BACKGROUND Bone metastasis has various negative impacts.Activities of daily living(ADL)and quality of life(QOL)can be significantly decreased,survival may be impacted,and medical expenses may increase.It is estimated ...BACKGROUND Bone metastasis has various negative impacts.Activities of daily living(ADL)and quality of life(QOL)can be significantly decreased,survival may be impacted,and medical expenses may increase.It is estimated that at least 5%cancer patients might be suffering from bone metastases.In 2016,we published the Comprehensive Guidelines for the Diagnosis and Treatment of Bone Metastasis.Since then,the therapeutic outcomes for patients have gradually improved.As life expectancy is a major determinant of surgical intervention,the strategy should be modified if the prolongation of survival is to be achieved.AIM To monitor how bone metastasis treatment has changed before and after launch of our guidelines for bone metastasis.METHODS For advanced cancer patients with bone metastasis who visited the Department of Clinical Oncology at Akita University hospital between 2012 and 2023,parameters including the site and number of bone metastases,laboratory data,and survival time,were extracted from electronic medical records and the Katagiri score was calculated.The association with survival was determined for each factor.RESULTS Data from 136 patients were obtained.The 1-year survival rate for the poor prognosis group with a higher Katagiri score was 20.0%in this study,which was 6%and an apparent improvement from 2014 when the scoring system was developed.Other factors significantly affecting survival included five or more bone metastases than less(P=0.0080),and treatment with chemotherapy(P<0.001),bone modifying agents(P=0.0175)and immune checkpoint inhibitors(P=0.0128).In recent years,advances in various treatment methods have extended the survival period for patients with advanced cancer.It is necessary not only to simply extend survival time,but also to maintain ADL and improve QOL.CONCLUSION Various therapeutic interventions including surgical approach for bone metastasis,which is a disorder of locomotor organs,are increasingly required.Guidelines and scoring system for prognosis need to be revised promptly.展开更多
程序性死亡因子1(programmed death 1,PD-1)、程序性死亡因子1配体(PD-L1)与肿瘤发生、发展密切相关,PD-1/PD-L1信号通路的激活有助于肿瘤免疫逃逸,而阻断该通路可以减少肿瘤对机体抗肿瘤免疫效应的抑制,更好地发挥人体自身的免疫系统...程序性死亡因子1(programmed death 1,PD-1)、程序性死亡因子1配体(PD-L1)与肿瘤发生、发展密切相关,PD-1/PD-L1信号通路的激活有助于肿瘤免疫逃逸,而阻断该通路可以减少肿瘤对机体抗肿瘤免疫效应的抑制,更好地发挥人体自身的免疫系统抵御肿瘤的能力,理论上说抗PD-1/PD-L1信号通路具有治疗各种类型肿瘤的能力。前期针对PD-1/PD-L1通路的免疫疗法在晚期恶性黑色素瘤以及非小细胞肺癌中已经获得了令人振奋的效果,故PD-1/PD-L1信号通路在原发性肝癌中的应用也值得期待。本文对PD-1/PD-L1分子信号通路、原发性肝癌中的表达、PD-1/PD-L1抑制剂在原发性肝癌治疗中的临床研究进行综述,探讨PD-1在肝癌治疗的临床应用前景和以后可能发展的方向。展开更多
耗竭性T细胞(exhausted T cells)是一群效应功能减弱,持续表达抑制性受体的T细胞,在肿瘤中表现为T细胞功能缺陷状态,主要特征为一系列抑制性受体表达增加及细胞因子分泌减少。耗竭性T细胞主要通过细胞表面的抑制性分子,细胞因子和免疫...耗竭性T细胞(exhausted T cells)是一群效应功能减弱,持续表达抑制性受体的T细胞,在肿瘤中表现为T细胞功能缺陷状态,主要特征为一系列抑制性受体表达增加及细胞因子分泌减少。耗竭性T细胞主要通过细胞表面的抑制性分子,细胞因子和免疫调节细胞类型改变等参与肿瘤免疫负调控,从而引起肿瘤免疫逃逸。而T细胞耗竭状态并非不可逆转,应用相应单克隆抗体靶向免疫调控点可以有效逆转耗竭性T细胞,恢复机体抗肿瘤免疫反应,提高肿瘤控制率。因此,通过逆转肿瘤患者体内的耗竭性T细胞可能是肿瘤免疫治疗的新途径之一。展开更多
In this review,we will highlight the importance of cancer germline antigen-specific cytotoxic CD8^(+) T lymphocytes(CTL)and the factors affecting antitumor CTL responses.In light of cancer immunotherapy,we will emphas...In this review,we will highlight the importance of cancer germline antigen-specific cytotoxic CD8^(+) T lymphocytes(CTL)and the factors affecting antitumor CTL responses.In light of cancer immunotherapy,we will emphasis the need to further understand the features,characteristics,and actions of modulatory receptors of human cancer germline-specific CTLs,in order to determine the optimal conditions for antitumor CTL responses.展开更多
