1,470 research outputs found
Preparation of Ultra-High Temperature CeramicsâBased Materials by Sol-Gel Routes
Ultraâhigh temperature ceramics (UHTCs) are a class of inorganic materials that have melting point over 3000°C and are typically borides, carbides, and nitrides of early transition metals. UHTCs are considered as the promising candidate used in the extreme environment involved with the hypersonic aviation thermal protective system. Synthesis of UHTCâbased materials can be divided into solidâbased and solutionâbased protocols according to the state of the raw materials. A solâgel technique is one of the solutionâbased protocols for the preparation of UHTCâbased materials, which involves the hydrolysis, condensation of the metal organic and/or metal inorganic compounds, gelation, and the posthigh temperature treatment of the dried gels. The solâgel technique enables the synthesis of UHTCâbased materials at 1300â1600°C. UHTCâbased materials with desired shapes, such as nanopowders, fibers, and porous monoliths, can also be prepared via solâgel routes
M2I-1 disrupts the in vivo interaction between CDC20 and MAD2 and increases the sensitivities of cancer cell lines to anti-mitotic drugs via MCL-1s
Background
Drugs such as taxanes, epothilones, and vinca alkaloids are widely used in the treatment of breast, ovarian, and lung cancers but come with major side effects such as neuropathy and loss of neutrophils and as single agents have a lack of efficacy. M2I-1 (MAD2 inhibitor-1) has been shown to disrupt the CDC20-MAD2 interaction, and consequently, the assembly of the mitotic checkpoint complex (MCC).
Results
We report here that M2I-1 can significantly increase the sensitivity of several cancer cell lines to anti-mitotic drugs, with cell death occurring after a prolonged mitotic arrest. In the presence of nocodazole or taxol combined with M2I-1 cell death is triggered by the premature degradation of Cyclin B1, the perturbation of the microtubule network, and an increase in the level of the pro-apoptotic protein MCL-1s combined with a marginal increase in the level of NOXA. The elevated level of MCL-1s and the marginally increased NOXA antagonized the increased level of MCL-1, a pro-survival protein of the Bcl-2 family.
Conclusion
Our results provide some important molecular mechanisms for understanding the relationship between the mitotic checkpoint and programmed cell death and demonstrate that M2I-1 exhibits antitumor activity in the presence of current anti-mitotic drugs such as taxol and nocodazole and has the potential to be developed as an anticancer agent
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