Navigation Links
Study shows how chronic inflammation can cause cancer
Date:11/12/2012

  • Chronic inflammation like sunburn can sometimes cause cancer, but how it happens remains unknown.
  • This study shows for the first time how a substance made by the body to promote inflammation can cause an aggressive form of leukemia.
  • This knowledge enabled the researchers to develop a possible treatment for the leukemia.

COLUMBUS, Ohio A hormone-like substance produced by the body to promote inflammation can cause an aggressive form of leukemia when present at high levels, according to a new study by researchers at the Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC James).

The study shows that high levels of interleukin-15 (IL-15) alone can cause large granular lymphocytic (LGL) leukemia, a rare and usually fatal form of cancer, in an animal model. The researchers also developed a treatment for the leukemia that showed no discernible side effects in the animal model.

Published in the journal Cancer Cell, the findings show that IL-15 is also overexpressed in patients with LGL leukemia and that it causes similar cellular changes, suggesting that the treatment should also benefit people with the malignancy.

"We know that inflammation can cause cancer, but we don't know the exact mechanism," says principal investigator Dr. Michael A. Caligiuri, CEO of The James Cancer Hospital and Solove Research Institute, and director of Ohio State's Comprehensive Cancer Center.

"Here, we show one way it can happen, and we used that information to potentially cure the cancer."

Normally, the body releases IL-15 to stimulate the development, survival and proliferation of natural-killer cells, which are immune cells that destroy cancer and virus-infected cells. This research shows that when IL-15 is present in high amounts in the body for prolonged periods, such as during chronic inflammation, it can cause certain immune cells called large granular lymphocytes, or LGLs, to become cancerous.

This malignant transformation begins when IL-15 attaches to receptors on the surface of normal LGLs, an event that boosts levels of a cancer-causing protein called Myc (pronounced "mick") inside the cells. The high Myc levels, in turn, bring changes that cause chromosome instability and additional gene mutations. The high Myc levels also activate a process called DNA methylation, which turns off a variety of genes, including important genes that normally suppress cancer growth.

"We stand the best chance of curing cancer when we understand its causes," says first author Anjali Mishra, a postdoctoral researcher in Caligiuri's laboratory. "Once we understood how this inflammatory hormone causes this leukemia, we used that information to develop a treatment by interfering with the process."

Caligiuri and Mishra were joined in this study by Dr. Guido Marcucci, associate director for Translational Research at the OSUCCC James, Dr. Robert Lee, professor of pharmaceutics and pharmaceutical chemistry in Ohio State's College of Pharmacy and a group of collaborators. The investigators conducted the research using cells isolated from patients with LGL leukemia and a mouse model of the disease. Key findings include:

  • Exposing normal, human, large granular lymphocytes to IL-15 caused cell proliferation, chromosomal instability and global DNA hypermethylation;
  • Excessive IL-15 activated the cancer-causing Myc oncogene in large granular lymphocytes, leading to genetic instability, DNA hypermethylation and malignant transformation;
  • Details of how Myc upregulation causes the genetic instability and hypermethylation.

Lee developed a liposomal formulation of the proteosome inhibitor bortezomib that shuts down the cancer-causing pathway, potentially curing the malignancy. Leukemic mice treated with the liposomal bortezomib showed 100 percent survival at 130 days versus 100 percent mortality at 60-80 days for control animals.

"We now plan to develop this drug for clinical use," says Marcucci, who holds the John B. and Jane T. McCoy Chair in Cancer Research in Cancer Research.
'/>"/>

Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University Medical Center
Source:Eurekalert

Related medicine news :

1. National study shows protective eyewear reduces eye, head, and facial injuries
2. Study: Rheumatoid Arthritis Plus Depression May Be Deadly
3. Cataract Patients Relax to a Soothing Beat, Study Says
4. New form of brain plasticity: Study shows how social isolation disrupts myelin production
5. Income May Influence Outcome of Knee Replacement Surgery: Study
6. Hip Surgery Increases Stroke Risk in Older Patients: Study
7. Some Kids May Overcome or Outgrow Egg Allergy, Study Suggests
8. Rheumatoid arthritis patients can get gout too, Mayo Clinic Study finds
9. Study overturns common assumption about knee replacements in morbidly obese individuals
10. Study Ties Obesity-Related Gene to Weaker Memory
11. Another Study Links Sexting to Sexual Activity in Teens
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/8/2016)... Somerset, N.J. (PRWEB) , ... December 08, 2016 ... ... advanced delivery technologies and development solutions for drugs, biologics and consumer health products, ... The PSCI was set up in 2006 as a non-profit organization to unite ...
(Date:12/8/2016)... ... December 08, 2016 , ... Today’s patients are ... this in mind, SIGVARIS has created a new line of anti-embolism stockings to ... and provide the benefits of graduated compression when transitioning from recovery to early ...
(Date:12/8/2016)... ... December 08, 2016 , ... ... services from offices headquartered in Hamilton County, is embarking on a charity drive ... specializes in finding new homes for orphaned or neglected senior dogs in the ...
(Date:12/8/2016)... ... December 08, 2016 , ... The Compretta Insurance Agency, a family owned ... and around the Hancock County area, is announcing the launch of a charity effort ... The Hancock County Food Pantry has worked for more than 30 years to meet ...
(Date:12/7/2016)... ... , ... Students attending Envision’s summer 2017 National Youth ... experience in an emergency medical simulation, When Care is Hours Away. This dynamic ... skills that are critical success in a future career and beyond. , The ...
Breaking Medicine News(10 mins):
(Date:12/8/2016)... DUBLIN , Dec 8, 2016 Research ... Electrodes Market Analysis and Trends - Adhesion Type, Application, Usability - ... ... The Global Cardiology Electrodes Market is poised to grow at a ... prominent trends that the market is witnessing include advancements in extracellular ...
(Date:12/8/2016)...  Pennsylvania Physician General Dr. Rachel Levine ... Gary Tennis released safe prescribing guidelines ... developed with the help of a task force. ... frequently prescribed for anxiety or insomnia," said Dr. ... pain medications, benzodiazepines pose a significant risk for ...
(Date:12/8/2016)... , Dec. 8, 2016  EIP Pharma, LLC ... obtained proof-of-mechanism for neflamapimod (previously code named VX-745), ... 2a clinical trials that demonstrated significant Alzheimer,s disease ... (12-week treatment) and Study 303 (6-week treatment) are ... in Alzheimer,s Disease (CTAD) scientific conference in ...
Breaking Medicine Technology: