Targeted Nanocarrier Combination Based Therapy for Lung Cancer

靶向纳米载体组合治疗肺癌

• 批准号: 8355084
• 负责人: Mandip Singh Sachdeva
• 金额: $ 16.48万
• 依托单位: FLORIDA AGRICULTURAL AND MECHANICAL UNIV
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-16 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8355084
• 关键词: A549; Adverse effects; African American; Age; Biological Availability; Bypass; Cancer Center; Cancer Patient; Cell Line; Combination Drug Therapy; Community Services; Death Rate; Dose; Drug Formulations; Exhibits; Frequencies; Future; Growth; Human; Incidence; Investigation; Laboratories; Lung Neoplasms; Lymphatic; Malignant Neoplasms; Malignant neoplasm of lung; Metabolism; Methods; Minority Groups; Modeling; Molecular; Non-Small-Cell Lung Carcinoma; Noscapine; Nude Mice; Oral; Oral Administration; Outcome; Pharmaceutical Preparations; Platinum; Population; Research Project Grants; Research Training; System; TdT-Mediated dUTP Nick End Labeling Assay; Therapeutic; Woman; absorption; anticancer activity; anticancer research; base; caucasian American; chemotherapeutic agent; chemotherapy; improved; in vivo; indexing; man; mannosamine; mortality; nanocarrier; novel; novel strategies; racial and ethnic; research study; response; tumor; tumor growth; tumor xenograft

Research Project 1- Targeted Nanocarrier Combination Based Therapy for Lung Cancer - Dr. Mandip Sachdeva: Lung cancer incidence rate in African American is 50% higher than that of white Americans. African Americans have the highest cancer incidence and mortality rates of any racial/ethnic minority group in the U.S. Furthermore, its incidence continues to steadily rise among both African and white American women. The age adjusted death rate among African American population from lung cancer was found to be 12%. The recommended first line of chemotherapy In NSCLC is platinum based combination chemotherapy. Despite recent advances in chemotherapy, response rates in NSCLC remain <50% and also chemotherapy is associated with adverse effects. This necessitates investigation on chemotherapeutic options having potent anticancer activity and lower side effects to improve therapeutic outcomes in treatment of lung cancer. Noscapine (Nos). an antimicrotubular agent, has been shown to have promising anticancer activity. Our laboratory has already demonstrated that oral administration of Nos significantiy regress tumor growth in dose dependent manner in H460 xenograft tumor model. The use of Nos has been limited due to extensive first pass metabolism and poor bioavailability. Therefore, enhancing oral bioavailability of Nos using nanocarrier delivery system which can bypass the first pass effect (coated with mannosamine) and delivering in combination with chemotherapeutic agents to exert synergistic antitumor activity is a novel approach in treatment of lung cancer.

研究项目1-靶向纳米载体组合为基础的治疗肺癌-博士。 Mandip Sachdeva：非裔美国人的肺癌发病率比白色美国人高50%。非裔美国人的癌症发病率和死亡率是美国任何种族/少数民族群体中最高的。此外，非裔和白色美国妇女的癌症发病率继续稳步上升。非裔美国人肺癌的年龄调整死亡率为12%。NSCLC推荐的一线化疗是以铂为基础的联合化疗。尽管最近在化疗方面取得了进展，但NSCLC的反应率仍<50%，并且化疗也与不良反应相关。这需要研究具有有效抗癌活性和较低副作用的化学治疗选择以改善肺癌治疗中的治疗结果。诺斯卡品（Nos）。一种抗微管剂，已显示具有有希望的抗癌活性。 我们的实验室已经证明，在H460异种移植肿瘤模型中，口服施用Nos以剂量依赖性方式显著地使肿瘤生长消退。由于广泛的首过代谢和较差的生物利用度，Nos的使用受到限制。因此，利用甘露糖胺包裹的纳米载体系统提高一氧化氮的口服生物利用度，并与化疗药物联合给药，发挥协同抗肿瘤活性，是肺癌治疗的一条新途径。