Receptor tyrosine kinase-like orphan receptor 1(ROR1)is a member of the type I receptor tyrosine kinase family.ROR1 is pivotal in embryonic development and cancer,and serves as a biomarker and therapeutic target.It ha...Receptor tyrosine kinase-like orphan receptor 1(ROR1)is a member of the type I receptor tyrosine kinase family.ROR1 is pivotal in embryonic development and cancer,and serves as a biomarker and therapeutic target.It has soluble and membrane-bound subtypes,with the latter highly expressed in tumors.ROR1 is conserved throughout evolution and may play a role in the development of gastrointestinal cancer through multiple signaling pathways and molecular mechanisms.Studies suggest that overexpression of ROR1 may increase tumor invasiveness and metastasis.Additionally,ROR1 may regulate the cell cycle,stem cell characteristics,and interact with other signaling pathways to affect cancer progression.This review explores the structure,expression and role of ROR1 in the development of gastrointestinal cancers.It discusses current antitumor strategies,outlining challenges and prospects for treatment.展开更多
Objective：To explore the effect of Bushen Huoxue Decoction（补肾活血饮,BHD） on the orphan receptor（Nurr1） and tyrosine hydroxylase（TH） in the brain of rats with Parkinson＇s disease（PD）.Methods：One hundred an...Objective：To explore the effect of Bushen Huoxue Decoction（补肾活血饮,BHD） on the orphan receptor（Nurr1） and tyrosine hydroxylase（TH） in the brain of rats with Parkinson＇s disease（PD）.Methods：One hundred and twenty SD rats were divided into 100 in the model group and 20 in the normal control group,fifty-eight SD rats from the model group,established into PD model successfully by injuring their substantia nigra （SSN） with 6-hydroxydopamine,were divided equally into the model group and the test group,and they were treated with saline and BHD,respectively,for eight successive weeks.The change in the rats＇ behavior before and after treatment was observed by counting the cycles of rotation induced by apomorphine injection; the pathology of neurons,level of Nurr1 mRNA expression,and amount of TH positive cells in SSN were observed after treatment.Results：The rats＇ behavior was improved in the tested group significantly,the rotation cycle after treatment being 84.0±20.0 cycles/40 min,which was significantly lower than that in the model group（377.0±62.3 cycles/40 min,P〈0.01）.Besides,the Nurr1 mRNA expression and TH positive cell in the test group were 0.97±0.15 and 49.40±14.72,respectively,which were significantly higher than those in the model group,0.22±0.03 and 5.45±2.58,respectively（all P〈0.01）.Conclusion：BHD could treat PD by enhancing the Nurr1 mRNA expression,increasing the TH content in brain,and promoting the repairing of injured neuron in cerebral SSN.展开更多
Expression and cellular localization of orphan receptor TR2 mRNA in relation to germ cell apoptosis in cryptorchid testes of rat and rhesus monkey have been studied by using in situ hybridization and in situ 3’-end l...Expression and cellular localization of orphan receptor TR2 mRNA in relation to germ cell apoptosis in cryptorchid testes of rat and rhesus monkey have been studied by using in situ hybridization and in situ 3’-end labeling of DNA fragments (T躈EL). The results show that: (i) TR2 mRNA is specifically expressed in the germ cells, mainly in the spermatocytes, round and elongated spermatids. The expression level of TR2 mRNA varies with the seminiferous cycle. (ii) in the rat cryptorchid testes on days 3 and 5 after the surgery, the germ cells began to undergo apoptosis with no evident decrease in TR2 mRNA level. On day 7.5, however, most germ cells underwent apoptosis, while the expression level of TR2 mRNA declined markedly, and TR2 mRNA was rarely expressed on day 10 thereafter. (iii) On days 15 and 20 of the cryptorchid testes of rhesus monkey, TR2 mRNA was only expressed in a few of primary spermatocytes and the mRNA was almost undetectable on days 30, 45, 60. These results suggest that TR2 mRNA展开更多
