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Promise and Progress - CRF Research Grant Summaries

Sidney Kimmel Gives Hopkins Its Biggest Gift Ever

CRF Research Grant Summaries

Date: December 1, 2002

Breast Cancer

Yin Yao, M.D., Ph.D.

BRCA2 Mutations: Relating Genetic and Epidemiological Studies of Common Cancers

While the BRCA1 and BRCA2 mutations provided key insights into the molecular genetic causes of breast cancer, they may be just one piece in a much larger puzzle. In epidemiological studies, 67 percent of families with four or five cases of early onset breast cancer could not be linked to these genes. Hopkins scientists believe other genes work with BRCA2 to increase breast cancer risk and to control the age of onset and are studying the BRCA2 pathway to identify other genetic culprits in breast cancer.

Kathy Helzlsouer, M.D., M.H.S.

Ductal Lavage as an Adjunct to Mammography

The ability of mammography to detect early breast cancer is reduced in younger women and women with dense breast tissue. Ductal lavage is a technique used to flush cells from the lining of breast cancer ducts, where breast cancer begins. The cells can then be examined to determine if cancerous cells are present, similar to a pap test for cervical cancer. It is not known yet how well this technique can pick up early cancers and if it is better than existing screening methods. It could be a powerful addition to available screening techniques, to improve early breast cancer detection rates, particularly among women at high risk for developing breast cancer. This study will take the first steps to determine the sensitivity and specificity of ductal lavage.

Cervical Cancer

Cornelia L. Trimble, M.D.

A System Using Dimers to Identify HPV16 E7-Specific T cell Response to Improve Understanding of Cancer Risk Factors

Cervical cancer has long been linked to the sexually transmitted human papillomavirus (HPV). HPV-associated cervical disease is three times the national average within Baltimore City’s minority communities.A newly established Cervical Diseases Center at Johns Hopkins and within these communities begins clinical studies of a HPV-targeted intervention to stimulate immunity to HPV antigens and prevent the initiation of cervical cancer.

Colon Cancer

Victor E. Velculescu, M.D., Ph.D.

Mutational Analysis of Colorectal Cancer Genome

Though scientists have revealed cancer as a genetic disease caused by alterations in specific genes, many of these genes have yet to be identified. This is particularly true of colon cancer, where Hopkins researchers were among the first to identify a series of genetic mutations associated with this disease. They continue this work with a genomewide analysis of colon and rectal cancer to identify the compendium of genetic changes in colon cancer, including those that may be prevalent among certain minority groups, revealing novel approaches to screening and diagnosis.

Maria Cruz-Correa, M.D.

Epidemiology of Loss of Imprinting in Colorectal Cancer in Maryland

The loss of imprinting of the IGF2 gene may be a genetic alteration common to colon cancer that could serve as a potential biomarker for the disease. In a unique combined cancer genetics and epidemiological approach, researchers are using tissue obtained in screening colonoscopies to characterize the role of loss of imprinting of IGF2 gene in colorectal cancer in Marylanders.

Lung Cancer

Anthony Alberg, Ph.D.

Estimation of the Joint Influence of Active and Passive Smoking on Cancer Incidence

Using the unique Johns Hopkins resource, the 30-year-old Washington County cohort study, investigators will estimate the effects of active and passive smoking on all cancer sites. Calculation of site-specific cancer incidence will be done. The contributions of all sources of tobacco smoke will be estimated and reported.

Julie Brahmer, M.D.

Lung Cancer Prevention

Researchers are studying DNA obtained from lung sputum samples to identify tumor suppressor genes silenced by a genetic alteration known as hypermethylation. Researchers believe this alteration can be reversed with certain drugs reactivating the genes and their roles of suppressing tumor growth. Among the drugs being studied for their ability to “demethylate” suppressor genes are two natural products, ginseng and selenium.

Shyam Biswal

Chemoprevention and Biomarker Discovery for Cigarette Smoke-induced Lung Cancer

Construction of a cigarette smoke-exposure facility for small animal exposure and validation of a mouse model for cigarette smoke-induced lung cancer by Hopkins investigators is opening new avenues for lung cancer biomarker discovery and the preclinical trials of chemopreventive agents. Proteomics, which studies the expression, function, and interactions of proteins expressed by genes, is a new tool for discovery in cancer research. Hopkins investigators are now leading the first attempt to use proteomics in this mouse model to identify protein biomarkers associated with the onset of lung cancer after exposure to cigarette smoke. The scientists are seeking to identify proteins that will help in diagnostics, intervention, and risk assessment of cigarette smoke-associated lung cancer. Several chemopreventive agents will be evaluated.

