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  • Online Resource  (2)
  • American Association for Cancer Research (AACR)  (2)
  • Brigman, Brian E.  (2)
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  • Online Resource  (2)
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  • American Association for Cancer Research (AACR)  (2)
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  • 1
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2020
    In:  Molecular Cancer Therapeutics Vol. 19, No. 7 ( 2020-07-01), p. 1448-1461
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 19, No. 7 ( 2020-07-01), p. 1448-1461
    Abstract: Therapeutic advances for osteosarcoma have stagnated over the past several decades, leading to an unmet clinical need for patients. The purpose of this study was to develop a novel therapy for osteosarcoma by reformulating and validating niclosamide, an established anthelminthic agent, as a niclosamide stearate prodrug therapeutic (NSPT). We sought to improve the low and inefficient clinical bioavailability of oral dosing, especially for the relatively hydrophobic classes of anticancer drugs. Nanoparticles were fabricated by rapid solvent shifting and verified using dynamic light scattering and UV-vis spectrophotometry. NSPT efficacy was then studied in vitro for cell viability, cell proliferation, and intracellular signaling by Western blot analysis; ex vivo pulmonary metastatic assay model; and in vivo pharmacokinetic and lung mouse metastatic model of osteosarcoma. NSPT formulation stabilizes niclosamide stearate against hydrolysis and delays enzymolysis; increases circulation in vivo with t1/2 approximately 5 hours; reduces cell viability and cell proliferation in human and canine osteosarcoma cells in vitro at 0.2–2 μmol/L IC50; inhibits recognized growth pathways and induces apoptosis at 20 μmol/L; eliminates metastatic lesions in the ex vivo lung metastatic model; and when injected intravenously at 50 mg/kg weekly, it prevents metastatic spread in the lungs in a mouse model of osteosarcoma over 30 days. In conclusion, niclosamide was optimized for preclinical drug delivery as a unique prodrug nanoparticle injected intravenously at 50 mg/kg (1.9 mmol/L). This increased bioavailability of niclosamide in the blood stream prevented metastatic disease in the mouse. This chemotherapeutic strategy is now ready for canine trials, and if successful, will be targeted for human trials in patients with osteosarcoma.
    Type of Medium: Online Resource
    ISSN: 1535-7163 , 1538-8514
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2062135-8
    SSG: 12
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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 4316-4316
    Abstract: Limb-sparing surgery for extremity soft tissue sarcoma removes all cancer cells at the primary tumor site in the majority of patients. However, without radiation therapy, microscopic residual sarcoma cells left behind in the tumor bed will cause a tumor recurrence in approximately one-third of patients. Therefore, adjuvant radiation therapy is delivered to most patients, even when the tumor bed lacks residual cancer. Here, we present an imaging system for residual cancer assessment, consisting of a novel wide field-of-view imaging device and a protease-activated fluorescent probe. We demonstrate that this system directly images microscopic residual sarcoma cells in the tumor bed of mice when primary soft tissue sarcomas are resected. Moreover, this system can detect single tumor cells that have activated the fluorescent probe in vivo. This technology has the potential to be used as an intra-operative tool to identify microscopic residual disease for soft tissue sarcoma and other cancers with the goal of reducing rates of local recurrence, re-operation for positive margins, and adjuvant radiation therapy to tumor beds that lack residual cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4316.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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