The cellular localization and expression of TR2 mRNA in rhesus monkey testis were investigated by the methods of in situ and Northern hybridization using the digoxigenin labeled in vitro transcripted cRNA probe from a...The cellular localization and expression of TR2 mRNA in rhesus monkey testis were investigated by the methods of in situ and Northern hybridization using the digoxigenin labeled in vitro transcripted cRNA probe from a TR2 cDNA fragment template and α-<sup>32</sup>P-dCTP labeled cDNA probe from the same TR2 cDNA fragment. It is demonstrated that TR2 mRNA was localized specifically in the germ cells, and was predominantly expressed in the meiotic more advanced cells. The expression level was various in different seminiferous tubules, and there was stronger expression in the tubules where spermatogenesis was vigorously going on. The expression level of TR2 mRNA was low in the immature rhesus monkey testis and increased dramatically in the adult and varied with a seminiferous cycle. These data suggest for the first time that orphan receptor TR2 may have an important function in regulating spermatogenesis at later stages of germ cell development in rhesus monkey.展开更多
By in situ hybridization, the localization of orphan receptor TR3 mRNA has been observed in early developmental follicles. TR3 mRNA is first expressed in the ovarian interstitial cells on day 2 after birth, and then i...By in situ hybridization, the localization of orphan receptor TR3 mRNA has been observed in early developmental follicles. TR3 mRNA is first expressed in the ovarian interstitial cells on day 2 after birth, and then in granulosa cells (GC) in primary follicles on day 4. The expression level of TR3 mRNA in GC increases following the follicular development. Its higher expression can be observed in the outer layer of GC and inner layer of theca cells (TC) on day 6, where the cells present active proliferation and differentiation. The expression of TR3 is in an increasing manner until the large antral follicles on day 30. The mRNA is only expressed in the healthy, but not atretic follicles in adult rat ovaries. Injection of epidermal growth factor (EGF) has dramatically enhanced its expression in the early stage of developmental follicles. It is therefore suggested that TR3 may play a role in regulating growth and differentiation of ovarian somatic cells in the early stage, and its expression is regulated展开更多
The cellular localization and specific expression of TR3 mRNA in rat testis were investigated by the method of immunohistochemistry and in situ hybridization. It was demonstrated that orphan receptor TR3 was expressed...The cellular localization and specific expression of TR3 mRNA in rat testis were investigated by the method of immunohistochemistry and in situ hybridization. It was demonstrated that orphan receptor TR3 was expressed in a significant amount in rat testis and TR3 protein and mRNA were specifically localized in germ cells, suggesting that TR3 may have an important function in regulating rat germ cell development.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
Pancreatic ductal adenocarcinoma(PDAC)is a devastating disease with a median overall survival time of5 mo and the five years survival less than 5%,a rate essentially unchanged over the course of the years.A well defin...Pancreatic ductal adenocarcinoma(PDAC)is a devastating disease with a median overall survival time of5 mo and the five years survival less than 5%,a rate essentially unchanged over the course of the years.A well defined progression model of accumulation of genetic alterations ranging from single point mutations to gross chromosomal abnormalities has been introduced to describe the origin of this disease.However,due to the its subtle nature and concurring events PDAC cure remains elusive.Nuclear receptors(NR)are