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:
+ New Gene Target Found for Colon and Other Cancers
+ Inactivated Genes Put First Chink in Colon Cell's Anti-Tumor Armor
+ Combination of Toxin and Arsenic May Be Novel Treatment for Leukemia
NEWS BRIEFS:
Young Investigators' Day Celebration April 8
Rodent Surgery Class April 8
Animal Welfare Lecture April 15
Grant Writing Workshop April 22, 23
AWARDS AND HONORS:
Angell Receives Samuel Asper Award
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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.
For more info on a story, click the accompanying hyperlink.
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RESEARCH HIGHLIGHTS:
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3/11/04
New Gene Target Found for Colon and Other Cancers
Scientists at the Johns Hopkins Kimmel Cancer Center and the Howard Hughes Medical Institute have found mutations in a gene linked to the progression of colon and other cancers. The findings, published in Science's online express section on March 11, may lead to new therapies and diagnostic tests that target this gene.
The gene, called PIK3CA, is part of a family of genes encoding lipid kinases, enzymes that modify fatty molecules and direct cells to grow, change shape and move. Although scientists have been studying the biochemical properties of this gene family for more than a decade, until now, no study had revealed that mutations in this family were involved in cancer. Moreover, the scientists' results demonstrate that PIK3CA mutations are actually fairly common in cancers.
"These findings open the door to developing specific therapies that may prove useful for the treatment of cancers with mutations in PIK3CA," says senior author Victor Velculescu, MD, PhD, assistant professor of oncology.
In their current experiments, the scientists sequenced the molecular code of genes in this lipid kinase family and found mutations in one particular gene, called PIK3CA, that increase the gene's activity. PIK3CA mutations were found in 32 % of colon cancer samples (74/234), 27 % (4/15) of glioblastomas, 25 % (3/12) of gastric cancers, 8 % (1/12) breast cancers and 4 % (1/24) of lung cancers.
By studying 76 additional premalignant colon tumors, the scientists found that PIK3CA mutations may occur at or near the time a tumor is about to invade other tissues, says first author Yardena Samuels, PhD, a postdoctoral fellow.
http://www.hopkinsmedicine.org/Press_releases/2004/03_11_04.html
Science, published online March 11
http://www.sciencemag.org/cgi/content/abstract/1096502v1
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3/14/04
Inactivated Genes Put First Chink in Colon Cell's Anti-Tumor Armor
Johns Hopkins Kimmel Cancer Center scientists have identified a switched-off family of genes that may prove to be a significant and early dent in a colon cell's anti-cancer armor.
Under normal circumstances, the gene family, called SFRPs (for secreted frizzled-related proteins), stops a pathway of cell-growth directed by the WNT gene. SFRPs' inactivation is an early step en route to cancer, the researchers report in the March 14 advance online edition of Nature Genetics.
In addition, because attachment of extra methyl groups, a reversible process, is what shuts down SFRP genes, the findings also suggest potential anti-cancer value in green tea and other compounds thought to affect methylation, the researchers say.
"Previously, we thought that mutations downstream of the WNT gene were enough to trigger the cell to stay alive, keep growing and develop into a tumor. Our key finding is that the cell also may need to shut off SFRP genes to become cancerous," says Stephen Baylin, MD, Ludwig Professor of Oncology and director for basic research at the Johns Hopkins Kimmel Cancer Center. "SFRP could be a great target for preventing cancer."
Adding SFRPs to colon cancer cells whose SFRP genes had been inactivated and whose WNT pathway carried mutations caused the cells to stop growing uncontrollably and to die. The research team also found that inactivation of SFRP genes occurs in the earliest form of lesion, called an atypical crypt foci (earlier than polyps or cancer), about 5 percent of which become colon cancers.
http://www.hopkinsmedicine.org/Press_releases/2004/03_14_04.html
Nat Gen, Advanced Online Publication, March 14.
http://www.nature.com/cgi-taf/DynaPage.taf?file=/ng/journal/vaop/ncurrent/full/ng1330.html
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3/15/04
Combination of Toxin and Arsenic May Be Novel Treatment for Leukemia
Johns Hopkins Kimmel Cancer Center scientists have discovered why arsenic has long been a successful way to treat certain leukemias, and have found that a combination of the poison and a second naturally occurring toxin may provide a potent new therapy.
