This is the twice-per-month electronic newsletter for basic, preclinical and translational research news related to the Johns Hopkins School of Medicine. Please forward freely. Direct comments or questions to Joanna Downer, PhD, in the Office of Corporate Communications (4-5105, jdowner1@jhmi.edu).
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IN THIS ISSUE:
+ Phosphatase Mutations May Highlight Targets For New Colon Cancer Drugs
+ Shortened Chromosomes Linked to Early Stages of Cancer Development
+ Mutant Ribosomes Make Proteins But Can't Let Go
NEWS BRIEFS:
New Contacts for Animal Protocols
Roses To Give Third McKusick Lecture July 8
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Do you have an interesting research finding about one month from publication or presentation? Send manuscripts to Joanna Downer at jdowner1@jhmi.edu or fax to 410-614-8951. Information about awards and honors received by laboratory personnel and others is welcomed also.
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RESEARCH HIGHLIGHTS:
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5/20/04
Phosphatase Mutations May Highlight Targets
For New Colon Cancer Drugs
In the hunt for new cancer drug targets, scientists from the Johns Hopkins Kimmel Cancer Center and the Howard Hughes Medical Institute have discovered mutations in a family of genes linked to more than a quarter of colon cancers, as well as several other common cancers including breast and lung.
Their research, described in the May 21 issue of Science, reveals more options for creating personalized therapies tailored to counteract mutated gene pathways present in individual tumors.
"What makes this discovery significant is that we've found mutations that directly affect cancer development," says Victor Velculescu, MD, PhD, assistant professor at the Johns Hopkins Kimmel Cancer Center.
After analyzing 157 colon cancers, the research team found 77 mutations in six genes that make tyrosine phosphatases, enzymes that help coordinate signals that manage cellular growth, death, differentiation and nearby tissue invasion. They normally turn off tumor growth, but in cancers they no longer work properly.
Rather than using cancer drugs to try to "fix" the loss of phosphatase activity, the investigators believe that balancing or counteracting that loss by shutting down the phosphatases' opposing enzymes, tyrosine kinases, may be useful.
http://www.hopkinsmedicine.org/Press_releases/2004/05_20_04.html
Science 21 May 2004;304(5674):1164-1166
http://www.sciencemag.org/cgi/content/full/304/5674/1164
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5/18/04
Shortened Chromosomes Linked to Early Stages
of Cancer Development
Scientists at the Johns Hopkins Kimmel Cancer Center say they have evidence that abnormally short telomeres -- the end-caps on chromosomes that normally preserve genetic integrity -- appear to play a role in the early development of many types of cancer.
Studying tissue taken from small precancerous lesions in the bladder, esophagus, large intestine, mouth and cervix, the research team found abnormal telomere lengths in 97 percent of the cases examined. In particular, abnormally short telomeres were found in 88 percent of cases.
"We were surprised how often you see shortened telomeres this early in the development of these cancers," says Alan Meeker, PhD, a postdoctoral fellow in urology and pathology. "It's a strong indicator that abnormal telomeres are likely playing a causal role in cancer development."
For the study, published in the May 15 issue of Clinical Cancer Research, Meeker and his colleagues used a technique called fluorescent in situ hybridization (FISH) to compare telomere length in cells from both precancerous lesions and normal surrounding cells.
http://www.hopkinsmedicine.org/Press_releases/2004/05_26a_04.html
Clinical Cancer Research 15 May 2004;10:3317-3326
http://clincancerres.aacrjournals.org/cgi/content/abstract/10/10/3317
(This journal can be accessed online only from Welch Library terminals or using an individual subscription. For information, visit http://www.welch.jhu.edu/eresources/notice_aacr.html .)
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5/27/04
Mutant Ribosomes Make Proteins But Can't Let Go
Writing in the May 28 issue of Cell, Johns Hopkins researchers report that four critical components of cells' protein-building machine don't do what scientists had long assumed.
The machine, called the ribosome, is a ball of RNA surrounded by proteins. In the RNA center, genetic instructions are read, the right protein building block is added onto a growing chain, and at the appropriate time the chain is snipped and released. But exactly how the ribosome adds to growing proteins and how it releases the finished product is still unclear.
In the hunt for these details, scientists have focused on four RNA building blocks, or nucleotides, deep within the ribosome that are identical in every species, from bacteria to humans. Because they sit where the protein chain is actually built, these universally conserved nucleotides were thought to help that process.
In laboratory experiments, Biochemistry and Molecular Biology graduate student Elaine Youngman and her colleagues found that ribosomes with these key spots changed could put proteins together as well as normal ribosomes, but let go of the finished product much more slowly.
The researchers' work suggests a brand new model for how the ribosome works, says Rachel Green, PhD, associate professor of molecular biology and genetics and a Howard Hughes Medical Institute associate investigator. http://www.hopkinsmedicine.org/Press_releases/2004/05_27b_04.html
Cell 28 May 2004;117(5):589-599
http://www.cell.com/content/article/fulltext?uid=PIIS0092867404004118
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NEWS BRIEFS:
New Contacts for Animal Protocols -- Amy Fish, the Administrative Manager of the Institutional Animal Care and Use Committee, resigned at the end of May due to pressing health issues of a member of her extended family. Due to this change, investigators whose last names begin with the letters A-K should direct email and phone correspondence to Lisa Wetzelberger, and those whose last names begin with L-Z should contact Miriam Bell-Frazier. The IACUC office number is 443-287-3738.
http://www.jhu.edu/animalcare/
Roses To Give Third McKusick Lecture July 8 -- Allen D. Roses, MD, will give the third Victor A. McKusick Lecture, "Genetics and Pharmacogenetics in Discovering and Developing Medicines," beginning at 4 pm, Thursday, July 8, in the auditorium of the Wood Basic Science Building. A reception will follow. Roses, Senior Vice President, Genetics Research at GlaxoSmithKline, was charged with organizing genetic strategies for susceptibility gene discovery, pharmacogenetics strategy and implementation, and integration of genetics into medicine discovery and development. For more information email Donna Sims at simsdo@jhmi.edu .
http://www.insidehopkinsmedicine.org/news/news_detail.cfm?id=2002
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