members of a large superfamily of evolutionarily conserved ligand-regulated DNA-binding transcription factors functionally involved in important cellular functions ranging from regulation of metabolism,to growth and development.Given the nature of their ligands,NR are very tempting drug targets and their pharmacological modulation has been widely exploited for the treatment of metabolic and inflammatory diseases.There are now clear evidences that both classical ligand-activated and orphan NR are involved in the pathogenesis of PDAC from its very early stages;nonetheless many aspects of their role are not fully understood.The purpose of this review is to highlight the striking connections that link peroxisome proliferator activated receptors,retinoic acid receptors,retinoid X receptor,androgen receptor,estrogen receptors and the orphan NR Nur,chicken ovalbumin upstream promoter transcription factorⅡand the liver receptor homologue-1 receptor to PDAC development,connections that could lead to the identification of novel therapies for this disease.展开更多
The adoptive transfer of T cells is a promising approach to treat cancers. Primary human T cells can be modified using viral and non-viral vectors to promote the specific targeting of cancer cells via the introduction...The adoptive transfer of T cells is a promising approach to treat cancers. Primary human T cells can be modified using viral and non-viral vectors to promote the specific targeting of cancer cells via the introduction of exogenous T-cell receptors(TCRs) or chimeric antigen receptors(CARs). This gene transfer displays the potential to increase the specificity and potency of the anticancer response while decreasing the systemic adverse effects that arise from conventional treatments that target both cancerous and healthy cells. This review highlights the generation of clinical-grade T cells expressing CARs for immunotherapy, the use of these cells to target B-cell malignancies and, particularly, the first clinical trials deploying the Sleeping Beauty gene transfer system, which engineers T cells to target CD19+ leukemia and non-Hodgkin's lymphoma.展开更多
目的探究视黄酸相关孤儿受体(RORγt)白细胞介素23(IL-23)通路调节辅助性T细胞17(Th17)在老年盐敏感性高血压发病中的作用。方法对内蒙古自治区的村民进行调查,2021年1月至2022年1月选取289例老年高血压患者作为研究对象,采用Sullivan...目的探究视黄酸相关孤儿受体(RORγt)白细胞介素23(IL-23)通路调节辅助性T细胞17(Th17)在老年盐敏感性高血压发病中的作用。方法对内蒙古自治区的村民进行调查,2021年1月至2022年1月选取289例老年高血压患者作为研究对象,采用Sullivan盐负荷试验将患者进行分组,盐敏感高血压患者103例作为研究组,非盐敏感高血压患者186例作为对照组,给予慢性盐负荷试验。结果研究组收缩压、舒张压、MAP、心率在D10、D17均显著高于对照组(P<0.01)。2组尿量、尿钠、尿钾、尿肌酐水平在基线D3比较无显著差异(P>0.05),D10与对照组比较,研究组尿钠[(315.32±57.21)mmol/24 h vs(226.64±58.53)mmol/24 h,P=0.000]、尿肌酐[(12.46±1.64)mmol/24 h vs(10.12±1.17)mmol/24 h,P=0.000]显著增高。2组Th17比例、IL-17A水平在D4、D5、D10逐渐上升,在D17下降,且研究组Th17比例、IL-17A水平在D4、D5、D10、D17均显著高于对照组(P<0.01)。结论Th17参与了盐敏感性高血压的发生,RORγt-IL-23受体信号通路可诱导Th17细胞分化。展开更多
基金Supported by the Hangzhou Medical Health Science and Technology Project,No.B20220173the Public Welfare Technology Project of Zhejiang Province,No.LGF21H160033Zhejiang Medical Technology Plan Project,No.2021KY047.
文摘Receptor tyrosine kinase-like orphan receptor 1(ROR1)is a member of the type I receptor tyrosine kinase family.ROR1 is pivotal in embryonic development and cancer,and serves as a biomarker and therapeutic target.It has soluble and membrane-bound subtypes,with the latter highly expressed in tumors.ROR1 is conserved throughout evolution and may play a role in the development of gastrointestinal cancer through multiple signaling pathways and molecular mechanisms.Studies suggest that overexpression of ROR1 may increase tumor invasiveness and metastasis.Additionally,ROR1 may regulate the cell cycle,stem cell characteristics,and interact with other signaling pathways to affect cancer progression.This review explores the structure,expression and role of ROR1 in the development of gastrointestinal cancers.It discusses current antitumor strategies,outlining challenges and prospects for treatment.
