Electronic cigarettes, oxidative stress and development of breast tumor

电子烟、氧化应激与乳腺肿瘤的发生

基本信息

  • 批准号:
    10629814
  • 负责人:
  • 金额:
    $ 14.35万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-08-05 至 2027-07-31
  • 项目状态:
    未结题

项目摘要

Abstract Breast cancer is a complex disease that is sensitive to environmental factors like cigarette smoke (CS), which contains many toxic chemicals that are mutagenic and increases the risk of many cancers, including breast cancer. Electronic cigarettes (E-Cigs) are battery-powered devices that entered the market in 2007 to provide a safe alternative for cigarette smokers and has taken the younger population by storm. However, concerning reports are emerging that E-Cig, with or without nicotine, also contains similar to CS, scores of toxic chemicals that are deleterious to health. Therefore, it is important to examine key players that contribute to short and long-term effects of E-Cig on breast cancer, which is susceptible to DNA damage and genomic instability. Our preliminary data in E-Cig exposed breast cancer MDA-MB-468 xenografts in Balb/c mice indicates higher tumor growth, which was accompanied by increased reactive oxygen species (ROS), reduced super oxide dismutase (SOD) activity, increased NF-kB signaling and upregulated chemokines implicated in immune evasion. Based on our preliminary findings, we hypothesize that E-Cig exposure induces oxidative stress to reprogram cancer cells and tumor microenvironment to promote breast cancer growth. We will test our hypothesis under these Specific Aims: Aim 1: To determine whether 1A) E-Cig-induced oxidative stress up-regulates pro- survival pathways to promote breast tumor growth, and 1B) Genetic and pharmacological modulation of oxidative stress influences E-Cig-induced breast tumor growth. E-Cig exposed xenografts in Balb/c nude mice from African American (MDA-MB-468 and HCC70) and Caucasian (MDA-MB-231 and BT549) breast cancer cells will be analyzed for tumor growth, markers for oxidative stress (ROS/SOD/Nrf2/NOX), TNF-α/NF-KB signaling and subset of mammary cancer stem cells (MCSC). Effect of genetic and pharmacological manipulation of ROS on breast tumor growth will be assessed by SOD shRNA and anti-oxidants. Aim 2: To determine whether- 2A) E-Cig preferentially re-programs cancer/host cells to facilitate immune evasion within tumor microenvironment and promote breast cancer progression, and 2B) Treatment with CD25 monoclonal antibody suppresses regulatory T cells (Tregs) function and reduces E-Cig-mediated breast tumor growth. RNA sequencing data (for human and mouse genes) from AA and CA TNBC xenografts Balb/c nude mice will be subjected to computational analysis for immune gene signatures in tumor/host cells. The immune signatures will be validated in transgenic MMTV-PyMT mice exposed to E-Cig aerosol/saline. We will also examine the effect of anti-CD25 monoclonal antibody treatment on suppression of Tregs and E-Cig-induced breast tumor growth. Successful completion of this project will facilitate submission of highly competitive future NIH grants and enhance institutional research capacity building to engage CDU undergraduate and medical students in biomedical research.
摘要

项目成果

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SHEHLA PERVIN其他文献

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{{ truncateString('SHEHLA PERVIN', 18)}}的其他基金

Beige Adipocytes and African American Breast Tumors
米色脂肪细胞和非裔美国人乳腺肿瘤
  • 批准号:
    10202503
  • 财政年份:
    2018
  • 资助金额:
    $ 14.35万
  • 项目类别:
Targeting pERK1/2 in Human Mammary Cancer Stem Cells
靶向人类乳腺癌干细胞中的 pERK1/2
  • 批准号:
    8078639
  • 财政年份:
    2011
  • 资助金额:
    $ 14.35万
  • 项目类别:
Targeting pERK1/2 in Human Mammary Cancer Stem Cells
靶向人类乳腺癌干细胞中的 pERK1/2
  • 批准号:
    8677817
  • 财政年份:
    2011
  • 资助金额:
    $ 14.35万
  • 项目类别:
Targeting pERK1/2 in Human Mammary Cancer Stem Cells
靶向人类乳腺癌干细胞中的 pERK1/2
  • 批准号:
    8881968
  • 财政年份:
    2011
  • 资助金额:
    $ 14.35万
  • 项目类别:
Targeting pERK1/2 in Human Mammary Cancer Stem Cells
靶向人类乳腺癌干细胞中的 pERK1/2
  • 批准号:
    8299474
  • 财政年份:
    2011
  • 资助金额:
    $ 14.35万
  • 项目类别:
Targeting pERK1/2 in Human Mammary Cancer Stem Cells
靶向人类乳腺癌干细胞中的 pERK1/2
  • 批准号:
    8509637
  • 财政年份:
    2011
  • 资助金额:
    $ 14.35万
  • 项目类别:
Drew National High School Student Summer Research Apprentice Program
德鲁国家高中生暑期研究学徒计划
  • 批准号:
    9024513
  • 财政年份:
    2007
  • 资助金额:
    $ 14.35万
  • 项目类别:
p38 MAP Kinase and Akt Interaction in HUVEC
HUVEC 中 p38 MAP 激酶和 Akt 相互作用
  • 批准号:
    7253731
  • 财政年份:
    2007
  • 资助金额:
    $ 14.35万
  • 项目类别:

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