首页 > 最新文献

Acta materia medica最新文献

英文 中文
The 'New (Nu)-clear' evidence for the tumor-driving role of PI3K. PI3K 推动肿瘤作用的 "新(Nu)-明确 "证据。
Pub Date : 2022-01-01 Epub Date: 2022-05-16 DOI: 10.15212/amm-2022-0013
Franklin Mayca Pozo, Tony Hunter, Youwei Zhang

The classical phosphatidylinositol 3-kinases (PI3Ks) are heterodimers of p110 and p85. PIK3CA, the gene encoding the catalytic p110α subunit, is one of the most frequently mutated oncogenes in human cancers with hot spot mutations occurring in the helical domain or in the kinase domain. Tumors with these two types of PIK3CA mutations show overlapping yet distinct phenotypes; however, the underlying mechanisms remain unclear. In a recent publication [1], Hao et al revealed exciting findings about the PI3K p85β regulatory subunit in promoting PIK3CA helical domain mutation-driven cancer progression. The authors found that p85β disassociated from the PI3K complex and translocated into the nucleus only in cancer cells harboring PIK3CA helical domain mutations. Disrupting nuclear localization of p85β suppressed mouse tumor growth of cancer cells with PIK3CA helical domain mutation. Mechanistically, they elegantly showed that nuclear p85β recruited the deubiquitinase USP7 to stabilize the histone methyltransferases EZH1/2, leading to enhanced H3K27 trimethylation and gene transcription. Combining an EZH inhibitor with a PI3K inhibitor specifically resulted in regression of mouse xenograft tumors with PIK3CA helical domain mutations. These findings illustrate a previously uncharacterized function of p85β in tumor development and suggest an effective approach to target tumors with PIK3CA helical mutations.

经典的磷脂酰肌醇 3 激酶(PI3K)是 p110 和 p85 的异二聚体。PIK3CA 是编码催化 p110α 亚基的基因,是人类癌症中最常发生突变的致癌基因之一,其热点突变发生在螺旋结构域或激酶结构域。这两类PIK3CA突变的肿瘤表现出重叠但不同的表型;然而,其潜在机制仍不清楚。在最近发表的一篇论文[1]中,Hao 等人揭示了 PI3K p85β 调节亚基在促进 PIK3CA 螺旋结构域突变驱动的癌症进展方面的激动人心的发现。作者发现,只有在携带 PIK3CA 螺旋结构域突变的癌细胞中,p85β 才会脱离 PI3K 复合物并转位到细胞核中。破坏 p85β 的核定位可抑制 PIK3CA 螺旋结构域突变癌细胞的小鼠肿瘤生长。从机理上讲,他们清楚地表明,核p85β招募去泛素化酶USP7来稳定组蛋白甲基转移酶EZH1/2,从而导致H3K27三甲基化和基因转录增强。将 EZH 抑制剂与 PI3K 抑制剂结合使用,可使 PIK3CA 螺旋结构域突变的小鼠异种移植肿瘤消退。这些发现说明了 p85β 在肿瘤发生发展过程中的一种之前未被描述的功能,并提出了一种针对 PIK3CA 螺旋结构突变肿瘤的有效方法。
{"title":"The 'New (Nu)-clear' evidence for the tumor-driving role of PI3K.","authors":"Franklin Mayca Pozo, Tony Hunter, Youwei Zhang","doi":"10.15212/amm-2022-0013","DOIUrl":"10.15212/amm-2022-0013","url":null,"abstract":"<p><p>The classical phosphatidylinositol 3-kinases (PI3Ks) are heterodimers of p110 and p85. <i>PIK3CA</i>, the gene encoding the catalytic p110α subunit, is one of the most frequently mutated oncogenes in human cancers with hot spot mutations occurring in the helical domain or in the kinase domain. Tumors with these two types of <i>PIK3CA</i> mutations show overlapping yet distinct phenotypes; however, the underlying mechanisms remain unclear. In a recent publication [1], Hao et al revealed exciting findings about the PI3K p85β regulatory subunit in promoting <i>PIK3CA</i> helical domain mutation-driven cancer progression. The authors found that p85β disassociated from the PI3K complex and translocated into the nucleus only in cancer cells harboring <i>PIK3CA</i> helical domain mutations. Disrupting nuclear localization of p85β suppressed mouse tumor growth of cancer cells with <i>PIK3CA</i> helical domain mutation. Mechanistically, they elegantly showed that nuclear p85β recruited the deubiquitinase USP7 to stabilize the histone methyltransferases EZH1/2, leading to enhanced H3K27 trimethylation and gene transcription. Combining an EZH inhibitor with a PI3K inhibitor specifically resulted in regression of mouse xenograft tumors with <i>PIK3CA</i> helical domain mutations. These findings illustrate a previously uncharacterized function of p85β in tumor development and suggest an effective approach to target tumors with <i>PIK3CA</i> helical mutations.</p>","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":"1 2","pages":"193-196"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10191166/pdf/nihms-1849224.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9496355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cytotoxic compounds from marine actinomycetes: Sources, Structures and Bioactivity. 海洋放线菌的细胞毒性化合物:来源、结构和生物活性。
Pub Date : 2022-01-01 DOI: 10.15212/amm-2022-0028
Ziyan Qiu, Yinshuang Wu, Kunyan Lan, Shiyi Wang, Huilin Yu, Yufei Wang, Cong Wang, Shugeng Cao

