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Conquest - Progress-Though Hampered-Continues Despite Huge Cuts

Making the Connection Update 2009-2010

Progress-Though Hampered-Continues Despite Huge Cuts

Date: May 1, 2010

The CRF has played a key role in many of this decade’s major research advances at the Kimmel Cancer Center and in establishing the careers of bright, young investigators and clinicians. Despite drastic cuts that slashed the research grant from $2.15 million in 2008 to $1.6 million in 2009 and its current low of $401,000, our investigators remain committed to making progress.  While cancer research under the CRF continues, the pace of discovery is slowed due to limited funding.  In the past, research with key findings was extended with continued CRF grants to the investigators.  Under current funding, these continuation grants are no longer being given.   Just two research grants and support for three young faculty members could be awarded for 2010, compared to ten or more grants in years when our CRF research grant was fully funded.  In addition, the amount per grant has been significantly reduced.

Malcolm Brock, M.D. (2009)
Epigenetics Laboratory
The Johns Hopkins Kimmel Cancer Center is the recognized leader in epigenetics, the study of alterations to the environment of the cells rather than directly to its DNA.  These alterations are believed to occur very early in the cancer process, making them useful targets for cancer detection, screening, and treatment. CRF has been a partner in this progress, and the current continued support of the epigenetics laboratory will aid investigators and clinicians in moving these discoveries to patients.  Work in this laboratory will help uncover epigenetic biomarkers of cancer that will become screening tests, help oncologists monitor the progress and aggressiveness of tumors and determine if treatments are working, and help surgeons ensure all cancerous tissue is removed. Using targeted therapies to block a hallmark epigenetic alteration, known as hypermethylation, could activate non-functioning cancer-suppressing genes.

Jean Ford, M.D. (2009)
Colorectal Cancer Screening in African-American Adults
Nearly 80 percent of colon cancers are diagnosed in elderly people.  While these citizens have Medicare coverage for colonoscopy, currently the most effective screening method for early detection of colon cancer, many do not have the test.  CRF funding through the public health grant helped the Kimmel Cancer Center establish a system for educating and screening underserved citizens of Baltimore.  The success in prostate cancer screening among uninsured men, earned Ford an additional grant through the Center for Medicare and Medicaid Services to guide African-American adults with Medicare through colon cancer screening and treatment. The CRF partnership is now allowing us to further expand these services beyond colon cancer to guide this population through breast, cervical, and prostate cancer screenings, and if necessary, follow-up care.

Alison Geyh, Ph.D. (2009)
Metal Particles in the Air and Lung Cancer
As automobiles travel on our roadways, through normal wear and tear, microscopic pieces of metal break away and make their way into the air we breathe.  These unseen particles in the air, known as particulate matter, are toxic and contain carcinogens that increase the risk for lung cancer deaths.  Geyh and team have developed a method for characterizing the metal particles found in the air and tracing them back to their sources.  This fingerprinting of particulate matter allows investigators to determine the sources of the pollution and neighborhoods and areas where citizens are most at risk. Such a process was used by researchers in Los Angeles with surprising results.  It revealed that the majority of metal particulates in the air were not caused by cars, as suspected, but rather by diesel cargo ships in the harbor.  Geyh will perform this same type of research in Baltimore, scientifically determining the specific sources of dangerous particles in the air providing information necessary for effective public policies to mediate these risks.

James Herman, M.D. (2009)
Epigenetic Changes and Inflammation in Lung and Esophageal Cancer
Epigenetic changes have been referred to as the ghost in our genes.  Unlike mutations that directly leave their mark on our genes, epigenetic alterations silence key tumor suppressing genes without changing a cell’s DNA.  In epigenetics, investigators must look for modifications in the environment of cells that alter the way genes behave.  It has long been suspected that chronic inflammation plays a role in cancer initiation. A condition known as Barrett’s Esophagus that leaves the esophagus in a continued state of inflammation is a major risk factor for esophageal cancer. Similar inflammatory processes in the lung, such as those caused by smoking, also have been linked to cancer.  Herman suspects that inflammation may be an early precancerous event, causing epigenetic changes that put the cancer process in motion.  He is studying chronic inflammatory conditions in the esophagus and lung to identify and understand the origination of these epigenetic alterations and the cellular changes they cause that lead to cancer development.

Mollie Howerton, Ph.D. (2009)
Removing Barriers to Cancer Clinical Trial Participation
Just two to three percent of adults with cancer enter clinical trials, and minorities and low-income patients are even less likely to participate.  Clinical trials are the mechanism by which research institutions move new research discoveries to patients and confirm their safety and effectiveness and incrementally improve the standard of care for cancer patients. To begin to solve the problem, we must first identify and understand the reasons for low participation. To this end, Howerton launched the IMPORT (Improving Participation in Oncology Research Trials) study to identify specific factors that keep patients from entering clinical trials.  Exploring factors such as proximity to trial sites, awareness of trials, income, health insurance status, and cultural and social issues, she is working to better understand why patients, particularly minorities and those with low-incomes, do not enroll in clinical trials. Howerton has since moved to the National Cancer Institute, expanding this research nationally.  Her co-investigators continue the research at the Kimmel Cancer Center.

