Environmental Cancer Core (ECC)

Directors: Chung S. Yang, PhD and Michael Gallo, PhD

Members:
Elisa Bandera, PhD
Suzie Chen, PhD
Allan Conney PhD
Jun-Yan Hong, PhD
Ah-Ng (Tony) Kong, PhD
Dipak Sarkar, PhD
Susan Shapses, PhD
Judith Storch, PhD
Nanjoo Suh, PhD
Paul Thomas, PhD
Jay Tischfield, PhD
Mehmet Uzumcu, PhD
Lori A. White, PhD
Helmut Zarbl, PhD

Overview:
Understanding the contribution of the environment to cancer(s) has been a major Center focus since its inception. Many aspects of carcinogenesis are being studied including: the molecular and cellular basis of cancer, the genetic basis for differential susceptibility, the role of diet as a contributor and/ or a preventive agent in GI, lung, mammary, and skin cancers, the critical role of steroid hormones and endocrine modulators play in breast and prostate cancer, and molecular markers of melanoma in mouse models and humans. A major effort has been to develop reproducible animal models for human disease and to allow for translation to clinical and population-based studies. This effort has fostered strong links to clinicians at The Cancer Institute of New Jersey (CINJ), an NCI-Designated Comprehensive Cancer Center, and has allowed Center investigators to see their efforts go from the bench to clinical testing. The practical application of mechanistic research within this Core has been the development of cancer chemopreventive strategies. Diet is arguably the largest source of chemical exposures to humans and serves as a key contributor to environmentally-related diseases. However, dietary constituents can also serve in a protective capacity against cancers, neurodegenerative and cardiovascular diseases. Thus, it is essential to develop a better understanding of the potential impact of dietary factors on the prevention of environmentally-related complex diseases such as cancer, and to extend these insights to other environmental diseases. The Core is organized into two working groups, the Genetic Susceptibility and Mechanism of Carcinogenesis Working Group and the Dietary Prevention of Cancer Working Group.

Overall Goals:
The goal of this Disease Core is to advance the molecular understanding of existing carcinogenesis models for direct comparisons to clinical samples and to utilize this information to challenge existing model systems in four ways: 1) elucidate possible chemopreventive strategies (diet, lifestyle, pharmaceuticals and nutraceuticals) and their modes of action; 2) identify biological response indicators of susceptibility (genetic and environmental); 3) initiate translational trials with colleagues at the CINJ and other Centers; and 4) investigate environmental carcinogens to characterize mechanisms of susceptibility and  pathogenesis.

Goals of the Genetic Susceptibility and Mechanism of Carcinogenesis Group

Short Term:

• Use genetic and genomic approaches to elucidate environmental cancer susceptibility genes.
• Identify biological response indicators comprising signaling networks activated by chemical carcinogens
• Compare expression profiles from susceptible and non-susceptible strains and use bioinformatics approaches to identify biological response indicators linked to mechanisms of carcinogenesis.
• Compare expression profiles in mammary tissue following in vivo and in vitro exposure to E2 and its metabolites and compare these profiles to patients’ tissues from CINJ.
• Translate finding from model organisms to clinical and population based studies.

Long Term:

• Study the role of neuroleptic drugs and toxicants (dopaminergic disruptors) in central and local tissue control of prolactin and its receptor in breast cancer.
• Use biological response indicators to develop mechanistically based assays for cancer screening, risk assessment, and evaluating efficacy of interventions.
• Develop mechanistically based interventions to reduce the burden of environmental cancer.

Goals of the Dietary Prevention of Cancer Working Group

Short Term:

• Continue mechanistic and genetic susceptibility studies on environmentally-related cancers, e.g., lung, skin, colon, and mammary cancer.
• Implement dietary studies on novel agents such as g-tocopherol in collaboration with investigators in the Neurological Diseases and Disorders and the Cardiopulmonary Disease Cores.
• Implement dietary studies on the ability of methylselenocysteine to alter circadian rhythm and degradation of the estrogen receptor in animal models, and eventually in women shift workers.
• Use combinations of agents to increase efficacy and reduce chances for side effects.
• Develop dietary exposure and biological effect markers for use in prevention studies.

Long Term:

• Establish additional multi-Center cancer chemoprevention trials with agents developed in this Core
• Contribute to dietary recommendations for the prevention of cancer.
• Core research on environmental and dietary factors in cancer will be disseminated by the COEC through the NJ Chapter of the American Cancer Society partnership, and directly to the greater New Brunswick community. 

 

Use of Facility Cores:
New opportunities exist to extend Center research on chemoprevention of dietary chemicals, to other Disease Cores. These are logical new research directions that maximize the potential for multidisciplinary collaborations among Center investigators on the basis of pathogenic mechanisms, such as oxidative stress, that are shared among diseases and disorders. These interactions are facilitated by the technologies in our Biological Response Indicators Facility Core and through the IHSFC. Core investigators have extensively utilized the Center's Facility Cores. The Biological Response Indicators Core is routinely used for genotyping, gene expression analysis, conduct genetic analyses, cell cycle and apoptosis analyses, imaging tumor growth in rodents and histopathological and immunohistochemical analyses. The Bioinformatics, Biostatistics and Computational Toxicology Core assists with experimental design and data analysis. The IHSFC is instrumental in assisting Core members in conducting small scale human studies, such as blood sample collection for pharmacokinetic analysis, as well as protein analyses and metabolite profiling studies in the Chemical Analysis Facility Core. The latter Facility Core is also used extensively by A. Kong's and CS. Yang's groups to study tissue levels and pharmacokinetics of chemopreventive agents.  The use of the Chemical Analysis Facility Core mass spectrometer capabilities enables CS. Yang's group to identify many metabolites of tea polyphenols and develop exposure small molecule and protein indicators for consumption of tea and other chemopreventive dietary components.