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
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
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
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
目的观察酪氨酸羟化酶(tyrosine hydroxylase,TH)和孤儿核受体相关因子1(nuclear receptor related factor1,Nurr1)基因修饰的骨髓间充质干细胞(MSCs)移植治疗帕金森病(PD)大鼠的有效性,验证并评价Nurr1对TH所起的调控作用,探寻TH在特...目的观察酪氨酸羟化酶(tyrosine hydroxylase,TH)和孤儿核受体相关因子1(nuclear receptor related factor1,Nurr1)基因修饰的骨髓间充质干细胞(MSCs)移植治疗帕金森病(PD)大鼠的有效性,验证并评价Nurr1对TH所起的调控作用,探寻TH在特定环境中适量表达的调控机制。方法将稳定转染TH、TH-Nurrl的和未经转染的MSCs分别移植至PD大鼠后运用旋转试验观测PD大鼠的行为学变化。移植后第9周应用免疫组织化学和Western blot检测移植治疗后TH的表达情况。结果基因修饰组PD大鼠行为学较MSCs组明显改善(P<0.05),且TH-Nurr1组动物行为改善和TH抗原阳性率均高于TH组(P<0.05)。结论基因修饰的MSCs移植后能高效稳定地表达TH,且双基因的协同表达将极大提高PD基因治疗的效果,从而为PD治疗的基因选择提供新的依据和思路。展开更多
AIM： To investigate the expression and clinical significance of Wnt member 5a （Wnt5a） and receptor tyrosine kinase-like orphan receptor 2 （Ror2） in hepatocellular carcinoma （HCC）.METHODS： In HCC tissues obtain...AIM： To investigate the expression and clinical significance of Wnt member 5a （Wnt5a） and receptor tyrosine kinase-like orphan receptor 2 （Ror2） in hepatocellular carcinoma （HCC）.METHODS： In HCC tissues obtained from 85 patients, the protein expressions of Wnt5a, Rot2, 13-catenin, and Ki-67 via immunohistochemical staining using the Envision Plus System. The antibody binding was visualized with 3, 3＇-diaminobenzidine tetrahydrochloride （DAB） before brief counterstaining with Mayer＇s hematoxylin. The degree of immunohistochemical staining was recorded using a semiquantitative and subjective grading system. The mRNA expression of Rot2 was examined by real time reverse transcription polymerase chain reaction, including nineteen of the 85 HCC and three normal liver tissues. The ratios of Ror2 to the housekeeping gene GAPDH represented the normalized relative levels of Ror2 expression. To determine the prognostic factor, the outcome of the 82 patients was determined by reviewing their medical charts. The overall and diseasefree survival rates were estimated using the Kaplan-Meier method and compared with the logrank test. The prognostic analysis was carried out with univariate and multivariate Cox regressions models.RESULTS： Compared to nontumorous （hepatitis or cirrhotic） tissues, Rot2 mRNA expression was clearly decreased in HCC. Rot2 and Wnt5a protein expressions in the majority of HCC patients （63% and 77%, respectively） was significantly less in tumor tissues, as compared to adjacent nontumorous tissues, and this reduction was correlated with increasing serum α-fetoprotein and tumor stage. In 68% （58/85） of the HCC cases, the expression of IB-catenin in tumor tissues was either downregulated in the cellular membrane, upregulated in the cytoplasm, or both. Survival analysis indicated that Wnt5a and Ror2 protein expressions could be regarded as independent prognostic factors for HCC; HCC patients with decreased Wnt5a or Ror2 protein expression had a poorer prognosis than those with elevated Wnt5a and Ror2 expression （P = 0.016, P = 0.007, respectively）.CONCLUSION： Wnt5a and Ror2 may serve as tumor suppressor genes in the development of HCC, and may serve as clinicopathologic biomarkers for prognosis in HCC patients.展开更多
目的:预测并鉴定乳腺癌相关抗原受体酪氨酸激酶样孤儿受体1(receptor tyrosine kinase like orphan receptor 1,ROR1)H-2Kd限制性细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL)表位,为研究以ROR1为靶点的乳腺癌免疫治疗奠定基础。方法...目的:预测并鉴定乳腺癌相关抗原受体酪氨酸激酶样孤儿受体1(receptor tyrosine kinase like orphan receptor 1,ROR1)H-2Kd限制性细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL)表位,为研究以ROR1为靶点的乳腺癌免疫治疗奠定基础。方法:采用生物信息学方法预测乳腺癌相关抗原ROR1 H-2Kd限制性CTL表位,选取预测软件中评分较高的抗原表位肽进行人工合成及纯化。肽结合试验检测抗原表位肽与H-2Kd分子的亲和力。选用亲和力较高的抗原表位肽体外刺激脾淋巴细胞,ELISA法检测细胞因子γ-干扰素(interferon-γ,IFN-γ)和白介素-12(interleukin-12,IL-12)的分泌。结果:预测的4条候选ROR1 CTL表位肽均具有较高的亲和力,其荧光指数(fluorescence index,FI)在30μg/ml时均大于1.5。ELISA结果显示表位肽ROR1(NYMFPSQGI)可在体外有效诱导IFN-γ和IL-12细胞因子的产生。结论:ROR1(NYMFPSQGI)为乳腺癌相关抗原ROR1H-2Kd限制性CTL表位,为研究以ROR1为靶点的乳腺癌免疫治疗奠定了基础。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.
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.
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.
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 The fund of Nature Science Foundation of Shandong Province,No.ZR2009CM041
文摘AIM： To investigate the expression and clinical significance of Wnt member 5a （Wnt5a） and receptor tyrosine kinase-like orphan receptor 2 （Ror2） in hepatocellular carcinoma （HCC）.METHODS： In HCC tissues obtained from 85 patients, the protein expressions of Wnt5a, Rot2, 13-catenin, and Ki-67 via immunohistochemical staining using the Envision Plus System. The antibody binding was visualized with 3, 3＇-diaminobenzidine tetrahydrochloride （DAB） before brief counterstaining with Mayer＇s hematoxylin. The degree of immunohistochemical staining was recorded using a semiquantitative and subjective grading system. The mRNA expression of Rot2 was examined by real time reverse transcription polymerase chain reaction, including nineteen of the 85 HCC and three normal liver tissues. The ratios of Ror2 to the housekeeping gene GAPDH represented the normalized relative levels of Ror2 expression. To determine the prognostic factor, the outcome of the 82 patients was determined by reviewing their medical charts. The overall and diseasefree survival rates were estimated using the Kaplan-Meier method and compared with the logrank test. The prognostic analysis was carried out with univariate and multivariate Cox regressions models.RESULTS： Compared to nontumorous （hepatitis or cirrhotic） tissues, Rot2 mRNA expression was clearly decreased in HCC. Rot2 and Wnt5a protein expressions in the majority of HCC patients （63% and 77%, respectively） was significantly less in tumor tissues, as compared to adjacent nontumorous tissues, and this reduction was correlated with increasing serum α-fetoprotein and tumor stage. In 68% （58/85） of the HCC cases, the expression of IB-catenin in tumor tissues was either downregulated in the cellular membrane, upregulated in the cytoplasm, or both. Survival analysis indicated that Wnt5a and Ror2 protein expressions could be regarded as independent prognostic factors for HCC; HCC patients with decreased Wnt5a or Ror2 protein expression had a poorer prognosis than those with elevated Wnt5a and Ror2 expression （P = 0.016, P = 0.007, respectively）.CONCLUSION： Wnt5a and Ror2 may serve as tumor suppressor genes in the development of HCC, and may serve as clinicopathologic biomarkers for prognosis in HCC patients.