Norma Kanarek, Ph.D. (2009)
Traffic-Related Air Pollution and Cancer in Maryland
There is increasing evidence that people who live in communities close to highways and high traffic areas are at higher risk for cancer and respiratory diseases because of their continued exposure to the toxic emissions of these vehicles. Kanarek is studying correlations between traffic-related air pollution and cancer rates in Maryland communities and has compiled a database to analyze cancer incidence, air quality, and traffic volume throughout the state.

Thomas Kensler, Ph.D. (2009)
Curing Cancer at Stage 0
Stage 1 typically describes cancers that are detected at a very early and more curable state. Now, researchers are interested in intercepting and attacking cancers even earlier by reversing cellular changes at the very beginning of the cancer process. The work is leading to the first-ever clinical trials for Stage 0 cancers, malignant changes so early in the cancer process that they are not even on the diagnostic staging scale. Kensler developed a special mouse model to begin first-of-its-kind clinical trials for Stage 0 cancer—interventions that prevent cancers from ever occurring.  He is using the model to test very small doses, called micro doses, of nutrients, such as vitamin D, for their ability to repair precancerous cellular damage caused by diet, pollution, and other environmental exposures. Targeting and eliminating cancer cells before they become tumors and can take hold in organs could dramatically alter incidence and death rates.

Elizabeth Platz, Sc.D., Angelo De Marzo, M.D., Vasan Yegnasubramanian, M.D., Ph.D., and William Nelson, M.D., Ph.D. (2009)
Inflammation, Methylation, and Prostate Cancer
Does chronic inflammation cause cellular assaults that lead to prostate cancer? Our researchers suspect that an epigenetic alteration called hypermethylation that can turn off key tumor suppressor genes conspires with chronic inflammation of the prostate to cause the initiation of prostate cancer. Their studies will determine if environmental exposures, such as diet, influence hypermethylation and lead to inflammation of the prostate gland, and whether these events work together to increase men’s risks of developing prostate cancer. If proven, they will work to develop clinical interventions to interfere with the process.

Elizabeth Platz, Sc.D. and Aravinda Chakravarti, Ph.D. (2009)
Cancer Prevention Resource
The identification of genetic and epigenetic biomarkers of  risk is believed essential to the development of clinical interventions to prevent, detect, and treat cancer. With their first CRF grant in 2004, the research team began assembling a centralized bank of blood samples, and today has gathered a resource of 2,550 specimens now available to investigators for their research studies.  Samples are racially diverse, and the majority has been collected from Maryland residents resulting in findings directly applicable to all Maryland citizens.

Francis Stillman, Ed.D. (2009)
Cancer Prevention in African-American Young Adults

David Holtgrave, Ph.D. (2010)
Smoking Cessation Strategies that Work
African-American men have higher rates of bronchial and lung cancers than Caucasian men, and these cancers are smoking related. In a Johns Hopkins CRF and Howard University partnership, Stillman and team are undertaking community-based research to better understand the factors that influence tobacco use among 18 to 24-year-old African American blue collar workers. Stillman and team have learned that African-American adults in Baltimore smoke for social reasons and purchase individual cigarettes rather than packs. These and other findings are allowing the team to develop culturally relevant strategies and make policy recommendations that could impact smoking rates.  In addition, Stillman and team are exploring whether similar patterns are involved in high smoking rates among the Hispanic population in Baltimore.

Holtgrave, a 2010 recipient of CRF support is expanding on Stillman and team’s research and applying it to young adults throughout the nation.  To date, Holtgrave found, that no study has found an effective smoking cessation strategy for young adults age 20 to 25. However, his research finds that policy interventions, including even modest price increases, and prohibiting smoking in public places, have been effective. Moreover, his studies find that most young adults who smoke say they would like to quit.
Smoking remains the leading risk factor for cancer. The National Cancer Institute associates lung, esophagus, larynx (voice box), mouth, throat, kidney, bladder, pancreas, stomach, and cervix cancers and acute myeloid leukemia with smoking.

James Yager, Ph.D. (2009 and 2010)
Understanding and Preventing Breast Cancer
Yager’s research has been one of the first victims of drastic cuts to CRF funding at Johns Hopkins. Funding in 2009 allowed him to develop an animal model that resembles human breast cancer. He used the model to study how estrogen metabolism can alter gene expression and lead to breast cancer. With dramatic cuts to the CRF research grant, Yager’s 2010 award was slashed. To balance the cut to his grant, he has partnered with former CRF investigator Kala Visvanathan, who earned supplemental support from the Komen Foundation, to weave his research of the relationship between elevated estrogen levels and breast cancer with her studies of sulforaphane and breast cancer prevention.
The team’s research revealed that sulforaphane, a natural compound richly found in broccoli sprouts, blocks breast cancer in animal models. Visvanathan now heads clinical trials testing a sulphoraphane-based broccoli sprouts tea for its ability to alter enzymes in the epithelial cells, or lining of breast ducts. The researchers are tracking the effects of sulphoraphane to see if it influences precursors to breast cancer, and if it can be used to alter the pathway to breast cancer.

Articles in this Issue

The CRF Supports a Decade of Cancer Research Advances

CRF Research Grants Fill Unmet Research Funding

Essential Support for Young Faculty

CRF By the Numbers