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Minggu, 25 Maret 2012

Discovery Could Lead To Novel Drugs To Prevent Cancer Metastasis

A Loyola University Chicago Stritch School of Medicine study has revealed details of the complex molecular process involving a protein that enables cancer cells to establish tumors in distant parts of the body.

The finding could lead the way to new drugs to prevent breast cancer and other cancers from spreading to new sites.

The study by Adriano Marchese, PhD, and colleagues is published in the March 16 issue of the Journal of Biological Chemistry.

The study involves a molecule on the surface of cells called CXCR4. There is an abnormal abundance of this molecule in 23 types of cancer, including cancers of the breast, lung, pancreas and thyroid.

What usually kills patients is the spread of cancer from the primary site to other sites. A tumor cell breaks away from the primary site and circulates through the body. A molecule called CXCL12 acts like a beacon to CXCR4, signaling the cancer cell to land and start a new tumor.

The goal of the study was to better understand this complex signaling pathway. (A signaling pathway involves a group of molecules that work together in a cell. After the first molecule in the pathway receives a signal, it activates another molecule, and the process is repeated until the last molecule is activated.)

"We understand the final outcome of this signaling pathway," Marchese said. "What we are trying to do now is understand the molecular details."

In the study, Marchese and colleagues used a line of human cancer cells called HeLa. (The cell line is the subject of the best-selling book "The Immortal Life of Henrietta Lacks".)

Using HeLa cancer cells, the researchers identified a molecule that is a critical link in the signaling pathway. Researchers hope to target this molecule, thereby disabling the signaling pathway and preventing the cancer cell from setting up shop in a new site, Marchese said.

The next step will be to develop a drug that blocks the target molecule. Researchers then would test the drug on an animal model. If the drug worked in animals, it later could be tested in a clinical trial of cancer patients, Marchese said.

"We are laying the groundwork for the development of new drugs to stop cancer from spreading," Marchese said.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our breast cancer section for the latest news on this subject. Marchese is an associate professor in the Department of Molecular Pharmacology and Therapeutics of Loyola University Chicago Stritch School of Medicine. His co-authors are Rohit Malik, PhD (first author); Unice J.K. Soh, PhD; and JoAnn Trejo, PhD.
The study was supported by a grant from the National Institutes of Health. Malik was supported by a predoctoral fellowship from the American Heart Association. He graduated in December 2011 and is doing postdoctoral training at the University of Michigan.
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Gene Chip May Help Prevent Heart Disease

Worldwide, coronary heart disease (CHD) is the leading cause of death. According to a study published online in The Lancet, anti-inflammatory medications may become a new way to prevent and treat the disease.

Using a gene analysis tool called the Cardiochip, the researchers examined a specific gene variant associated with inflammation and heart disease. The chip was designed by Brendan J. Keating, Ph.D., co-author of the study and a researcher in the Center for Applied Genomics at The Children's Hospital of Philadelphia.

Even though researchers are aware of the association between inflammation and atherosclerosis - a disorder in which fat, cholesterol, and other fatty deposits build up in the walls of arteries - they have been unable to find an inflammatory agent that causes the diseases, until now. In addition, researchers did not know whether a drug targeted at reducing inflammation might treat the disease.

The team focused on the signaling protein interleukin-6 receptor (IL6R). IL6R is found in the blood and increases inflammatory responses.

Keating explained:

"This study provides robust evidence that IL6R is implicated in coronary heart disease. Furthermore, our analysis showed that an existing anti-inflammatory drug, acting on this receptor, may offer a new potential approach for preventing CHD."

The meta-analysis study was conducted by the IL6R Mendelian Randomization Analysis Consortium, and international team of investigators led by Dr. Juan Pablo Casas, Professor Aroon. D. Hingorani, and Dr. Daniel I. Swerdlow, all of University College London, UK.

The researchers examined data from 40 previous studies that involved almost 133,500 individuals from Europe and the United States. Mendelian randomization is a research technique that utilizes knowledge of genes and biological mechanisms in order to figure out the likely effects of a new medication before a clinical trial is conducted, with its potential risk of adverse effects and high cost.

In the same issue of The Lancet, an associated report conducted by the IL6R Genetics Consortium and Emerging Risk Factors Collaboration, discovered that a genetic variant of the IL6R gene, which carries the code for the IL6R protein, decreases inflammation and therefore reduces the risk of heart disease.

The primary focus of the study Keating participated in was on SNPs (single nucleotide polymorphisms) single-base changes in the IL6R gene that codes for the IL6R protein.

The researchers used the IBC Human CVD BeadChip (a DNA array), also called the Cardiochip. The chip, which contains DNA markers for 2,000 gene variants implicated in cardiovascular disease, was developed in 2006 by Keating and has been used in several large gene studies.

When the chip is brought into contact with test samples of DNA from study participants, it identifies specific SNPs in the sample - gene variants that could potentially affect biological functions as well as risks of cardiovascular disease among the study participants.

The researchers discovered that one SNP, the gene variant rs8192284, changed numerous biological markers linked to inflammation. These results were comparable to results found in studies of tocilizumab, an anti-inflammatory drug currently used to treat individuals suffering with rheumatoid arthritis. This medication decreased the painful inflammation common in rheumatoid arthritis by preventing the action of IL6R.

After examining data from patients with CHD and controls, the researchers also found that individuals carrying the gene variant had a lower risk of developing CHD.

Keating said:

"What this tells us is that IL6R blockers such as tocilizumab mimic the benefits of having this gene variant. A next step will be for cardiology researchers to design and carry out clinical trials to determine whether tocilizumab or similar anti-inflammatory drugs will prevent heart disease."

Written by Grace Rattue
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

Visit our heart disease section for the latest news on this subject. “The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomization analysis” The Interleukin-6 Receptor Mendelian Randomisation Analysis (IL6R MR) Consortium
The Lancet, published online March 14, 2012, doi:10.1016/S0140-6736(12)60110-X Please use one of the following formats to cite this article in your essay, paper or report:

MLA

Grace Rattue. "Gene Chip May Help Prevent Heart Disease." Medical News Today. MediLexicon, Intl., 17 Mar. 2012. Web.
17 Mar. 2012. APA

Please note: If no author information is provided, the source is cited instead.


'Gene Chip May Help Prevent Heart Disease'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam)

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.



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