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
目的研究受体酪氨酸激酶样孤儿受体1(receptor tyrosine kinase-like orphan rectetpor 1,ROR1)在不同病理亚型肺腺癌组织中的表达与气腔播散(spread through air space,STAS)发生的关系。方法收集昆明医科大学第一附属医院病理科2017年...目的研究受体酪氨酸激酶样孤儿受体1(receptor tyrosine kinase-like orphan rectetpor 1,ROR1)在不同病理亚型肺腺癌组织中的表达与气腔播散(spread through air space,STAS)发生的关系。方法收集昆明医科大学第一附属医院病理科2017年6月至2022年1月,肺腺癌组织蜡块标本618例,采用HE染色切片判断病理亚型与病理特征,记数STAS数量并分级,免疫组化染色,半定量判读ROR1表达水平,统计分析ROR1表达与STAS数量及与病理亚型的关系。结果ROR1在微乳头型与实体型肺腺癌(低分化)中的表达高于其它亚型肺腺癌,差异有统计学意义(P<0.001);ROR1在低STAS、高STAS组中表达率分别为88.0%、94.1%,高于无STAS组且差异有统计学意义(P<0.001)。结论ROR1高表达于低分化肺腺癌并提示更高的STAS发生率。ROR1有望成为新的肺腺癌诊断生物标志物用于指导临床治疗及辅助预后判断,并可能成为STAS阳性肺腺癌的潜在治疗靶点。展开更多
目的研究受体酪氨酸激酶样孤儿受体1(receptor tyrosine kinase like orphan receptor 1,ROR1)及微管相关蛋白1B(microtubule associated protein 1B,MAP1B)在年龄相关性白内障(age-related-cataract,ARC)患者晶状体前囊膜组织中的mRNA...目的研究受体酪氨酸激酶样孤儿受体1(receptor tyrosine kinase like orphan receptor 1,ROR1)及微管相关蛋白1B(microtubule associated protein 1B,MAP1B)在年龄相关性白内障(age-related-cataract,ARC)患者晶状体前囊膜组织中的mRNA和蛋白表达情况,并初步探讨其临床意义及蛋白表达的相关性。方法收集ARC患者晶状体前囊膜组织20例为ARC组,眼外伤发生晶状体脱出的患者15例为对照组,通过RT-qPCR、Western blot、免疫组织化学染色检测组织中ROR1与MAP1B的表达情况,利用STRING数据库预测蛋白之间相关性。结果与对照组相比,ARC组ROR1、MAP1B的mRNA表达水平[分别为(0.265±0.150)、(0.155±0.069)]呈现低表达,其蛋白表达水平[分别为(0.66±0.015)、(0.75±0.036)]呈现低表达,差异具有统计学意义(P<0.05);PPI网络显示ROR1与MAP1B蛋白呈现间接调控关系。结论ROR1与MAP1B在ARC中呈明显低表达,且二者可能以间接调控关系介导ARC的发生发展。展开更多
While receptor tyrosine kinase-like orphan receptor 1(ROR1)is typically expressed at low levels or absent in normal tissues,its expression is notably elevated in various malignant tumors and conditions,including chron...While receptor tyrosine kinase-like orphan receptor 1(ROR1)is typically expressed at low levels or absent in normal tissues,its expression is notably elevated in various malignant tumors and conditions,including chronic lymphocytic leukemia(CLL),breast cancer,ovarian cancer,melanoma,and lung adenocarcinoma.This distinctive feature positions ROR1 as an attractive target for tumor-specific treatments.Currently,several targeted drugs directed at ROR1 are undergoing clinical development,including monoclonal antibodies,antibody-drug conjugates(ADCs),and chimeric antigen receptor T-cell therapy(CAR-T).Additionally,there are four small molecule inhibitors designed to bind to ROR1,presenting promising avenues for the development of PROTAC degraders targeting ROR1.This review offers updated insights into ROR1's structural and functional characteristics,embryonic development implications,cell survival signaling pathways,and evolutionary targeting strategies,all of which have the potential to advance the treatment of malignant tumors.展开更多
文摘目的研究受体酪氨酸激酶样孤儿受体1(receptor tyrosine kinase-like orphan rectetpor 1,ROR1)在不同病理亚型肺腺癌组织中的表达与气腔播散(spread through air space,STAS)发生的关系。方法收集昆明医科大学第一附属医院病理科2017年6月至2022年1月,肺腺癌组织蜡块标本618例,采用HE染色切片判断病理亚型与病理特征,记数STAS数量并分级,免疫组化染色,半定量判读ROR1表达水平,统计分析ROR1表达与STAS数量及与病理亚型的关系。结果ROR1在微乳头型与实体型肺腺癌(低分化)中的表达高于其它亚型肺腺癌,差异有统计学意义(P<0.001);ROR1在低STAS、高STAS组中表达率分别为88.0%、94.1%,高于无STAS组且差异有统计学意义(P<0.001)。结论ROR1高表达于低分化肺腺癌并提示更高的STAS发生率。ROR1有望成为新的肺腺癌诊断生物标志物用于指导临床治疗及辅助预后判断,并可能成为STAS阳性肺腺癌的潜在治疗靶点。
基金financial support from National Key Research and Development Program of China (2023YFF1205104)National Natural Science Foundation of China (22037003,32071446,82204197,82170406,and 81970238)+3 种基金the Open Project of Shenzhen Bay Laboratory (SZBL2021080601004)Ningbo Natural Science Foundation (2023J033,2022J018)State Key Laboratory of Structure-Based Drugs Design&Discovery of Ministry of Education,Shenyang Pharmaceutical Universitythe State Key Laboratory of Bioorganic and Natural Products Chemistry,Shanghai Institute of Organic Chemistry。
文摘While receptor tyrosine kinase-like orphan receptor 1(ROR1)is typically expressed at low levels or absent in normal tissues,its expression is notably elevated in various malignant tumors and conditions,including chronic lymphocytic leukemia(CLL),breast cancer,ovarian cancer,melanoma,and lung adenocarcinoma.This distinctive feature positions ROR1 as an attractive target for tumor-specific treatments.Currently,several targeted drugs directed at ROR1 are undergoing clinical development,including monoclonal antibodies,antibody-drug conjugates(ADCs),and chimeric antigen receptor T-cell therapy(CAR-T).Additionally,there are four small molecule inhibitors designed to bind to ROR1,presenting promising avenues for the development of PROTAC degraders targeting ROR1.This review offers updated insights into ROR1's structural and functional characteristics,embryonic development implications,cell survival signaling pathways,and evolutionary targeting strategies,all of which have the potential to advance the treatment of malignant tumors.
