Browsing by Author "Sano, Daisuke"

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    Evolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer
    (AACR, 2015) Neskey, David M.; Osman, Abdullah A.; Ow, Thomas J.; Katsonis, Panagiotis; McDonald, Thomas; Hicks, Stephanie C.; Hsu, Teng-Kuei; Pickering, Curtis R.; Ward, Alexandra; Patel, Ameeta; Yordy, John S.; Skinner, Heath D.; Giri, Uma; Sano, Daisuke; Story, Michael D.; Beadle, Beth M.; El-Naggar, Adel K.; Kies, Merrill S.; William, William N.; Caulin, Carlos; Frederick, Mitchell; Kimmel, Marek; Myers, Jeffrey N.; Lichtarge, Olivier
    TP53 is the most frequently altered gene in head and neck squamous cell carcinoma, with mutations occurring in over two-thirds of cases, but the prognostic significance of these mutations remains elusive. In the current study, we evaluated a novel computational approach termed evolutionary action (EAp53) to stratify patients with tumors harboring TP53 mutations as high or low risk, and validated this system in both in vivo and in vitro models. Patients with high-risk TP53 mutations had the poorest survival outcomes and the shortest time to the development of distant metastases. Tumor cells expressing high-risk TP53 mutations were more invasive and tumorigenic and they exhibited a higher incidence of lung metastases. We also documented an association between the presence of high-risk mutations and decreased expression of TP53 target genes, highlighting key cellular pathways that are likely to be dysregulated by this subset of p53 mutations that confer particularly aggressive tumor behavior. Overall, our work validated EAp53 as a novel computational tool that may be useful in clinical prognosis of tumors harboring p53 mutations.
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    Noncovalent Assembly of Targeted Carbon Nanovectors Enables Synergistic Drug and Radiation Cancer Therapyﾠin Vivo
    (American Chemical Society, 2012) Sano, Daisuke; Berlin, Jacob M.; Pham, Tam T.; Marcano, Daniela C.; Valdecanas, David R.; Zhou, Ge; Milas, Luka; Myers, Jeffrey N.; Tour, James M.; Smalley Institute for Nanoscale Science and Technology
    Current chemotherapeutics are characterized by efficient tumor cell-killing and severe side effects mostly derived from off-target toxicity. Hence targeted delivery of these drugs to tumor cells is actively sought. In anﾠin vitroﾠsystem, we previously demonstrated that targeted drug delivery to cancer cells overexpressing epidermal growth factor receptor (EGFR+) can be achieved by poly(ethylene glycol)-functionalized carbon nanovectors simply mixed with a drug, paclitaxel, and an antibody that binds to the epidermal growth factor receptor, cetuximab. This construct is unusual in that all three components are assembled through noncovalent interactions. Here we show that this same construct is effectiveﾠin vivo, enhancing radiotherapy of EGFR+ tumors. This targeted nanovector system has the potential to be a new therapy for head and neck squamous cell carcinomas, deserving of further preclinical development.
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    Therapeutic compositions and methods for targeted delivery of active agents
    (2014-12-23) Tour, James M.; Berlin, Jacob; Pham, Tam; Myers, Jeffrey N.; Sano, Daisuke; Rice University; Board of Regents of the University of Texas System; United States Patent and Trademark Office
    The present invention pertains to therapeutic compositions that comprise: (1) a nanovector, (2) an active agent; and (3) a targeting agent, wherein the active agent and the targeting agent are non-covalently associated with the nanovector. The present invention also pertains to methods of treating various conditions in a subject by utilizing the above-described therapeutic compositions. Methods of making the therapeutic compositions are also a subject matter the present invention.