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821.
Background
Adjuvant trastuzumab therapy has yielded conflicting results for overall survival, concerns about central nervous system (CNS) metastasis, and questions about optimal schedule. Therefore, we carried out a meta-analysis to assess the benefits of concurrent or sequential trastuzumab with adjuvant chemotherapy for early breast cancer patients with HER2-positive tumors.Methods
Computerized and manual searches were performed to identify randomized clinical trials comparing adjuvant chemotherapy with or without trastuzumab in HER2-positive early breast cancer patients. Odds ratios were used to estimate the association between the addition of trastuzumab to adjuvant chemotherapy and various survival outcomes. The fixed-effects or random-effects model was used to combine data.Findings
With six eligible studies identified, this analysis demonstrated that patients with HER2-positive breast cancer derived benefit in disease-free survival, overall survival, locoregional recurrence and distant recurrence (all P<0.001) from the addition of trastuzumab to adjuvant chemotherapy, whereas trastuzumab did worse in CNS recurrence as compared to the control group (P = 0.018). Furthermore, concomitant use of trastuzumab significantly lowered the hazard of death (P<0.001) but bore a higher incidence of CNS recurrence (P = 0.010), while statistical significance failed to be discerned for either overall survival (P = 0.069) or CNS metastasis (P = 0.374) between the sequential and observation arms.Conclusion
This analysis verifies the efficacy of trastuzumab in the adjuvant setting. Additionally, our findings indirectly corroborate the superiority of concurrent trastuzumab to sequential use and also illuminate that prolonged survival is the possible reason for the higher incidence of CNS with trastuzumab versus observation. 相似文献822.
Abscisic acid plays an important role in the regulation of strawberry fruit ripening 总被引:10,自引:0,他引:10
The plant hormone abscisic acid (ABA) has been suggested to play a role in fruit development, but supporting genetic evidence has been lacking. Here, we report that ABA promotes strawberry (Fragaria ananassa) fruit ripening. Using a newly established Tobacco rattle virus-induced gene silencing technique in strawberry fruit, the expression of a 9-cis-epoxycarotenoid dioxygenase gene (FaNCED1), which is key to ABA biosynthesis, was down-regulated, resulting in a significant decrease in ABA levels and uncolored fruits. Interestingly, a similar uncolored phenotype was observed in the transgenic RNA interference (RNAi) fruits, in which the expression of a putative ABA receptor gene encoding the magnesium chelatase H subunit (FaCHLH/ABAR) was down-regulated by virus-induced gene silencing. More importantly, the uncolored phenotype of the FaNCED1-down-regulated RNAi fruits could be rescued by exogenous ABA, but the ABA treatment could not reverse the uncolored phenotype of the FaCHLH/ABAR-down-regulated RNAi fruits. We observed that down-regulation of the FaCHLH/ABAR gene in the RNAi fruit altered both ABA levels and sugar content as well as a set of ABA- and/or sugar-responsive genes. Additionally, we showed that exogenous sugars, particularly sucrose, can significantly promote ripening while stimulating ABA accumulation. These data provide evidence that ABA is a signal molecule that promotes strawberry ripening and that the putative ABA receptor, FaCHLH/ABAR, is a positive regulator of ripening in response to ABA. 相似文献
823.
Guangwen Lu Jie Zhang Yan Li Zhixin Li Na Zhang Xiang Xu Tingting Wang Zhenhong Guan George F. Gao Jinghua Yan 《蛋白质与细胞》2011,2(1):64
Human NUDT16 (hNUDT16) is a decapping enzyme initially identified as the human homolog to the Xenopus laevis X29. As a metalloenzyme, hNUDT16 relies on divalent cations for its cap-hydrolysis activity to remove m7GDP and m227GDP from RNAs. Metal also determines substrate specificity of the enzyme. So far, only U8 small nucleolar RNA (snoRNA) has been identified as the substrate of hNUDT16 in the presence of Mg2+. Here we demonstrate that besides U8, hNUDT16 can also actively cleave the m7GDP cap from mRNAs in the presence of Mg2+ or Mn2+. We further show that hNUDT16 does not preferentially recognize U8 or mRNA substrates by our cross-inhibition and quantitative decapping assays. In addition, our mutagenesis analysis identifies several key residues involved in hydrolysis and confirms the key role of the REXXEE motif in catalysis. Finally an investigation into the subcellular localization of hNUDT16 revealed its abundance in both cytoplasm and nucleus. These findings extend the substrate spectrum of hNUDT16 beyond snoRNAs to also include mRNA, demonstrating the pleiotropic decapping activity of hNUDT16. 相似文献
824.
种子植物在果实(种子)成熟后需要防御食果实动物捕食种子,同时要传播种子至适宜萌发的生境。很多植物依赖食果实动物传播种子,称动物传播植物。果实(种子)化学防御是抵御种子捕食者的重要手段。果实(种子)中次生物质包括各种生物碱、生氰糖苷、萜类和酚类等,种类繁多;次生物质的含量随果实成熟过程而变化。次生物质可以抵御动物的捕食,其毒性对种子传播者和种子捕食者没有选择性,即具泛毒性。果肉中的次生物质也可以起到轻泻剂的作用,缩短种子在动物消化道的滞留时间,以影响传播效率。果实(种子)次生物质的产生不受植物环境条件的影响,其产生与果实质量有关。在温带地区,通常SS型果实次生物质含量低,而FL型果实含量高。食果实动物可通过调整捕食行为、摄取环境中特殊物质和获得丰富营养等3个方面适应次生物质。果实(种子)中次生物质的研究对动植物相互作用、协同进化理论具有重要的意义。 相似文献
825.
