Lipid found critical to breast cancer cell.


Scientists in Spain report finding that breast cancer cells need to take up lipids from the extracellular environment so that they can continue to proliferate. The main protein involved in this process is LIPG, an enzyme found in the cell membrane and without which tumor cell growth is arrested. Analyses of more than 500 clinical samples from patients with various kinds of breast tumors reveal that 85% have high levels of LIPG expression.

The research (“FoxA and LIPG Endothelial Lipase Control the Uptake of Extracellular Lipids for Breast Cancer Growth”) is published in Nature Communications.

In Spain, breast cancer is the most common tumor in women and the fourth most common type in both sexes (data from the Spanish Society of Medical Oncology, 2012), registering more than 25,000 new diagnoses each year. According to figures from the World Health Organization, every year 1.38 million new cases of breast cancer are diagnosed and 458,000 people die from this disease (International Agency for Research on Cancer Globocan, 2008).

It was already known that cancer cells require extracellular glucose to grow and that they reprogram their internal machinery to produce greater amounts of lipids. The relevance of this study is that it reveals for the first time that tumor cells must import extracellular lipids to grow.

“This new knowledge related to metabolism could be the Achilles heel of breast cancer,” explains ICREA researcher and Institute for Research in Biomedicine–Barcelona group leader Roger Gomis, Ph.D., co-leader of the study together with Joan J. Guinovart, Ph.D., director of IRB Barcelona and professor at the University of Barcelona. Using animal models and cancer cell cultures, the scientists have demonstrated that blocking of LIPG activity arrests tumor growth.

“What is promising about this new therapeutic target is that LIPG function does not appear to be indispensable for life, so its inhibition may have fewer side effects than other treatments,” explains the first author of the study, Felipe Slebe, a Ph.D. Fellow at IRB Barcelona.

According to Dr. Guinovart, “because LIPG is a membrane protein, it is potentially easier to design a pharmacological agent to block its activity.”

“If a drug were found to block its activity, it could be used to develop more efficient chemotherapy treatments that are less toxic than those currently available,” adds Dr. Gomis.

The scientists are now looking into international collaborations for developing LIPG inhibitors.

Quality improvement initiatives required to reduce repeat lipid testing.


One-third of patients with coronary heart disease who reached target LDL levels underwent repeat lipid panels, suggesting that quality improvement efforts are needed to decrease unnecessary testing.

Salim S. Virani, MD, PhD, of the Michael E. DeBakey VA Medical Center and a researcher at the Health Services Research and Development Center of Excellence in Houston, and colleagues evaluated the number of patients with LDL levels lower than the Adult Treatment Panel III (ATP III) guideline-recommended LDL treatment target of 100 mg/dL who underwent repeat lipid testing within 11 months without medication intensification. They used data from patients with CHD in a VA network of seven medical centers with associated community-based outpatient clinics.

 “In these patients, repeat lipid testing may represent health resource overuse and possibly waste of health care resources,” the researchers wrote.

Potential waste of resources

Virani and colleagues identified 27,947 patients with CHDand LDL levels less than 100 mg/dL — 9,200 (32.9%) of whom underwent repeat lipid testing without intensification of treatment during the next 11 months. This translated to 12,686 repeat panels, with a mean of 1.38 additional tests per patient, according to study results.

“With a mean lipid panel cost of $16.08 based on Veterans Health Administration laboratory cost data, this is equivalent to $203,990 in annual costs for one VA network,” the researchers wrote.

“These results represent health care resource overuse and possibly their waste,” Virani told Cardiology Today. “Apart from the costs associated with these lipid panels, this also carries with it the cost for the patient’s time to undergo a repeat blood test and cost for the health care provider’s time to follow-up on these results after redundant testing and to inform the patient about these results.”

