Date: December 1, 2004
Business Week, November 25, 2003
Sidney Kimmel Makes Top Philanthropists List
Sidney Kimmel, who gave Johns Hopkins a landmark gift for cancer research and patient care in 2001, was named one of America's top philanthropists by Business Week magazine. Mr. Kimmel is listed at number 15 alongside such other notable philanthropists as Microsoft's Bill Gates and New York City Mayor Michael Bloomberg. As founder and Chairman of Jones Apparel Group, Sidney Kimmel is one of the nation's leading cancer philanthropists. He also has given numerous gifts to support education and the arts.
Popular Science, September 2003
Velculescu’s Research Called Brilliant
Victor E. Velculescu’s ways of identifying cancer-related genes is brilliant—so says Popular Science magazine. He was named by the publication in its second annual Brilliant 10, a survey of researchers and academics in fields from geophysics to quantum origami to identify scientisits whose work is, according to POPSCI’s editor, “just plain brilliant.”
Velculescu is recognized for his “maverick approach which ushered in a new way to finger cancer genes,” reports POPSCI. This approach is known as SAGE (Serial Analysis of Gene Expression). Of the approximately 100,000 genes in the human genome, only a fraction are thought to be active in each type of cell, but there are several thousand different types of cells in the human body, and each has a unique pattern of gene expression. SAGE allows researchers to study thousands of genes simultaneously, measure their expression, and quickly identify the genetic differences between normal and tumor cells.
Victor Velculescu, M.D, Ph.D., is a Maryland Cigarette Restitution Fund and National Cancer Institute-funded investigator.
Cancer Cell, June 23, 2003
Pancreatic Cancer Linked to Errant Reactivation of Cell Pathway
Steven D. Leach, M.D., has uncovered a novel pathway that triggers the development of pancreatic cancers. Working with cancer cells from 55 patients, the Hopkins team found that a growth signal normally turned off in adult tissues is mistakenly turned back on after injury or inflammation of the pancreas. “We think reactivation may be a first step in initiating pancreatic cancer, well before the onset of any alterations to the pancreatic cells’ genetic material,” says Leach, Paul K. Neumann Professor in Pancreatic Cancer. Using drugs to deactivate the pathway could prevent these cancer-causing events from occurring, according to Leach.
This research was funded by the National Institutes of Health, the Lustgarten Foundation for Pancreatic Cancer and a National Cancer Institute gastrointestinal SPORE (Specialized Programs of Research Excellence).
Nature, March 5, 2003
Embryo Cell Pathway is Target for New Lung Cancer Therapy
Researchers at the Johns Hopkins Kimmel Cancer Center may have uncovered a way to halt the smoking-induced cellular events that lead to 99 percent of all small cell lung cancers (SCLC).
They have identified a primitive cellular pathway, called Sonic Hedgehog (named for the cartoon character and spiky hairs it develops on fruit flies), which stays turned on long after it should be turned off in some lung cancers. "We believe chronic injury to the lungs by cigarette smoking reactivates genes in the Hedgehog pathway to repair cell damage in the lining of the lungs. The ongoing and regular assault to the lungs by cigarettes causes the usually dormant pathway to be stuck in activation mode, making too many new cells, ultimately resulting in cancer," says Neil Watkins, Ph.D., assistant professor of oncology.
The Sonic Hedgehog pathway has been well studied for its role in the development of mammalian embryonic cells, and more recently, for its relationship to cancer. But, this is one of the first attempts to therapeutically manipulate this cell pathway, according to Stephen Baylin, M.D., (pictured) Ludwig Professor of Oncology and director of cancer research. “It's a perfect example of how basic developmental science can have clinical implications in a relatively short period of time," he says. Investigators are testing drugs on mice, including one called cyclopamine, that block the Hedgehog pathway, but human clinical trials are still several years away.
This research was funded by the Flight Attendant Medical Research Institute and a National Cancer Institute lung cancer SPORE (Specialized Programs of Research Excellence).
Science, May 9, 2003
Analysis of Gene Family Points to New Treatments for Colon Cancer
In what appears to be the first systematic analysis of a disease-related gene family, researchers uncovered gene mutations linked to more than 30 percent of colon cancers. These genetic alterations could serve as targets for new treatments.
The research team studied 182 human colon cancers to identify mutations in the tyrosine kinase (TK) gene family. TK genes are thought to be good therapeutic targets for managing cancer because the proteins they encode play key roles in controlling cell growth, differentiation, motility, and nearby tissue invasion. Although a few TK genes have been shown to be mutated in specific cancers, until now, no study has revealed how many or how often members of the TK gene family are altered in a particular cancer type, according to Victor Velculescu, M.D., Ph.D., assistant professor of oncology. "Our findings open the door to individualized analysis and treatment of colorectal cancer. One could envision personalized therapeutics, based on mutations in different kinase genes and designed to match the mutated TK pathways present in each patient's particular tumor DNA,” he says.