Circulating tumor cells(CTCs)have received a lot of attention as a novel biomarker for cancer research in past decades.CTCs infiltrate the bloodstream derived from the primary tumor,and are significantly involved in c...Circulating tumor cells(CTCs)have received a lot of attention as a novel biomarker for cancer research in past decades.CTCs infiltrate the bloodstream derived from the primary tumor,and are significantly involved in cancer metastasis and recurrence.Although clinical applications have been challenging owing to the difficulties of CTC identification,recent development of technology for specific enrichment and detection of CTCs contributes to diagnosis and treatment.Furthermore,CTC analyses will shed new light on the biological mechanisms of cancer progression and metastasis.A number of clinical studies have already been carried out on the basis of CTC technology.Nevertheless,the clinical utility of CTCs is still unknown in gastric cancer.In this review,we elaborate on the latest advances of CTC research in gastric cancer.展开更多
Systemic sclerosis(SSc)is a rare connective tissue disorder.It is a chronic multisystem disease characterized by vascular dysfunction and progressive fibrosis of tissue,with skin hardening and thickening(known as scle...Systemic sclerosis(SSc)is a rare connective tissue disorder.It is a chronic multisystem disease characterized by vascular dysfunction and progressive fibrosis of tissue,with skin hardening and thickening(known as scleroderma)being the hallmark of the disease.It tends to affect females more than males and has a higher prevalence in African American population with earlier onset and more severe disease.While scleroderma can be a manifestation of conditions other than SSC,the presence of skin thickening of the fingers,extending proximally to metacarpophalangeal joints is sufficient to classify a patient as having SSc.SSc treatment is challenging given the heterogeneity of the disease,multiple organ involvement,different subtypes and poorly understood etiology and pathogenesis.Yet,systemic immunosuppressive therapy is often the treatment of choice.Here we present a 60-year-old white female who developed skin thickening of her fingers extending to the forearms and of her proximal thighs after being treated with pembrolizumab for metastatic non-small cell lung cancer.It was difficult to determine internal organ involvement given her history of metastatic lung cancer,but scleroderma specific autoantibodies were negative.Her symptoms improved after treatment with methotrexate and stopping pembrolizumab.This is one of the first case reports of scleroderma secondary to pembrolizumab.展开更多
目的对替雷利珠单抗治疗鳞状非小细胞肺癌进行临床综合评价,为临床用药决策提供证据支持。方法检索中国知网、万方数据、维普网、中国生物医学数据库、Pubmed、Cochrane Library、Web of science数据库关于替雷利珠单抗治疗鳞状非小细...目的对替雷利珠单抗治疗鳞状非小细胞肺癌进行临床综合评价,为临床用药决策提供证据支持。方法检索中国知网、万方数据、维普网、中国生物医学数据库、Pubmed、Cochrane Library、Web of science数据库关于替雷利珠单抗治疗鳞状非小细胞肺癌的系统评价/Meta分析、药物经济学研究,检索时间从建库至2024年03月1日公开发表的文献。对纳入的4篇文献,采用AMSTAR量表和CHEERS量表进行文献质量评价。基于循证证据定性描述替雷利珠单抗治疗sq-NSCLC有效性、安全性、经济性、创新性、适宜性和可及性。结果有效性方面:替雷利珠单抗作为一线治疗药物,其客观缓解率为72.5%~74.8%,无进展生存期的中位时间为7.6个月,两方面均优于信迪利单抗、帕博利珠单抗和阿替利珠单抗;舒格利单抗和卡瑞利珠单抗在延长PFS方面优于替雷利珠单抗。作为二线治疗药物替雷利珠单抗在延长患者总生存期的中位时间为17.2个月,效果优于纳武利尤单抗。安全性方面:替雷利珠单抗在一线治疗中≥3级AEs发生率为83.9%~85.8%,低于阿替利珠单抗,高于帕博利珠单抗、信迪利单抗、舒格利单抗和卡瑞利珠单抗。经济性方面:基于中国卫生体系角度,替雷利珠单抗作为一线治疗药物的成本-效益优于信迪利单抗、舒格利单抗、帕博利珠单抗,不如卡瑞利珠单抗;作为二线治疗药物,替雷利珠单抗优于纳武利尤单抗。替雷利珠单抗创新性较好,药品适宜性和可及性与其他药物相当。结论替雷利珠单抗治疗鳞状非小细胞肺癌安全有效;具有良好经济学优势;作为我国自主研发的一类新药,创新性强,药品技术及使用特点适宜;目前的可获得性尚处于较低水平,但可负担性好。展开更多
