3-MA-induced mitotic cell death occurred through caspase-dependent apoptosis

Although the baculovirus can mediate gene transduction effectively and achieve desirable expression in various tumor cell lines in vitro, there are still some obstacles to overcome concerning the in vivo application of this system in gene therapy. For example, a major concern is the inactivation of baculovirus by the serum complement in baculovirus-based gene therapy in vivo. In previous studies, SDM25N hydrochloride extrathyroidal tissues are generally not able to organify iodide after NIS gene transfer. In the contrast, 131I accumulates and is organified in the thyroid, which exhibits competitive inhibition in extrathyroidal tumor 131I uptake, preventing the delivery of a radiation dose high enough to affect cell viability; therefore, the therapeutic efficacy of 131I is limited. The application of alternative radioisotopes that are also transported by hNIS with a shorter physical half-life and a high energy to 131I may provide a powerful method for enhancing the therapeutic efficacy of hNIS-targeted radionuclide therapy. 188Re is a b-emitting radionuclide with a short physical half-life that has been used in a variety of therapeutic applications in humans, including cancer radioimmunotherapy and palliation of skeletal bone pain. Due to its higher relative energy compared to 131I, administration of 188Re offers the possibility of higher energy deposition over a shorter time period. Compared to 131I, 188Re has been proposed as an ideal alternative emitter to 131I for cancer treatment. Kang et al investigated 188Re accumulation of a human hepatocellular carcinoma cell line, SK-Hep1, by transfer of human sodium iodide symporter gene and found it has the potential to be used in hepatocellular carcinoma management. To date, no studies have explored whether lentivirus-mediated hNIS gene expression and 188Re uptake can be used for glioma imaging and therapy. In this study, we investigated the role of 188Re as a potential alternative radionuclide for hNIS-mediated imaging and treatment of human glioma in model mice. Most gliomas are resistant to currently available ST 1936 oxalate chemotherapy regimens. Besides tumor resection, external radiotherapy is a major curative therapy for glioma. However, patients are often either not responsive to or suffer from side effects from these conventional therapies. Radionuclide-based theranostic strategies have been widely used in the diagnosis and treatment of patients with hyperthyroidism or differentiated thyroid cancer, and the sodium iodide symporter gene is the radionuclide-based reporter gene used in theranostics.

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