First used as therapy for cancer in post-revolution China, arsenic is known to be effective against treatment-resistant acute promyelocytic leukemia (APL), a cancer of the blood and bone marrow characterized by unhealthy myeloid or white blood cells. While its anti-cancer effects have been linked to the creation of reactive oxygen species, exactly how arsenic triggers their production has been unclear.
Using molecular studies, the researchers tracked arsenic's target to NADPH oxidase, an enzyme complex that produces reactive oxygen species and is known to help white blood cells kill invading bacteria - and in the process kill themselves, says Chi Dang, MD, PhD, vice dean for research and professor of medicine, cell biology, pathology and oncology.
NADPH oxidase is also the target of bryostatin, a toxin found in coral-like aquatic organisms and, in synthetic forms, currently in clinical trials to treat a variety of cancers. In experiments with APL cell lines, the researchers discovered that a low-dose combination of bryostatin and arsenic worked synergistically to kill leukemic cells. The findings appear in the March 30 issue of Proceedings of the National Academy of Sciences (published online March 15).
Additional laboratory and animal studies are required before any clinical trial will be planned with APL patients, says first author Wen-Chien Chou, MD, PhD, a postdoctoral fellow.
http://www.hopkinsmedicine.org/Press_releases/2004/03_15_04.html
PNAS 2004;101(13):4578-4583
http://www.pnas.org/cgi/content/full/101/13/4578
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Young Investigators' Day Celebration April 8 -- The 27th annual Young Investigators' Day celebration, including a poster session and talks by awardees, is scheduled for 4 pm, April 8, in Mountcastle Auditorium, Pre-Clinical Teaching Building. A reception will follow in the Greenhouse Cafe. The schedule of events can be found at:
http://www.insidehopkinsmedicine.org/news/news_detail.cfm?id=1867
For a listing of this year's award recipients, visit:
http://www.hopkinsmedicine.org/Press_releases/2004/YoungInvestigators.html
http://www.insidehopkinsmedicine.org/young_investigators_day/2004_winners.cfm
Rodent Surgery Class April 8 -- The Institutional Animal Care and Use Committee still has room available in the Rodent Surgery class scheduled for 9 a.m., April 8, in Ross 450. Other animal research training opportunities in April include "Tips and Tricks for Writing an Animal Use Protocol," on April 22 at noon in Ross 403. Also, a reprise of "Orientation to Animal Care and Use at Johns Hopkins University" will be held April 19 at 11 a.m. in Ames Hall on the Homewood campus. To register for the Rodent Surgery Class or the Orientation, email pmatos1@jhmi.edu or call 443 287 3738. For a complete listing of all IACUC seminars visit
http://www.jhu.edu/animalcare/training4.html
Animal Welfare Lecture 4 pm April 15 -- Marilyn Brown, DVM, director of animal welfare and training at Charles River Laboratories, will give the next talk in the Enhancing Humane Science Lecture Series on Thursday, April 15, from 4 to 5 pm in the Bloomberg School of Public Health building, Room W2008. Her talk, "Animal Welfare: Enhancing a Culture of Caring," will be followed by a reception. The lecture series is sponsored by Johns Hopkins Center for Alternatives to Animal Testing and the Associate Provost for Animal Research and Resources. For more information contact mprincip@jhsph.edu .
Grant Writing Workshop April 22, 23 -- The JHMI Professional Development Office is offering a two-part workshop to help first-time applicants with writing an NIH or other peer-reviewed research proposal. The first part of the workshop is required for participants and takes place over two days, April 22 and 23. Then, on May 4 or 6 (for faculty) or May 7 (for postdocs), small group sessions will provide opportunities for participants to discuss and receive feedback on their own Abstract and Specific Aims sections. Registration forms are available at the PDO office (2-107, 1830 Building) or by email from JHMIPDO@jhmi.edu .
http://www.insidehopkinsmedicine.org/news/news_detail.cfm?id=1783
Angell Receives Samuel Asper Award -- Charles Angell, MD, assistant professor of medicine, has received the Samuel Asper Award for clinical excellence from the Maryland Chapter of the American College of Physicians (ACP). The award is named for the late Dr. Samuel Asper, a professor of medicine at Johns Hopkins and a former president of the ACP.
http://www.acponline.org/chapters/md/awards.htm
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