目的探讨Klinefelter综合征（克氏征）患者（47，XXY）的临床特点。方法回顾性分析227例接受供精人工授精（artificial insemination with donor，AID）治疗的47，XXY患者临床资料包括年龄、学历、身高、体重、体重指数；FSH、LH、睾酮...目的探讨Klinefelter综合征（克氏征）患者（47，XXY）的临床特点。方法回顾性分析227例接受供精人工授精（artificial insemination with donor，AID）治疗的47，XXY患者临床资料包括年龄、学历、身高、体重、体重指数；FSH、LH、睾酮、催乳素、雌二醇。结果这些患者身高（176．4±5．5）cm、体重（74．5±12．7）kg、体重指数（23．89±3．66）kg／m^2，超重者77例（33．92％），肥胖者34例（14．98％）。性激素FSH（38．35±14．33）IU／L，LH（19．40±9．oo）IU／L，睾酮（132．00±194．50）ng／dl，雌二醇（23．90±15．00）ng／L，催乳素（10．50±8．20）μg／L，雌二醇／睾酮0．21±0．80；睾丸体积与雄激素水平呈正相关（r=0．197，P=0．003）；体重指数与雄激素水平呈负相关（r=-0．284，P=0．000），与雌激素呈正相关（r=0．174，P=0．009）；与雌二醇／睾酮呈正相关（r=0．323，P=0．000）。年龄与睾酮、雌二醇、雌二醇／睾酮之间无相关性（P〉0．05）；与LH之间呈负相关关系（r=-0．154，P=0．02），与FSH之间呈负相关关系（r=-0．196，P=0．03）。高学历组平均年龄高于低学历组（P〈0．01），雄激素水平低于低学历组（P〈0．01）。结论克氏征患者（47，XXY）睾酮与患者睾丸体积密切相关；克氏征患者睾酮、雌二醇和雌二醇／睾酮与患者身高、体重指数、文化程度相关。展开更多
Described as a“don't eat me”signal,CD47 becomes a vital immune checkpoint in cancer.Its interaction with signal regulatory protein alpha(SIRPa)prevents macrophage phagocytosis.In recent years,a growing body of e...Described as a“don't eat me”signal,CD47 becomes a vital immune checkpoint in cancer.Its interaction with signal regulatory protein alpha(SIRPa)prevents macrophage phagocytosis.In recent years,a growing body of evidences have unveiled that CD47-based combination therapy exhibits a superior anti-cancer effect.Latest clinical trials about CD47 have adopted the regimen of collaborating with other therapies or developing CD47-directed bispecific antibodies,indicating the combination strategy as a general trend of the future.In this review,clinical and preclinical cases about the current combination strategies targeting CD47 are collected,their underlying mechanisms of action are discussed,and ideas from future perspectives are shared.展开更多
The third-generation epidermal growth factor receptor (EGFR) inhibitor osimertinib (OSI) has been approved as the first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore a r...The third-generation epidermal growth factor receptor (EGFR) inhibitor osimertinib (OSI) has been approved as the first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore a rational combination strategy for enhancing the OSI efficacy. In this study, OSI induced higher CD47 expression, an important anti-phagocytic immune checkpoint, via the NF-κB pathway in EGFR-mutant NSCLC HCC827 and NCI-H1975 cells. The combination treatment of OSI and the anti-CD47 antibody exhibited dramatically increasing phagocytosis in HCC827 and NCI-H1975 cells, which highly relied on the antibody-dependent cellular phagocytosis effect. Consistently, the enhanced phagocytosis index from combination treatment was reversed in CD47 knockout HCC827 cells. Meanwhile, combining the anti-CD47 antibody significantly augmented the anticancer effect of OSI in HCC827 xenograft mice model. Notably, OSI induced the surface exposure of “eat me” signal calreticulin and reduced the expression of immune-inhibitory receptor PD-L1 in cancer cells, which might contribute to the increased phagocytosis on cancer cells pretreated with OSI. In summary, these findings suggest the multidimensional regulation by OSI and encourage the further exploration of combining anti-CD47 antibody with OSI as a new strategy to enhance the anticancer efficacy in EGFR-mutant NSCLC with CD47 activation induced by OSI.展开更多