After adjustment for facility level clustering, data showed that those with a history of diabetes (OR=1.16; 95% CI, 1.10-1.22), hypertension (OR=1.21; 95% CI, 1.13-1.30), higher burden of illness (OR=1.39; 95% CI, 1.23-1.57) and more frequent primary care visits (OR=1.32; 95% CI, 1.25-1.39) had higher odds of undergoing repeat testing. In contrast, patients treated at a teaching facility (OR=0.74; 95% CI, 0.69-0.80) or from a physician provider (OR=0.93; 95% CI, 0.88-0.98) and patients with a medication possession ratio of 0.8 or higher (OR=0.75; 95% CI, 0.71-0.80) were less likely to have a repeat lipid panel.

The researchers also assessed 13,114 patients with CHD who met the ATP III optional treatment target of less than 70 mg/dL. In this population, 8,177 (62.4%) with LDL levels less than 70 mg/dL underwent repeat lipid testing during 11-month follow-up.

“This represents an area of redundant testing in patients and represents an opportunity to improve health care efficiency and reduce health care waste,” Virani said.

Interpretations

In an invited commentary, Joseph P. Drozda Jr., MD, of the Center for Innovative Care, Mercy, in Chesterfield, Mo., lauded the researchers’ study, noting that, with the implementation of electronic health records, future reports will likely identify other areas that require improvement and where waste can be reduced.

“This well-conceived study on a large clinical database, which has the advantage of containing pharmacy data for use in tracking medication adherence, delivers an important message regarding a type of waste that is likely widespread in health care and that goes under the radar because it involves a low-cost test. However, it is precisely these low-cost, high-volume tests and procedures that need to be addressed if significant saves from reduction of waste are to be realized,” he wrote.

For more information:

Drozda JP. JAMA Intern Med. 2013;doi:10.1001/jamainternmed.2013.6808.

Virani SS. JAMA Intern Med. 2013;doi:10.1001/jamainternmed/2013.8198.

Source: Endocrine Today

 

 

Revised Guidelines: Secondary Prevention and Risk Reduction in Patients with Atherosclerotic Disease.


New recommendations for cardiac rehabilitation and risk reduction are welcome, but updated guidance is lacking on lipid and blood pressure management.

Sponsoring Organizations: American Heart Association, American College of Cardiology

Background and Purpose: This revision updates the 2006 secondary prevention guidelines (JW Cardiol Jun 8 2006) and incorporates risk reduction into their title and purview. The guidelines continue to focus on important patient behaviors, including 30 minutes of physical activity daily, smoking cessation and avoidance of secondhand smoke, and weight management. However, the writing committee has deferred making major changes to the 2006 recommendations on blood pressure control and lipid management pending the revised versions of the National Heart, Lung, and Blood Institute‘s Joint National Committee guidelines (JNC) and Adult Treatment Panel report (ATP), respectively (both expected in 2012).

Key Points:
1. A new section of Class I and Class IIa recommendations highlights the importance of referring patients for cardiac rehabilitation.

2. The guideline authors have reorganized the section on lipid management to emphasize evidence-based use of statins rather than the achievement of target lipid levels. Although no new specific recommendations have been added, the lack of evidence supporting non-statin lipid-lowering agents has demoted the use of combined drug therapies from Class I to either Class IIa or IIb, depending on the agent.

3. The authors have updated recommendations regarding antiplatelet therapy, incorporating new data on prasugrel from TRITON TIMI 38 and ticagrelor from PLATO (Class I).

4. The recommendations for beta-blocker therapy have been expanded and clarified, reflecting evidence that the drugs are most efficacious in patients with recent myocardial infarction, left ventricular systolic dysfunction, or both.

5. The guidelines now identify and direct specific recommendations to populations at very high risk for poor outcomes.

6. A new section of Class IIa and Class IIb recommendations addresses screening for and management of depression.

Comment: The shift in focus toward risk reduction will help clinicians improve care for many patients, including older adults and those with depression. Although the guidelines are extensive and well written, the lack of new recommendations regarding the management of hyperlipidemia and hypertension decreases their immediate value. Virtually all patients with atherosclerotic disease have one or both of these conditions, and it is unfortunate that we must await the eighth edition of JNC and the fourth edition of ATP to inform current, evidence-based management decisions.

Source:Journal Watch Cardiology