Protein Being Studied To Fight Cancer; May Cause Toxicity In Cardiac Cells

Main Category: Cardiovascular / Cardiology
Also Included In: Cancer / Oncology;??GastroIntestinal / Gastroenterology;??Heart Disease
Article Date: 19 Jun 2013 - 0:00 PDT Current ratings for:
Protein Being Studied To Fight Cancer; May Cause Toxicity In Cardiac Cells

A study by researchers at Skaggs School of Pharmacy and Pharmaceutical Sciences and the Department of Pharmacology at the University of California, San Diego, shows that a protein called MCL-1, which promotes cell survival, is essential for normal heart function.

Their study, published in th journal Genes & Development, found that deletion of the gene encoding MCL-1 in adult mouse hearts led to rapid heart failure within two weeks, and death within a month.

MCL-1 (myeloid cell leukemia-1) is an anti-apoptotic protein, meaning that it prevents or delays the death of a cell. It is also a member of the BCL-2 family of proteins that regulate mitochondria - the cell's power producers - and cell death. Aberrant expression of anti-apoptotic BCL-2 family members is one of the defining features of cancer cells, and is strongly associated with resistance to current therapies. Thus, these proteins are currently major targets in the development of new therapies for patients with cancer.

But, while MCL-1 is up regulated in a number of human cancers, contributing to the overgrowth of cancer cells, it is found at high levels in normal heart tissue. Additionally, the researchers found that autophagy - a process which deals with mitochondrial maintenance and is normally induced by myocardial stress - was impaired in mice with MCL-1 deficient hearts.

In summary, the study demonstrated that the loss of MCL-1 led to rapid dysfunction of mitochondria, impaired autophagy and heart failure, even in the absence of cardiac stress.

"Cardiac injury, such as a heart attack, causes levels of MCL-1 to drop in the heart, and this process may increase cardiac cell death," said Asa B. Gustafsson, PhD, an associate professor at UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences. "Therefore, preserving normal levels of this protein in cardiac tissue could reduce damage after a heart attack and prevent progression to heart failure."

By compromising both autophagy and mitochondrial function, MCL-1 inhibitors are likely to affect the cells' energy supply. "Our findings raise concerns about the potential cardiac toxicity of drugs that block MCL-1 - drugs that have entered clinical trials because they increase cancer cell death," said the study's first author, Robert L. Thomas.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cardiovascular / cardiology section for the latest news on this subject. Additional contributors to the paper include David J. Roberts, Dieter A. Kubli, Youngil Lee, Melissa N. Quinsay, Jarvis B. Owens and Shigeki Miyamoto, UC San Diego; and Kimberlee M. Fischer, Mark A. Sussman, San Diego State University.
The study was supported in part by grants from the National Institutes of Health (grants R01HL087023 and 715 R01HL101217).
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Surgical Breast Biopsies Being Overused

A study conducted in Florida suggests that too many women are undergoing open, surgical breast biopsies instead of less invasive needle biopsies. These results were published in the American Journal of Surgery.

If a woman has a breast lump or an abnormal area of the breast seen by breast imaging, a sample of breast tissue may be removed for further evaluation. This is called a breast biopsy. Tissue may be removed through a needle, or in a more extensive procedure known as an open, surgical biopsy. Needle biopsies are a less invasive procedure and are preferred for most women.?

To explore the frequency of needle and surgical breast biopsies, researchers collected information about biopsies performed in Florida between 2003 and 2008.????

Although use of needle biopsies increased over the time period of the study, the overall rate of surgical biopsies remained high. An estimated 30% of breast biopsies involved open, surgical biopsy. The researchers note that if surgical breast biopsies were used in only 10% of all breast biopsies (a reasonable goal), it would save money and allow many women to avoid unnecessary surgery. A majority of women who undergo breast biopsy do not have breast cancer.?

The reasons for the high rates of open, surgical breast biopsy are uncertain.

Women who need a breast biopsy should talk with their physician about the type of biopsy that will be performed. A surgical biopsy may be required for some women, but many women will be candidates for a less invasive needle biopsy.

Reference: Gutwein LG, Ang DN, Liu H et al. Utilization of minimally invasive breast biopsy for the evaluation of suspicious breast lesions. American Journal of Surgery. Early online publication February 8, 2011.

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