Project 2: Enhancing Efficacy of Gemcitabine Nanoparticles in Pancreatic PDX Models

项目2：增强吉西他滨纳米颗粒在胰腺PDX模型中的功效

• 批准号: 10006213
• 负责人: Jose G Trevino
• 金额: $ 10.37万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-17 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10006213
• 关键词: 3-Dimensional; Affect; Animal Model; Antineoplastic Agents; Biological; Biopsy; Blood; Breast; California; Cancer Etiology; Cancer Patient; Carcinoma; Caucasians; Cessation of life; Characteristics; Chemosensitization; Chemotherapy and/or radiation; Classification; Clinical; Clinical Trials; Colon; Cytidine Deaminase; DNA; Data; Detection; Diagnosis; Disease; Drug Delivery Systems; Drug Kinetics; Drug usage; Early Diagnosis; Education; Effectiveness; Enzymes; Epidermal Growth Factor Receptor; Erlotinib; Fc Receptor; Fingers; Florida; Fluorouracil; Genetic; Growth; Health; High Prevalence; Human; Hyaluronan; Hyaluronidase; Incidence; Individual; Investigation; Knowledge; Latino; Link; Liver; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of pancreas; Malignant neoplasm of prostate; Mediating; Methods; Molecular; Molecular Profiling; Mutation Analysis; Nature; Operative Surgical Procedures; Paclitaxel; Pancreas; Pathway interactions; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Play; Prostate; Publishing; RRM1 gene; Rectal Cancer; Regimen; Reporting; Resected; Resistance; Surface; Survival Rate; Symptoms; Testing; Therapeutic; Tissues; Translating; Treatment Efficacy; Underrepresented Minority; Woman; Xenograft Model; amino group; anticancer research; base; cancer cell; cancer diagnosis; cancer genome; cancer health disparity; capecitabine; chemotherapeutic agent; chemotherapy; cytotoxicity; design; experience; experimental study; gemcitabine; health equity; improved; in vitro activity; in vivo; malignant breast neoplasm; men; mortality; nanoparticle; neoplastic cell; novel anticancer drug; novel therapeutics; overexpression; pancreas xenograft; pancreatic cancer patients; pancreatic neoplasm; personalized approach; personalized therapeutic; response; screening; therapeutic target; therapy resistant; tool; treatment response; tripolyphosphate; tumor

PROJECT SUMMARY/ABSTRACT: FULL PROJECT 2 Pancreatic Cancer (PCa) is a devastating disease for all affected. Presently, PCa is the 3rd leading cause of cancer-related death in the U.S. The five-year overall survival rate is a dismal 7.2%. While PCa has not be recorded as a cancer health disparity, the data is quite alarming, for example, Blacks experience a higher prevalence of compared to their Whites. Moreover, Black men and women have the lowest overall survival rates of PCa. Interestingly, while many cancers have demonstrated a reduction in incidence over a 5-year period (2008-2012), the incidence and number of deaths from PCa are projected to significantly increase among Blacks nationwide, further fingering PCa as a cancer health disparity. Additionally, although we have seen significant improvements in overall survival for prostate, breast, and colon/rectal cancer, PCa is projected to be the second leading cause of cancer deaths by 2030. Presently, there are no screening tests for PCa and early diagnosis is difficult because PCa often develops without any symptoms and indications are nonspecific. Thus there is a need, novel anticancer drug delivery that will enhance the efficacy of existing drugs, such as Gemcitabine for use to improve PCa patient outcomes. This collaborative study proposes to investigate critical barriers to PCa therapeutics and also define a more personalized therapeutic approach for underrepresented minority PCa patients. We will identify molecular charateristics that help differentiate molecular signature between pancreatic tumors among Blacks and Latinos which will allow for a more personalized approach to targeting PCa. We plan to design and develop stearoyl-linked-Gemcitabine with surface modified anti-EGFR antibody nanoparticles (GemEnps); evaluate GemEnps as a potential alternative chemotherapeutic agent in the treatment of PCa orthotopic PDX pancreatic animal models based on the similarities and differences in sequencing of pancreatic cancer genomes of Blacks, Latinos and Whites and translate knowledge of DNA changes to clinical tools for better management of Black and Latino with PCa.

项目摘要/摘要：完整项目2 胰腺癌(PCA)是一种对所有患者都具有破坏性的疾病。目前，PCA是第三大致病原因 美国与癌症相关的死亡。五年的总体存活率是令人沮丧的7.2%。而PCA并不是 记录为癌症健康差距的数据相当令人担忧，例如，黑人经历了更高的 与他们的白人相比，他们的患病率更高。此外，黑人男性和女性的总体存活率最低 前列腺癌的发生率。有趣的是，虽然许多癌症的发病率在五年内有所下降 在2008-2012年期间，预计自发性前列腺癌的发病率和死亡人数将大幅增加 在全国黑人中，进一步指出PCA是癌症健康差距。此外，尽管我们有 前列腺癌、乳腺癌和结肠癌/直肠癌的总体生存率显著改善，预计PCA 到2030年成为癌症死亡的第二大原因。目前，还没有PCA和Pca的筛查测试 早期诊断很困难，因为前列腺癌的发展通常没有任何症状，而且适应症也不具特异性。 因此，需要一种新型的抗癌药物输送，以增强现有药物的疗效，例如 吉西他滨用于改善PCA患者的预后。这项合作研究建议调查关键的 PCA治疗的障碍，并为代表不足的患者定义了更个性化的治疗方法 少数PCa患者。我们将识别有助于区分分子签名的分子特征 黑人和拉丁裔之间的胰腺肿瘤之间的关系，这将允许更个性化的方法 目标是PCA。我们计划设计和开发具有表面修饰的抗EGFR的硬脂酰基连接吉西他滨 抗体纳米粒(GemEnps)；评价GemEnps作为潜在的替代化疗药物 基于异同的PCa原位PDX胰腺动物模型的治疗 黑人、拉丁裔和白人胰腺癌基因组测序及DNA翻译知识 更改临床工具，以便通过PCA更好地管理黑人和拉丁裔。