Dynamic microtubules are necessary for proper mitotic spindle assembly and chromosome segregation during mitosis. Members of the kinesin superfamily of molecular motor proteins are important to spindle function. Of particular interest is the Kinesin-13 family member MCAK, which acts to regulate microtubule dynamics during spindle assembly and to ensure proper attachments of chromosomes to spindle microtubules. The unique ability of MCAK to regulate microtubule dynamics makes it a potential target for development of new drugs that alter spindle function. Here, we knocked down MCAK via RNAi in normal and malignant cell lines and found that the two tested malignant cell lines were acutely sensitive to MCAK knockdown, while the tested normal cells were less sensitive. In addition, we looked at the effect of combining MCAK knockdown and drug treatment with paclitaxel or vinblastine to identify spindle assembly defects. We found that MCAK knockdown increased the morphological defects of the microtubule cytoskeleton in HeLa cells caused by anti-microtubule drugs. Our studies support the idea that MCAK would be a good target for new chemotherapeutic development and may be particularly useful in combination therapies with currently available anti-microtubule agents.
Less than 10% of the narratives were related to DDPC, but the majority was positive. There was a significant overlap in professionalism themes between DDPC and control narratives. The results suggest student preparedness for primary palliative care may be improved by addressing the common professionalism challenges of clinical clerkships.
Advanced cancer patients who provide less optimistic estimates of life expectancy have increased anxiety and depression, but do not use chemotherapy more often. Increased patient trait hope is associated with more favorable oncologist estimates. These findings highlight the need for interventions to support both patients and oncologists as they clarify prognostic expectations and patients cope with the psychological distress of a limited life expectancy.
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