Possible new target for sarcoma treatment and prevention

ScienceDaily (May 23, 2011) — Researchers from Mount Sinai School of Medicine have discovered a protein signaling pathway that becomes hyperactivated in human sarcoma cells, suggesting that medications to inhibit this pathway may be effective in the treatment of human sarcomas. The research is published in the current issue of the journal Cancer Cell.

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A team of researchers led by Stuart Aaronson, MD, Jack and Jane B. Aron Professor and Chairman of the Department of Oncological Sciences at Mount Sinai School of Medicine, compared normal human mesenchymal stem cells to human sarcoma cells and found that the sarcoma cells displayed hyperactive signaling along the Wnt pathway -- a complex network of proteins that interact with each other in a highly ordered manner to regulate numerous biological functions of various species.

The hyperactive Wnt signaling increased the growth of several subtypes of human sarcoma cells by increasing the expression of CDC25A, a gene previously shown to be deregulated in various types of cancer. Increased protein levels of CDC25A enhances the rate of cell proliferation, and cancer cells often exhibit very high CDC25A protein levels compared to normal cells.

"The prevalence of Wnt signaling hyperactivity in human sarcoma cells gives researchers a potential new target as they develop medications to target human sarcoma," said Dr. Aaronson.

"Since several cancer types show increased CDC25A levels, it is regarded as a good target to generate therapeutic agents to dampen its functions and thus will be an important candidate in future drug development," said Sapna Vijayakumar, PhD, Instructor of Oncological Sciences, Mount Sinai School of Medicine, who was the first author of the study.

Normal Wnt functioning is critical for maintaining tissue homeostasis. Hyperactive (deregulated) Wnt signaling is reported to be one of the early causes of colon cancer, and it is also implicated in several other cancer types.

In many instances, hyperactive Wnt signaling increases the expression of certain genes that cause the cell to proliferate faster than normal. This uncontrolled proliferation, often accompanied by additional changes in gene or genes independent of Wnt signaling, can transform a normal cell into a cancerous one.

Sarcomas comprise about one percent of all adult cancers, but about 15 percent of all childhood cancers. There are many sarcoma "subtypes" that can arise from a variety of connective tissue structures, including nerves, muscles, joints, bone, fat, and blood vessels. The most frequent location for sarcomas are the limbs, where the majority of the body's connective tissue is located. About 20 percent of sarcomas are curable by surgery, while 30 percent can be cured by surgery with chemotherapy and/or radiation. About 12,000 new cases are diagnosed in the US each year and about 5,000 people die each year from sarcoma.

Sarcomas are subtyped based on where they occur in the body (in the bone, they are called osteosarcoma, in the smooth muscle they are leiomyosarcoma, in the cartilage they are chondrosarcoma, and so on). Studies suggest that even though sarcomas can occur in any part of the body, they commonly arise from the transformation of mesenchymal stem cells.

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Report outlines successes, challenges in cancer prevention efforts

ScienceDaily (May 19, 2011) — A new report from the American Cancer Society details cancer control efforts and outlines improvements as well as gaps in preventive behavior that contribute to cancer mortality. Increasing rates of obesity observed since the early 1980s appear to have slowed in the past decade, particularly among women and girls, but nearly one in five adolescents and about one in three adults is obese. Vaccination against the virus that causes cervical cancer is up, but smoking declines have stalled. Meanwhile, proven cancer screening tests remain underutilized, particularly in un- and under-insured populations.

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The report, Cancer Prevention & Early Detection Facts & Figures (CPED), says social, economic, and legislative factors profoundly influence individual health behaviors, and that meeting nationwide prevention goals will require improved collaboration among government agencies, private companies, nonprofit organizations, health care providers, policy makers, and the American public.

Since 1992, the American Cancer Society has published CPED as a resource to strengthen cancer prevention and early detection efforts at the local, state, and national levels. Below are highlights of this year's report.

Tobacco Use

Smoking rates in U.S. adults and youth have stalled. Among adults, the smoking rate remained unchanged in the past 6 years (2009: 20.6%). Among high school students, the smoking prevalence did not change significantly between 2003 and 2009 (19.5%), but use of smokeless products is increasing in some groups. Smoking among middle school students also did not change between 2006 and 2009 (5.2%). States' funding for tobacco control ($517.9 million) in 2011 was the lowest amount allocated since the 1999 Master Settlement Agreement (MSA), with only 2% of states' revenue from tobacco taxes and the MSA allocated for tobacco control. Federal tobacco control funding to some extent offset declines in states' funding. Several federal tobacco control initiatives, including U.S. Food and Drug Administration regulations and funding for tobacco control, went into effect in 2010. Provisions for tobacco dependence treatment coverage in the Affordable Care Act for previously uninsured individuals, Medicare, and Medicaid recipients either went into effect in 2010 or will be implemented in upcoming years. As tobacco marketing and sales become more restrictive due to regulations, the industry is moving toward unregulated venues and products. For example, point-of-source advertising and promotions are increasingly being targeted by the industry, as are products such as small cigars that are not subject to the same regulations governing cigarette sales and marketing.

Overweight and Obesity, Physical Activity, and Nutrition

Currently, an estimated 18.1% of adolescents and 34.3% of adults are obese. Increasing rates of obesity observed since the early 1980s appear to have slowed in the past decade, particularly among women and girls. In 2009, the prevalence of obesity among adults exceeded 20% in all states except Colorado (19.3%).

HPV Vaccination for Cervical Cancer Prevention

To prevent cervical cancer, vaccination against certain types of human papillomavirus (HPV) is recommended for adolescent girls. The initiation of the HPV vaccination series among U.S. females aged 13 to 17 increased from 25% in 2007 to 44% in 2009, and nearly one in three completed the entire series.

Cancer Screening

Mammography usage has not increased since 2000. In 2008, 53% of women aged 40 and older reported getting a mammogram in the past year. Women who lack health insurance have the lowest use of mammograms (26%). In 2008, 78.3% of adult women had a Pap test in the past three years. However, there is persistent under-use of the Pap test among women who are uninsured, recent immigrants, and those with low education. Colorectal cancer screening rates increased from 38% in 2000 to 53.2% in 2008; however, rates remain substantially lower in uninsured individuals. To date, 26 states and the District of Columbia have passed legislation ensuring coverage for the full range of colorectal cancer screening tests.

Improving these numbers, says the report, will require coordinated efforts. "For example," the authors write, "the price and availability of healthy foods, the incentives and opportunities for regular physical activity in schools and communities, the content of advertising aimed at children, and the availability of insurance coverage for screening tests and treatment for tobacco addiction all influence individual choices."

Full report.

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