Poly(ADP-ribose)polymerase 1(PARP1)is a multifunctional protein involved in diverse cellular functions,notably DNA damage repair.Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies.Des...Poly(ADP-ribose)polymerase 1(PARP1)is a multifunctional protein involved in diverse cellular functions,notably DNA damage repair.Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies.Despite the increased use of PARP inhibitors,challenges persist in achieving PARP1 selectivity and effective blood-brain barrier(BBB)penetration.The development of a PARP1-specific positron emission tomography(PET)radioligand is crucial for understanding disease biology and performing target occupancy studies,which may aid in the development of PARP1-specific inhibitors.In this study,we leverage the recently identified PARP1 inhibitor,AZD9574,to introduce the design and development of its ^(18)F-isotopologue([^(18)F]AZD9574).Our comprehensive approach,encompassing pharmacological,cellular,autoradiographic,and in vivo PET imaging evaluations in non-human primates,demonstrates the capacity of[^(18)F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB.These findings position[^(18)F]AZD9574 as a viable molecular imaging tool,poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.展开更多
As a member of the Cancer-Testis Antigens,the Melanoma-associated antigen(MAGE)family is typically expressed in normal tissues such as the testis.However,in various types of tumor cells,their expression is abnormally ...As a member of the Cancer-Testis Antigens,the Melanoma-associated antigen(MAGE)family is typically expressed in normal tissues such as the testis.However,in various types of tumor cells,their expression is abnormally activated,which is associated with multiple critical processes of tumor cells,including proliferation,apoptosis,immune evasion,DNA damage repair,and metastasis.The abnormal expression of MAGE family genes in multiple cancers and their multifaceted roles in tumor biology have made them an important target in cancer research and treatment.This review comprehensively explores various aspects of the relationship between the MAGE family and cancer,including the molecular characteristics of its members,transcriptional regulation mechanisms,expression patterns in different cancers,phenotypes and oncogenic mechanisms,poor clinical prognosis and potential as targets for immunotherapy.The expression patterns of these genes are closely linked to the clinical features of tumors,providing molecular markers and potential therapeutic targets for the early diagnosis,treatment,and prognostic assessment of cancer.展开更多
背景与目的apr1是我们在凋亡的人早幼粒白血病细胞HL-60中克隆的一个人类新基因,初步研究表明它可能是一个凋亡相关基因(GenBank ID NM_014061)。为进一步了解该基因的功能背景,我们克隆了该基因并进行了生物信息学分析和亚细胞定位。...背景与目的apr1是我们在凋亡的人早幼粒白血病细胞HL-60中克隆的一个人类新基因,初步研究表明它可能是一个凋亡相关基因(GenBank ID NM_014061)。为进一步了解该基因的功能背景,我们克隆了该基因并进行了生物信息学分析和亚细胞定位。方法利用逆转录PCR方法克隆该基因的cDNA序列,测序后利用生物信息学方法进行了基因组定位、氨基酸保守结构域搜索、同源蛋白比较和基因进化树分析;并进行了该基因的亚细胞定位。结果apr.1定位于人染色体上的Xp11.22,有两个MAGE家族结构域,基因进化上同源于MAGE.D1和Necdin,基因表达产物定位于真核细胞的细胞核。结论apr.1属于MAGE家族的一个新分子,可能属于Ⅱ类MAGE基因。展开更多
基金Steven H.Liang gratefully acknowledges the support provided,in part,by Emory Radiology Chair Fund and Emory School of Medicine Endowed Directorship(USA)James B.Daunais acknowledges the NIH grant support U01AA014106 and AA028007(USA)Jimmy S.Patel is the recipient of NCI cancer biology postdoctoral fellowship(T32CA275777,USA).
文摘Poly(ADP-ribose)polymerase 1(PARP1)is a multifunctional protein involved in diverse cellular functions,notably DNA damage repair.Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies.Despite the increased use of PARP inhibitors,challenges persist in achieving PARP1 selectivity and effective blood-brain barrier(BBB)penetration.The development of a PARP1-specific positron emission tomography(PET)radioligand is crucial for understanding disease biology and performing target occupancy studies,which may aid in the development of PARP1-specific inhibitors.In this study,we leverage the recently identified PARP1 inhibitor,AZD9574,to introduce the design and development of its ^(18)F-isotopologue([^(18)F]AZD9574).Our comprehensive approach,encompassing pharmacological,cellular,autoradiographic,and in vivo PET imaging evaluations in non-human primates,demonstrates the capacity of[^(18)F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB.These findings position[^(18)F]AZD9574 as a viable molecular imaging tool,poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.
基金supported by Startup Fund for Young Faculty at SJTU(SFYF at SJTU)(No.24X010500176).
文摘As a member of the Cancer-Testis Antigens,the Melanoma-associated antigen(MAGE)family is typically expressed in normal tissues such as the testis.However,in various types of tumor cells,their expression is abnormally activated,which is associated with multiple critical processes of tumor cells,including proliferation,apoptosis,immune evasion,DNA damage repair,and metastasis.The abnormal expression of MAGE family genes in multiple cancers and their multifaceted roles in tumor biology have made them an important target in cancer research and treatment.This review comprehensively explores various aspects of the relationship between the MAGE family and cancer,including the molecular characteristics of its members,transcriptional regulation mechanisms,expression patterns in different cancers,phenotypes and oncogenic mechanisms,poor clinical prognosis and potential as targets for immunotherapy.The expression patterns of these genes are closely linked to the clinical features of tumors,providing molecular markers and potential therapeutic targets for the early diagnosis,treatment,and prognostic assessment of cancer.
文摘背景与目的apr1是我们在凋亡的人早幼粒白血病细胞HL-60中克隆的一个人类新基因,初步研究表明它可能是一个凋亡相关基因(GenBank ID NM_014061)。为进一步了解该基因的功能背景,我们克隆了该基因并进行了生物信息学分析和亚细胞定位。方法利用逆转录PCR方法克隆该基因的cDNA序列,测序后利用生物信息学方法进行了基因组定位、氨基酸保守结构域搜索、同源蛋白比较和基因进化树分析;并进行了该基因的亚细胞定位。结果apr.1定位于人染色体上的Xp11.22,有两个MAGE家族结构域,基因进化上同源于MAGE.D1和Necdin,基因表达产物定位于真核细胞的细胞核。结论apr.1属于MAGE家族的一个新分子,可能属于Ⅱ类MAGE基因。
