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

基本信息

批准号：
10006098
负责人：
Romonia Renee REAMS
金额：
$ 15.02万
依托单位：
FLORIDA AGRICULTURAL AND MECHANICAL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-19 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10006098
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

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

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项目摘要

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）是受影响的所有人的毁灭性疾病。目前，PCA是第三主要原因在美国，与癌症有关的死亡五年的总生存率为7.2％。虽然PCA不是数据记录为癌症健康差异，数据令人震惊，例如，黑人经历了更高的与白人相比的患病率。此外，黑人男女的总生存最低 PCA的比率。有趣的是，尽管许多癌症在5年中显示出发病率的降低时期（2008-2012），PCA的发病率和死亡人数预计将显着增加在全国黑人中，将PCA作为癌症健康差异。此外，尽管我们有 PCA预测了前列腺，乳房和结肠癌/直肠癌的总体生存率显着提高到2030年成为癌症死亡的第二大原因。目前，PCA和早期诊断很困难，因为PCA通常没有任何症状，并且适应症是非特异性的。因此，有一种需要新颖的抗癌药物递送，可以增强现有药物的功效，例如用于改善PCA患者预后的吉西他滨。这项协作研究建议调查关键 PCA治疗剂的障碍，还为代表性不足定义了更个性化的治疗方法少数PCA患者。我们将确定有助于区分分子特征的分子外观在黑人和拉丁美洲人之间的胰腺肿瘤之间，这将允许采取更个性化的方法针对PCA。我们计划设计和开发与表面修饰的抗EGFR的链球菌连接的gemcitabine 抗体纳米颗粒（gemenps）；评估Gemenps作为潜在的替代化学治疗剂基于相似性和差异的PCA原位PDX PDX胰腺动物模型的处理黑人，拉丁裔和白人的胰腺癌基因组的测序，并翻译了DNA的知识使用PCA更好地管理黑人和拉丁裔的临床工具。