Category: Press Release

New way to determine cancer risk of chemicals found

August 25th, 2014 in Press Release, Publications

Press Release from July 24th 2014

A new study has shown that it is possible to predict long-term cancer risk from a chemical exposure by measuring the short-term effects of that same exposure. The findings, which currently appear in the journal PLOS ONE, will make it possible to develop simpler and cheaper tests to screen chemicals for their potential cancer causing risk.

Despite an overall decrease in incidence of and mortality from cancer, about 40 percent of Americans will be diagnosed with the disease in their lifetime, and around 20 percent will die of it. Currently fewer than two percent of the chemicals on the market have been tested for their ability to induce cancer.

Using an experimental model, researchers from Boston University School of Medicine (BUSM), Boston University School of Public Health, the BU Bioinformatics Program and the National Toxicology Program at the National Institute of Environmental Health measured the effects on healthy tissue from few days of exposure to a given chemical and assessed the effects on the gene expression response in the liver. “By comparing the responses to known chemical carcinogens and non-carcinogens, we were able to extract a “signature” and an associated predictive model capable of discriminating with high accuracy between the two,” explained corresponding author Stefano Monti, PhD, associate professor of medicine at BUSM and a member of the BU Superfund Research Program. “Furthermore, by inspection of the coordinated set of genes driving the response to chemical exposure, we were able to zoom in to the potential mechanisms driving cancer induction,” he added.

According to the researchers there is growing recognition that the role played by environmental pollutants in human cancer is under-studied and that more formal approaches to the analysis of the biological consequences of prolonged exposure to pollutants are needed. “This work has confirmed that it is possible to predict the long-term cancer risk by measuring the short term effects,” said Monti. “As a result of our findings we expect that accurate and cost-effective screening for evaluating the carcinogenic potential of the more than the 80,000 chemicals currently in commercial use soon will be a reality.”

Publication: Daniel Gusenleitner, Scott S. Auerbach, Tisha Melia, Harold F. Gómez, David H. Sherr, Stefano Monti. Genomic Models of Short-Term Exposure Accurately Predict Long-Term Chemical Carcinogenicity and Identify Putative Mechanisms of Action. PLoS ONE, 2014; 9 (7): e102579 DOI:10.1371/journal.pone.0102579

Story Source: The above story is based on materials provided by Boston University Medical Center. Note: Materials may be edited for content and length.

Links to additional press: Voice of America and Chemical Watch

BUSM Researchers Identify Molecule that Could Aid Lung Cancer Detection, Treatment

November 7th, 2013 in Press Release, Publications

Press Release: From October 28th 2013

Written by Jenny C Leary

Researchers at Boston University School of Medicine (BUSM) have discovered a molecule that could help lead to the non-invasive detection of lung cancer as well as its treatment. Using RNA sequencing, the team looked at airway epithelial cells and identified a regulatory molecule that was less abundant in people with lung cancer and inhibits lung cancer cell growth. The findings, which are published in the Proceedings of the National Academy of Sciences, suggest that this molecule may aid in diagnosing lung cancer in earlier stages and could potentially, when at healthy levels, aid in treating the disease.

According to the National Cancer Institute (NCI), lung cancer is the leading cause of cancer death among both men and women in the United States, and 90 percent of lung cancer deaths among men and approximately 80 percent of lung cancer deaths among women are due to smoking. The NCI also estimates that approximately 373,489 Americans are living with lung cancer and its treatment costs approximately $10.3 billion in the United States each year.

MicroRNA’s are a new class of molecules classified as important regulators of the activity of other genes. In this study, the research team used a next-generation RNA sequencing technology and identified that a microRNA named miR-4423 in epithelial airway cells plays a major role in how these cells develop. In epithelial cells from the airway of smokers with lung cancer, levels of miR-4423 were decreased.

“These results suggest measuring the levels of microRNAs like miR-4423 in cells that line the airway could aid in lung cancer detection through a relatively non-invasive procedure,” said Avrum Spira, MD, MSc, the Alexander Graham Bell professor of medicine and chief of the division of computational biomedicine at BUSM, one of the study’s senior authors.

Using experimental models in vitro and in vivo, the research team demonstrated that miR-4423 can both promote the development of the normal airway cells and suppress lung cancer cell growth. This suggests that miR-4423 plays a major regulatory role in cell fate decisions made by airway epithelial cells during maturation and low levels of miR-4423 contributes to lung cancer development. Interestingly, throughout the body, miR-4423 seems only to be present in high levels in the airway epithelium, suggesting this could be a very specific process occurring only in the lungs.

“Our findings open up the option to study whether returning the levels of miR-4423 to normal in the airway could help stop cancer growth and potentially be a way to treat lung cancer,” said Catalina Perdomo, PhD, a researcher in the division of computational biomedicine at BUSM who is the paper’s lead author.

“Interestingly, when we examined the genomes of other species for microRNAs that might function like miR-4423, we did not find anything in non-primates,” said Marc Lenburg, PhD, an associate professor in computational medicine and bioinformatics at BUSM who is one the study’s senior authors. “It makes us wonder what it is different about lung development in primates and excited that this could be a very specific process to target for lung cancer treatment.”

This study was funded in part by the National Institutes of Health’s National Cancer Institute Early Detection Research Network under grant award numbers R01 CA 124640 and U01 CA152751; the National Science Foundation Integrative Graduate Education and Research Traineeship under grant award number P50CA58184; and Merit Review grants 5I01BX000359 and R43HL088807-01.

