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Microvesicles - tiny membrane-covered sacs - released from glioblastoma cells contain molecules that may provide data that can guide treatment of the deadly brain tumor.

In their report in the December 2008 Nature Cell Biology, which is receiving early online release, Massachusetts General Hospital (MGH) researchers describe finding tumor-associated RNA and proteins in membrane microvesicles called exosomes in blood samples from glioblastoma patients. Detailed analysis of exosome contents identified factors that could facilitate a tumor's growth through delivery of genetic information or proteins, or signify its vulnerability to particular medications.

"Glioblastomas release exosomes in sufficient quantities to pass the blood-brain barrier. We were able to isolate them, analyze the RNA transcripts and show how they might be used as biomarkers to guide targeted therapy and monitor treatment response," says Johan Skog, PhD, the study's lead author, who works in the laboratory of Xandra Breakefield, PhD, at the MGH Neuroscience Center. "Exosomes also may someday be used to deliver therapeutic molecules to the site of a tumor," he added.

Many types of cells release exosomes as part of normal cell-to-cell communication, and several types of tumors are known to shed exosomes containing proteins that can alter the cellular environment to favor tumor growth. The current investigation is believed to be the first to carefully analyze the contents of exosomes shed from glioblastoma cells and characterize their contents.

The investigators first analyzed tumor cells from three glioblastomas and verified that the cells released exosomes containing RNA and protein molecules. Some messenger RNAs related to activities such as cell proliferation and migration, angiogenesis, and immune response were highly abundant in the exosomes. When glioblastoma exosomes were cultured with normal cells, tumor RNA was delivered into the normal cells and generated its encoded protein, supporting the role of exosome-delivered RNA in manipulating the cellular environment.

To study the potential of glioblastoma exosomes as markers of a tumor's genetic makeup, the researchers analyzed tumor tissue and blood serum from 25 glioblastoma patients and were able both to find tumor exosomes and to identify, in some tissue samples, a mutation in the epidermal growth factor receptor (EGFR) gene that characterizes a tumor subtype. In two patients, an EGFR mutation that did not appear in the tumor tissue sample was identified by exosome analysis, reflecting how a surgical biopsy can miss tissue conveying critical information because of the often-chaotic diversity of cells within a tumor.

"It is known that the effects of some anticancer drugs depend on a tumor's genetic mutational profile, so our results have broad implications for personalized medicine," explains Skog, who is an instructor in Neurology at Harvard Medical School. "Detecting mutational profiles through a noninvasive blood test could allow us to monitor how a tumor's genetic makeup changes in response to therapy, which may necessitate changes in treatment strategy." Skog, Breakefield and their colleagues are also investigating the role of exosomes in other solid tumors and how they may help monitor additional tumor-associated mutations.

The current study was supported by grants from the Wenner-Gren Foundation, Stiftelsen Olle Engkvist Byggmastare, the National Cancer Institute, the Brain Tumor Society and the American Brain Tumor Association. The MGH's provisional patent on the work described in this study has been exclusively licensed to Exosome Diagnostics, Inc. Subsequent to the completion of this work, Skog was appointed the company's director of Research, while maintaining his position at MGH.

http://www.mgh.harvard.edu/

Taking small tissue samples from patients with lung cancer and examining them under a microscope (a procedure called histology) is now being utilized to better tailor the chemotherapy treatments to improve survival in some patients with non-small cell lung cancer, according to a study presented at the 2008 Chicago Multidisciplinary Symposium in Thoracic Oncology, cosponsored by ASTRO, ASCO, IASLC and the University of Chicago.

Cancer researchers have begun to believe in a tailored approach to chemotherapeutic intervention based on the histology or tissue type in the treatment of non-small cell lung cancer. To prove this hypothesis, cancer researchers from Pennsylvania State Hershey Cancer Institute in Hershey, Pa., Medical University of Vienna in Vienna, Austria, University of Torino in Orbassano, Italy, and Eli Lilly and Company of Indianapolis, Ind., considered two large studies, each of which compared pemetrexed-based (chemotherapy-based) treatment to a control treatment. They analyzed each of these studies for the presence of a treatment-by-histology interaction. A treatment-by-histology interaction exists if the relative benefit of the pemetrexed-based treatment (compared to the control treatment) depends on histology. The analyses show that a strong treatment-by-histology interaction exists for both studies, indicating that pemetrexed-based treatment is more effective in patients with non-squamous histology as compared to squamous histology.

"Nonsquamous histology is predictive of improved efficacy of the chemotherapy agent pemetrexed in patients with non-small cell lung cancer," said Chandra Belani, M.D., a lung cancer specialist from Pennsylvania State Hershey Cancer Institute. "This study is building the body of evidence showing that examining tissue types can help doctors find the most effective treatments for patients with lung cancer and other diseases."

http://www.astro.org/

Identifying malnutrition before surgery in massive weight loss patients seeking body contouring will significantly decrease surgical complications, accelerate wound healing, improve scar quality and boost patient energy levels, according to a study in the December issue of Plastic and Reconstructive Surgery, the official medical journal of the American Society of Plastic Surgeons (ASPS).

Optimizing nutrition with the addition of supplements, such as powder drinks and multi-vitamin tablets formulated for massive weight loss patients, is vital to successful body contouring surgery, the study reveals.

"Body contouring procedures for massive weight loss patients are major operations with large incisions in many areas that demand a lot of the body during the healing process," said ASPS Member Surgeon and study co-author Dennis Hurwitz, MD. "By carefully monitoring nutritional deficiencies preoperatively and supplementing the patient with the necessary nutrients, minerals and vitamins, I have seen a significant decrease in complications and improved postoperative healing. In my practice, I won't do body contouring procedures on this patient population without a preoperative regimen of nutritional supplements."

The study was performed in two parts; First, medical literature regarding nutrition's effect on healing from the 1940s to the present was reviewed. The authors then compared healing and wound problems in 75 of their massive weight loss body contouring patients from 2001 to 2005 who did not receive supplementation, with 37 patients from 2006 to present, who participated in a uniquely designed nutritional supplement program prior to surgery. The study also noted the role of each nutrient in wound healing and immune response.

The study found that complications and wound problems occurred in 66 percent of the 75 patients who did not receive supplementation before 2006. In the 37 patients on the nutritional supplement regimen after 2006, major complication rates were reduced to 19 percent. The study found specifically that improving nutritional deficiencies in massive weight loss patients improved the healing process, wound tension, and scar quality, in addition to increasing patients' energy levels.

Because of reduced calorie intake for massive weight loss patients, they are highly susceptible to malnutrition, the study observed. At one year after bariatric surgery, most patients' food intake remains at about 1,000 calories per day, not even close to meeting standard recommendations regarding calories and protein intake. The study also noted the role various nutrients play in wound healing: Protein, vitamins A, B complex, C, arginine, glutamine, iron, zinc and selenium promote wound healing, collagen production and immune response; Vitamin B complex has also been associated with reducing the risk of deep vein thrombosis.

According to the ASPS, nearly 67,000 body contouring procedures after massive weight loss were performed in 2007.

http://www.plasticsurgery.org/

Community-based physical activity interventions designed to promote more active lifestyles among adults are cost-effective in reducing heart disease, stroke, colorectal and breast cancers, and type 2 diabetes, according to a study by the Centers for Disease Control and Prevention, with support from the Robert Wood Johnson Foundation.

Using a rigorous economic model developed to assess the cost-effectiveness of community-based physical activity interventions, the study found these interventions to be cost-effective; reducing new cases of many chronic diseases and improving quality of life.

Researchers found that community-based physical activity programs appeared to reduce new cases of disease by: 5-15 cases per 100,000 people for colon cancer; 15-58 cases per 100,000 for breast cancer; 59-207 cases per 100,000 for type 2 diabetes; and 140-476 cases per 100,000 for heart disease.

Community-based physical activity interventions broadly fall under the following strategies:

• Community campaigns such as mass communication efforts (TV/radio, newspapers, billboards, advertisements).
• Social support networks such as exercise groups to encourage behavior change.
• Tailored behavior change to encourage people to set physical activity goals and monitor their individual progress.
• Enhanced access to services that support active lifestyles such as fitness centers, bike paths and walking trails.    

"Our study found that public health strategies that promote physical activity are cost effective, and compared with other well-accepted prevention strategies, such as treatment for high cholesterol or motor vehicle air bags, offer good value for the money spent," said Larissa Roux, M.D., Ph.D., lead author of the study.

The study, "Cost Effectiveness of Community-Based Physical Activity Intervention," is being published in the online version of the American Journal of Preventive Medicine.

"This study supports the value and effectiveness of the physical activity interventions that were studied," said William Dietz, M.D., Ph.D., director of CDC's Division of Nutrition, Physical Activity and Obesity. "This study also shows the importance of the new physical activity guidelines put forth last month by the U.S. Department of Health and Human Services."

The HHS guidelines recommend:

• Two and a half hours each week of moderate-intensity aerobic activity, such as brisk walking or,
• An hour and 15 minutes each week of vigorous-intensity aerobic activity such as jogging or running.    

In addition, all adults should include muscle strengthening activities that work all the major muscle groups on two or more days per week.

CDC's Division of Nutrition, Physical Activity and Obesity funds programs in 23 states designed to prevent obesity and promote healthy lifestyle habits such as physical activity.

The full study is available by sending a request to eAJPM@ucsd.edu. For more information about physical activity visit www.cdc.gov/physicalactivity/index.html.

For more information about the U.S. Department of Health and Human Services Physical Activity Guidelines visit www.health.gov/paguidelines.

http://www.cdc.gov/

Findings published in the journal Cancer Research, a journal of the American Association for Cancer Research, identify dietary intake of saturated fats as a possible risk factor for cancer of the small intestine, advancing the understanding of cancer development in this and other areas of the digestive tract.

While relatively rare, rates of cancer of the small intestine have been increasing since the 1970s. Individuals with this cancer are at increased risk of developing a second primary malignancy, particularly colorectal cancer.

"Identifying modifiable risk factors for cancer of the small intestine is important not only because the incidence of this cancer is on the rise, but it may enable us to further understand other gastrointestinal malignancies" said Amanda Cross, Ph.D., a National Cancer Institute researcher and the study's lead author.

Diets high in red and processed meats are associated with cancer of the large intestine. However, this is the first prospective study to examine meat and fat intake in relation to cancer of the small intestine.

Cross and other researchers from the National Cancer Institute used food frequency questionnaires to track food intake in a half million men and women enrolled in the NIH -AARP Diet and Health study over an eight-year period. Through state cancer registries and national death indexes researchers noted the development of 60 adenocarcinomas and 80 carcinoid tumors of the small intestine.

While findings showed no clear connection between red and processed meat and these tumors, they suggested a noticeably elevated risk for carcinoid tumors in the small intestine in association with saturated fat intake.

"Furthermore, there is some evidence to suggest that cancers of the small and large bowel both arise from adenomatous polyp precursor lesions, suggesting the adenoma-carcinoma sequence is relevant to both sites. For unknown reasons, the large intestine is much more susceptible to malignant transformation," said Cross. "Identifying risk factors that are unique as well as those that are similar for the two sites may aid our understanding of the comparative resistance of the small intestine to carcinogenesis."

These associations need to be further investigated in other populations and different types of saturated fat need to be studied specifically in order to understand the potential mechanisms involved, said Cross.

http://www.aacr.org