文摘BACKGROUND Bone metastasis has various negative impacts.Activities of daily living(ADL)and quality of life(QOL)can be significantly decreased,survival may be impacted,and medical expenses may increase.It is estimated that at least 5%cancer patients might be suffering from bone metastases.In 2016,we published the Comprehensive Guidelines for the Diagnosis and Treatment of Bone Metastasis.Since then,the therapeutic outcomes for patients have gradually improved.As life expectancy is a major determinant of surgical intervention,the strategy should be modified if the prolongation of survival is to be achieved.AIM To monitor how bone metastasis treatment has changed before and after launch of our guidelines for bone metastasis.METHODS For advanced cancer patients with bone metastasis who visited the Department of Clinical Oncology at Akita University hospital between 2012 and 2023,parameters including the site and number of bone metastases,laboratory data,and survival time,were extracted from electronic medical records and the Katagiri score was calculated.The association with survival was determined for each factor.RESULTS Data from 136 patients were obtained.The 1-year survival rate for the poor prognosis group with a higher Katagiri score was 20.0%in this study,which was 6%and an apparent improvement from 2014 when the scoring system was developed.Other factors significantly affecting survival included five or more bone metastases than less(P=0.0080),and treatment with chemotherapy(P<0.001),bone modifying agents(P=0.0175)and immune checkpoint inhibitors(P=0.0128).In recent years,advances in various treatment methods have extended the survival period for patients with advanced cancer.It is necessary not only to simply extend survival time,but also to maintain ADL and improve QOL.CONCLUSION Various therapeutic interventions including surgical approach for bone metastasis,which is a disorder of locomotor organs,are increasingly required.Guidelines and scoring system for prognosis need to be revised promptly.
文摘程序性死亡因子1(programmed death 1,PD-1)、程序性死亡因子1配体(PD-L1)与肿瘤发生、发展密切相关,PD-1/PD-L1信号通路的激活有助于肿瘤免疫逃逸,而阻断该通路可以减少肿瘤对机体抗肿瘤免疫效应的抑制,更好地发挥人体自身的免疫系统抵御肿瘤的能力,理论上说抗PD-1/PD-L1信号通路具有治疗各种类型肿瘤的能力。前期针对PD-1/PD-L1通路的免疫疗法在晚期恶性黑色素瘤以及非小细胞肺癌中已经获得了令人振奋的效果,故PD-1/PD-L1信号通路在原发性肝癌中的应用也值得期待。本文对PD-1/PD-L1分子信号通路、原发性肝癌中的表达、PD-1/PD-L1抑制剂在原发性肝癌治疗中的临床研究进行综述,探讨PD-1在肝癌治疗的临床应用前景和以后可能发展的方向。
文摘耗竭性T细胞(exhausted T cells)是一群效应功能减弱,持续表达抑制性受体的T细胞,在肿瘤中表现为T细胞功能缺陷状态,主要特征为一系列抑制性受体表达增加及细胞因子分泌减少。耗竭性T细胞主要通过细胞表面的抑制性分子,细胞因子和免疫调节细胞类型改变等参与肿瘤免疫负调控,从而引起肿瘤免疫逃逸。而T细胞耗竭状态并非不可逆转,应用相应单克隆抗体靶向免疫调控点可以有效逆转耗竭性T细胞,恢复机体抗肿瘤免疫反应,提高肿瘤控制率。因此,通过逆转肿瘤患者体内的耗竭性T细胞可能是肿瘤免疫治疗的新途径之一。
基金This work was supported by Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFMS),China(grant number:2018-I2M-2-002)MRC Human Immunology Unit Core and Nuffield Department of Medicine,Oxford University.Illustrations were created with BioRender(Biorender.com)。
文摘In this review,we will highlight the importance of cancer germline antigen-specific cytotoxic CD8^(+) T lymphocytes(CTL)and the factors affecting antitumor CTL responses.In light of cancer immunotherapy,we will emphasis the need to further understand the features,characteristics,and actions of modulatory receptors of human cancer germline-specific CTLs,in order to determine the optimal conditions for antitumor CTL responses.
