Introduction: Collaborative interactions between several diverse biological processes govern the onset and progression of breast cancer. These processes include alterations in cellular metabolism, anti-tumor immune responses, DNA damage repair, proliferation, anti-apoptotic signals, autophagy, epithelial-mesenchymal transition, components of the non-coding genome or onco-mIRs, cancer stem cells and cellular invasiveness. The last two decades have revealed that each of these processes are also directly regulated by a component of the cell cycle apparatus, cyclin D1.
Area covered: The current review is provided to update recent developments in the clinical application of cyclin/CDK inhibitors to breast cancer with a focus on the anti-tumor immune response.
Expert opinion: The cyclin D1 gene encodes the regulatory subunit of a proline-directed serine-threonine kinase that phosphorylates several substrates. CDKs possess phosphorylation site selectivity, with the phosphate-acceptor residue preceding a proline. Several important proteins are substrates including all three retinoblastoma proteins, NRF1, GCN5, and FOXM1. Over 280 cyclin D3/CDK6 substrates have b\een identified. Given the diversity of substrates for cyclin/CDKs, and the altered thresholds for substrate phosphorylation that occurs during the cell cycle, it is exciting that small molecular inhibitors targeting cyclin D/CDK activity have encouraging results in specific tumors. 相似文献
IntroductionThe continuous deployments of polio resources, infrastructures and systems for responding to other disease outbreaks in many African countries has led to a number of lessons considered as best practice that need to be documented for strengthening preparedness and response activities in future outbreaks.MethodsWe reviewed and documented the influence of polio best practices in outbreak preparedness and response in Angola, Nigeria and Ethiopia. Data from relevant programmes of the WHO African Region were also analyzed to demonstrate clearly the relative contributions of PEI resources and infrastructure to effective disease outbreak preparedness and response.ResultsPolio resources including, human, financial, and logistic, tool and strategies have tremendously contributed to responding to diseases outbreaks across the African region. In Angola, Nigeria and Ethiopia, many disease epidemics including Marburg Hemorrhagic fever, Dengue fever, Ebola Virus Diseases (EVD), Measles, Anthrax and Shigella have been controlled using existing polio Eradication Initiatives resources. Polio staffs are usually deployed in occasions to supports outbreak response activities (coordination, surveillance, contact tracing, case investigation, finance, data management, etc.). Polio logistics such vehicles, laboratories were also used in the response activities to other infectious diseases. Many polio tools including micro planning, dashboard, guidelines, SOPs on preparedness and response have also benefited to other epidemic-prone diseases. The Countries’ preparedness and response plan to WPV importation as well as the Polio Emergency Operation Center models were successfully used to develop, strengthen and respond to many other diseases outbreak with the implication of partners and the strong leadership and ownership of governments. This review has important implications for WHO/AFRO initiative to strengthening and improving disease outbreak preparedness and responses in the African Region in respect to the international health regulations core capacities. 相似文献
Problem: The Leaders in Indigenous Medical Education (LIME) Network aims to improve the quality and effectiveness of Indigenous health in medical education as well as best practice in the recruitment, retention, and graduation of Indigenous medical students. Intervention: In this article we explore the utility of Etienne Wenger's “communities of practice” (CoP) concept in providing a theoretical framework to better understand the LIME Network as a form of social infrastructure to further knowledge and innovation in this important area of health care education reform. Context: The Network operates across all medical schools in Australia and New Zealand. Outcome: Utilizing a model of evaluation of communities of practice developed by Fung-Kee-Fung et al., we seek to analyze the outcomes of the LIME Network as a CoP and assess its approach and contribution to improving the implementation of Indigenous health in the medical curriculum and the graduation of Indigenous medical students. Lessons Learned: By reflecting on the Network through a community of practice lens, this article highlights the synthesis between the LIME Network and Wenger's theory and provides a framework with which to measure Network outputs. It also posits an opportunity to better capture the impact of Network activities into the future to ensure that it remains a relevant and sustainable entity. 相似文献
To investigate primary care physician clinical practice patterns, barriers, and education surrounding pediatric physical activity (PA), and to compare practice patterns by discipline. 相似文献