Oral Cancers

Joseph Califano, M.D.

Molecular Screening in a Population at Risk of Head and Neck Cancer

Hopkins scientists are analyzing DNA of cells obtained from oral rinses and blood from 900 participants, including Cau-casian, African American and Latino volunteers at high risk for head and neck cancer, to look for early genetic events in the development of squamous cell cancers of the head and neck. The participants also receive a free head and neck examination to screen for cancer. This disease can best be treated when caught in an early stage, but some of these cancers (those that occur at the base of the tongue, in the tonsils and larynx) are often difficult to detect through conventional methods. Molecular analysis, to look for subtle genetic changes in cells shed in saliva and blood, could lead to new prevention, diagnostic and treatment methods.

Maura Gillison, M.D., Ph.D.

Papillomavirus and Risk of Oro-pharyngeal Cancer: A Case Control Study

Tobacco and alcohol use are known to contribute to the development of oral cancers. Hopkins scientists hypothesize that the sexually transmitted human papillomavirus may augment these risks. Prior studies suggest that HPV-positive head and neck cancers may comprise a distinct molecular, clinical, and pathologic disease very different from other types of the disease.   They are further exploring the role of HPV in the initiation of certain oral cancers in the presence of the more traditional risk factors.

Prostate Cancer

Bruce J. Trock, Ph.D.

Impact of Environmental Cadmium Exposure on Prostate Cancer Risk in the Baltimore Metro Area

Cadmium is one of the few environmental exposures linked to prostate cancer. Hopkins scientists believe that this metal may generate damaging free radicals and displace beneficial zinc in prostate cells, potentially contributing to the development of cancer. They are testing this hypothesis in studies of cadmium, zinc, and selenium levels in prostate tissue samples from men known to work or reside in high cadmium exposure areas.

Multiple Cancers

Jim Zabora, Sc.D.

Kathleen M. Conlan, M.S.

Elizabeth Platz, Ph.D.

The Laborers’ International Union of North American (LIUNA) Prospective Cohort Study on Cancer

While the causes of many cancers remain unclear, there are certain behaviors, including cigarette smoking, certain diets, environmental exposures, and alcohol use, that are known to increase cancer risk. Hopkins investigators are working with an 800,000-member, racially diverse and economically modest labor union to identify modifiable behaviors and environmental factors linked to breast, lung, prostate, and colon cancers. The first step in assembling the cohort is to identify a method of data collection that will yield the greatest and most reliable responses from the union members in Maryland. The racial diversity of the group in the Maryland locals may help uncover racial variations in cancer rates and lead to new interventions that could reduce statewide cancer risk.

Saeed R. Khan, Ph.D.

Novel Drug Development for Solid Tumors

Hopkins scientists are working in the laboratory to synthesize bioactive molecules and create new anti-cancer drugs to treat prostate, breast and colon cancers. These new compounds are being designed to be selectively toxic to cancer cells, particularly at metastatic sites now resistant to standard therapies, while sparing normal cells from damage. The project will provide critical capacity for small molecule drug development at our institution.

Hee-Soon Juan, Ph.D.

Cancer Educational Program for Korean American Women: Pilot Study

Cancer is a leading cause of death among Korean women age 24 to 64. Breast and cervical cancers are among the most commonly diagnosed cancers in Korean American women. These women have low usage of mammography and pap tests because they lack knowledge of screening and have limited access to these cancer-screening methods. Hopkins clinician-scientists are working with local Korean churches to develop culturally sensitive materials to educate women and enroll them in screening programs in an effort to impact cancer death rates.

Environmental Cancers

Timothy J. Buckley, Ph.D., and Thomas Burke, Ph.D.

Cancer-causing Agents in the Maryland Environment

Cancer is an important public health concern in Maryland and Baltimore City. The state and city consistently have some of the highest rates in the nation. Based on ambient air toxin levels, Baltimore City and Maryland are ranked as first and third in the nation for estimated excess cancer. Exposure to many important environmental carcinogens, such as pesticides, polycyclic aromatic hydrocarbons, and volatile organic compounds, can occur in combination and from multiple media (air, water, diet, dust, soil) and through multiple routes (ingestion, inhalation, and absorption through the skin). Hopkins researchers are identifying and prioritizing environmental carcinogens in Maryland based on the potential for exposure and risk. This work will provide focus and definition for future efforts to study cancer epidemiology and prevention.