文摘目的探讨Klinefelter综合征（克氏征）患者（47，XXY）的临床特点。方法回顾性分析227例接受供精人工授精（artificial insemination with donor，AID）治疗的47，XXY患者临床资料包括年龄、学历、身高、体重、体重指数；FSH、LH、睾酮、催乳素、雌二醇。结果这些患者身高（176．4±5．5）cm、体重（74．5±12．7）kg、体重指数（23．89±3．66）kg／m^2，超重者77例（33．92％），肥胖者34例（14．98％）。性激素FSH（38．35±14．33）IU／L，LH（19．40±9．oo）IU／L，睾酮（132．00±194．50）ng／dl，雌二醇（23．90±15．00）ng／L，催乳素（10．50±8．20）μg／L，雌二醇／睾酮0．21±0．80；睾丸体积与雄激素水平呈正相关（r=0．197，P=0．003）；体重指数与雄激素水平呈负相关（r=-0．284，P=0．000），与雌激素呈正相关（r=0．174，P=0．009）；与雌二醇／睾酮呈正相关（r=0．323，P=0．000）。年龄与睾酮、雌二醇、雌二醇／睾酮之间无相关性（P〉0．05）；与LH之间呈负相关关系（r=-0．154，P=0．02），与FSH之间呈负相关关系（r=-0．196，P=0．03）。高学历组平均年龄高于低学历组（P〈0．01），雄激素水平低于低学历组（P〈0．01）。结论克氏征患者（47，XXY）睾酮与患者睾丸体积密切相关；克氏征患者睾酮、雌二醇和雌二醇／睾酮与患者身高、体重指数、文化程度相关。
基金supported by The Science and Technology Development Fund,Macao SAR,China(File No.:0129/2019/A3)Internal Research Grant of the State Key Laboratory of Quality Research in Chinese Medicine,University of Macao(File No.:QRCM-IRG2022-016,China)+1 种基金the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab,File No.:2020B1212030006,China)the National Natural Science Foundation of China(File No.:81973516)。
文摘Described as a“don't eat me”signal,CD47 becomes a vital immune checkpoint in cancer.Its interaction with signal regulatory protein alpha(SIRPa)prevents macrophage phagocytosis.In recent years,a growing body of evidences have unveiled that CD47-based combination therapy exhibits a superior anti-cancer effect.Latest clinical trials about CD47 have adopted the regimen of collaborating with other therapies or developing CD47-directed bispecific antibodies,indicating the combination strategy as a general trend of the future.In this review,clinical and preclinical cases about the current combination strategies targeting CD47 are collected,their underlying mechanisms of action are discussed,and ideas from future perspectives are shared.
基金the Science and Technology Development Fund,Macao SAR(File no.0129/2019/A3).
文摘The third-generation epidermal growth factor receptor (EGFR) inhibitor osimertinib (OSI) has been approved as the first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore a rational combination strategy for enhancing the OSI efficacy. In this study, OSI induced higher CD47 expression, an important anti-phagocytic immune checkpoint, via the NF-κB pathway in EGFR-mutant NSCLC HCC827 and NCI-H1975 cells. The combination treatment of OSI and the anti-CD47 antibody exhibited dramatically increasing phagocytosis in HCC827 and NCI-H1975 cells, which highly relied on the antibody-dependent cellular phagocytosis effect. Consistently, the enhanced phagocytosis index from combination treatment was reversed in CD47 knockout HCC827 cells. Meanwhile, combining the anti-CD47 antibody significantly augmented the anticancer effect of OSI in HCC827 xenograft mice model. Notably, OSI induced the surface exposure of “eat me” signal calreticulin and reduced the expression of immune-inhibitory receptor PD-L1 in cancer cells, which might contribute to the increased phagocytosis on cancer cells pretreated with OSI. In summary, these findings suggest the multidimensional regulation by OSI and encourage the further exploration of combining anti-CD47 antibody with OSI as a new strategy to enhance the anticancer efficacy in EGFR-mutant NSCLC with CD47 activation induced by OSI.
