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Extramural Papers of the Month

By Jerry Phelps
April 2009

Nanotechnology Delivers -- First Report of Targeted Killing of Tumor Cells

Within the family of nanomaterials, carbon nanotubes have emerged as a new alternative and efficient tool for transporting drugs. In new research sponsored by NIEHS, researchers report the first targeted killing of cancer cells in animals using a single wall carbon nanotube drug-delivery system.

Single-walled carbon nanotubes are on the order of a few nanometers (about 1/50,000th of the width of a human hair) in diameter and can be several millimeters in length. They have many novel properties that make them potentially useful in a number of applications including electronics, optics, material sciences, architecture and as targeted drug-delivery devices.

In the current study, carbon nanotubes were conjugated with the anti-cancer agent cisplatin along with epidermal growth factor (EGF) to specifically target head and neck squamous carcinoma cells in mice. In vitro experiments showed that cancer cells treated with carbon nanotubes bound to cisplatin and epidermal growth factor killed selectively. Control treatments that did not include epidermal growth factor did not affect cell proliferation. In vivo experiments demonstrated rapid regression of tumor growth in mice treated with carbon nanotubes with both cisplatin and epidermal growth factor. Other studies showed that without epidermal growth factor, carbon nanotubes were cleared from the treated areas in less than 20 minutes. These results point to the potential of carbon nanotubes as targeted anti-cancer drug-delivery systems.

Citation: Bhirde AA, Patel V, Gavard J, Zhang G, Sousa AA, Masedunskas A, Leapman RD, Weigert R, Gutkind JS, Rusling JF. ( Exit NIEHS 2009. Targeted killing of cancer cells in vivo and in vitro with EGF-directed carbon nanotube-based drug delivery. ACS Nano 3(2):307-316.

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New Genetic Markers Identified for Increased Heart Attack Risk

An international team of scientists partially supported by NIEHS has found nine new gene variants, also known as single nucleotide polymorphisms, associated with an increased risk of myocardial infarction or heart attack. These polymorphisms provide new insight for understanding genetic patterns of heart attack and for developing new treatment options.

One key finding of the report is that people who carry more than one of the markers have more than twice the risk for heart attack. The scientists performed a genome-wide scan of thousands of patients with hundreds of thousands of genetic markers. Heart attack patients, previously enrolled in an existing study, and healthy control persons participated in the study.

In one study, suspect genes were mapped to chromosomes 3 and 12. One of these genes, known as MRAS, plays an important role in cardiovascular biology. Another gene, HNF1A, is closely associated with cholesterol metabolism. Another study identified three previously unknown genes on chromosome 2, 6 and 21. Results from this study show that the higher the number of disease genes a person has, the higher the risk for heart attack.

The scientists conclude that the knowledge gained from their work will aid in addressing the risk of heart attack in order to develop preventive and early intervention strategies.

Citation: Myocardial Infarction Genetics Consortium. ( Exit NIEHS 2009. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat Genet 41(3):334-341.

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Autism Increase Not Due to Better Diagnosis

A study conducted by NIEHS-funded researchers at the University of California Davis found that the seven- to eight-fold increase since 1990 in the number of children born in California and later diagnosed with autism cannot be explained by changes in how the condition is diagnosed or counted. The researchers also conclude that the trend is not slowing and suggest that the research focus should shift from genetics to the multitude of chemical and infectious agents in the environment that could be involved in the rapid rise in the incidence of autism.

The results of the investigation show that the incidence of autism by age six in California increased from fewer than 9 cases per 10,000 children born in 1990 to more than 44 per 10,000 children born in 2000. Migration patterns and changes in diagnosis were ruled out as possible reasons for the increase. The results show that less than one-tenth of the increase can be attributed to the inclusion of milder cases of autism.

These researchers are currently involved in two large studies aimed at discovering possible environmental factors and gene-environment interactions responsible for autism. They are focusing on the potential effects of metals, pesticides and infectious agents on neurodevelopment.

Citation: Hertz-Picciotto I, Delwiche L. ( Exit NIEHS 2009. The rise in autism and the role of age at diagnosis. Epidemiology 20(1):84-90.

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Extreme Temperature and Mortality Risk

A study on weather-related mortality conducted by Yale University researchers with funding from NIEHS found that extremes of hot and cold temperatures are risk factors for all cause mortality. The study was conducted in 107 communities in the U.S. It identified regional variation, susceptible populations, acclimatization strategies and air pollution as mediating factors.

Previous studies have identified links between mortality and temperature extremes, and extreme weather events such as the 2003 European heat wave, and concerns over global climate change have focused more attention on the issue. The researchers point out that a better understanding of how temperature affects mortality and susceptible populations is critical for the medical community, community leaders and policy makers responsible for intervention strategies.

Results show that heat-related mortality has a shorter lag time than cold-related mortality, suggesting differences in intervention strategies. The strongest heat-related mortality association occurred with previous or same day exposure while cold-related mortality lagged up to 25 days, suggesting that cold temperatures affect mortality more indirectly. Some of this lag is attributable to death from infectious diseases.

Heat effects were generally lower in communities with higher average temperatures, suggesting that communities and individuals can adapt even to extreme weather changes. However, adaptation to extreme cold even in communities with average lower temperatures was not as apparent.

Citation: Anderson BG, Bell ML. ( Exit NIEHS 2009. Weather-related mortality: how heat, cold, and heat waves affect mortality in the United States. Epidemiology 20(2):205-213.

(Jerry Phelps is a program analyst in the NIEHS Division of Extramural Research and Training. Each month, he contributes summaries of extramural papers to the Environmental Factor.)

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