Free Radical and Radiation Biology Program, B180 Medical Laboratories, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa 52242.
Radiat Res. 2023 Nov 1;200(5):456-461. doi: 10.1667/RADE-23-00006.1.
Diffuse intrinsic pontine gliomas (DIPG) are an aggressive type of pediatric brain tumor with a very high mortality rate. Surgery has a limited role given the tumor's location. Palliative radiation therapy alleviates symptoms and prolongs survival, but median survival remains less than 1 year. There is no clear role for chemotherapy in DIPGs as trials adding chemotherapy to palliative radiation therapy have failed to improve survival compared to radiation alone. Thus, there is a critical need to identify tissue-specific radiosensitizers to improve clinical outcomes for patients with DIPGs. Pharmacologic (high dose) ascorbate (P-AscH-) is a promising anticancer therapy that sensitizes human tumors, including adult high-grade gliomas, to radiation by acting selectively as a generator of hydrogen peroxide (H2O2) in cancer cells. In this study we demonstrate that in contrast to adult glioma models, P-AscH- does not radiosensitize DIPG. DIPG cells were sensitive to bolus of H2O2 but have faster H2O2 removal rates than GBM models which are radiosensitized by P-AscH-. These data support the hypothesis that P-AscH- does not enhance DIPG radiosensitivity, likely due to a robust capacity to detoxify and remove hydroperoxides.
弥漫性内在脑桥神经胶质瘤（DIPG）是一种具有极高死亡率的侵袭性儿童脑肿瘤。鉴于肿瘤的位置，手术的作用有限。姑息性放射治疗可以缓解症状并延长生存期，但中位生存期仍不到 1 年。化疗在 DIPG 中的作用并不明确，因为将化疗与姑息性放射治疗联合应用的试验并未提高生存率，与单独放射治疗相比。因此，迫切需要确定组织特异性放射增敏剂，以改善 DIPG 患者的临床预后。药物（高剂量）抗坏血酸（P-AscH-）是一种很有前途的抗癌疗法，它通过在癌细胞中选择性地充当过氧化氢（H2O2）的生成剂，使包括成人高级别神经胶质瘤在内的人类肿瘤对辐射敏感。在这项研究中，我们证明与成人神经胶质瘤模型相反，P-AscH-不会使 DIPG 放射增敏。DIPG 细胞对 H2O2 的爆发敏感，但比 GBM 模型清除 H2O2 的速度更快，而 P-AscH-可使 GBM 模型放射增敏。这些数据支持了这样的假设，即 P-AscH-不会增强 DIPG 的放射敏感性，可能是因为其具有强大的解毒和清除过氧化物的能力。
