Although there are many patients with brain tumors worldwide, there are numerous difficulties in overcoming brain tumors. Among brain tumors, glioblastoma, with a 5-year survival rate of 5.1%, is the most malignant. In addition to surgical operations, chemotherapy and radiotherapy are generally performed, but the patients have very limited options. Temozolomide is the most commonly prescribed drug for patients with glioblastoma. However, it is difficult to completely remove the tumor with this drug alone. Therefore, it is necessary to discuss the potential of anticancer drugs, other than temozolomide, against glioblastomas. Since the discovery of cisplatin, platinum-based drugs have become one of the leading chemotherapeutic drugs. Although many studies have reported the efficacy of platinum-based anticancer drugs against various carcinomas, studies on their effectiveness against brain tumors are insufficient. In this review, we elucidated the anticancer effects and advantages of platinum-based drugs used in brain tumors. In addition, the cases and limitations of the clinical application of platinum-based drugs are summarized. As a solution to overcome these obstacles, we emphasized the potential of a novel approach to increase the effectiveness of platinum-based drugs.

Cranial irradiation is the main therapeutic strategy for treating primary and metastatic brain tumors. However, radiation is well-known to induce several unexpected side effects including emotional disorders. Although radiation-induced depression may cause decreased quality of life after radiotherapy, investigations of its molecular mechanism and therapeutic strategies are still insufficient. In this study, we found that behavioral symptoms of depression on mice models with the decrease of BrdU/NeuN- and Dcx-positive populations and MAP-2 expression in hippocampus were induced by cranial irradiation, and transthyretin (TTR) was highly expressed in hippocampus after irradiation. It was shown that overexpression of TTR resulted in the inhibition of retinol-mediated neuritogenesis. PAK1 phosphorylation and MAP-2 expression were significantly reduced by TTR overexpression following irradiation. Moreover, we observed that treatment of allantoin and neferine, the active components of Nelumbo nucifera, interrupted irradiation-induced TTR overexpression, consequently leading to the increase of PAK1 phosphorylation, neurite extension, BrdU/NeuN- and Dcx-positive populations, and MAP-2 expression. Behavioral symptoms of depression following cranial irradiation were also relieved by treatment of allantoin and neferine. These findings demonstrate that TTR plays a critical role in neurogenesis after irradiation, and allantoin and neferine could be potential drug candidates for recovering the effects of radiation on neurogenesis and depression.

Purpose: Hyperthermia (HT), a clinical treatment involving delivery of heat to tumors, has been used in combination with traditional chemotherapy and radiotherapy to enhance their effects. However, the molecular mechanism underlying the high efficacy of combination therapy is not clear. This study was conducted to identify the molecular mechanism underlying the sensitization of lung cancer to radiotherapy by HT. Materials and methods: Nuclear receptor subfamily 4, group A, member 3 (NR4A3) and Krüppel-like factor 11 (KLF11) expression in non-small-cell lung cancer cells was confirmed by performing real-time quantitative reverse transcription–polymerase chain reaction. Tumor cell proliferation and apoptosis were assessed via a colony-forming assay and Annexin V/propidium iodide staining. Results and conclusions: Expression profile analysis revealed elevated levels of NR4A3 and KLF11 in A549 lung cancer cells after treatment with HT combined with radiation. We also confirmed that NR4A3 and KLF11 induced apoptosis and inhibited cell proliferation by elevating intracellular reactive oxygen species levels. Knockdown of NR4A3 or KLF11 using siRNA led to decreased effects of radiohyperthermia. Finally, the effect of these two factors on lung cancer progression was evaluated by in vivo xenograft studies. Taken together, the results suggest that NR4A3 and KLF11 are critical for increasing the efficacy of radiotherapy in combination with HT.