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Aliquots ó research highlights from VUMC laboratories

3/29/2012 -  

Factor sensitizes cancer to radiation

Head and neck cancers have repeatedly been linked to infection with human papillomavirus (HPV), with more than half of oropharyngeal squamous cell carcinomas (HNSCCs) positive for HPV. Interestingly, HPV-positive HNSCCs respond better to radiation therapy and have a better prognosis than HPV-negative tumors. But the molecular pathways responsible for their different sensitivities are unclear.

In the March 1 issue of Clinical Cancer Research, Natalia Issaeva, Ph.D., and colleagues report that an enzyme called SMG-1 (which participates in sensing DNA damage and is thought to be a tumor suppressor) may play a key role. They found that HPV-positive HNSCC cells and tumors have reduced expression of SMG-1 – and that low SMG-1 expression correlates with positive HPV status and improved patient survival. Depleting SMG-1 in HPV-negative cells increased their sensitivity to radiation, whereas overexpressing the protein in HPV-positive cells protected them from radiation therapy.

The results suggest that assessing SMG-1 levels in tumor biopsies may help to predict how likely a patient’s tumor is to respond to radiation therapy.

The work was supported by an endowment provided to the Barry Baker Laboratory for Head and Neck Oncology at Vanderbilt University.

Melissa Marino

 

Gut germs govern growth

(iStockphoto.com)

(iStockphoto.com)

Nearly half the world’s population is colonized by the gut bacterium Helicobacter pylori. Not only can this infection cause stomach ulcers and increase one’s risk of gastric cancer, colonization can also significantly slow growth in children. Antibiotic treatment to clear H. pylori infection causes growth to rebound in the short term, but it is unclear whether this improvement is long-lasting.

To assess the long-term impact of treating children for H. pylori, Pelayo Correa, M.D., and colleagues tracked the growth of school-age Colombian children for four years after treatment (compared to untreated children).

They report, in the March issue of The Pediatric Infectious Disease Journal, that children who remained positive for H. pylori were 1.45 cm shorter than children who cleared the infection – and 1.76 cm shorter by the end of the observation period than children who were always negative.

The results show that treating H. pylori infection can have long-lasting effects on growth, suggesting that school-age children with H. pylori may benefit from antibiotic treatment.

Melissa Marino

 

Plant compound quells inflammation

Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn’s disease, is characterized by chronic inflammation of the intestinal tract. Developing new strategies to treat IBD has been a challenge.

(iStockphoto.com)

(iStockphoto.com)

Berberine, a compound found in plants including barberry and Oregon grape, has been used as an herbal medicine to treat bacteria-associated diarrhea and intestinal parasitic infections. Fang Yan, M.D., Ph.D., and colleagues explored the effect of berberine in a mouse model of intestinal injury and colitis (caused by dextran sulfate sodium, DSS).

They report in the March AJP – Gastrointestinal and Liver Physiology that berberine promotes recovery of DSS-induced colitis. It mitigates weight loss, shortening of the colon, intestinal injury and inflammation. The researchers demonstrated the berberine reduces pro-inflammatory cytokine levels by inhibiting signaling pathways involved in cytokine production in colonic macrophages and epithelial cells, and that it preserves barrier function in the colon of DSS-treated mice.

The findings suggest that berberine may represent a new therapeutic approach for treating gastrointestinal inflammatory disorders.

This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center for Complementary and Alternative Medicine and the National Cancer Institute of the National Institutes of Health, by the Vanderbilt University Digestive Disease Research Center, and by the Department of Veterans Affairs.

Leigh MacMillan

 

New tool hooks heart failure drugs

Despite advances in understanding the biology of myocardial hypertrophy (enlargement of heart cells) and congestive heart failure, finding therapeutics aimed at preventing these conditions has been difficult. Cell-based methods do not capture the complexity of the intact cardiovascular system.

Using zebrafish embryos, Jason Becker, M.D., and colleagues have established a screening tool to identify chemical and genetic regulators of heart failure. Their system takes advantage of a cardiac natriuretic peptide gene – part of a signaling pathway that is “turned on” in myocardial hypertrophy and congestive heart failure in humans.

The researchers demonstrated that the gene, linked to a bioluminescent marker, responds to heart failure-associated pathological stimuli (both pharmacologic and genetic). In a screen of selected chemicals, they showed that two agents could block the response to a genetic stimulus that causes myocardial hypertrophy.

The screening tool, described in the March 1 issue of Cardiovascular Research, offers a unique approach for discovering potential therapeutics for myocardial hypertrophy and heart failure.

This research was supported by the National Heart, Lung and Blood Institute of the National Institutes of Health and by the Vanderbilt Physician Scientist Development Program.

Leigh MacMillan

 

We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to: aliquots@vanderbilt.edu.

Past Aliquots

June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012
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