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Lingling Gao Xin Nie Rui Gou Yuexin Hu Hui Dong Xiao Li Bei Lin 《Journal of cellular and molecular medicine》2021,25(23):10916-10929
Ovarian cancer, one of the malignant gynaecological tumours with the highest mortality rate among female reproductive system, is prone to metastasis, recurrence and chemotherapy resistance, causing a poor prognosis. Exosomes can regulate the epithelial-mesenchymal plasticity of tumour cells, remodel surrounding tumour microenvironment, and affect tumour cell proliferation, invasion and metastasis. However, the function and mechanism of exosomes in the intraperitoneal implantation of ovarian cancer remain unclear. In this study, exosomal annexin A2 (ANXA2) derived from ovarian cancer cells was co-cultured with human peritoneal mesothelial (HMrSV5) cells; functional experiments were conducted to explore the effects of exosomal ANXA2 on the biological behaviour of HMrSV5 and the related mechanisms. This study showed that ANXA2 in ovarian cancer cells can be transferred to HMrSV5 cells through exosomes, exosomal ANXA2 can not only promote the migration, invasion and apoptosis of HMrSV5 cells, but also regulates morphological changes and fibrosis of HMrSV5 cells. Furthermore, ANXA2 promotes the mesothelial-mesenchymal transition (MMT) and degradation of the extracellular matrix of HMrSV5 cells through PI3K/AKT/mTOR pathway, finally affects pre-metastasis microenvironment of ovarian cancer, which provides a new theoretical basis for the mechanism of intraperitoneal implantation and metastasis of ovarian cancer. 相似文献
54.
Zhisheng Wu Xuanjun Wu Yuhui Yang Ting-bin Wen Shoufa Han 《Bioorganic & medicinal chemistry letters》2012,22(20):6358-6361
N-(rhodamine B)-deoxylactam-5-amino-1-pentanol (dRB-APOH) was designed and prepared as the chromo-fluorogenic sensor for detection of a nerve agent simulant via analyte triggered tandem phosphorylation and opening of the intramolecular deoxylactam. The successful detection of diethyl chlorophosphate suggests the utility of rhodamine-deoxylactams as the chromo-fluorogenic signal reporting platform for design of sensors targeting reactive chemical species via various chemistries. 相似文献
55.
Dima A. Sabbah Neka A. Simms Wang Wang Yuxiang Dong Edward L. Ezell Michael G. Brattain Jonathan L. Vennerstrom Haizhen A. Zhong 《Bioorganic & medicinal chemistry》2012,20(24):7175-7183
This work describes our efforts to optimize the lead PI3Kα inhibitor N-benzyl 4-hydroxy-2-quinolone-3-carboxamide using structure-based design and molecular docking. We identified a series of N-phenyl 4-hydroxy-2-quinolone-3-carboxamides as selective inhibitors of mutant H1047R versus wild-type PI3Kα and we also showed that the cell growth inhibition by these compounds likely occurs by inhibiting the formation of pAKT and induction of apoptosis. 相似文献
56.
Han Zhang 《Autophagy》2017,13(3):627-628
Macroautophagy/autophagy is a well-established process involved in maintaining cellular homeostasis, but its role in cancer is complex and even controversial. Many studies have reported a correlative relationship between increased autophagy and evolving cancer cells under stress conditions such as nutrient or oxygen deprivation; however, there has been a lack of a plausible mechanistic link to properly target the autophagy process in the context of this microenvironment. We recently unveiled a positive regulatory loop involving TGM2 (transglutaminase 2)-NFKB/NF-κB signaling, IL6 and autophagy in cancer using mantle cell lymphoma (MCL) as a model system. These pathways are functionally connected to each other, thereby promoting malignant B cell survival and leading to enhanced lymphoma progression both in mice and in patients. Disruption of this network could provide an opportunity to increase the efficacies of current therapies and to reduce MCL drug resistance. 相似文献
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Colin R. Andrew Jane Han Tanneke den Blaauwen Gertie van Pouderoyen Erik Vijgenboom Gerard W. Canters Thomas M. Loehr J. Sanders-Loehr 《Journal of biological inorganic chemistry》1997,2(1):98-107
In the redox center of azurin, the Cu(II) is strongly coordinated to one thiolate S from Cys 112 and two imidazole Ns from
His 46 and 117. This site yields a complex resonance Raman (RR) spectrum with >20 vibrational modes between 200 and 1500 cm–1. We have investigated the effects of ligand-selective isotope replacements on the RR spectrum of Pseudomonas aeruginosa azurin to determine the relative spectral contribution from each of the copper ligands. Growth on 34S-sulfate labels the cysteine ligand and allows the identification of a cluster of bands with Cu–S(Cys) stretching character
between 370 and 430 cm–1 whose frequencies are consistent with the trigonal or distorted tetrahedral coordination in type 1 sites. In type 2 copper-cysteinate
sites, the lower ν (Cu–S) frequencies between 260 and 320 cm–1 are consistent with square-planar coordination. Addition of exogenous
15N-labeled imidazole or histidine to the His117Gly mutant generates type 1 or type 2 sites, respectively. Because neither the
above nor the His46Gly mutant reconstituted with 15N-imidazole exhibits significant isotope dependence, the histidine ligands can be ruled out as important contributors to the
RR spectrum. Instead, a variety of evidence, including extensive isotope shifts upon global substitution with 15N, suggests that the multiple RR modes of azurin are due principally to vibrations of the cysteine ligand. These are resonance-enhanced
through kinematic coupling with the Cu–S stretch in the ground state or through an excited-state A-term mechanism involving
a Cu-cysteinate chromophore that extends into the peptide backbone.
Received: 29 July 1996 / Accepted: 9 November 1996 相似文献
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The transition of gene switch induced by external noises (multiplicative external noise and additive external noise) and external signals is investigated in the genetic regulatory system. Results show that the state-to-state transition of gene switch as well as resonant behaviors, such as the explicit coherence resonance (ECR), implicit coherence resonance (ICR) and control parameter coherence biresonance (CPCBR), can appear when noises are injected into the genetic regulatory system. The ECR is increased with the increase of the control parameter value when starting from the supercritical Hopf bifurcation parameter point, and there exists a critical control parameter value for the occurrence of ECR. However, the ICR is decreased as the control parameter value is increased when starting from the subcritical Hopf bifurcation point. In particular, the coherence of ECR is higher and more sensitive to noise than that of ICR. When an external signal is introduced into the system, the enhancement or suppression of the CPCBR and the number of peaks strongly depend on the frequency and amplitude of the external signal. Furthermore, the gene regulation system can selectively enhance or decrease the noise-induced oscillation signals at preferred frequency and amplitude of an external signal. 相似文献