The cells expressing the T674I point mutant of FIP1-like-1-platelet-derived growth factor receptor alpha (FIP1L1-PDGFRα) in hypereosinophilics syndrome (HES) are resistant to imatinib and some ...second-generation tyrosine kinase inhibitors (TKIs). There is a desperate need to develop therapy to combat this acquired drug resistance. DCC-2036 has been synthesized as a third-generation TKI to combat especially the Bcr-Abl T315I mutant in chronic myeloid leukemia. This study evaluated the effect of DCC-2036 on FIP1L1-PDGFRα-positive cells, including the wild type (WT) and the T674I mutant. The in vitro effects of DCC-2036 on the PDGFRα signal pathways, proliferation, cell cycling and apoptosis of FIP1L1-PDGFRα-positive cells were investigated, and a nude mouse xenograft model was employed to assess the in vivo antitumor activity. We found that DCC-2036 decreased the phosphorylated levels of PDGFRα and its downstream targets without apparent effects on total protein levels. DCC-2036 inhibited proliferation, and induced apoptosis with MEK-dependent up-regulation of the pro-apoptotic protein Bim in FIP1L1-PDGFRα-positive cells. DCC-2036 also exhibited in vivo antineoplastic activity against cells with T674I FIP1L1-PDGFRα. In summary, FIP1L1-PDGFRα-positive cells are sensitive to DCC-2036 regardless of their sensitivity to imatinib. DCC-2036 may be a potential compound to treat imatinib-resistant HES.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Reactive oxygen species (ROS), byproducts of aerobic metabolism, are increased in many types of cancer cells. Increased endogenous ROS lead to adaptive changes and may play pivotal roles in ...tumorigenesis, metastasis, and resistance to radiation and chemotherapy. In contrast, the ROS generated by xenobiotics disturb the redox balance and may selectively kill cancer cells but spare normal cells.
Cancer stem cells (CSCs) are integral parts of pathophysiological mechanisms of tumor progression, metastasis, and chemo/radio resistance. Currently, intracellular ROS in CSCs is an active field of research.
Normal stem cells such as hematopoietic stem cells reside in niches characterized by hypoxia and low ROS, both of which are critical for maintaining the potential for self-renewal and stemness. However, the roles of ROS in CSCs remain poorly understood.
Based on the regulation of ROS levels in normal stem cells and CSCs, future research may evaluate the potential therapeutic application of ROS elevation by exogenous xenobiotics to eliminate CSCs.
Based on the Pt nanozyme modified mesoporous polydopamine in situ, a multi-functional nanoplatform was established, which could overcome tumour hypoxia by catalyzing overexpressed H2O2 in tumour ...cells to enhance photodynamic therapy. In vivo results confirmed that the tumour growth was inhibited efficiently by synergetic therapy.
Previous studies have demonstrated that the activation of stereotype conflict is similar to the N400 congruency effect shown by the activation of semantic violation. In order to distinguish the ...differences between the two, the first experiment used gender stereotype trait words as target stimuli, and used "male/female" and "synonym of trait words/antonym of trait words" as priming stimuli respectively, so that the subjects completed the consistency determination task. In experiment 2, gender stereotyped behavior pictures were used as target stimuli, and "male/female" was used as priming stimuli, so that the subjects completed the task of consistency determination. The results showed that both gender stereotype conflict and semantic violation could induce N400 a congruency effect. Importantly, the N400 amplitude and response latency induced by gender stereotype activation are both smaller than those induced by semantic activation. These results show that stereotype activation is distinct from semantic activation, further demonstrating that the brain preferentially processes information related to gender stereotypes, and gender stereotype cognitive processing is more likely to happen than semantic knowledge processing.
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BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Previous studies have demonstrated that the activation of stereotype conflict is similar to the N400 congruency effect shown by the activation of semantic violation. In order to distinguish the ...differences between the two, the first experiment used gender stereotype trait words as target stimuli, and used "male/female" and "synonym of trait words/antonym of trait words" as priming stimuli respectively, so that the subjects completed the consistency determination task. In experiment 2, gender stereotyped behavior pictures were used as target stimuli, and "male/female" was used as priming stimuli, so that the subjects completed the task of consistency determination. The results showed that both gender stereotype conflict and semantic violation could induce N400 a congruency effect. Importantly, the N400 amplitude and response latency induced by gender stereotype activation are both smaller than those induced by semantic activation. These results show that stereotype activation is distinct from semantic activation, further demonstrating that the brain preferentially processes information related to gender stereotypes, and gender stereotype cognitive processing is more likely to happen than semantic knowledge processing.
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BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Fourteen undescribed diterpenoids caryopterisoids D - Q, three undescribed iridoid glucoside derivatives caryopterisides F - H, and 8 known diterpenoids were isolated from the 95% aqueous ethanolic ...extract of Caryopteris glutinosa. Their structures were elucidated on the basis of spectroscopic data analysis and chemical derivation studies. The structure and absolute configuration of caryopterisoid D were confirmed by X-ray crystallographic analysis. Caryopterisoids K and R, royleanone, 6α-hydroxydemethylcryptojaponol, and teuvincenone E were shown to reduce the biosynthesis of estrogen E2 with IC50 values from 0.25 to 3.06 μM in cell-based estrogen biosynthesis assays system.
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•Seventeen unprecedented natural products were identified from Caryopteris glutinosa.•Caryopterisoids D - Q (1 – 14) are diterpenoids and diterpenoid derivatives.•Caryopterisides F – H (15 - 17) are iridoid glucosides modified with vanillic acid.•The absolute configurations of 1 were confirmed by X-ray crystallographic analysis.•Compounds 8, 14, 19, 21, and 25 reduce E2 biosynthesis with IC50 = 0.25–3.06 μM.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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