Evaluation of Pre-Analytical Factors of Urine Samples for Urine Cancer Cell Cultures (UCCC) --A Non-Invasive Biomarker – in Monitoring Response and Recurrence of Bladder Cancer

尿癌细胞培养 (UCCC) 尿液样本分析前因素的评估——一种非侵入性生物标志物 — 用于监测膀胱癌的反​​应和复发

• 批准号: 10640606
• 负责人: Xuefeng Liu
• 金额: $ 36.03万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-06 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10640606
• 关键词: Address; Affect; Antibiotics; Antibody-drug conjugates; Biological Markers; Bladder; Cancer Center; Cancer Detection; Cancer Patient; Cell Count; Cell Culture System; Cell Culture Techniques; Cell Survival; Cell model; Cells; Clinic; Clinical; Clinical Treatment; Clinical Trials; Coculture Techniques; Collection; Conditioned Culture Media; Cystoscopy; Data; Development; Diagnosis; Early Diagnosis; Epithelial Cell Proliferation; European; Evaluation; FDA approved; Freezing; Funding; Future; General Anesthesia; Goals; Health Personnel; Hypoxia; Immunotherapy; Intravesical Instillation; Laboratories; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Medical; Methods; Modeling; Monitor; Monitoring for Recurrence; Needle biopsy procedure; Non-Invasive Detection; Operative Surgical Procedures; Patients; Persons; Pharmacotherapy; Procedures; Prognosis; Proteins; Protocols documentation; Recurrence; Recurrent Malignant Neoplasm; Recurrent tumor; Relapse; Sampling; Specimen; Specimen Handling; Standardization; System; Technology; Temperature; Testing; Therapeutic Agents; Time; Tissues; Transportation; Transurethral Resection; Treatment outcome; Urine; Urology; Variant; Work; X-Ray Computed Tomography; cancer cell; cancer recurrence; cancer type; chemotherapy; clinical application; clinical assay development; clinically relevant; contextual factors; cost; drinking water; drug sensitivity; evidence base; high risk; improved; invention; liquid biopsy; member; mortality; patient response; predicting response; protein kinase inhibitor; response; rho; sample collection; success; targeted treatment; tumor progression

PROJECT SUMMARY Bladder cancer is one of the top 10 most frequent cancers, yet the most underfunded cancer by NCI based on funding dollars and ratio of funding/mortality. There has been no significant improvement in overall survival and prognosis over the last thirty years except for the recent development of immunotherapy. After initial diagnosis and treatment, over 60% of the BC patients will relapse within two years and progression into advanced stages in up to 25% of patients. Therefore, almost all patients will need long-term expensive cystoscopy which makes bladder cancer the costliest cancer (per case) of all cancer types. If a sensitive but less expensive method to detect cancer were available, it would improve the treatment outcomes and decrease the cost. Dr. Xuefeng Liu (PI) and his team recently invented a robust method of conditional reprogramming (CR) technology to establish patient-derived cell models from cystoscopy or needle biopsies and urine samples of BC patients. The overall success rate was near 100%. These urine cancer cell cultures (UCCC) provide a simple, non-invasive, comfortable, reliable method to detect BC recurrence, and represent a living biomarker to predict patients’ response to chemotherapy and targeted therapy. Several cancer centers and laboratories including PI’s lab are actively involved in clinical trials to validate clinical utility of the UCCC in BC clinics. Since a variety of patient- context and collection, storage and transportation of urine samples to laboratories for cell cultures affect enrichment and viability of cancer cells in urine samples, it is urgent needed to evaluate pre-analytical factors of urine samples for UCCC and optimize these non-Invasive and living liquid biopsies as a routine approach in monitoring recurrence and prediction of response of BC patients. In this application, we propose to address the gaps by extending the work done by our team members on evaluating effects of sample processing protocols on UCCC analysis, to further investigate effect of patient-specific context. In this application, we will first further optimization of UCCC system to establish a culture kit for clinical applications, specifically we will optimize and simplify conditions with co-culture kits, conditioned medium (CM), hypoxic condition for maximal efficiency and robustness. Second, we will establish a Standard of Procedure - SOP- for urine collection and transportation in clinics: we will test pH, temperatures, minimal cell number, a cocktail with anti-biotics and Y-27632 affect UCCC cultures and success rate. Last, we will determine patient-context factors that affect UCCC cultures: we will evaluate how urine timing (days before surgery, and after surgery, early morning, noon, night, drinking water before urine collection, etc), urine volume affect cell viability and UCCC. Last, we will optimize a self- sampling procedures for BC patients. The overall goal is to expedite UCCC clinical assay development through evidence-based standardization of urine collection and handling practices, potentially approved by FDA as a standard method for bladder clinics.

项目概要 膀胱癌是最常见的 10 种癌症之一，也是 NCI 资助最不足的癌症 资助金额和资助/死亡率比率 总体生存率和死亡率没有显着改善。 除了免疫疗法的最新发展之外，过去三十年的预后在初步诊断后。 超过60%的BC患者会在两年内复发并进展至晚期 高达25%的患者因此几乎所有患者都需要长期昂贵的膀胱镜检查。 如果是一种敏感但较便宜的方法，膀胱癌是所有癌症类型中成本最高的癌症（每例）。 检测癌症是可行的，这将改善治疗效果并降低费用。 （PI）和他的团队最近发明了一种强大的条件重编程（CR）技术方法来建立 来自膀胱镜检查或针吸活检以及 BC 患者尿液样本的患者来源的细胞模型。 这些尿液癌细胞培养 (UCCC) 提供了一种简单、非侵入性的方法，成功率接近 100%。 舒适、可靠的方法来检测 BC 复发，并代表预测患者病情的活生物标志物 一些癌症中心和实验室（包括 PI 实验室）对化疗和靶向治疗的反应。 积极参与临床试验，以验证 UCCC 在 BC 诊所中的临床实用性。 尿液样本的收集、储存和运输到实验室进行细胞培养会影响 尿液样本中癌细胞的富集和活力，迫切需要评估分析前因素 UCCC 的尿液样本，并优化这些非侵入性活体液体活检作为常规方法 BC 患者的复发监测和反应预测在本应用中，我们建议解决以下问题。 通过扩展我们的团队成员在评估样品处理方案的效果方面所做的工作来弥补差距 UCCC 分析，以进一步研究患者特定背景的影响。在此应用中，我们将首先进一步研究。 优化UCCC系统，建立临床应用的培养试剂盒，具体我们将优化和 使用共培养套件、条件培养基 (CM)、低氧条件简化条件，以实现最大效率和 其次，我们将制定尿液收集和运输的程序标准（SOP）。 诊所：我们将测试 pH、温度、最小细胞数量、抗生素混合物和 Y-27632 的影响 最后，我们将确定影响 UCCC 培养的患者背景因素：我们。 将评估排尿时间（手术前几天、手术后、清晨、中午、晚上、饮酒 尿液收集前的水等），尿量影响细胞活力和 UCCC 最后，我们将优化自我。 BC 患者的采样程序是通过加速 UCCC 临床检测的开发。 基于证据的尿液收集和处理实践标准化，可能被 FDA 批准为 膀胱诊所的标准方法。