Health Disparities Across the Breast Cancer Continuum

OBJECTIVES: To provide a brief overview of disparities across the spectrum of breast cancer incidence, treatment, and long-term care during the survivorship period. DATA SOURCES: Review of the literature including research reports, review papers and clinically based papers available through PubMed and CINAHL. CONCLUSION: Minority women generally experience worse breast cancer outcomes despite a lower incidence of breast cancer than whites. A variety of factors contribute to this disparity, including advanced stage at diagnosis, higher rates of aggressive breast cancer subtypes, and lower receipt of appropriate therapies including surgery, chemotherapy, and radiation. Disparities in breast cancer care also extend into the survivorship trajectory, including lower rates of endocrine therapy use among some minority groups as well as differences in follow-up and survivorship care. IMPLICATIONS FOR NURSING PRACTICE: Breast cancer research should include improved minority representation and analyses by race and ethnicity and socioeconomic status. While we cannot yet change the biology of this disease, we can encourage adherence to screening and treatment and help address the many physical, psychological, spiritual and social issues minority women face in a culturally sensitive manner

Multi-Kinase Inhibitor C1 Triggers Mitotic Catastrophe of Glioma Stem Cells Mainly through MELK Kinase Inhibition

Glioblastoma multiforme (GBM) is a highly lethal brain tumor. Due to resistance to current therapies, patient prognosis remains poor and development of novel and effective GBM therapy is crucial. Glioma stem cells (GSCs) have gained attention as a therapeutic target in GBM due to their relative resistance to current therapies and potent tumor-initiating ability. Previously, we identified that the mitotic kinase maternal embryonic leucine-zipper kinase (MELK) is highly expressed in GBM tissues, specifically in GSCs, and its expression is inversely correlated with the post-surgical survival period of GBM patients. In addition, patient-derived GSCs depend on MELK for their survival and growth both in vitro and in vivo. Here, we demonstrate evidence that the role of MELK in the GSC survival is specifically dependent on its kinase activity. With in silico structure-based analysis for protein-compound interaction, we identified the small molecule Compound 1 (C1) is predicted to bind to the kinase-active site of MELK protein. Elimination of MELK kinase activity was confirmed by in vitro kinase assay in nano-molar concentrations. When patient-derived GSCs were treated with C1, they underwent mitotic arrest and subsequent cellular apoptosis in vitro, a phenotype identical to that observed with shRNA-mediated MELK knockdown. In addition, C1 treatment strongly induced tumor cell apoptosis in slice cultures of GBM surgical specimens and attenuated growth of mouse intracranial tumors derived from GSCs in a dose-dependent manner. Lastly, C1 treatment sensitizes GSCs to radiation treatment. Collectively, these data indicate that targeting MELK kinase activity is a promising approach to attenuate GBM growth by eliminating GSCs in tumors