Targeting Folate Receptors to Treat Invasive Urinary Bladder Cancer
| Autor: | James F. Naughton, Nikki Parker, Lindsey M. Fourez, Ryan Rothenbuhler, Linda M. Murphy, Joseph A. Reddy, Liang Cheng, Christopher P. Leamon, Jane C. Stewart, José A. Ramos-Vara, Iontcho Radoslavov Vlahov, Philip S. Low, Michael O. Koch, Patrick J. Klein, Deborah W. Knapp, Deepika Dhawan |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Maximum Tolerated Dose Invasive urothelial carcinoma Urology Mice Nude Antineoplastic Agents Pilot Projects Biology Neutropenia Vinblastine Scintigraphy Mice Dogs Folic Acid Cell Line Tumor medicine Animals Humans Receptor Aged Aged 80 and over Carcinoma Transitional Cell Lung medicine.diagnostic_test Folate Receptors GPI-Anchored Middle Aged medicine.disease Disease Models Animal medicine.anatomical_structure Urinary Bladder Neoplasms Oncology Toxicity Immunohistochemistry Female medicine.drug |
| Zdroj: | Cancer Research. 73:875-884 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Folate receptors (FR) may be of use for targeted delivery of cytotoxic drugs in invasive urothelial carcinoma (iUC), for which improved therapy is needed. FR expression and function in iUC were explored and the antitumor activity and toxicity of a folate-targeted vinblastine conjugate were evaluated in dogs with naturally occurring iUC, an excellent model for human iUC. FR immunohistochemistry was carried out on iUC and normal human and dog bladder tissues together with nuclear scintigraphy in dogs to monitor iUC folate uptake. Dose escalation of a folate-targeted vinblastine compound, EC0905, was conducted in dogs with biopsy-confirmed, FR-positive iUC. FRs were detected by immunohistochemistry (PU17) in most primary iUC and many nodal and lung metastases from dogs, and scintigraphy confirmed folate uptake in both primary and metastatic lesions. The maximum tolerated dose of EC0905 in dogs was 0.25 mg/kg IV weekly, with neutropenia at higher doses. Tumor responses included partial remission (≥50% reduction in tumor volume) in five dogs and stable disease ( |
| Databáze: | OpenAIRE |
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