文摘Circulating tumor cells(CTCs)have received a lot of attention as a novel biomarker for cancer research in past decades.CTCs infiltrate the bloodstream derived from the primary tumor,and are significantly involved in cancer metastasis and recurrence.Although clinical applications have been challenging owing to the difficulties of CTC identification,recent development of technology for specific enrichment and detection of CTCs contributes to diagnosis and treatment.Furthermore,CTC analyses will shed new light on the biological mechanisms of cancer progression and metastasis.A number of clinical studies have already been carried out on the basis of CTC technology.Nevertheless,the clinical utility of CTCs is still unknown in gastric cancer.In this review,we elaborate on the latest advances of CTC research in gastric cancer.
文摘Systemic sclerosis(SSc)is a rare connective tissue disorder.It is a chronic multisystem disease characterized by vascular dysfunction and progressive fibrosis of tissue,with skin hardening and thickening(known as scleroderma)being the hallmark of the disease.It tends to affect females more than males and has a higher prevalence in African American population with earlier onset and more severe disease.While scleroderma can be a manifestation of conditions other than SSC,the presence of skin thickening of the fingers,extending proximally to metacarpophalangeal joints is sufficient to classify a patient as having SSc.SSc treatment is challenging given the heterogeneity of the disease,multiple organ involvement,different subtypes and poorly understood etiology and pathogenesis.Yet,systemic immunosuppressive therapy is often the treatment of choice.Here we present a 60-year-old white female who developed skin thickening of her fingers extending to the forearms and of her proximal thighs after being treated with pembrolizumab for metastatic non-small cell lung cancer.It was difficult to determine internal organ involvement given her history of metastatic lung cancer,but scleroderma specific autoantibodies were negative.Her symptoms improved after treatment with methotrexate and stopping pembrolizumab.This is one of the first case reports of scleroderma secondary to pembrolizumab.
文摘目的对替雷利珠单抗治疗鳞状非小细胞肺癌进行临床综合评价,为临床用药决策提供证据支持。方法检索中国知网、万方数据、维普网、中国生物医学数据库、Pubmed、Cochrane Library、Web of science数据库关于替雷利珠单抗治疗鳞状非小细胞肺癌的系统评价/Meta分析、药物经济学研究,检索时间从建库至2024年03月1日公开发表的文献。对纳入的4篇文献,采用AMSTAR量表和CHEERS量表进行文献质量评价。基于循证证据定性描述替雷利珠单抗治疗sq-NSCLC有效性、安全性、经济性、创新性、适宜性和可及性。结果有效性方面:替雷利珠单抗作为一线治疗药物,其客观缓解率为72.5%~74.8%,无进展生存期的中位时间为7.6个月,两方面均优于信迪利单抗、帕博利珠单抗和阿替利珠单抗;舒格利单抗和卡瑞利珠单抗在延长PFS方面优于替雷利珠单抗。作为二线治疗药物替雷利珠单抗在延长患者总生存期的中位时间为17.2个月,效果优于纳武利尤单抗。安全性方面:替雷利珠单抗在一线治疗中≥3级AEs发生率为83.9%~85.8%,低于阿替利珠单抗,高于帕博利珠单抗、信迪利单抗、舒格利单抗和卡瑞利珠单抗。经济性方面:基于中国卫生体系角度,替雷利珠单抗作为一线治疗药物的成本-效益优于信迪利单抗、舒格利单抗、帕博利珠单抗,不如卡瑞利珠单抗;作为二线治疗药物,替雷利珠单抗优于纳武利尤单抗。替雷利珠单抗创新性较好,药品适宜性和可及性与其他药物相当。结论替雷利珠单抗治疗鳞状非小细胞肺癌安全有效;具有良好经济学优势;作为我国自主研发的一类新药,创新性强,药品技术及使用特点适宜;目前的可获得性尚处于较低水平,但可负担性好。
