Receptor Tyrosine kinases (RTKs) play a crucial role in the signal transduction pathways at cellular levels. RTK plays a vital role in cellular communication and transmission of signals to the adjacent cells and regul...Receptor Tyrosine kinases (RTKs) play a crucial role in the signal transduction pathways at cellular levels. RTK plays a vital role in cellular communication and transmission of signals to the adjacent cells and regulates different functions of the cell, such as cellular growth, differentiation, metabolism and motility. RTK s triggers growth factor receptors such as epidermal growth factor, insulin growth factor-1 receptor, platelet derived growth factor receptor, and fibro blast growth factor receptor and vascular endothelial growth factor receptor, thereby initiating and regulating cell growth and proliferation. MAPK/RAS and PI3/AKT pathways are the major pathways of RTK’s function. Dysregulation of these RTK’s and pathways often leads to many diseases such as Noonan Syndrome, Logius Syndrome, CFC syndrome and different types of cancer. Point mutation and over expression of receptors and mutations in Ras leads to 30% of human cancers. Also over expression of different growth factor receptors by RTK too lead to several types of cancers as Glioblastoma, Thyroid cancer, Colon cancer and Non-small cell lung cancer. PTEN mutation in PI3/AKT pathway often leads to carcinoma relative to Thyroid, Skin, Large intestine, eye and Bone. Therefore, these RTK’s often used as targets for cancer therapies. The medical sector uses various types of small molecule tyrosine kinase inhibitors such as ATP competitive inhibitors, Allosteric inhibitors and covalent inhibitors which are known as Afatinib, Crizotinib, Eroltinib, Icotinib, Lepatinib and Lenvatinib in treatment and management of differential carcinomas.展开更多
目的:探讨鸢尾素调节Janus蛋白酪氨酸激酶2(Janus protein tyrosine kinase 2,JAK2)/信号转导和转录激活子3(Signal transduction and activator of transcription 3,STAT3)信号通路对牙周炎大鼠牙周组织损伤的影响。方法:通过结扎和接...目的:探讨鸢尾素调节Janus蛋白酪氨酸激酶2(Janus protein tyrosine kinase 2,JAK2)/信号转导和转录激活子3(Signal transduction and activator of transcription 3,STAT3)信号通路对牙周炎大鼠牙周组织损伤的影响。方法:通过结扎和接种牙龈卟啉单胞菌液建立牙周炎大鼠模型,将大鼠随机分为模型组、鸢尾素低(鸢尾素-L,50 mg/kg)、中(鸢尾素-M,100 mg/kg)、高剂量(鸢尾素-H,200 mg/kg)组、鸢尾素-H+激活剂(200 mg/kg鸢尾素+2 mg/kg香豆霉素)组,每组10只,并以注射等体积生理盐水的正常大鼠对照组。干预结束后,对大鼠牙龈出血指数、牙齿松动度评分;牙槽骨吸收、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、白细胞介素(Interleukin,IL)-6、IL-1β以及丙二醛(Malondialdehyde,MDA)、超氧化物歧化酶(Superoxide dismutase,SOD)水平分别以Micro-CT试剂盒检测;HE检测牙周组织病理学变化;Western blot检测JAK2、STAT3、p-JAK2、p-STAT3蛋白表达。结果:与对照组相比,模型组大鼠牙周组织被破坏,炎性浸润严重,牙龈出血指数、牙齿松动度评分、牙槽骨吸收、TNF-α、IL-6、IL-1β、MDA水平、p-JAK2/JAK2、p-STAT3/STAT3表达显著增加,SOD水平显著降低(P<0.05);与模型组相比,不同剂量的鸢尾素组大鼠病理损伤得到改善,牙龈出血指数、牙齿松动度评分、牙槽骨吸收、TNF-α、IL-6、IL-1β、MDA水平、p-JAK2/JAK2、p-STAT3/STAT3表达显著降低,SOD水平显著增加,具有剂量依赖性(P<0.05);与鸢尾素-H组相比,鸢尾素-H组+激活剂组大鼠病理损伤加重,大鼠牙龈出血指数、牙齿松动度评分、牙槽骨吸收、TNF-α、IL-6、IL-1β、MDA水平、p-JAK2/JAK2、p-STAT3/STAT3表达显著增加,SOD水平显著降低(P<0.05)。结论:鸢尾素抑制牙周炎大鼠氧化应激、炎性反应,减轻大鼠牙周组织损伤,减少牙槽骨吸收,可能与抑制JAK2/STAT3信号通路有关。展开更多
Objective:This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2(ROR2)in triple-negative breast cancer(TNBC).Methods:ROR2 expression in primary TNBC and metastatic TNBC tissues was...Objective:This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2(ROR2)in triple-negative breast cancer(TNBC).Methods:ROR2 expression in primary TNBC and metastatic TNBC tissues was analyzed by immunohistochemical staining and PCR.ROR2 expression in TNBC cell lines was detected by PCR and Western blot analysis.The migration,invasion and chemosensitivity of TNBC cells with overexpression or knockdown of ROR2 were examined.Results:ROR2 expression was high in metastatic TNBC tissues.ROR2 knockdown suppressed the migration,invasion and chemoresistance of TNBC cells.ROR2 overexpression in MDA-MB-435 cells promoted the migration,invasion,and chemoresistance.Moreover,ROR2 knockdown in HC1599 and MDA-MB-435 adriamycin-resistant cells enhanced chemosensitivity to adriamycin.ROR2 could activate PI3K/AKT/mTOR signaling in TNBC cells.Conclusion:ROR2 is upregulated and promotes metastatic phenotypes of TNBC by activating PI3K/AKT/mTOR signaling.展开更多
文摘Receptor Tyrosine kinases (RTKs) play a crucial role in the signal transduction pathways at cellular levels. RTK plays a vital role in cellular communication and transmission of signals to the adjacent cells and regulates different functions of the cell, such as cellular growth, differentiation, metabolism and motility. RTK s triggers growth factor receptors such as epidermal growth factor, insulin growth factor-1 receptor, platelet derived growth factor receptor, and fibro blast growth factor receptor and vascular endothelial growth factor receptor, thereby initiating and regulating cell growth and proliferation. MAPK/RAS and PI3/AKT pathways are the major pathways of RTK’s function. Dysregulation of these RTK’s and pathways often leads to many diseases such as Noonan Syndrome, Logius Syndrome, CFC syndrome and different types of cancer. Point mutation and over expression of receptors and mutations in Ras leads to 30% of human cancers. Also over expression of different growth factor receptors by RTK too lead to several types of cancers as Glioblastoma, Thyroid cancer, Colon cancer and Non-small cell lung cancer. PTEN mutation in PI3/AKT pathway often leads to carcinoma relative to Thyroid, Skin, Large intestine, eye and Bone. Therefore, these RTK’s often used as targets for cancer therapies. The medical sector uses various types of small molecule tyrosine kinase inhibitors such as ATP competitive inhibitors, Allosteric inhibitors and covalent inhibitors which are known as Afatinib, Crizotinib, Eroltinib, Icotinib, Lepatinib and Lenvatinib in treatment and management of differential carcinomas.
基金supported by Medical and Health Research Project of Nanjing Health Science and Technology Development Special Fund(ZKX21040).
文摘Objective:This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2(ROR2)in triple-negative breast cancer(TNBC).Methods:ROR2 expression in primary TNBC and metastatic TNBC tissues was analyzed by immunohistochemical staining and PCR.ROR2 expression in TNBC cell lines was detected by PCR and Western blot analysis.The migration,invasion and chemosensitivity of TNBC cells with overexpression or knockdown of ROR2 were examined.Results:ROR2 expression was high in metastatic TNBC tissues.ROR2 knockdown suppressed the migration,invasion and chemoresistance of TNBC cells.ROR2 overexpression in MDA-MB-435 cells promoted the migration,invasion,and chemoresistance.Moreover,ROR2 knockdown in HC1599 and MDA-MB-435 adriamycin-resistant cells enhanced chemosensitivity to adriamycin.ROR2 could activate PI3K/AKT/mTOR signaling in TNBC cells.Conclusion:ROR2 is upregulated and promotes metastatic phenotypes of TNBC by activating PI3K/AKT/mTOR signaling.