FUNDC1 regulates mitochondrial dynamics at the ER–mitochondrial contact site under hypoxic conditions 下载免费PDF全文
Wen Li Haixia Zhuang Xingliang Zhang Hao Chen Shupeng Li Yue Yang Yue Lu Jingjing Wang Runzhi Zhu Liangqing Zhang Senfang Sui Ning Tan Bin Zhao Jingjing Zhang Longxuan Li Du Feng 《The EMBO journal》2016,35(13):1368-1384
In hypoxic cells, dysfunctional mitochondria are selectively removed by a specialized autophagic process called mitophagy. The ER–mitochondrial contact site (MAM) is essential for fission of mitochondria prior to engulfment, and the outer mitochondrial membrane protein FUNDC1 interacts with LC3 to recruit autophagosomes, but the mechanisms integrating these processes are poorly understood. Here, we describe a new pathway mediating mitochondrial fission and subsequent mitophagy under hypoxic conditions. FUNDC1 accumulates at the MAM by associating with the ER membrane protein calnexin. As mitophagy proceeds, FUNDC1/calnexin association attenuates and the exposed cytosolic loop of FUNDC1 interacts with DRP1 instead. DRP1 is thereby recruited to the MAM, and mitochondrial fission then occurs. Knockdown of FUNDC1, DRP1, or calnexin prevents fission and mitophagy under hypoxic conditions. Thus, FUNDC1 integrates mitochondrial fission and mitophagy at the interface of the MAM by working in concert with DRP1 and calnexin under hypoxic conditions in mammalian cells. 相似文献
826.
Ashima Bhattacharjee Haojun Yang Megan Duffy Emily Robinson Arianrhod Conrad-Antoville Ya-Wen Lu Tony Capps Lelita Braiterman Michael Wolfgang Michael P. Murphy Ling Yi Stephen G. Kaler Svetlana Lutsenko Martina Ralle 《The Journal of biological chemistry》2016,291(32):16644-16658
Copper-transporting ATPase ATP7A is essential for mammalian copper homeostasis. Loss of ATP7A activity is associated with fatal Menkes disease and various other pathologies. In cells, ATP7A inactivation disrupts copper transport from the cytosol into the secretory pathway. Using fibroblasts from Menkes disease patients and mouse 3T3-L1 cells with a CRISPR/Cas9-inactivated ATP7A, we demonstrate that ATP7A dysfunction is also damaging to mitochondrial redox balance. In these cells, copper accumulates in nuclei, cytosol, and mitochondria, causing distinct changes in their redox environment. Quantitative imaging of live cells using GRX1-roGFP2 and HyPer sensors reveals highest glutathione oxidation and elevation of H2O2 in mitochondria, whereas the redox environment of nuclei and the cytosol is much less affected. Decreasing the H2O2 levels in mitochondria with MitoQ does not prevent glutathione oxidation; i.e. elevated copper and not H2O2 is a primary cause of glutathione oxidation. Redox misbalance does not significantly affect mitochondrion morphology or the activity of respiratory complex IV but markedly increases cell sensitivity to even mild glutathione depletion, resulting in loss of cell viability. Thus, ATP7A activity protects mitochondria from excessive copper entry, which is deleterious to redox buffers. Mitochondrial redox misbalance could significantly contribute to pathologies associated with ATP7A inactivation in tissues with paradoxical accumulation of copper (i.e. renal epithelia). 相似文献
827.
828.
829.
Yolanda M. Drozdowicz Yu-Ping Lu Vijay Patel Sorel Fitz-Gibbon Jeffrey H. Miller Philip A. Rea 《FEBS letters》1999,460(3)
Vacuolar-type H+-translocating pyrophosphatases (V-PPases) have been considered to be restricted to plants, a few species of phototrophic proteobacteria and protists. Here, we describe PVP, a thermostable, sequence-divergent V-PPase from the facultatively aerobic hyperthermophilic archaeon Pyrobaculum aerophilum. PVP shares only 38% sequence identity with both the prototypical V-PPase from Arabidopsis thaliana and the H+-PPi synthase from Rhodospirillum rubrum, yet possesses most of the structural features characteristic of V-PPases. Heterologous expression of PVP in Saccharomyces cerevisiae yields a Mr 64 000 membrane polypeptide that specifically catalyzes Mg2+-dependent PPi hydrolysis. The existence of PVP implies that PPi-energized H+-translocation is phylogenetically more deeply rooted than previously thought. 相似文献
830.
The antifungal activity and mechanism of fengycin in the presence and absence of commercial surfactin against Rhizopus stolonifer were investigated. The MIC (minimal inhibitory concentration) of fengycin without commercial surfactin added was 0.4 mg/ml
while the MIC of fengycin with commercial surfactin added was 2.0 mg/ml. Fengycin acted on cell membrane and cellular organs
and inhibited DNA synthesis. The antifungal effect of fengycin was reduced after commercial surfactin was added. All these
results suggest that the fungal cell membrane may be the primary target of fengycin action and commercial surfactin may reduce
the antifungal activity of fengycin. 相似文献