miércoles, 19 de septiembre de 2012

Study Reveals How Breast Cancer Spreads to Lymph Nodes ► NCI Cancer Bulletin for September 18, 2012 - National Cancer Institute

NCI Cancer Bulletin for September 18, 2012 - National Cancer Institute

Study Reveals How Breast Cancer Spreads to Lymph Nodes

A recent study offers new insights into how breast cancer may spread to nearby lymph nodes and also suggests that a drug commonly used to treat heart failure, digoxin, may be able to interrupt the process. The findings Exit Disclaimer were reported September 10 in the Proceedings of the National Academies of Sciences (PNAS).
The lymphatic system is an important route through which cancer cells reach the circulatory system and travel to distant organs, where they develop into metastatic tumors. Metastasis—which is responsible for most cancer deaths—is not well understood, and few treatments actively target it. In breast cancer, nearly all women with metastatic disease have lymph node involvement.
Using mice, Dr. Gregg Semenza of Johns Hopkins University and his colleagues showed that hypoxia-inducible factor-1 alpha (HIF-1α) plays a direct role in the spread of breast cancer cells to the lymph nodes. HIF-1 α is a subunit of the HIF-1 protein, which promotes blood vessel formation under low-oxygen conditions, such as those in tumors. HIF-1α, the researchers found, activates the PDGF-B gene, which codes for platelet-derived growth factor (PDGF-B).
When mice with tumors formed from injected human breast cancer cells were treated with digoxin (which inhibits HIF-1α) or with imatinib (Gleevec; which inhibits PDGF-B), cancer cell spread was dramatically reduced.
In addition, mice with tumors formed from breast cancer cells that were genetically modified to block production of HIF-1α had 75 percent fewer lymph node metastases than mice with tumors formed from unmodified breast cancer cells.
In biopsy samples from human breast cancers, the authors also found that
  • PDGF-B was highly active in cells that were starved of oxygen, 
  • HIF-1α directly activated transcription of PDGF-B,
  • the HIF-1α and PDGF-B proteins were found near each other in almost all of the biopsy samples they studied, and 
  • levels of expression of these proteins in biopsy samples correlated with tumor grade.
Other studies have linked HIF-1α and PDGF-B to metastatic spread. “But this is the first time that anybody has connected all the dots in a single cancer,” Dr. Semenza explained.
Later this year, the Hopkins researchers plan to launch an early-phase clinical trial to test digoxin in women with operable breast cancer, Dr. Semenza said. Digoxin, an off-patent drug, will be given for about 2 weeks before surgery, and the researchers will analyze pre- and post-surgical tumor samples to determine whether the drug is inhibiting HIF-1 and its downstream target genes.
If the trial suggests that the drug is having the intended molecular effects, an early-phase trial combining digoxin with other standard treatments would likely be launched.
Also in the Journals: Smoky Coal Associated with Increased Risk of Lung Cancer in Rural China
Results from a large retrospective cohort study conducted in China suggest that use of smoky (bituminous) coal substantially increases the lifetime risk of developing lung cancer. The findings appeared August 29 in the British Medical Journal.
Researchers compared deaths from lung cancer between lifelong users of smoky coal and of smokeless (anthracitic) coal for cooking and heating in Xuanwei County, Yunnan Province. More than 37,000 people were followed from 1976 to 1996, and more than 2,000 deaths from lung cancer were recorded during that time.
After accounting for other risk factors, including tobacco use, users of smoky coal had a 30-fold greater risk of developing lung cancer than users of smokeless coal. The absolute risk of lung cancer death before age 70 among smoky coal users was 18 percent for men and 20 percent for women, with most of these deaths in nonsmokers. By contrast, the risk was less than 0.5 percent among users of smokeless coal.

“The risks from smoky coal are almost as high as those reported for heavy smoking in Western countries and likely represent one of the strongest effects of environmental pollution reported for cancer risk,” said co-author Dr. Qing Lan of NCI’s Division of Cancer Epidemiology and Genetics.
This study was supported in part by NCI's Intramural Research Program.
Also in the Journals: Best Practices Can Reduce Central-Line Infections in Children with Cancer
By using best practices, health providers at Johns Hopkins Children’s Center reduced central line-associated bloodstream infections by 20 percent over 2 years, according to a study published in Pediatrics.
Hospitalized cancer patients often have a central venous access catheter, or central line, inserted into a major blood vessel as a portal for medication, fluids, or blood draws. These central lines can also introduce infection; children with cancer whose treatment has suppressed their immune systems are particularly vulnerable.
The best practices included improved disinfection and a daily assessment to determine whether each central line was needed, could be consolidated, and/or eliminated. In addition, care teams met monthly to discuss the root cause of each central line infection. Family members also received wallet cards describing the correct care of central lines and were encouraged to observe their child’s care and to report any inconsistencies with the best practices.
This study was funded in part by the National Institutes of Health (5Kl2RR025006).

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