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Inhibition of Akt enhances the chemopreventive effects of topical rapamycin in mouse skin

The PI3Kinase/Akt/mTOR pathway has important roles in cancer development for multiple tumor types, including UV-induced non-melanoma skin cancer. Immunosuppressed populations are at increased risk of aggressive cutaneous squamous cell carcinoma (SCC). Individuals who are treated with rapamycin, (sirolimus, a classical mTOR inhibitor) have significantly decreased rates of developing new cutaneous SCCs compared to those that receive traditional immunosuppression. However, systemic rapamycin use can lead to significant adverse events. Here we explored the use of topical rapamycin as a chemopreventive agent in the context of solar simulated light (SSL)-induced skin carcinogenesis. In SKH-1 mice, topical rapamycin treatment decreased tumor yields when applied after completion of 15 weeks of SSL exposure compared to controls. However, applying rapamycin during SSL exposure for 15 weeks, and continuing for 10 weeks after UV treatment, increased tumor yields. We also examined whether a combinatorial approach might result in more significant tumor suppression by rapamycin. We validated that rapamycin causes increased Akt (S473) phosphorylation in the epidermis after SSL, and show for the first time that this dysregulation can be inhibited in vivo by a selective PDK1/Akt inhibitor, PHT-427. Combining rapamycin with PHT-427 on tumor prone skin additively caused a significant reduction of tumor multiplicity compared to vehicle controls. Our findings indicate that patients taking rapamycin should avoid sun exposure, and that combining topical mTOR inhibitors and Akt inhibitors may be a viable chemoprevention option for individuals at high risk for cutaneous SCC.

Cancer Prevention Research

Aquatic invasive species: Lessons from cancer research

Aquatic invasive species are disrupting ecosystems with increasing frequency. Successful control of these invasions has been rare: Biologists and managers have few tools for fighting aquatic invaders. In contrast, the medical community has long worked to develop tools for preventing and fighting cancer. Its successes are marked by a coordinated research approach with multiple steps: prevention, early detection, diagnosis, treatment options and rehabilitation. The authors discuss how these steps can be applied to aquatic invasive species, such as the American bullfrog (Lithobates catesbeianus), in the Northern Rocky Mountain region of the United States, to expedite tool development and implementation along with achievement of biodiversity conservation goals.

American Scientist

Earth science and public health: Proceedings of the Second National Conference on USGS Health-Related Research

The mission of the U.S. Geological Survey (USGS) is to serve the Nation by providing reliable scientific information to describe and understand the earth; minimize loss of life and property from natural disasters; manage water, biological, energy, and mineral resources; and enhance and protect our quality of life. As the Nation?s largest water, earth, and biological science and civilian mapping agency, the USGS can play a significant role in providing scientific knowledge and information that will improve our understanding of the relations of environment and wildlife to human health and disease. USGS human health-related research is unique in the Federal government because it brings together a broad spectrum of natural science expertise and information, including extensive data collection and monitoring on varied landscapes and ecosystems across the Nation. USGS can provide a great service to the public health community by synthesizing the scientific information and knowledge on our natural and living resources that influence human health, and by bringing this science to the public health community in a manner that is most useful. Partnerships with health scientists and managers are essential to the success of these efforts. USGS scientists already are working closely with the public health community to pursue rigorous inquiries into the connections between natural science and public health. Partnering agencies include the Armed Forces Institute of Pathology, Agency for Toxic Substances Disease Registry, Centers for Disease Control and Prevention, U.S. Environmental Protection Agency, Food and Drug Administration, Mine Safety and Health Administration, National Cancer Institute, National Institute of Allergy and Infectious Disease, National Institute of Environmental Health Sciences, National Institute for Occupational Safety and Health, U.S. Public Health Service, and the U.S. Army Medical Research Institute of Infectious Diseases. Collaborations between public health scientists and earth scientists can lead to improved solutions for existing and emerging environmental health problems. This report summarizes the presentations and discussions held at the Second National Conference on USGS Health-Related Research, held at the USGS national headquarters in Reston, Virginia. The report presents 68 abstracts of technical presentations made at the conference and summaries of six topical breakout sessions. The abstracts cover a broad range of issues and demonstrate connections between human health and the quality and condition of our environment and wildlife. The summaries of the topical breakout sessions present ideas for advancing interdisciplinary science in areas of earth science and human health.

Scientific Investigations Report

The role of fish in a globally changing food system

Applied research and adaptive management techniques can assist with the necessary evolution of sustainable food systems to include a stronger emphasis on fish and other aquatic organisms. Fish provide key macro‐ and micronutrients and protein, are low in saturated fat, and have been linked to a wide array of health benefits for the developing fetus, infants, and adults. Diet quality is not only important for reducing nutrient deficiency, but is now regarded as essential for preventing chronic diseases such as obesity, type 2 diabetes, hypertension, coronary artery disease, and cancers. Small‐scale aquaculture also contributes to poverty alleviation and promotes food and nutrition security in less developed parts of the world. Climate change and climate variability influence aquatic ecosystems and fish populations. Ocean acidification is most commonly cited as being detrimental to marine invertebrates and algae that build carbonate structures.

Book chapter