Marine actinomycetes produce a substantial number of natural products with cytotoxic activity. The strains of actinomycetes were isolated from different sources like fishes, coral, sponges, seaweeds, mangroves, sediments etc. These cytotoxic compounds can be categorized briefly into four classes: polyketides, non-ribosomal peptides and hybrids, isoprenoids and hybrids, and others, among which majority are polyketides (146). Twenty two out of the 254 compounds showed potent cytotoxicity with IC50 values at ng/mL or nM level. This review highlights the sources, structures and antitumor activity of 254 natural products isolated from marine actinomycetes, which were new when they were reported from 1989 to 2020.

海洋放线菌产生大量具有细胞毒性活性的天然产物。从鱼类、珊瑚、海绵、海藻、红树林、沉积物等不同来源中分离到放线菌菌株。这些细胞毒性化合物可以简单地分为四类:聚酮类、非核糖体多肽和杂交种、类异戊二烯和杂交种等,其中大多数是聚酮类(146)。254个化合物中有22个具有较强的细胞毒性,IC50值在ng/mL或nM水平。本文综述了1989 ~ 2020年报道的254种海洋放线菌天然产物的来源、结构和抗肿瘤活性。
{"title":"Cytotoxic compounds from marine actinomycetes: Sources, Structures and Bioactivity.","authors":"Ziyan Qiu,&nbsp;Yinshuang Wu,&nbsp;Kunyan Lan,&nbsp;Shiyi Wang,&nbsp;Huilin Yu,&nbsp;Yufei Wang,&nbsp;Cong Wang,&nbsp;Shugeng Cao","doi":"10.15212/amm-2022-0028","DOIUrl":"https://doi.org/10.15212/amm-2022-0028","url":null,"abstract":"<p><p>Marine actinomycetes produce a substantial number of natural products with cytotoxic activity. The strains of actinomycetes were isolated from different sources like fishes, coral, sponges, seaweeds, mangroves, sediments etc. These cytotoxic compounds can be categorized briefly into four classes: polyketides, non-ribosomal peptides and hybrids, isoprenoids and hybrids, and others, among which majority are polyketides (146). Twenty two out of the 254 compounds showed potent cytotoxicity with IC<sub>50</sub> values at ng/mL or nM level. This review highlights the sources, structures and antitumor activity of 254 natural products isolated from marine actinomycetes, which were new when they were reported from 1989 to 2020.</p>","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":"1 4","pages":"445-475"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9802659/pdf/nihms-1850447.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10475769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Drug discovery is an eternal challenge for the biomedical sciences 药物发现是生物医学科学的永恒挑战
Pub Date : 2022-01-01 DOI: 10.15212/amm-2022-1001
L. Hua, Wei Wenyi, Hongxi Xu
aWuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, China School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China bDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States cSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
aWuya创新学院,教育部基于结构的药物设计与发现重点实验室,沈阳药科大学,中国沈阳药学院,华中科技大学同济医学院,中国武汉b病理学系,哈佛医学院贝斯以色列女执事医疗中心,波士顿,MA 02215,美国上海中医药大学药学院,上海,201203
{"title":"Drug discovery is an eternal challenge for the biomedical sciences","authors":"L. Hua, Wei Wenyi, Hongxi Xu","doi":"10.15212/amm-2022-1001","DOIUrl":"https://doi.org/10.15212/amm-2022-1001","url":null,"abstract":"aWuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, China School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China bDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States cSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44489865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 55
期刊
Acta materia medica
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1