Xiaoyun Lu  Zhang Zhang  Xiaomei Ren  Deping Wang 《Journal of enzyme inhibition and medicinal chemistry》2017,32(1):331-336

Bcr-Abl^T315I induced drug resistance remains a major challenge to chronic myelogenous leukemia (CML) treatment. Herein, we reported GZD856 as a novel orally bioavailable Bcr-Abl^T315I inhibitor, which strongly suppressed the kinase activities of both native Bcr-Abl and the T315I mutant with IC₅₀ values of 19.9 and 15.4?nM, and potently inhibited proliferation of corresponding K562, Ba/F3^WT and Ba/F3^T315I cells with IC₅₀ values of 2.2, 0.64 and 10.8?nM. Furthermore, GZD856 potently suppressed tumor growth in mouse bearing xenograft K562 and Ba/F3 cells expressing Bcr-Abl^T315I. Thus, GZD856 may serve as a promising lead for the development of Bcr-Abl inhibitors overcoming acquired imatinib resistance.  相似文献   

    

《Molecular cell》2023,83(7):1165-1179.e11

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Lei Zhang  Xiaorui Liu  Jiuzeng Cui  Sicheng Che  Yuexia Liu  Xiaopeng An  Binyun Cao  Yuxuan Song 《Journal of cellular physiology》2019,234(4):4754-4767

Despite the fact that long noncoding RNAs (lncRNAs) play roles in almost all biological processes, little is known about their biological function in the endometrium during the formation of endometrial receptivity. In this study, a comprehensive analysis of lncRNAs in goat endometrial tissues on Day 5 (prereceptive endometrium, PE) and Day 15 (receptive endometrium, RE) of pregnancy was performed by using RNA-Seq. As a result, 668 differentially expressed lncRNAs (DELs) were found between the PE and RE. Further study showed that lncRNA882, regulated by estrogen (E2) and progestin (P4), could act as competing endogenous RNAs (ceRNAs) for miR-15b, which inhibited the expression of transforming growth factor-b-activated kinase 1 binding protein 3 (TAB3) and then indirectly regulated the level of leukemia inhibitory factor (LIF). This was helpful for the formation of endometrial receptivity in dairy goats. In conclusion, we elucidated the endometrium lncRNA profiles of PE and RE in dairy goats; lncRNA882 acted as a ceRNA for miR-15b and then indirectly regulated the level of LIF in goat endometrial epithelium cells. Thus, this study helped us to better understand the molecular regulation of endometrial receptivity in dairy goats.  相似文献   

    

《Cell calcium》2019

L-asparaginase treatment is used in the clinic to treat acute lymphoblastic leukemia (ALL) patients. Lee et al. (2019, Blood 133:2222-2232) demonstrated that L-asparaginase induces apoptosis by activating inositol 1,4,5-trisphosphate (IP₃)-induced Ca²⁺ signaling in a Huntingin-associated protein 1 (HAP1)-dependent manner. Moreover, HAP1 levels inversely correlate with the sensitivity of the ALL cells to L-asparaginase. HAP1 can therefore be used as biomarker for evaluating L-asparaginase resistance.  相似文献   

    

《Cell calcium》2019

The calcium-activated chloride channel TMEM16A is intimately linked to cancers. Over decades, TMEM16A over-expression and contribution to prognosis have been widely studied for multiple cancers strengthening the idea that TMEM16A could be a valuable biomarker and a promising therapeutic target. Surprisingly, from the survey of the literature, it appears that TMEM16A has been involved in multiple cancer-related functions and a large number of molecular targets of TMEM16A have been proposed. Thus, TMEM16A appears to be an ion channel with a multifaceted role in cancers.In this review, we summarize the latest development regarding TMEM16A contribution to cancers. We will survey TMEM16A contribution in cancer prognosis, the origins of its over-expression in cancer cells, the multiple biological functions and molecular pathways regulated by TMEM16A. Then, we will consider the question regarding the molecular mechanism of TMEM16A in cancers and the possible basis for the multifaceted role of TMEM16A in cancers.  相似文献   

    

Danna Wei  Tingting Lu  Dan Ma  Kunlin YU  Xinyao Li  Bingqing Chen  Ji Xiong  Tianzhuo Zhang  Jishi Wang 《Journal of cellular physiology》2019,234(4):5252-5263

Resistance towards imatinib (IM) remains troublesome in treating many chronic myeloid leukemia (CML) patients. Heme oxygenase-1 (HO-1) is a key enzyme of antioxidative metabolism in association with cell resistance to apoptosis. Our previous studies have shown that overexpression of HO-1 resulted in resistance development to IM in CML cells, while the mechanism remains unclear. In the current study, the IM-resistant CML cells K562R indicated upregulation of some of the histone deacetylases (HDACs) compared with K562 cells. Therefore, we herein postulated HO-1 was associated with HDACs. Silencing HO-1 expression in K562R cells inhibited the expression of some HDACs, and the sensitivity to IM was increased. K562 cells transfected with HO-1 resisted IM and underwent obvious some HDACs. These findings related to the inhibitory effects of high HO-1 expression on the reactive oxygen species (ROS) signaling pathway that negatively regulated HDACs. Increased expression of HO-1 activated HDACs by inhibiting ROS production. In summary, HO-1, which is involved in the development of drug resistance in CML cells by regulating the expression of HDACs, is probably a novel target for improving CML therapy.  相似文献   

    

Cigir Biray Avci  Bakiye Goker Bagca  Asli Tetik Vardarli  Guray Saydam  Cumhur Gunduz 《Journal of cellular biochemistry》2019,120(3):4555-4563

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Duarte L. Martins  Jure Sencar  Nikolaus Hammerschmidt  Bjrn Tille  Johanna Kinderman  Thomas R. Kreil  Alois Jungbauer 《Biotechnology journal》2019,14(8)

Continuous virus inactivation (VI) remains one of the missing pieces while the biopharma industry moves toward continuous manufacturing. The challenges of adapting VI to the continuous operation are two‐fold: 1) achieving fluid homogeneity and 2) a narrow residence time distribution (RTD) for fluid incubation. To address these challenges, a dynamic active in‐line mixer and a packed‐bed continuous virus inactivation reactor (CVIR) are implemented, which act as a narrow RTD incubation chamber. The developed concept is applied using solvent/detergent (S/D) treatment for inactivation of two commonly used model viruses. The in‐line mixer is characterized and enables mixing of the viscous S/D chemicals to ±1.0% of the target concentration in a small dead volume. The reactor's RTD is characterized and additional control experiments confirm that the VI is due to the S/D action and not induced by system components. The CVIR setup achieves steady state rapidly before two reactor volumes and the logarithmic reduction values of the continuous inactivation process are identical to those obtained by the traditional batch operation. The packed‐bed reactor for continuous VI unites fully continuous processing with very low‐pressure drop and scalability.  相似文献   

    

《Molecular cell》2022,82(5):1003-1020.e15

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Isolation of multipotent stem cells from adult rat periodontal ligament by neurosphere-forming culture system   总被引：1，自引：0，他引：1  

Techawattanawisal W  Nakahama K  Komaki M  Abe M  Takagi Y  Morita I 《Biochemical and biophysical research communications》2007,357(4):917-923

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