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Electronic cigarettes, oxidative stress and development of breast tumor

Award Number: R16GM149471
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/05/2023
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Electronic cigarettes, oxidative stress and development of breast tumor - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $143,500 )
2025	2025	CHARLES R. DREW UNIVERSITY OF MEDICINE AND SCIENCE	1731 E 120TH ST	LOS ANGELES	CA	90059	LOS ANGELES	USA	Biomedical Research and Research Training	000	3	8/19/2025	NON-COMPETING CONTINUATION	$143,500
														Subtotal = $143,500

Issue Date FY: 2024 ( Subtotal = $143,500 )
2024	2024	CHARLES R. DREW UNIVERSITY OF MEDICINE AND SCIENCE	1731 E 120TH ST	LOS ANGELES	CA	90059	LOS ANGELES	USA	Biomedical Research and Research Training	000	2	8/23/2024	NON-COMPETING CONTINUATION	$143,500
														Subtotal = $143,500

Issue Date FY: 2023 ( Subtotal = $143,500 )
2023	2023	CHARLES R. DREW UNIVERSITY OF MEDICINE AND SCIENCE	1731 E 120TH ST	LOS ANGELES	CA	90059	LOS ANGELES	USA	Biomedical Research and Research Training	000	1	8/4/2023	NEW	$143,500
														Subtotal = $143,500

Grand Total All Awards = $430,500

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Electronic cigarettes, oxidative stress and development of breast tumor

Award Number: R16GM149471

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/05/2023

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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