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  • EphB appears to be a

    2020-01-14

    EphB4 appears to be a low-affinity receptor for rhEpo based on the biochemical data. The concentration of rhEpo used for the biological experiments (50 IU/ml) corresponds to 10–15 nM, which is 1% to 2% of the KD value (KD = 881 nM) for the binding of rhEpo to EphB4, as measured in the MST assay. These data suggest that as a relatively low-affinity binding event, interaction between rhEpo and EphB4 is a pharmacologically efficient process. Other ligand-receptor systems that display similar phenomena have been reported previously (Authier and Desbuquois, 2008, Hutchinson et al., 2003, Mason and Tager, 1985). Whether EphB4 exists as a dimer in cancer apexbio chemicals is not known and will require additional work. Our findings can also be extrapolated to the mechanism by which Epo could potentially induce neovascularization in normal organs (Davies et al., 2009, Salvucci et al., 2006), a process also regulated by EphB4.
    Experimental Procedures
    Author Contributions
    Conflicts of Interest
    Acknowledgments We thank Carmen Cruz, Cristina Castro, and Belisa Suarez for the collection of breast tumor samples and data. We also thank Dr. Rene Nieves Alicea, Dr. Mario Quintero, Nicholas Jennings, Donna Reynolds, Francesca Diella, Drs. Ramos, and Bharat B. Aggarwal for helpful discussion and guidance and Rahul Mitra for admistrative assistance. Portions of this work were supported by Molecular Health, the NIH (CA 109298, P50 CA083639, P50 CA098258, CA 177909, U54CA151668, UH2 TR000943, CA 16672, and U54 CA 096300), the Ovarian Cancer Research Fund (Program Project Development Grant), the DOD (OC 120547 and OC 093416), CPRIT (RP110595 and RPI 20214), the RGK Foundation, the Gilder Foundation, the Judi A. Rees Ovarian Cancer Research Fund, the Chapman Foundation, the Blanton-Davis Ovarian Cancer Research Program, and the Betty Anne Asche Murray Distinguished Professorship. A.M.N., B.Z., R.L.S., R.A.P., J.M.H., and H.J.D. were supported by NCI-DHHS-NIH T32 Training Grant (T32 CA101642). K.M. was supported by the GCF/OCRF Ann Schreiber Ovarian Cancer Research grant and an award from the Meyer and Ida Gordon Foundation #2. L.J.S. and J.E.L. were supported by the G. Harold and Leila Y. Mathers Charitable Foundation. S.Y.W. was supported by the Ovarian Cancer Research Fund, the Foundation for Women’s Cancer, and Cancer Prevention Research Institute of Texas training grants (RP101502, RP101489, and RP110595).
    Introduction Photothermal therapy (PTT) employs photo-absorbing agents to generate heat from optical energy, leading to the ‘burning’ of tumor cells [1]. Recently, PTT has aroused widespread interest for the following reasons: 1) PTT presents a minimally invasive treatment of cancer; 2) unlike chemotherapy, PTT has the advantage of killing cancer cells without causing resistance regardless of the genetic background, and thus can be applied to all cancer patients [2]. Near infrared (NIR) light, as a photosource, has been used widely in PTT, because it has a deeper penetration inside the body and causes less damage comparing to a shorter wavelength light to tissues. A large number of nanomaterials, including various gold-based nanomaterials with strong optical absorbance in the NIR tissue transparency window, have been proposed as photo-absorbing agents for PTT treatment of cancer [3], [4], [5], [6], [7], [8], [9], [10]. Recently, we synthesized a class of gold nanoparticles, hollow gold nanospheres (HAuNS), which have plasmon absorption in NIR region and display a strong photothermal conducting property. We employed HAuNS as a photothermal agent for PTT of cancer [11], [12], and as a delivery vehicle to shuttle biomolecules or to trigger drug release under NIR light irradiation [12], [13], [14], [15], [16], [17]. For future use of PTT in clinic, real-time imaging of in vivo distribution of photothermal agents and monitoring of post-treatment therapeutic outcomes are very important to design and optimize personalized PTT treatment [18], [19], which presents to ‘burn’ the tumors efficiently and avoid the damage of normal tissues around the tumors. Theranostic nanomedicine, which combines therapeutic and diagnostic functions in a single nanomaterial, has attracted increasing attention because of its potential to benefit patients by providing individualized treatment [20].