This research was funded by the Benjamin Baker Scholarship Fund, the National Cancer Research Alliance, and grants from the National Institutes of Health.
Journal of the National Cancer Institute, April 16, 2003
Common Thyroid Cancer Gene Mutation Found
A single genetic mistake causes about two-thirds of papillary thyroid cancers. New therapies to counteract the mistake are now being studied. A mutation of the BRAF (pronounced b-raf) gene was found in 68 percent (24 of 35 samples) of papillary thyroid cancers. These tumors account for about 75 percent of all thyroid cancer and occur mostly in women. “Until now, there have been no other major genetic events identified for common thyroid cancers,” says David Sidransky, M.D., professor of otolaryngology and oncology. “Our goal is to find better diagnostics and drug therapies designed to target the effects of this mutation.”
The mistake involves a subtle change in the chemical bases (adenine, thymine, cytosine, and guanine) that make up DNA. The order in which these bases—or nucleotides—occurs determines the information genes communicate to cells much like specific letters of the alphabet combine to form words and sentences. In the case of BRAF, the nucleotides are altered, and T (thymine) is switched to an A (adenine). The researchers found that this single coding error among more than 2,000 nucleotides in the gene causes it to be stuck in the “on” position, making thyroid cells continuously grow and divide, ultimately turning into cancer.
Improvements in diagnostic tests and treatments using this new discovery about the BRAF mutation could speed up diagnosis and help patients survive advanced disease.
This research was partially funded by the National Cancer Institute.
Cancer Research, May 14, 2003
Fanconi’s Anemia Genes are Culprits in Early Onset Pancreatic Cancer
Three genes, long linked to a rare inherited disease known as Fanconi’s anemia (FA), appear to play a role in ten percent or more of pancreatic cancers.
The genes, BRCA2, FANCC, and FANCG, have all been associated with Fanconi's anemia. Those affected are born with only a single normal copy of one or more of the genes. Though they do not develop FA, these people often develop pancreatic cancer, usually in their 40s and 50s, about a decade earlier than the average.
“The upside is that while these gene mutations cause a horrific disease, they may actually be the Achilles’ heel of the tumor and make these particular cancers more responsive to treatment," says Scott Kern, M.D., professor of oncology and pathology. The culprit genes appear to make pancreatic cancer cells highly susceptible to treatment with two FDA-approved cancer drugs, mitomycin C and cisplatin. Human clinical trials are now being planned.
This research was funded by a National Cancer Institute gastrointestinal SPORE (Specialized Programs of Research Excellence) grant
Science, May 14,
Test May Predict Colon Cancer Risk
A simple blood test may provide physicians a way to identify those people who may be at higher than normal risk for the most common form of colon cancer. The research focuses on genetic “red flags” housed not in the sequence of the DNA building blocks themselves, but in other subtle modifications made to the genetic code.
“We hope these findings will have the ability to identify people at increased risk for colon cancer so that we may follow them closely and prevent disease, or at least catch it early, similar to the approach doctors use in identifying patients at risk of heart disease,” says Andrew Feinberg, M.D., King Fahd Professor of Medicine.
Right now, the blood tests are for research purposes only. “More efficient tests will take several more years at least to develop,” says Feinberg. “We also need to follow patients over time to see if they develop cancer after the test is positive,” he adds.
This research was funded by the National Cancer Institute and Maryland Cigarette Restitution Fund.
Arthritis and Rheumatism, January 10, 2003
Cancer Therapy May Offer Lupus Patients New Hope
In a collaborative study, researchers at the Johns Hopkins Kimmel Cancer Center and Lupus Center have successfully used high doses of the anti-cancer drug cyclophosphamide to treat patients with moderate and severe forms of lupus, a chronic and sometimes fatal autoimmune disease.
Fourteen patients with lupus, who had failed standard therapies and were suffering from significant organ failure, underwent four days of high-dose intravenous cyclophosphamide. After an average follow-up of more than two and a half years, five patients had complete responses and three of those patients have remained disease-free after completely discontinuing treatment. Six patients achieved a partial response and take lower doses of previously ineffective immune-suppressing drugs. Two patients did not respond to the therapy, and one patient had some response but developed new renal disease.
“Living with long-term severe lupus is devastating as the body’s immune system attacks itself,” says Michelle Petri, M.D., professor of rheumatology. “Lupus has permanently damaged one or more organ systems in about half of all our patients, in spite of currently available therapies. The idea with this treatment is to blast the lupus once and wipe out the abnormal immune system and allow the body to relearn and function normally without further therapy,” says Petri.
This research was funded by the National Institutes of Health and the Leukemia and Lymphoma Society of America