Navigation Links
Genes identified that protect against heart damage from chemotherapy
Date:12/3/2007

A series of genes that protect cells from the powerful, common chemotherapeutic agent doxorubicin has been identified by researchers working to understand how the drug also can destroy the heart.

We found a series of genes that are very important for cell survival in the face of doxorubicin, says Dr. Hernan Flores-Rozas, cancer researcher at the Medical College of Georgia Cancer Center. At the moment you start inactivating these genes, the cells become very sensitive and dont grow any more. So now we know which genes we need to inactivate in the cell to make it very sensitive to the drug.

Doxorubicin is widely used to treat solid tumors from breast cancer to prostate and ovarian cancer. A slightly modified version, daunorubicin, is a powerful fighter of leukemia and lymphoma and often is used in children.

Unfortunately, just as cancer treatment ends, heart problems can begin for some patients who get these drugs. Heart cells, called cardiomyocytes, can commit suicide, or apoptosis, says Dr. Ling Xia, a graduate student at the Department of Cardiology at Chinas Wuhan University who is part of an exchange program with MCG. The result is dilative cardiomyopathy, in which the heart becomes a boggy organ that can no longer pump blood out to the body. Damage can even show up years after treatment, she says noting there is no known way to prevent or treat it, short of a heart transplant.

The long-term goal of their research is prevention and maybe enhanced cancer treatment through development of ways to turn these genes off in cancer cells and on in heart cells, says Dr. Flores-Rozas, corresponding author on the study published in the Dec. 1 issue of Cancer Research. Dr. Xia is first author.

Another possibility is turning down their protection in cancer cells, which should necessitate less drug and result in less heart damage, says Dr. Flores-Rozas, noting that its dose related and cumulative.

They did studies in relatively simple yeast cells from Dr. Anil Cashikars yeast knockout collection. Yeast, which have about 6,000 genes compared to humans 30,000, are good models for study of human cells because they include the same basic cellular functions such as replication, DNA repair, signaling and even cell death, says Dr. Cashikar, MCG geneticist and a study co-author.

They found 71 genes that conveyed varying degree of protection from doxorubicin. The cell does not have a unique mechanism to protect from doxorubicin; its a very complex response, says Dr. Flores-Rozas. Some genes protect better than others. But in the absence of some of these genes, the cells will die from exposure to the drug.

The genes may even protect cancer and cardiac cells differently, he says noting one way doxorubicin stops cancer cells is by preventing their classic rapid division. Cardiac cells, on the other hand, dont divide. Still theres some common ground between the cells when it comes to protection. Cardiac cells have been known to use heat shock proteins to protect themselves from toxic injuries. This enables proteins made by cells to continue to function properly. If you have activated heat shock response, you have more activate proteins, says Dr. Flores-Rozas. If you have proteins that dont function, the cell is eventually going to die. The MCG researchers have shown the heat shock response also is activated in a stressed cancer cell.

He notes these newly identified protective genes likely already are expressed at some level before the cells are confronted with a stress such as a chemotherapeutic agent, then step up expression in response. If it doesnt, doxorubicin will kill them, Dr. Flores-Rozas says.

The MCG researchers suspect the genes may be protective from other stresses, such as a viral infection, as well.

They already are looking at their function and expression in cancer and cardiac cells normally and when exposed to doxorubicin.


'/>"/>

Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia  
Source:Eurekalert

Related medicine news :

1. Pathway links inflammation, angiogenesis and breast cancer
2. Traffic Fumes Plus Genes Boosts Kids Asthma Risk
3. New Database to Help Speed Search for Bipolar Disorder Genes
4. Is Perfect Pitch All in the Genes?
5. Discovery suggests location of genes for breast density, a strong risk factor for breast cancer
6. Genes Boost Risk for Rheumatoid Arthritis, Lupus
7. The genes involved in rheumatoid arthritis identified
8. If you think cancer genes are simple, you dont know JAK
9. Test for lung cancer looks for discomforting quiet among protective genes
10. Hushed Genes Might Mean Higher Lung Cancer Risk
11. EURYI project to understand how the brain wires during embryogenesis
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Genes identified that protect against heart damage from chemotherapy
(Date:6/25/2016)... ... June 25, 2016 , ... First Choice Emergency Room , ... Sesan Ogunleye, as the Medical Director of its new Mesquite-Samuell Farm facility. , ... our new Mesquite location,” said Dr. James M. Muzzarelli, Executive Medical Director of First ...
(Date:6/25/2016)... ... 25, 2016 , ... Dr. Calvin Johnson has dedicated his ... implemented orthobiologic procedures as a method for treating his patients. The procedure is ... to perform the treatment. Orthobiologics are substances that orthopaedic surgeons use to help ...
(Date:6/25/2016)... , ... June 25, 2016 , ... Conventional wisdom preaches ... success. In terms of the latter, setting the bar too high can result in ... than just slow progress toward their goal. , Research from PsychTests.com ...
(Date:6/24/2016)... , ... June 24, 2016 , ... Those who have ... these feelings, many turn to unhealthy avenues, such as drug or alcohol abuse, as ... Michigan, has released tools for healthy coping following a traumatic event. , Trauma sufferers ...
(Date:6/24/2016)... ... , ... Marcy was in a crisis. Her son James, eight, was out of control. Prone ... physically. , “When something upset him, he couldn’t control his emotions,” remembers Marcy. “If ... at my other children and say he was going to kill them. If we ...
Breaking Medicine News(10 mins):
(Date:6/26/2016)... LAS VEGAS , June 26, 2016 ... movement to value-based care operating models within the health ... that enable greater financial efficiency , Deloitte offers ... address the key business issues impacting efficient cost optimization: ... alignment , These services facilitate better outcomes and ...
(Date:6/24/2016)... June 24, 2016 ... announced the addition of the " Global Markets ... This report focuses ... an updated review, including its applications in various applications. ... market, which includes three main industries: pharmaceutical and biotechnology, ...
(Date:6/24/2016)... 24, 2016 Research and Markets has ... Companion Diagnostic Tests" report to their offering. ... Diagnostics The World Market for Companion Diagnostics ... diagnostics. Market analysis in the report includes the following: ... Vitro Diagnostic Kits) by Region (N. America, EU, ROW), 2015-2020 ...
Breaking Medicine Technology: