Early Detection and Intervention of Surgery-Induced Lymphatic Insufficiency

项目摘要 淋巴循环功能不全，临床表现为水肿，是最常见的术后 乳腺癌患者的手术并发症，并显着损害他们的生活质量。 乳腺癌相关性水肿是由淋巴结阻塞引起的 为肿瘤分期和预后进行的解剖，以及癌症的术后放射治疗 治疗受损的细胞不能正确地运输组织间液、免疫细胞和组织 周转分子，所有这些都积累在受影响的地区，最终导致毁容， 疼痛的组织肿胀。据报道，乳腺癌相关性水肿的发病率从6%到10%不等。 到50%，取决于手术类型，后续治疗，肥胖和切除的淋巴结数量 结重要的是，随着乳腺癌生存率的逐年提高，预计会有更多的患者 患上了水肿病目前在管理乳腺癌相关疾病方面的挑战 水肿包括缺乏标准化的诊断标准，临床发病不可预测， 症状，以及缺乏有效的治疗方法，解决潜在的分子病因， 物理压缩这项研究的目的是确定一个分子迹象的发展水肿 可以在临床症状出现之前准确预测和诊断淋巴功能不全。 我们建议将受影响组织中的局部游离透明质酸含量作为生物特征 这不仅有助于建立标准化的诊断标准，而且还可以预测是否以及何时 疾病发生。此外，为了进一步扩展我们最近的研究， 维甲酸（RA）在淋巴再生和水肿中的功效，我们旨在优化和 改善类风湿关节炎的治疗方案，以帮助治疗水肿。通过创新性地将 透明质酸辅助的早期检测和基于RA的分子治疗，我们的目标是开发一个原型 乳腺癌相关性水肿的早期干预体系，并建立实验性 为游离透明质酸作为生物标志物和RA作为治疗药物的潜在未来临床应用奠定了基础 用于治疗人水肿患者的药物。

PROJECT SUMMARY Lymphatic circulation insufficiency, clinically manifested as lymphedema, is the most common post- operative complication among breast cancer patients and significantly compromises their quality of life. Breast cancer-associated lymphedema is caused by lymphatic obstruction due to lymph node dissection performed for tumor staging and prognosis, and post-operative irradiation therapy for cancer treatment. Damaged lymphatics fail to properly transport interstitial fluids, immune cells and tissue turnover molecules, all of which accumulate in the affected area, eventually causing a disfiguring and painful tissue swelling. Reported incidence of breast cancer-associated lymphedema ranges from 6% to 50%, depending on surgery types, follow-up treatments, obesity and number of resected lymph nodes. Importantly, as the breast cancer survival rate increases each year, more patients are expected to develop and suffer from lymphedema. Current challenges in managing breast cancer-related lymphedema include the lack of standardized diagnostic criteria, unpredictable onset of clinical symptoms, and the lack of effective treatments addressing the underlying molecular etiology other than physical compression. The goal of this study is to identify a molecular sign of developing lymphedema that can precisely predict and diagnose lymphatic insufficiency before the clinical symptoms appear. We propose to characterize the local free hyaluronan content in the affected tissues as a bio-signature that will not only help to set up standardized diagnostic criteria, but also to predict whether and when the disease occurs. In addition, to further extend our recent study demonstrating the therapeutic efficacy of retinoic acids (RAs) in lymphatic regeneration and lymphedema, we aim to optimize and improve the therapeutic protocol of RA to help treat lymphedema. By innovatively combining the hyaluronan-assisted early detection and RA-based molecular therapies, we aim to develop a prototype early intervention system against breast cancer-related lymphedema, and to establish an experimental foundation for potential future clinical use of free hyaluronan as a biomarker and RAs as therapeutic agents to treat human lymphedema patients.