基金Supported by National Natural Science Foundation of China (No.30672762)
文摘Objective：To explore the effect of Bushen Huoxue Decoction（补肾活血饮,BHD） on the orphan receptor（Nurr1） and tyrosine hydroxylase（TH） in the brain of rats with Parkinson＇s disease（PD）.Methods：One hundred and twenty SD rats were divided into 100 in the model group and 20 in the normal control group,fifty-eight SD rats from the model group,established into PD model successfully by injuring their substantia nigra （SSN） with 6-hydroxydopamine,were divided equally into the model group and the test group,and they were treated with saline and BHD,respectively,for eight successive weeks.The change in the rats＇ behavior before and after treatment was observed by counting the cycles of rotation induced by apomorphine injection; the pathology of neurons,level of Nurr1 mRNA expression,and amount of TH positive cells in SSN were observed after treatment.Results：The rats＇ behavior was improved in the tested group significantly,the rotation cycle after treatment being 84.0±20.0 cycles/40 min,which was significantly lower than that in the model group（377.0±62.3 cycles/40 min,P〈0.01）.Besides,the Nurr1 mRNA expression and TH positive cell in the test group were 0.97±0.15 and 49.40±14.72,respectively,which were significantly higher than those in the model group,0.22±0.03 and 5.45±2.58,respectively（all P〈0.01）.Conclusion：BHD could treat PD by enhancing the Nurr1 mRNA expression,increasing the TH content in brain,and promoting the repairing of injured neuron in cerebral SSN.
文摘Expression and cellular localization of orphan receptor TR2 mRNA in relation to germ cell apoptosis in cryptorchid testes of rat and rhesus monkey have been studied by using in situ hybridization and in situ 3’-end labeling of DNA fragments (T躈EL). The results show that: (i) TR2 mRNA is specifically expressed in the germ cells, mainly in the spermatocytes, round and elongated spermatids. The expression level of TR2 mRNA varies with the seminiferous cycle. (ii) in the rat cryptorchid testes on days 3 and 5 after the surgery, the germ cells began to undergo apoptosis with no evident decrease in TR2 mRNA level. On day 7.5, however, most germ cells underwent apoptosis, while the expression level of TR2 mRNA declined markedly, and TR2 mRNA was rarely expressed on day 10 thereafter. (iii) On days 15 and 20 of the cryptorchid testes of rhesus monkey, TR2 mRNA was only expressed in a few of primary spermatocytes and the mRNA was almost undetectable on days 30, 45, 60. These results suggest that TR2 mRNA
文摘The cellular localization and expression of TR2 mRNA in rhesus monkey testis were investigated by the methods of in situ and Northern hybridization using the digoxigenin labeled in vitro transcripted cRNA probe from a TR2 cDNA fragment template and α-<sup>32</sup>P-dCTP labeled cDNA probe from the same TR2 cDNA fragment. It is demonstrated that TR2 mRNA was localized specifically in the germ cells, and was predominantly expressed in the meiotic more advanced cells. The expression level was various in different seminiferous tubules, and there was stronger expression in the tubules where spermatogenesis was vigorously going on. The expression level of TR2 mRNA was low in the immature rhesus monkey testis and increased dramatically in the adult and varied with a seminiferous cycle. These data suggest for the first time that orphan receptor TR2 may have an important function in regulating spermatogenesis at later stages of germ cell development in rhesus monkey.
文摘By in situ hybridization, the localization of orphan receptor TR3 mRNA has been observed in early developmental follicles. TR3 mRNA is first expressed in the ovarian interstitial cells on day 2 after birth, and then in granulosa cells (GC) in primary follicles on day 4. The expression level of TR3 mRNA in GC increases following the follicular development. Its higher expression can be observed in the outer layer of GC and inner layer of theca cells (TC) on day 6, where the cells present active proliferation and differentiation. The expression of TR3 is in an increasing manner until the large antral follicles on day 30. The mRNA is only expressed in the healthy, but not atretic follicles in adult rat ovaries. Injection of epidermal growth factor (EGF) has dramatically enhanced its expression in the early stage of developmental follicles. It is therefore suggested that TR3 may play a role in regulating growth and differentiation of ovarian somatic cells in the early stage, and its expression is regulated
文摘The cellular localization and specific expression of TR3 mRNA in rat testis were investigated by the method of immunohistochemistry and in situ hybridization. It was demonstrated that orphan receptor TR3 was expressed in a significant amount in rat testis and TR3 protein and mRNA were specifically localized in germ cells, suggesting that TR3 may have an important function in regulating rat germ cell development.
