Hepatocellular carcinoma (HCC) is a dreadful cancer and a major cause of death among patients with chronic liver disease and cirrhosis. The apparent alterations in a diversity of intracellular pathways found in HCC ha...Hepatocellular carcinoma (HCC) is a dreadful cancer and a major cause of death among patients with chronic liver disease and cirrhosis. The apparent alterations in a diversity of intracellular pathways found in HCC has set the rational for developing molecular-directed drugs that simultaneously inhibit multiple pathways, such as the multi-kinase inhibitor Sorafenib. However, recently this concept has been challenged by showing that HCC is heavily dependent on a single oncogene designated late SV-40 factor (LSF), a transcription factor that is over-expressed in liver cancer cells and that its expression is strongly correlated with tumor grade and aggressiveness. Furthermore, using an intensive screening for drugs that inhibit LSF activity, Grant et al have found a molecule designated factor quinolinone inhibitor 1 that can specifically block the ability of LSF to bind its target promoters, resulting in a massive death of HCC cells both in vitro and in vivo. The innovative findings of HCC representing "oncogene addiction" to LSF and the ability of a single molecule to block the activity of this oncogene resulting in tumor abolishment are encouraging and provide us with the hope that the "Achilles heel" of HCC has been found.展开更多
Artemisinin, the key ingredient of first-line antimalarial drugs, has large demand every year. The native plant, which produces small quantities of artemisinin, remains as its main source and thus results in a short s...Artemisinin, the key ingredient of first-line antimalarial drugs, has large demand every year. The native plant, which produces small quantities of artemisinin, remains as its main source and thus results in a short supply of artemisinin. Intensified efforts have been carried out to elevate artemisinin production. However, the routine metabolic engineering strategy, via overexpressing or down-regulating genes in artemisinin biosynthesis branch pathways, was not very effective as desired. Glandular secretory trichomes, sites of artemisinin biosynthesis on the surface of Artemisia annua L.(A. annua), are the new target for increasing artemisinin yield. In general, the population and morphology of glandular secretory trichomes in A. annua(Aa GSTs) are often positively correlated with artemisinin content. Improved understanding of Aa GSTs will shed light on the opportunities for increasing plant-derived artemisinin. This review article will refresh classification of trichomes in A. annua and provide an overview of the recent achievements regarding Aa GSTs and artemisinin. To have a full understanding of Aa GSTs,factors that are associated with trichome morphology and density will have to be further investigated, such as genes,micro RNAs and phytohormones. The purpose of thisreview was to(1) update the knowledge of the relation between Aa GSTs and artemisinin, and(2) propose new avenues to increase artemisinin yield by harnessing the potential biofactories, Aa GSTs.展开更多
文摘Hepatocellular carcinoma (HCC) is a dreadful cancer and a major cause of death among patients with chronic liver disease and cirrhosis. The apparent alterations in a diversity of intracellular pathways found in HCC has set the rational for developing molecular-directed drugs that simultaneously inhibit multiple pathways, such as the multi-kinase inhibitor Sorafenib. However, recently this concept has been challenged by showing that HCC is heavily dependent on a single oncogene designated late SV-40 factor (LSF), a transcription factor that is over-expressed in liver cancer cells and that its expression is strongly correlated with tumor grade and aggressiveness. Furthermore, using an intensive screening for drugs that inhibit LSF activity, Grant et al have found a molecule designated factor quinolinone inhibitor 1 that can specifically block the ability of LSF to bind its target promoters, resulting in a massive death of HCC cells both in vitro and in vivo. The innovative findings of HCC representing "oncogene addiction" to LSF and the ability of a single molecule to block the activity of this oncogene resulting in tumor abolishment are encouraging and provide us with the hope that the "Achilles heel" of HCC has been found.
基金supported by the National Natural Science Foundation of China (Grant Nos. 31300159 U1405215)+2 种基金‘‘Pujiang Talent’’ program (13PJ1411000) Shanghai Science and Technology Development Funds (14QB1402700)Program 15391900500 from Science and Technology Commission of Shanghai Municipality and Technology Committee and Seedling Cultivation Fund of Outstanding Master, Second Military Medical University
文摘Artemisinin, the key ingredient of first-line antimalarial drugs, has large demand every year. The native plant, which produces small quantities of artemisinin, remains as its main source and thus results in a short supply of artemisinin. Intensified efforts have been carried out to elevate artemisinin production. However, the routine metabolic engineering strategy, via overexpressing or down-regulating genes in artemisinin biosynthesis branch pathways, was not very effective as desired. Glandular secretory trichomes, sites of artemisinin biosynthesis on the surface of Artemisia annua L.(A. annua), are the new target for increasing artemisinin yield. In general, the population and morphology of glandular secretory trichomes in A. annua(Aa GSTs) are often positively correlated with artemisinin content. Improved understanding of Aa GSTs will shed light on the opportunities for increasing plant-derived artemisinin. This review article will refresh classification of trichomes in A. annua and provide an overview of the recent achievements regarding Aa GSTs and artemisinin. To have a full understanding of Aa GSTs,factors that are associated with trichome morphology and density will have to be further investigated, such as genes,micro RNAs and phytohormones. The purpose of thisreview was to(1) update the knowledge of the relation between Aa GSTs and artemisinin, and(2) propose new avenues to increase artemisinin yield by harnessing the potential biofactories, Aa GSTs.
