No idea is off limits in cancer fight against cancer

June 10, 2008

Scientists have been aware for many years that if cancer patients are not able to deal with the stress associated with being sick, the cancer will progress faster than in calmer patients. To counteract this phenomenon, physicians encourage treatments that help cancer patients handle their stress. Scientists theorized that the stress relief may have come as a result of increased beta-endorphin peptide (BEP), the "feel good" hormones in the brain that are released during exercise, a good conversation, and many other aspects of life that give humans pleasure.

Researchers at Rutgers hypothesized that BEP producing neurons do not just make us feel good, but also play roles in regulating the stress response and immune functions to control tumor growth and progression. In a paper published today in the Proceedings of the National Academy of Science, Dipak K. Sarkar and his colleagues demonstrate the physical mechanisms that support their hypothesis.

"Our findings show promise for future therapeutic treatments for bolstering the immune function," says Sarkar, professor of animal sciences and director of the Endocrinology Program at the Rutgers School of Environmental and Biological Sciences, and principal investigator of the research project.

Previous research has shown that too few, or inactive, BEP neurons are associated with various diseases. For example, low numbers of BEP neurons have been identified in the brains of patients with depression and schizophrenia. Neurons that produce too little BEP are found in many obese patients. In both these cases the patients also had higher levels of infection and more incidence of cancer.

To test their hypothesis about the role of BEP in controlling tumor growth and progression, the Rutgers scientists took neural stem cells, transformed them into BEP neurons by treating them with particular chemicals, and then transplanted them into brains of live rats. The authors studied tumor growth in the rats that had been given carcinogens to induce prostate tumors. The authors noted that the BEP neurons boosted the immune system by increasing the activity of particular immune cell types and decreasing inflammation.

The neurons also protected the rats against prostate cancer 90 percent of the time. The researchers discovered that the "natural killer," or NK cells that typically attack cancer cells in the body, are activated by the inserted BEP neurons. The NK cells reduced inflammation around the cancer cells, which slowed down caner cell growth and killed many of these cells.

"We are optimistic that this research can be applied to human medicine," said Sarkar. "Instead of transplanting cells, we will investigate whether we can increase BEP using a chemical approach."

Rutgers School of Environmental and Biological Sciences, http://sebs.rutgers.edu/

SOURCE: Rutgers Univ.

Novel strategy for colon cancer treatment suggested by new genetic regulator

A team of scientists at the Genome Institute of Singapore (GIS), a research institute of the Asian city-state's Agency for Science, Technology and Research (A*STAR), and the Univ. of California at San Francisco have developed a pharmacological approach to kill colon cancer cells.

Genetic and epigenetic defects in the signaling of a protein called Wnt/β-catenin, which is often found to be abnormally activated in human malignance, play important roles in colorectal cancer development. The team of scientists identified a gene, called DACT3, whose function is to inhibit Wnt/β-catenin, is often lost (or transcriptionally silenced) in colorectal cancer.

Apart from the findings on DACT3, they have also developed a pharmacological approach to restore the expression of DACT3, which results in the effective inhibition of Wnt/β-catenin massive death of colon cancer cells. Their discovery was published in Cancer Cell on June 9, 2008.

GIS Group Leader, Yu Qiang, Ph.D., says, "This work identifies a significant new regulator of the Wnt/β-catenin avenue for future colorectal cancer research."

Edison Liu, M.D., executive director of GIS, adds, "This is indeed a very significant discovery. It suggests a novel therapy for colorectal cancer, an important step towards clinical treatment for the disease, which is one of the leading causes of death from tumours."

The team is now working with other A*STAR research institutes and industry partners for the development of potential drug candidates based on this technology.

Genome Institute of Singapore, www.gis.a-star.edu.sg

Agency for Science, Technology and Research, www.a-star.edu.sg

SOURCE: Agency for Science, Technology and Research (A*STAR), Singapore

A key new biomarker for prostrate cancer is found

A new study reveals a previously unidentified candidate oncogene that appears to play a significant role in a subset of prostate cancers. The research, published by Cell Press in the June issue of the journal Cancer Cell, describes a new strategy that can be used to find "outlier" genes in cancer subtypes that are not well understood.

"We know that ETS gene fusions occur in 40%-80% of prostate-specific antigen (PSA)-screened prostate cancers, leaving 20%-60% of prostate cancers in which the key genetic aberration is unknown. Further, we have shown that ETS-positive and --negative cancers have distinct transcriptional signatures, suggesting that unique oncogenes and downstream targets play a role in fusion-negative cancers," explains lead author, Arul M. Chinnaiyan from the Univ. of Michigan Medical School.

Chinnaiyan and colleagues sought out oncogenes that drive ETS-negative prostate cancers using a refined version of a newly developed approach called, Cancer Outlier Profile Analysis (COPA), that identifies outlier oncogenes in a specific subset of cancer cases. Using this methodology to examine data from seven prostate cancer profiling studies, they identified SPINK1 (serine peptidase inhibitor, Kazal type 1) as being overexpressed in prostate cancer when compared to benign prostate cells and displaying mutually exclusive overexpression with ETS family members.

SPINK1 outlier expression could be detected noninvasively in urine and SPINK1 outlier expression was shown to be an effective independent predictor of prostate cancer recurrence after surgical resection. Further, the aggressive ETS-negative 22RV1 cell line was identified as a SPINK1 outlier expression model. Reduction of SPINK1 in these cells could reduce invasion, suggesting a functional role for SPINK1 in ETS-negative prostate cancers.

These results identify SPINK1 as a biomarker specific to a subset of aggressive ETS-negative prostate cancers. Further studies are needed to determine the mechanism by which SPINK1 is overexpressed in ETS-negative cancers. "Our study also extends the utility of our original COPA approach by using a meta-COPA strategy to nominate candidate oncogenes in specific types of cancer," concludes Chinnaiyan.

The study abstract is available here, http://www.cancercell.org/content/article/abstract?uid=PIIS1535610808001529&feed=CCELL

SOURCES: Cell Press; ScienceDaily