T H E M A RY L A N D C I G A R E T T E R E S T I T U T I O N F U N D S AT J O H N S H O P K I N S
2 0 0 1 R E S E A R C H AWA R D S
IN JULY 2001 , the first research grants under the CRF were funded. Fourteen, one-year grants were competitively funded. Of these first grants, six represented seed funding for young investigators that led to internationallyrecognized, awarding-winning research advances. These discoveries, jumpstarted with CRF support, included a cervical cancer vaccine, the first comprehensive blueprints of the colon, breast, pancreatic and brain cancer genomes, the connection of HPV to a distinct subset of oral cancers and related risk factors, the identification of statins in prostate cancer prevention, pioneering work in the emerging field of epigenetics, and identification of a carcinogen-detoxifying gene pathway. 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. Under the direction of researcher C O N N I E T R I M B L E , M . D. , a Cervical Diseases Center is established at Johns Hopkins to treat cervical dysplasia (the precursor to cervical cancer) and clinical studies of HPVtargeted interventions to stimulate immunity to HPV antigens and prevent the initiation of cervical cancer begin. ■
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. S H YA M B I S WA L , P H . D. , led 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. Biswal and team will identify proteins that may help in diagnostics, intervention, and risk assessment of cigarette smoke-associated lung cancer. Several chemopreventive agents will be evaluated. ■
ACTIVE AND PASSIVE SMOKING AND CANCER INCIDENCE
BREAST CANCER-CAUSING PATHWAYS
Using the 30-year-old Washington County cohort study, a unique Johns Hopkins resource, investigators led by A N T H O N Y A L B E R G , P H . D. , estimated the effects of active and passive smoking on all cancer sites. Calculation of site-specific cancer incidence was done and the contributions of all sources of tobacco smoke will be estimated and reported. ■
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. Y I N YA O , M . D. , P H . D. , and team believe other genes work with BRCA2 to increase breast cancer risk and to control the age of onset and studied the BRCA2 pathway to identify other genetic culprits in breast cancer. ■
CERVICAL CANCER IMMUNITY
NEW LUNG CANCER TARGETS J U L I E B R A H M E R , M . D. ,
and team 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. ■
SMOKING AND LUNG CANCER
Construction of a cigarette smoke exposure facility for small animal exposure and validation of a mouse model for cigarette smokeinduced lung cancer is pointing to new avenues for lung cancer biomarker discovery
IMPROVING BREAST CANCER DETECTION
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, led by K AT H Y H E L Z L S O U E R , M . D. , M . H . S . , took the first steps in determining the sensitivity and specificity of ductal lavage. ■ MOLECULAR SCREENING OF HEAD AND NECK CANCER
Scientists led by J O S E P H C A L I FA N O , M . D. , analyzed DNA of cells obtained from oral rinses and blood from 900 participants, including Caucasian, African American and Latino volunteers at high risk for head and neck cancer, to look for early genetic events in the development of these cancers. Head and neck cancers 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. ■ HPV’S ROLE IN ORAL CANCER
Tobacco and alcohol use are known to contribute to the development of oral cancers. Scientists hypothesize that the sexually transmitted human papillomavirus may augment these risks. Prior studies by M A U R A G I L L I S O N , M . D. , P H . D. , suggested 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 further explored the role of HPV in the initiation of certain oral cancers in the presence of the more traditional risk factors. ■ ANALYSIS OF THE COLORECTAL CANCER GENOME
Though a team of Johns Hopkins scientists,