Ki-67 is required for maintenance of cancer stem cells but not cell proliferation.

Ki-67 expression is correlated with cell proliferation and is a prognostic marker for various cancers; however, its function is unknown. Here we demonstrate that genetic disruption of Ki-67 in human epithelial breast and colon cancer cells depletes the cancer stem cell niche. Ki-67 null cells had a proliferative disadvantage compared to wildtype controls in colony formation assays and displayed increased sensitivity to various chemotherapies. Ki-67 null cancer cells showed decreased and delayed tumor formation in xenograft assays, which was associated with a reduction in cancer stem cell markers. Immunohistochemical analyses of human breast cancers revealed that Ki-67 expression is maintained at equivalent or greater levels in metastatic sites of disease compared to matched primary tumors, suggesting that maintenance of Ki-67 expression is associated with metastatic/clonogenic potential. These results elucidate Ki-67's role in maintaining the cancer stem cell niche, which has potential diagnostic and therapeutic implications for human malignancies.

Knowledge, attitudes, and practices regarding dengue infection among public sector healthcare providers in Machala, Ecuador.

BACKGROUND: Dengue fever is a rapidly emerging infection throughout the tropics and subtropics with extensive public health burden. Adequate training of healthcare providers is crucial to reducing infection incidence through patient education and collaboration with public health authorities. We examined how public sector healthcare providers in a dengue-endemic region of Ecuador view and manage dengue infections, with a focus on the 2009 World Health Organization (WHO) Dengue Guidelines. METHODS: A 37-item questionnaire of dengue knowledge, attitudes, and practices was developed and administered to dengue healthcare providers in Machala, Ecuador. Survey focus areas included: "Demographics," "Infection and Prevention of Dengue," "Dengue Diagnosis and the WHO Dengue Guide," "Laboratory Testing," "Treatment of Dengue," and "Opinions Regarding Dengue." RESULTS: A total of 76 healthcare providers participated in this study, of which 82 % were medical doctors and 14 % were nurses. Fifty-eight percent of healthcare professionals practiced in ambulatory clinics and 34 % worked in a hospital. Eighty-nine percent of respondents were familiar with the 2009 WHO Dengue Guidelines, and, within that group, 97 % reported that the WHO Dengue Guide was helpful in dengue diagnosis and clinical management. Knowledge gaps identified included Aedes aegypti mosquito feeding habits and dengue epidemiology. Individuals with greater dengue-related knowledge were more likely to consider dengue a major health problem. Only 22 % of respondents correctly reported that patients with comorbidities and dengue without warning signs require hospital admission, and 25 % of providers reported never admitting patients with dengue to the hospital. Twenty percent of providers reported rarely (≤25 % of cases) obtaining laboratory confirmation of dengue infection. Providers reported patient presumptive self-medication as an ongoing problem. Thirty-one percent of healthcare providers reported inadequate access to resources needed to diagnose and treat dengue. CONCLUSION: Participants demonstrated a high level of knowledge of dengue symptoms and treatment, but additional training regarding prevention, diagnosis, and admission criteria is needed. Interventions should not only focus on increasing knowledge, but also encourage review of the WHO Dengue Guidelines, avoidance of presumptive self-medication, and recognition of dengue as a major health problem. This study provided an assessment tool that effectively captured healthcare providers' knowledge and identified critical gaps in practice.