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Conquest - 2005 Research Awards

Making the Connection 2001-2008

2005 Research Awards

Date: April 20, 2010

THE YEAR 2005 finds trends in cancer rates in Maryland moving in the right direction. After decades of dismal rates, ranking Maryland among the worst in the nation, the tables turned. Combined investments by the Cigarette Restitution Fund, Maryland Cancer Control Plan, National Cancer Institute, and individuals and groups such as the Flight Attendants Medical Research Institute paid off. Maryland went from having the third highest cancer death rates in the nation to 19th. According to the Centers for Disease
Control, this translates to 16,200 Marylanders whose lives were saved.

Research led by MARY ARMANIOS, M.D. , identified the genetic culprits that trigger a
hereditary form of a fatal lung disease, known as idiopathic pulmonary fibrosis in two genes that produce an enzyme which helps lengthen the fragile ends of chromosomes.
Chromosome ends, or telomeres, contain repetitive bits of DNA code that wear down each time a cell divides. The mutations were spotted in two genes that regulate the enzyme telomerase, which keeps telomere length extended just beyond the borders of needed genes. With mutations in telomerase, however, chromosome ends fray and wear down far more quickly, which can trigger cell death. Telomere shortening is also believed to play a role in the development of cancer.

A novel area of gene research is relating the expression from thousands of gene sequences
to how advanced or aggressive a cancer is and predicting how it may react to exposure
to anticancer drugs. Though genetic research has uncovered countless genes related to the
cancer process, many investigators have been left with data on thousands of genes with no statistical method for analyzing the data. The investigators, directed by GIOVANNI
PARMIGIANI, PH.D. , have developed a statistical method for analyzing data from as
few as a single gene sample. The method has already been used successfully to identify
genes associated with T cell pathways and in stem cell research. The method has also been applied to gene studies of skin cancer, papillarythyroid cancer, and Alzheimers’ disease. The scientists built upon this success by further refining their analysis of gene expression to better understand and characterize the differences, or subtypes, within specific cancers and other diseases. ?

Hopkins Early Lung Cancer Prevention Program (HELP) is a comprehensive program
that encompasses translational and community- based research. HELP studies include
basic laboratory genetic research, new investigational drugs, and an outreach prevention
program with study participants representative of minority groups throughout Maryland.
“Each of our investigators brings an appropriate mix of laboratory and clinical
experience to the team,” says JULIE R. BRAHMER, M.D. , a co-director of HELP.
“Our goal is to make a much needed impact on lung cancer incidence and death rates by
being a driving force in prevention studies, both at our own institution and as collaborators
in national studies,” says Brahmer. Several potential prevention strategies were tested. The drugs Iressa and Zarnestra were studied in current and former smokers for their ability to halt early cellular changes caused by smoking that can lead to lung cancer. A national collaborative study focused on the drug Iloprost, which may be able to reverse cellular changes in the bronchial lining that often appear as a precursor to lung cancer. Investigators continue to study sulforaphane, a broccoli extract, that Hopkins researchers found protects cells by detoxifying the carcinogens that lead to lung cancer initiation. ?

With the ever-growing list of genetic targets being investigated, there became a growing
need for readily accessible and well-characterized biological samples from cases and controls to move these findings from the research phase to cancer detection and treatment for people.The Cancer Prevention and Control Resource Core, directed by ELIZABETH PLATZ, SC.D., M.P. H . , addressed this need by centralizing the collection of blood samples and health and self-reported exposure data from consenting cancer patients seen at the Kimmel Cancer Center, as well as from consenting relatives and friends of patients
as a ready source of controls. This Core enhances cancer biomarkers research by permitting investigators to quickly identify appropriate blood samples of well- haracterized
individuals, allowing studies of biomarkers to be conducted rapidly, efficiently, and cost effectively.

Medically underserved populations are those that lack easy access to, or do not make use of, high-quality cancer prevention, screening and early detection, treatment, or rehabilitation services. According to the National Cancer Institute (NCI), in general, these groups experience higher cancer death rates than the U.S. population as a whole. In addition, many of these populations remain underrepresented in NCI-funded cancer clinical trials. Steps towards participation in clinical trials include awareness, acceptance, and retention. Unfortunately, there is limited information about evidence-based strategies for recruitment of underserved populations into cancer-related trials. JEAN FORD,
M.D. and MOLLIE HOWERTON, PH.D. , worked to identify and understand the barriers to care and increase participation in cancer prevention and treatment trials. ?

CHARLES RUDIN, M.D. , developed a translational lung cancer program in 2003 and continued the program with CRF funding. Rudin has begun studies of the pathways involved in cell death and how these pathways can be exploited to improve lung cancer therapy. New research focuses on a small molecule that targets a gene known as BCL2. Inhibiting BCL2 could increase therapeutic sensitivity in small cell lung cancer. ?

Oral HPV (human papillomavirus) infection is a recently recognized public health problem. This is in great part due to the work of Johns Hopkins CRF investigator MAURA GILLISON, M.D. , P H . D. She was the first to definitely link infection with HPV to oral cancers and to uncover how it works in correlation with other known risk factors, like tobacco and alcohol, to impact treatment prognosis. Gillison is particularly interested in
cancer of the tonsils, which is on the rise in American men with HIV (human immunodeficiency virus). She suspects that immune suppression caused by HIV makes individuals more susceptible to oral HPV infection. Working in conjunction with Johns
Hopkins HIV clinic, she has begun the Human Oral Papillomavirus Etiology (HOPE) project and hopes to follow 800 HIV-infected men and women. More than 200 patients have already enrolled. Patients will be followed for four years so investigators can observe the natural history of HPV infection and how sexual behavior, smoking, and alcohol use
impact its progression to oral cancer. Gillison believes the study will generate information key to the care of individuals with joint HPV and HIV infection, a population expected to grow considerably in the coming years.

DAVID SIDRANSKY, M.D. is the nation’s leading expert in isolating DNA from blood, tissue, and body fluids to examine them for genetic and epigenetic alterations indicative of cancer. This success has led to high demand on his laboratory. CRF funding is helping expand his laboratory so that he can provide investigators throughout Johns Hopkins with
timely molecular tests targeted to newly discovered biomarkers to determine their feasibility as screening tests for cancer. ?

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