Development of a novel enzyme-targeting radiosensitizer (KORTUC) containing hydrogen peroxide for intratumoral injection for patients with low linear energy transfer-radioresistant neoplasms
Development of a novel enzyme-targeting radiosensitizer (KORTUC) containing hydrogen peroxide for intratumoral injection for patients with low linear energy transfer-radioresistant neoplasms
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DOI：
10.3892/ol.2010.184
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发表时间：
2010-11-01
期刊：
影响因子：
2.9
通讯作者：
Nshioka, Akihito
中科院分区：
文献类型：
--
作者：
Tokuhiro, Shiho;Ogawa, Yasuhiro;Nshioka, Akihito
对于直径数厘米以上的较大肿瘤，由于肿瘤细胞大量缺氧，且存在大量的过氧化物酶/过氧化氢酶等抗氧化酶，直线加速器放疗的治疗效果降低至三分之一。研究了将过氧化氢注入肿瘤组织的最有效方法。事实证明这很困难，因为 3% w/v 过氧化氢溶液 (Oxydol) 是一种皮肤损伤的防腐剂。因此，注射到受影响的病变部位可能会导致过氧化氢渗入体腔，可能导致动脉内氧栓塞。本研究旨在确定最有效的含过氧化氢药物组合，以缓解注射部位的局部疼痛并保持高瘤内氧浓度。透明质酸-过氧化氢被认为是最有效的含过氧化氢药物组合，可在瘤内注射该药物后 24 小时内保持高瘤内氧浓度。基于该研究结果，针对晚期乳腺癌、软组织肉瘤和颈部淋巴结转移等恶性肿瘤，启动了新型酶靶向放射增敏治疗——高知双氧水放射治疗不可切除癌（KORTUC）的临床应用。此外，我们还开发了用于局部晚期肝细胞癌的 KORTUC III 和用于局部晚期胰腺癌（IVa 期）的 KORTUC IV。
The therapeutic effect of radiotherapy using linear accelerators for relatively large tumors of more than several centimeters in diameter is reduced to one third due to a large number of hypoxic tumor cells and a significant amount of anti-oxidative enzymes including peroxidase/catalase. The most effective method by which to inject hydrogen peroxide into tumor tissue was examined. This proved difficult as 3% w/v hydrogen peroxide solution (Oxydol) is an antiseptic agent for skin lesions. Thus, injection into an affected lesion may result in hydrogen peroxide soaking into a body cavity, possibly causing an intra-arterial oxygen embolism. This study aimed to identify the most effective combination of drugs containing hydrogen peroxide in order to relieve local pain at the injection site and preserve high intratumoral oxygen concentration. Hyaluronate-hydrogen peroxide was identified as the most effective combination of drugs containing hydrogen peroxide for the preservation of high intratumoral oxygen concentration for 24 h following intratumoral injection with the agent. Based on the results, the clinical application of a novel enzyme-targeting radiosensitization treatment, Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas (KORTUC), was initiated for malignant tumors including advanced breast cancer, soft tissue sarcoma and cervical lymph node metastasis. Moreover, we have developed KORTUC III for locally advanced hepatocellular carcinoma and KORTUC IV for locally advanced pancreas cancer (stage IVa).