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:5/25/2016)... ... May 25, 2016 , ... DKT International, one of ... world, is pleased to release their 2015 global impact data. In 2015, DKT ... 14,000 maternal deaths and 3.8 million unsafe abortions across 21 countries worldwide. ...
(Date:5/25/2016)... ... May 25, 2016 , ... ... ranging from medical and pharmaceutical, to food and HVAC facilities. Their knowledgeable staff ... training. , For medical applications, Afrimesure offers a variety of MadgeTech systems ...
(Date:5/25/2016)... Vallarta, Mexico (PRWEB) , ... May 25, 2016 , ... ... surrounding the restorative properties of precious stones to complement its new wellness suites ... over two floors and feature a plethora of special services and insuite amenities, from ...
(Date:5/25/2016)... , ... May 25, 2016 , ... The University of ... and Health Professions. She will lead a team of more than 100 full-time faculty ... begin her role as dean in late August. , Baker comes to USF from ...
(Date:5/25/2016)... ... ... more than fifty years, we've suffered whiplash as each new scientific study seemed to contradict ... nutritional advice – advice that was supposed to keep us healthy and slim. And what ... are considered to be overweight and more than 1 in 3 adults are considered to ...
Breaking Medicine News(10 mins):
(Date:5/24/2016)... 24, 2016 Een app die ... zij collectief patiënten kunnen behandelen, hun kennis kunnen delen ... achter de nieuwe en revolutionaire MDLinking App, ontwikkeld door ... vaatchirurg dr. Hans Flu en oncologisch chirurg dr. ... beschikbaar is, wordt op dinsdag 24 mei officieel gepresenteerd ...
(Date:5/23/2016)... May 23, 2016 Transparency Market ... Exocrine Pancreatic Insufficiency Market - Global Industry Analysis, Size, ... According to the report, the exocrine pancreatic insufficiency market ... from 2015 to 2023 to reach US$2.85 Bn by ... condition characterized by the deficiency of the exocrine pancreatic ...
(Date:5/23/2016)... 23, 2016 Non-invasive diagnostic test ... multiple diseases; ,Technology to be presented at Yissum’s booth, ... Research Development Company of the Hebrew University of Jerusalem ... agreement with Aurum Ventures MKI, the technology investment arm of ... new diagnostic approach for early detection of multiple diseases ...
Breaking Medicine Technology: