Navigation Links
Researchers discover link between organ transplantation and increased cancer risk
Date:7/15/2008

PHILADELPHIA Researchers have determined a novel mechanism through which organ transplantation often leads to cancer, and their findings suggest that targeted therapies may reduce or prevent that risk.

In the July 15, 2008, issue of Cancer Research, researchers at Harvard Medical School found in animal and laboratory experiments that the anti-rejection, immunosuppressive drug cyclosporine ramps up expression of vascular endothelial growth factor (VEGF), which signals the growth of new blood vessels that can feed tumors.

They also found that simultaneously administering an anti-VEGF therapy with cyclosporine in mice repressed this tumor growth. Several inhibitors of VEGF are already in use in human cancer therapy.

The findings could offer some good news for the 15 to 20 percent of transplant patients who develop cancer within a decade of receiving new organs, according to the study's senior investigator, Soumitro Pal, Ph.D., an assistant professor at Harvard Medical School's Transplantation Research Center at Children's Hospital in Boston.

"It may be that anti-VEGF agents given judiciously after transplantation can reduce future cancer occurrence," he said.

VEGF expression is markedly increased in patients post-transplantation, and this can aid in the development of a blood supply to a transplanted organ, helping it survive and thrive. "But once the organ has stabilized, it may be possible to lower the level of VEGF expression to prevent tumor growth," he said. "We would need to figure out how to balance benefit and risk to keep cancer at bay."

Tumors that develop after transplantation may have three potential sources: they may have pre-existed or could have been a recurrence of previous cancer and in both of these cases, a patient's pre-transplant immune system might have kept these cancers in check or cancer-causing viruses could have come from the donor organ. Physicians have long observed that immunosuppressive agents, such as the class of calcineurin inhibitors that includes cyclosporine, appear to promote cancer development, often in organs that are not transplanted, but the cause of this was unclear. The Harvard team tested the ability of cyclosporine to promote growth of pre-existing tumors in mice implanted with human renal (kidney) cancer cells. Mice treated with the agent formed tumors faster than untreated mice, but anti-VEGF therapy substantially reduced that excessive growth.

Digging deeper into the biological pathway of VEGF activation, the scientists found that cyclosporine activates two of the three forms of the common protein catalyst, protein kinase C, which leads to increased expression of VEGF.

"We think PKC-mediated VEGF transcriptional activation is a key component in the progression of cyclosporine-induced post-transplantation cancer," Pal said. "It is likely not the whole story, but this gives us a clue that we might be able to use existing or novel therapies to reduce cancer risk in transplanted patients."


'/>"/>

Contact: Jeremy Moore
Jeremy.moore@aacr.org
267-646-0557
American Association for Cancer Research
Source:Eurekalert

Related biology news :

1. Dartmouth researchers discover gene signatures for scleroderma
2. Louisiana Tech researchers feature drug reformulation in prestigious journal
3. UCLA researchers locate and image prostate cancer as it spreads to lymph nodes
4. Researchers catch ion channels in their opening act
5. UGA researchers discover mechanism that explains how cancer enzyme winds up on ends of chromosomes
6. Researchers hack final part of the immune system code
7. Iowa State researchers study ground cover to reduce impact of biomass harvest
8. From foe to friend: Researchers use salmonella as a way to administer vaccines in the body
9. Researchers reveal types of genes necessary for brain development
10. Researchers identify cancer preventive properties in common vitamin supplement
11. UT Southwestern researchers identify new targets for RNAs that regulate genes
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/5/2017)... 2017  The Allen Institute for Cell Science today ... one-of-a-kind portal and dynamic digital window into the human ... first application of deep learning to create predictive models ... and a growing suite of powerful tools. The Allen ... future publicly available resources created and shared by the ...
(Date:4/3/2017)... April 3, 2017  Data captured by ... platform, detected a statistically significant association between ... to treatment and objective response of cancer ... to predict whether cancer patients will respond ... as well as to improve both pre-infusion potency ...
(Date:3/29/2017)... 2017  higi, the health IT company that operates ... America , today announced a Series B investment ... EveryMove. The new investment and acquisition accelerates higi,s strategy ... transform population health activities through the collection and workflow ... higi collects and secures data today on behalf of ...
Breaking Biology News(10 mins):
(Date:5/26/2017)... ... May 25, 2017 , ... Throughout this webinar, participants will ... process development and economic goals were achieved in both industry and academic settings. ... system, along with techniques for scaling production of mesenchymal stem cells (MSCs) and ...
(Date:5/24/2017)... BOUNTIFUL, Utah (PRWEB) , ... May 24, 2017 ... ... announces the selection and implementation of CLEARAS Water Recovery’s Advanced Biological Nutrient Recovery ... a key component of a $24 million plant upgrade to sustainably meet current ...
(Date:5/24/2017)... May 23, 2017 As Ebola resurfaces in the ... deaths and 20 suspected cases now reported, a new analysis ... database, showed a correlation between the 2014 and 2017 outbreaks ... rose sharply in 2012-13, which preceded the 2014 outbreak. An ... Ebola gene Replikin counts in 2014-15, which again precedes the ...
(Date:5/23/2017)... ... May 23, 2017 , ... Genedata, a ... anniversary, marking the occasion with a strong presence at Bio-IT World Conference & ... further extends an invitation to all attendees to view posters on the ...
Breaking Biology Technology: