the non-cancerous gastric tissues and gastric carcinoma （P 〈 0.05）. Elevated expression of Shh and Glil in gastric tubular adenocarcinoma was associated with poorly differentiated tumors while the expression was absent in gastric mucinous adenocarcinoma. CONCLUSION： The elevated expression of Shh and Glil in gastric adenocarcinoma and gastric squamous cell carcinoma shows the involvement of activated Shh signaling in the cellular proliferation of gastric carcinogenesis. It suggests Shh signaling gene may be a new and good target gene for gastric tumor diagnosis and therapy.
基金supported by the National Natural Science Foundation of China,No.30772840,81273824,and 81473764
文摘Baihui（DU20）-penetrating-Qubin（GB7） acupuncture can inhibit inflammatory reactions and activate signaling pathways related to proliferation after intracerebral hemorrhage.However,there is no research showing the relationship between this treatment and cell apoptosis.Rat models of intracerebral hemorrhage were established by injecting 60 μL of autologous blood into the right side of the caudate-putamen.Six hours later,the needle traveled subcutaneously from the Baihui acupoint to Qubin acupoint.The needle was alternately rotated（180 ± 10 turns/min） manually along clockwise and counter-clockwise directions.Stimulation lasted for 7 days,and was performed three times each for 6 minutes with 6-minute intervals between stimulations.Rats intraperitoneally receiving Sonic hedgehog pathway activator,purmorphamine（1 mg/kg per day）,served as positive controls.Motor and sensory function were assessed using the Ludmila Belayev test.Extent of pathological changes were measured in the perihemorrhagic penumbra using hematoxylin-eosin staining.Apoptosis was examined by terminal deoxynucleotidyl transferase（Td T）-mediated d UTP nick end labeling assay.Expression of smoothened（Smo） and glioma-associated homolog 1（Gli1） was determined by western blot assay.Our results showed that Baihui-penetrating-Qubin acupuncture promoted recovery of motor and sensory function,reduced the apoptotic cell percentage in the perihemorrhagic penumbra,and up-regulated Smo and Gli1 expression.We conclude that Baihui-penetrating-Qubin acupuncture can mitigate hemorrhage and promote functional recovery of the brain in a rat model of intracerebral hemorrhage,possibly by activating the Sonic hedgehog pathway.
基金supported by grants from the National Cancer Institute CA155086Riley Children's Foundation+1 种基金Jeff Gurdon Children's Research FoundationWells Center for Pediatric Research
文摘Pancreatic cancer, mostly pancreatic ductal adenocarcinoma （PDAC）, is a leading cause of cancer-related death in the US, with a dismal median survival of 6 months. Thus, there is an urgent unmet need to identify ways to diagnose and to treat this deadly cancer. Although a number of genetic changes have been identified in pancreatic cancer, their mechanisms of action in tumor development, progression and metastasis are not completely understood. Hedgehog signaling, which plays a major role in embryonic development and stem cell regulation, is known to be activated in pancreatic cancer; however, specific inhibitors targeting the smoothened molecule failed to improve the condition of pancreatic cancer patients in clinical trials. Furthermore, results regarding the role of Hh signaling in pancreatic cancer are controversial with some reporting tumor promoting activities whereas others tumor suppressive actions. In this review, we will summarize what we know about hedgehog signaling in pancreatic cancer, and try to explain the contradicting roles of hedgehog signaling as well as the reason（s） behind the failed clinical trials. In addition to the canonical hedgehog signaling, we will also discuss several non-canonical hedgehog signaling mechanisms.
文摘[目的]探讨SRSF2/tGLI1轴调控Her2阳性乳腺癌侵袭的潜在机制。[方法]在TCGA和GEO数据集(GSE12276、GSE2034、GSE2603、GSE5327、GSE14020)中,分析SRSF2在正常组织和HER2阳性乳腺癌组织中的表达水平以及对无远处转移生存的影响。过表达或敲低SRSF2或GLI1后,检测HER2阳性乳腺癌细胞SKBR-3、HCC1419、AU-565的侵袭细胞数。敲低SRSF2后分析GLI1的剪接形式,并且过表达GLI1不同剪接形式(fGLI1和tGLI1)后检测HER2阳性乳腺癌细胞的侵袭细胞数。[结果]在TCGA和GEO数据集中,与正常组织相比,HER2阳性乳腺癌组织中SRSF2的mRNA表达上升5倍(1.00±0.05 vs 5.74±0.37,P<0.05)。同时,SRSF2高表达的HER2阳性乳腺癌患者具有更短的无远处转移生存(P<0.05)。过表达SRSF2后,HER2阳性乳腺癌细胞的侵袭细胞数上升2倍(152.88±25.15个vs 376.47±32.31个,P<0.05)。敲低SRSF2后,HER2阳性乳腺癌细胞中fGLI1的mRNA表达上升,tGLI1的mRNA表达下降。过表达tGLI1后,HER2阳性乳腺癌细胞的侵袭细胞数上升3倍(147.43±21.99个vs 397.42±34.03个,P<0.05)。[结论]SRSF2通过选择性剪接将GLI1剪接成tGLI1的形式后,可促进HER2阳性乳腺癌的侵袭能力(152.88±25.15 vs 376.47±32.31,P<0.05)。
