Please enable JavaScript or talk to your local administrator to get JavaScript enabled.
Skip filters
Skip facets
Funder
  • 133

  • 50

  • 20

  • 16

  • 15

  • 12

  • 10

  • 10

  • 8

  • 8

Funder Group
Research Organization
FOR (ANZSRC) Category
RCDC Category
Researcher
City
State
Country
Country of Funder
Start Year
Active Year
Similar Projects for

Project

DNA adductome of human bladder from the tobacco exposome

Funder: National Institute of Environmental Health Sciences

Funding period
USD 468 K
Funding amount
Abstract
Summary More than 70 chemicals in tobacco smoke are carcinogens. Tobacco smoking is a risk factor for bladder cancer; however, despite many years of study, the principal chemicals in tobacco smoke and environment that damage DNA of the bladder are unknown. Aromatic amines (AAs) and heterocyclic aromatic amines (HAAs) arise in tobacco smoke and are responsible for much of the mutagenicity in urine of smokers. Some AAs (and possibly HAAs) are bladder carcinogens, and also induce liver, bladder, and colorectal cancer in rodents, and likely contribute to these cancers in humans. 4-Aminobiphenyl (4-ABP) is a human bladder carcinogen; however, several alkylanilines and structurally related HAAs occur in tobacco smoke at levels up to 100-fold greater than 4-ABP. Some epidemiological studies have linked N-nitroso compounds and polycyclic aromatic hydrocarbons as risk factors for bladder cancer. Robust measurements of DNA adducts are important to understand the chemi- cals in tobacco smoke, the environment, and diet that damage the bladder and may contribute to bladder cancer. Apart from 4-ABP, the chemicals in tobacco smoke that damage bladder DNA are unknown. The objective of this application is to apply robust screening tools to identify DNA adducts derived from exogenous and endogenous sources that damage bladder DNA. We will employ our newly developed mass spectrometry (MS) adductomic tools to identify the major chemicals in tobacco smoke condensate that form DNA adducts in the bladder of smokers. In Aim 1, we will conduct studies with cigarette smoke extract (CSE) and human bladder cells incubated alone or in co-culture with hepatocytes to assess the role of liver metabolism in DNA damage of the bladder. The panel of DNA adducts formed in bladder cells with CSE will serve as a guide to facilitate the characterization of the DNA adductome of the urothelium of smokers and nonsmokers undergoing bladder cancer surgery in Aim 2. Some procarcinogens in CSE can reach the bladder and undergo bioactivation by P450s expressed in the bladder, particularly aromatic amines and HAAs. Therefore, in Aim 3, we will examine the urinary exposome of AAs and HAAs in smokers participating in a tobacco cessation study by novel mass- tagging methods to measure the totality of these potential bladder carcinogens in urine, and assess the capacity of bladder enzymes to bioactivate these compounds. Our research is relevant to NIH's mission on public health. Our studies will provide a greater understanding about genotoxicants in tobacco smoke the environment that damage bladder DNA and contribute to bladder cancer. By merging chemical exposures and DNA adducts with mutational data, clues about the identities of environ- mental, dietary and endogenous genotoxicants can be established to identify subjects at risk for bladder cancer. Once identified, pragmatic measures can be taken to reduce human exposure to chemicals, by changes in life- style or mitigation of environmental exposures, which are probably the most efficient means of chemoprevention.

 
359
Projects
USD 201.6 M
Aggregated funding amount
USD 607 K
Average funding amount
Project list item
Identifying Immunological Basis for Bladder Cancer Sex Bias

Canadian Institutes of Health Research to Hyunwoo Kwon, Zihai Li

USD 26,219
2019 - 2022
Project list item
Chromatin Modifier Gene Mutation and Enhancer Dysfunction in Bladder Cancer

National Cancer Institute to BYRON H LEE

USD 243,205
2019 - 2024
Project list item
Combatting Bladder Cancer by Inducing Epithelial Turnover

National Cancer Institute to SOMAN N ABRAHAM

USD 203,510
2019 - 2021
Project list item
Identifying DNA Biomarkers of Bacillus Calmette-Guerin (BCG) Resistance in Non-Muscle-Invasive Bladder Cancer

Canadian Institutes of Health Research to Jack Victor Warren Bacon, Alexander William Wyatt

USD 847
2018 - 2019
Project list item
SPORE in Bladder Cancer

National Cancer Institute to DEAN F. BAJORIN, TIMOTHY AN-THY CHAN, IRINA OSTROVNAYA, HIKMAT AL-AHMADIE, MICHAEL STEPHEN GLICKMAN, DAVID B SOLIT

USD 2,299,837
2018 - 2023
Project list item
Modeling bladder cancer metastasis using human patient-derived tumor organoids

Bladder Cancer Advocacy Network to Michael M Shen

USD 300,000
2018 - 2020
Project list item
Regulation of Bladder Umbrella Cell Paracellular Permeability by Stretch

National Institute of Diabetes and Digestive and Kidney Diseases to AMITY FENN EATON

USD 89,540
2018 - 2021
Project list item
Circulating tumor DNA as a predictive biomarker in metastatic bladder cancer

Canadian Institutes of Health Research to Gillian Rae Vandekerkhove, Alexander William Wyatt

USD 53,221
2018 - 2021
Project list item
Intra-operative MRI-guided Robotic System for Photothermal Therapy of Bladder Cancer

University Grants Committee to Kwok Ka Wai, Wong Kenneth Kin Yip, Vardhanabhuti Varut Vince, TEOH Yuen Chun Jeremy

USD 80,682
2018 - 2021
Project list item
Identify the DNA Adduct and Associated Metabolic Alterations in Bladder Cancer of Smokers

National Cancer Institute to NAGIREDDY PUTLURI, RANDA A EL-ZEIN

USD 810,976
2018 - 2023
Project list item
Ty21a immunotherapy of non-muscle-invasive bladder cancer

Swiss National Science Foundation to Denise Nardelli Haefliger, Mathieu Chevalier, Patrice Jichlinski, Lenka Chalupova

USD 436,670
2018 - 2021
Project list item
CISTO: Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer

Patient-Centered Outcomes Research Institute to John Gore

USD 8,500,000
2018 - 2022
Project list item
Circulating tumour DNA as a precision oncology tool for metastatic bladder cancer

Canadian Institutes of Health Research to Alexander William Wyatt

USD 98,846
2017 - 2020
Project list item
Non invasive Cell Based Liquid Biopsy Platform for Bladder Cancer

European Commission

USD 4,291,985
2017 - 2020
Project list item
INTRAVESICAL ONCOLYTIC THERAPY FOR BLADDER CANCER

National Cancer Institute to ROSA MARIA DIAZ, BRADLEY C. LEIBOVICH, LUKKANA SUKSANPAISAN

USD 1,081,593
2017 - 2020
Project list item
Improved detection of bladder cancer recurrence using a biophysical biomarker

National Cancer Institute to MICHAEL D HENRY

USD 299,860
2017 - 2019
Project list item
(PQ3) Immune epigenetic biomarkers of bladder cancer outcomes

National Cancer Institute to BROCK CLARKE CHRISTENSEN

USD 1,235,254
2017 - 2022
load more...