Browsing by Author "Lin, Ka Wai"

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    Insulin Signaling & Hypoxic Response in Brain Cancer
    (2015-12-14) Lin, Ka Wai; Qutub, Amina A
    Glioblastoma patient survival rate has stagnated for the past 30 years, with median survival time less than 1 year. Only 20% of the young (0-19 years old) glioblastoma patients survive past 5 years, and this number drops to just less than 5% for patients above 40 years old. Due to poor survival rate of glioblastoma patients, there is a pressing need to develop more effective treatment methods. In this project, we investigated the effects of the insulin signaling pathway on the glioblastoma growth. Glioblastoma growth has been shown to be promoted by three key molecular signaling factors: IGFI, IGFBP2 and HIF1α. We used both the current literature data and our own experimental data to understand the interactions between these molecular factors on glioblastoma growth via a mathematical model. The model predicted that the activation of HIF1α by IGFBP2 is a crucial driver in the glioblastoma growth. We then used in vitro experiments to validate the findings of the model, and to further explore the response of glioblastoma progression by the stimulation of IGFBP2 and IGFI. This research demonstrates how IGFI and IGFBP2 influence glioblastoma growth, and suggest that future research should investigate the effects of both IGFI and IGFBP2 to control the glioblastoma progression system as a whole.
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    Simulation Predicts IGFBP2-HIF1α Interaction Drives Glioblastoma Growth
    (Public Library of Science, 2015) Lin, Ka Wai; Liao, Angela; Qutub, Amina A.
    Tremendous strides have been made in improving patients’ survival from cancer with one glaring exception: brain cancer. Glioblastoma is the most common, aggressive and highly malignant type of primary brain tumor. The average overall survival remains less than 1 year. Notably, cancer patients with obesity and diabetes have worse outcomes and accelerated progression of glioblastoma. The root cause of this accelerated progression has been hypothesized to involve the insulin signaling pathway. However, while the process of invasive glioblastoma progression has been extensively studied macroscopically, it has not yet been well characterized with regards to intracellular insulin signaling. In this study we connect for the first time microscale insulin signaling activity with macroscale glioblastoma growth through the use of computational modeling. Results of the model suggest a novel observation: feedback from IGFBP2 to HIF1α is integral to the sustained growth of glioblastoma. Our study suggests that downstream signaling from IGFI to HIF1α, which has been the target of many insulin signaling drugs in clinical trials, plays a smaller role in overall tumor growth. These predictions strongly suggest redirecting the focus of glioma drug candidates on controlling the feedback between IGFBP2 and HIF1α.