Featured Research

from universities, journals, and other organizations

Genes Identified That Protect Against Heart Damage From Chemotherapy

Date:
December 4, 2007
Source:
Medical College of Georgia
Summary:
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.

Dr. Ling Xia, graduate exchange student, and Dr. Hernan Flores-Rozas, MCG cancer researcher.
Credit: Phil Jones

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 don't 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 China's 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 it's dose related and cumulative.

They did studies in relatively simple yeast cells from Dr. Anil Cashikar's 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; it's 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, don't divide. Still there's 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 don't 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 doesn't, 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.

The research was funded by the National Institutes of Health. Dr. Flores-Rozas is a Georgia Cancer Coalition Distinguished Cancer Scholar.


Story Source:

The above story is based on materials provided by Medical College of Georgia. Note: Materials may be edited for content and length.


Cite This Page:

Medical College of Georgia. "Genes Identified That Protect Against Heart Damage From Chemotherapy." ScienceDaily. ScienceDaily, 4 December 2007. <www.sciencedaily.com/releases/2007/12/071203173016.htm>.
Medical College of Georgia. (2007, December 4). Genes Identified That Protect Against Heart Damage From Chemotherapy. ScienceDaily. Retrieved August 28, 2014 from www.sciencedaily.com/releases/2007/12/071203173016.htm
Medical College of Georgia. "Genes Identified That Protect Against Heart Damage From Chemotherapy." ScienceDaily. www.sciencedaily.com/releases/2007/12/071203173016.htm (accessed August 28, 2014).

Share This




More Health & Medicine News

Thursday, August 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Killer Amoeba Found in Louisiana Water System

Killer Amoeba Found in Louisiana Water System

AP (Aug. 28, 2014) State health officials say testing has confirmed the presence of a killer amoeba in a water system serving three St. John the Baptist Parish towns. (Aug. 28) Video provided by AP
Powered by NewsLook.com
Who Could Be Burnt by WHO's E-Cigs Move?

Who Could Be Burnt by WHO's E-Cigs Move?

Reuters - Business Video Online (Aug. 28, 2014) The World Health Organisation has called for the regulation of electronic cigarettes as both tobacco and medical products. Ciara Lee looks at the impact of the move on the tobacco industry. Video provided by Reuters
Powered by NewsLook.com
CDC Director On Ebola Outbreak: 'It's Worse Than I Feared'

CDC Director On Ebola Outbreak: 'It's Worse Than I Feared'

Newsy (Aug. 28, 2014) CDC director Tom Frieden says the Ebola outbreak is even worse than he feared. But he also said there's still hope to contain it. Video provided by Newsy
Powered by NewsLook.com
How A 'Rule Of Thumb' Could Slow Down Drinking

How A 'Rule Of Thumb' Could Slow Down Drinking

Newsy (Aug. 28, 2014) A study suggests people who follow a "rule of thumb" when pouring wine dispense less than those who don't have a particular amount in mind. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins