Prevention of erectile dysfunction following prostate cancer radiotherapy

预防前列腺癌放射治疗后的勃起功能障碍

• 批准号: 8714389
• 负责人: MICHAEL D KAYTOR
• 金额: $ 22.49万
• 依托单位: HUMANETICS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2016-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8714389
• 关键词: Acute; Address; Advanced Development; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Biological; Biological Availability; C57L/J Mouse; Cancer Patient; Cancer Survivor; Cell Cycle; Chest; Clinical; Clinical Trials; Contracts; Data; Development; Diagnosis; Dose; Drug Formulations; Emotional; Ensure; Erectile dysfunction; Exhibits; Fibrosis; Funding; Future; Genistein; Goals; Hour; Inflammation; Inflammatory; Injury; Intervention; Lead; Left; Life; Link; Literature; Malignant Neoplasms; Malignant neoplasm of prostate; Medical; Modality; Modeling; Mus; Nerve; Nerve Tissue; Normal tissue morphology; Nude Mice; Oral; Oxidation-Reduction; Oxidative Stress; Oxidative Stress Pathway; Pathologic; Pathway interactions; Patients; Personal Satisfaction; Pharmacologic Substance; Phase; Physiological; Play; Prevention; Property; Prostate; Publishing; Radiation; Radiation Pneumonitis; Radiation induced damage; Radiation therapy; Radioprotection; Rattus; Rodent Model; Role; Sex Functioning; Sexual Health; Signal Transduction; Survival Rate; Suspension substance; Suspensions; Therapeutic; Tissues; Toxic effect; Treatment Efficacy; Tumor Pathology; Tumor Tissue; United States; base; cancer radiation therapy; commercialization; cytotoxicity; design; effective therapy; health related quality of life; improved; inflammatory marker; irradiation; men; novel; pre-clinical; prevent; prostate cancer model; psychologic; public health relevance; research study; response; social; tool; tumor; tumor growth; young man

DESCRIPTION (provided by applicant): The aim of this proposal is to evaluate BIO 300 as an effective therapy to prevent and/or mitigate the erectile dysfunction (ED) that is commonly observed following radiotherapy (RT) for prostate cancer. Prostate cancer is the most common cancer among men in the United States. Approximately half of prostate cancer patients will undergo RT as a part of their treatment. Even though 5 year survival rates are high (>99.2%), about half of the men who receive RT will develop ED within 5 years. Radiation-induced ED remains an unmet medical need that severely impacts the sexual health-related quality of life of cancer survivors, especially younger men. Significantly, possible loss of sexual function plays an important role in treatment-related decisions for men with prostate cancer. Humanetics Corporation is developing BIO 300 oral suspension to treat the delayed effects of acute radiation exposure (DEARE), including radiation-induced pneumonitis and fibrosis. BIO 300 has substantial radioprotective effects linked to its strong antioxidant and anti-inflammatory properties, and its effects on cell cycle division. A strong scientific rationale suggests that inflammation and oxidative stress are critica to development of RT-induced ED. Key biological targets of BIO 300 include redox signaling, inflammatory pathways, and oxidative stress pathways. In mice exposed to a lethal dose of thoracic irradiation, BIO 300 was shown to mitigate normal tissue injury and improve survival when treatment was started 24 hours after radiation and continued for just 14 days. These data support the hypothesis that BIO 300 will be equally effective at preventing RT-induced ED. The aims of this proposal are designed to provide scientific support for this hypothesis. The first aim will determine the therapeutic efficacy of BIO 300 in a model of RT-induced ED, using objective physiological endpoints and immunostaining for oxidative stress markers. The second aim will determine the effect of BIO 300 on tumor development in a rodent model of prostate cancer. Toward that goal, the RT-induced tumor growth delay and tumor pathology will be compared for animals treated with BIO 300 vs. those that do not receive BIO 300 therapy. The goal of this aim is to ensure that BIO 300 does not negatively interfere with RT directed at tumors. In actuality, based on a published literature, BIO 300 in combination with RT is expected to enhance tumor growth delay. If successful, these studies will advance the development of BIO 300 as a treatment option for RT-induced ED, and will positively impact cancer survivors living with ED as well as patients diagnosed with prostate cancer in the future.

描述（由申请人提供）： 该提案的目的是评估BIO 300作为预防和/或减轻勃起功能障碍（ED）的有效疗法，该勃起功能障碍（ED）通常在放疗（RT）（RT）治疗前列腺癌后观察到。前列腺癌是美国男性中最常见的癌症。大约一半的前列腺癌患者将接受RT作为治疗的一部分。即使5年的生存率很高（> 99.2％），但在5年内收到RT的男性中，大约有一半。辐射引起的ED仍然是未满足的医疗需求，严重影响了与性健康相关的癌症幸存者，尤其是年轻男性的生活质量。值得注意的是，性功能的可能丧失在前列腺癌男性的治疗相关决策中起着重要作用。人类材料公司正在开发生物300口服悬浮液，以治疗急性辐射暴露（Deare）的延迟作用，包括辐射诱发的肺炎和纤维化。生物300具有与其强抗氧化剂和抗炎特性以及其对细胞周期分裂的影响有关的实质性放射保护作用。强烈的科学原理表明，炎症和氧化应激是RT引起的ED发展的批评。生物300的关键生物学靶标包括氧化还原信号传导，炎症途径和氧化应激途径。在暴露于致命的胸腔照射的小鼠中，生物300被证明可减轻正常组织损伤并改善辐射后24小时开始治疗时的生存率，仅持续14天。这些数据支持以下假设：生物300在防止RT诱导的ED方面同样有效。该提案的目的旨在为这一假设提供科学支持。第一个目标 将使用客观的生理终点和氧化应激标记的免疫染色来确定BIO 300在RT诱导的ED模型中的治疗功效。第二个目标将确定生物300对前列腺癌模型中肿瘤发育的影响。为了实现这一目标，与未接受生物300治疗的动物相比，将比较RT诱导的肿瘤生长延迟和肿瘤病理学。此目的的目的是确保生物300不会对针对肿瘤的RT负面影响。实际上，根据已发表的文献，Bio 300与RT结合使用，预计将增强肿瘤生长延迟。如果成功的话，这些研究将推动BIO 300作为RT诱导的ED的治疗选择的发展，并将积极影响与ED的癌症幸存者以及未来诊断为前列腺癌的患者。