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.
基金Supported by Fondo per gli Investimenti della Ricerca di Base(FIRB)(RBAP10MY35_002)by Ente Cassa di Risparmio di Firenzeby FiorGen ONLUS to Galli A
文摘Pancreatic ductal adenocarcinoma(PDAC)is a devastating disease with a median overall survival time of5 mo and the five years survival less than 5%,a rate essentially unchanged over the course of the years.A well defined progression model of accumulation of genetic alterations ranging from single point mutations to gross chromosomal abnormalities has been introduced to describe the origin of this disease.However,due to the its subtle nature and concurring events PDAC cure remains elusive.Nuclear receptors(NR)are members of a large superfamily of evolutionarily conserved ligand-regulated DNA-binding transcription factors functionally involved in important cellular functions ranging from regulation of metabolism,to growth and development.Given the nature of their ligands,NR are very tempting drug targets and their pharmacological modulation has been widely exploited for the treatment of metabolic and inflammatory diseases.There are now clear evidences that both classical ligand-activated and orphan NR are involved in the pathogenesis of PDAC from its very early stages;nonetheless many aspects of their role are not fully understood.The purpose of this review is to highlight the striking connections that link peroxisome proliferator activated receptors,retinoic acid receptors,retinoid X receptor,androgen receptor,estrogen receptors and the orphan NR Nur,chicken ovalbumin upstream promoter transcription factorⅡand the liver receptor homologue-1 receptor to PDAC development,connections that could lead to the identification of novel therapies for this disease.
文摘The adoptive transfer of T cells is a promising approach to treat cancers. Primary human T cells can be modified using viral and non-viral vectors to promote the specific targeting of cancer cells via the introduction of exogenous T-cell receptors(TCRs) or chimeric antigen receptors(CARs). This gene transfer displays the potential to increase the specificity and potency of the anticancer response while decreasing the systemic adverse effects that arise from conventional treatments that target both cancerous and healthy cells. This review highlights the generation of clinical-grade T cells expressing CARs for immunotherapy, the use of these cells to target B-cell malignancies and, particularly, the first clinical trials deploying the Sleeping Beauty gene transfer system, which engineers T cells to target CD19+ leukemia and non-Hodgkin's lymphoma.
文摘目的探究视黄酸相关孤儿受体(RORγt)白细胞介素23(IL-23)通路调节辅助性T细胞17(Th17)在老年盐敏感性高血压发病中的作用。方法对内蒙古自治区的村民进行调查,2021年1月至2022年1月选取289例老年高血压患者作为研究对象,采用Sullivan盐负荷试验将患者进行分组,盐敏感高血压患者103例作为研究组,非盐敏感高血压患者186例作为对照组,给予慢性盐负荷试验。结果研究组收缩压、舒张压、MAP、心率在D10、D17均显著高于对照组(P<0.01)。2组尿量、尿钠、尿钾、尿肌酐水平在基线D3比较无显著差异(P>0.05),D10与对照组比较,研究组尿钠[(315.32±57.21)mmol/24 h vs(226.64±58.53)mmol/24 h,P=0.000]、尿肌酐[(12.46±1.64)mmol/24 h vs(10.12±1.17)mmol/24 h,P=0.000]显著增高。2组Th17比例、IL-17A水平在D4、D5、D10逐渐上升,在D17下降,且研究组Th17比例、IL-17A水平在D4、D5、D10、D17均显著高于对照组(P<0.01)。结论Th17参与了盐敏感性高血压的发生,RORγt-IL-23受体信号通路可诱导Th17细胞分化。