Journal Reference: Perdomo C, Campbell J.D., Gerrein J, Tellez C, Garrison C.B., Walser T.C., Drizik E, Si H, Gower A.C., Vick J, Anderlind C, Jackson G.R., Mankus C, Schembri F, O’Hara C, Gomperts B.N., Dubinett S.M., Hayden P, Belinsky S.A., Lenburg M.E., Spira A (2013) MicroRNA 4423 is a primate-specific regulator of airway epithelial cell differentiation and lung carcinogenesis. Proc Natl Acad Sci USA, 10.1073/pnas.1220319110 PMID: 24158479

Links to additional press: The Daily Free Press and Boston Magazine’s HubHealth

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Never Smoker Lung Cancer

January 24th, 2013 in Press Release

Press Release : BU Today January 22 2013

Never Smoked. Lived Right. Died of Lung Cancer.

By Rich Barlow

Avrum Spira’s aunt died of lung cancer almost 20 years ago. She was a nonsmoking exercise buff in her 40s who hadn’t been exposed to any known toxins; she worked in a government office, not a coal mine. “One of the healthiest people you could imagine, did everything right,” says Spira (ENG’02), who at the time was an internal medicine resident at the University of Toronto.

The one thing she didn’t do right wasn’t her fault: she’d been born to a nonsmoking mother who had died from the same illness. “I’m absolutely convinced she had a genetic predisposition” to lung cancer, says Spira, a School of Medicine professor and chief of computational biomedicine. That conviction set him on a quest for the genetic key to a medical mystery: why some people who have never smoked fall victim to this scourge of cigarette users.

Lung cancer kills more Americans than any other cancer, and twice as many women die from it than from breast cancer, although the latter gets greater public attention, says Spira. In 2008, the last year for which data was available, more than 208,000 Americans were diagnosed with lung cancer and almost 158,600 died from it. Spira says between 10 and 15 percent of these annual victims are nonsmokers (the percentage has been edging up slowly in recent years) with no apparent exposure to other toxins—a crucial caveat. “How do you know someone has been or has not been exposed to something in the environment?” he asks. Some potential toxins, like radon, are invisible, he notes, “so people who we’re seeing now, with higher rates of nonsmoking lung cancer—is it because they were exposed to radon 20 years ago?”

It’s true that worldwide, the rise in the incidence of lung cancer—from the eighth leading cause of death in 1990 to fifth in 2010—is mostly a function, perversely, of good news: as living standards have improved in the developing world, more people survive into adulthood, meaning a decline in childhood deaths from malnutrition and infectious diseases. That has brought an accompanying uptick in the number of people dying from diseases mostly found in wealthier countries, among them cancer. Moreover, air pollution in industrializing countries has resulted in more lung cancer in nonsmokers there, Spira says.

But in the United States, he says, doctors believe there’s a similar spurt in lung cancers in nonsmokers who’ve had no apparent contact with other toxins. The most extensive studies, incorporating detailed questionnaires and visits to peoples’ homes to see their environment, show that “there hasn’t been a clear association among nonsmokers who are getting lung cancer with exposures to other things.”

An ongoing, as-yet-unpublished study by a team that includes Spira is looking at tumor tissue and adjacent, noncancerous tissue from the lungs of 32 subjects with lung cancer: 8 smokers, 11 former smokers, and 13 who never smoked and had no apparent exposure to other toxins. The researchers ran the samples through a gene sequencer at MED, which “can give us unprecedented insight into the genomic changes leading to lung cancer” in nonsmokers, says Rebecca Kusko (MED’14), a graduate student spearheading the study in Spira’s lab.

With the sequencer, “we study the normal cells from each person as a control,” says Spira, “and then what happens in their tumor right next door, and say, what’s changed?” Preliminary results suggest that in the smokers, “a huge number of cancer pathways are activated,” as genes controlling cell growth in the tumors turned on. But those pathways weren’t necessarily activated in the nonsmokers, who showed different gene changes between their healthy lung tissue and their tumorous tissue. The researchers’ hypothesis is that the nonsmokers had a genetic predisposition, a pathway, to cancer that was activated by something in their environment.

That trigger, Spira theorizes, may be a viral infection (cervical, liver, and head and neck cancers are all caused by viruses, he says). The researchers are now sequencing the tumor tissue of the nonsmokers to try and find any viral genes. “Even if there’s one viral gene per million human genes, we might pick it up, we believe,” he says. The work will take a year or two.

Potential therapies—which are many more years away, he warns—might include screening people with the genetic predisposition and then giving those with the predisposition regular lung scans to catch cancers early. Another possibility would be drugs that could turn off uncontrolled growth in cancerous cells. (Spira got attention in 2010 for research suggesting that the natural compound myo-inositolcould turn off incipient lung cancer in smokers.)

Those who walk Commonwealth Avenue and have to dodge fumes from smokers on break may wonder about secondhand smoke. Research is mixed, but Spira, who researches the amount of smoke necessary to change gene expression and possibly lead to lung cancer, believes that it takes a big dose—perhaps exposure over months or years.

Almost half a century after the surgeon general first warned of smoking’s dangers, Spira says that even Hollywood is catching on that not all cancer victims heedlessly bring the disease on themselves. In 2011, he was a presenter at the Prism Awards, given for accurate portrayals of illness in entertainment media. He handed an award to an actress whose character on the soap opera The Bold and the Beautifulhad lung cancer.

The character was a nonsmoker.

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