Browsing by Author "Yu, Dihua"

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    Needle-based fluorescence endomicroscopy via structured illumination with a plastic, achromatic objective
    (Society of Photo-Optical Instrumentation Engineers, 2013-09) Kyrish, Matthew; Dobbs, Jessica; Jain, Shalini; Wang, Xiao; Yu, Dihua; Richards-Kortum, Rebecca; Tkaczyk, Tomasz S.
    In order to diagnose cancer, a sample must be removed, prepared, and examined under a microscope, which is expensive, invasive, and time consuming. Fiber optic fluorescence endomicroscopy, where an image guide is used to obtain high-resolution images of tissue in vivo, has shown promise as an alternative to conventional biopsies. However, the resolution of standard endomicroscopy is limited by the fiber bundle sampling frequency and out-of-focus light. A system is presented which incorporates a plastic, achromatic objective to increase the sampling and which provides optical sectioning via structured illumination to reject background light. An image is relayed from the sample by a fiber bundle with the custom 2.1-mm outer diameter objective lens integrated to the distal tip. The objective is corrected for the excitation and the emission wavelengths of proflavine (452 and 515 nm). It magnifies the object onto the fiber bundle to improve the systemﾒs lateral resolution by increasing the sampling. The plastic lenses were fabricated via single-point diamond turning and assembled using a zero alignment technique. Ex vivo images of normal and neoplastic murine mammary tissues stained with proflavine are captured. The system achieves higher contrast and resolves smaller features than standard fluorescence endomicroscopy.
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    Src Inhibition Blocks c-Myc Translation and Glucose Metabolism to Prevent the Development of Breast Cancer
    (AACR, 2015) Jain, Shalini; Wang, Xiao; Chang, Chia-Chi; Ibarra-Drendall, Catherine; Wang, Hai; Zhang, Qingling; Brady, Samuel W.; Li, Ping; Zhao, Hong; Dobbs, Jessica; Kyrish, Matt; Tkaczyk, Tomasz S.; Ambrose, Adrian; Sistrunk, Christopher; Arun, Banu K.; Richards-Kortum, Rebecca; Jia, Wei; Seewaldt, Victoria L.; Yu, Dihua
    Preventing breast cancer will require the development of targeted strategies that can effectively block disease progression. Tamoxifen and aromatase inhibitors are effective in addressing estrogen receptor–positive (ER+) breast cancer development, but estrogen receptor–negative (ER−) breast cancer remains an unmet challenge due to gaps in pathobiologic understanding. In this study, we used reverse-phase protein array to identify activation of Src kinase as an early signaling alteration in premalignant breast lesions of women who did not respond to tamoxifen, a widely used ER antagonist for hormonal therapy of breast cancer. Src kinase blockade with the small-molecule inhibitor saracatinib prevented the disorganized three-dimensional growth of ER− mammary epithelial cells in vitro and delayed the development of premalignant lesions and tumors in vivo in mouse models developing HER2+ and ER− mammary tumors, extending tumor-free and overall survival. Mechanistic investigations revealed that Src blockade reduced glucose metabolism as a result of an inhibition in ERK1/2–MNK1–eIF4E–mediated cap-dependent translation of c-Myc and transcription of the glucose transporter GLUT1, thereby limiting energy available for cell growth. Taken together, our results provide a sound rationale to target Src pathways in premalignant breast lesions to limit the development of breast cancers.