Acta materia medicaPub Date : 2022-01-01Epub Date: 2022-05-16DOI: 10.15212/amm-2022-0013
Franklin Mayca Pozo, Tony Hunter, Youwei Zhang
{"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}
{"title":"Cytotoxic compounds from marine actinomycetes: Sources, Structures and Bioactivity.","authors":"Ziyan Qiu, Yinshuang Wu, Kunyan Lan, Shiyi Wang, Huilin Yu, Yufei Wang, Cong Wang, 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}
{"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}