New function of two molecules involved in metastasis

Nov. 14, 2013 — Researchers from IMIM (Hospital del Mar Medical Research Institute) lead by Dr. Sandra Peiro have described a new function for two key molecules involved in tumor progression. Transcription factor SNAIL1 and enzyme LOXL2 are essential to Epithelial-Mesenchymal Transition (EMT); meaning the process by which tumor cells are able to move and reach other tissues. The study has been published in the Molecular Cell Journal and places enzyme LOXL2 as a possible therapeutic target to treat cancers such as breast, lung or skin cancer.

Transcription factors are proteins that regulate gene expression. They activate or deactivate a gene's function. Researchers at IMIM have studied the function of one of these transcription factors, Snail1, in mouse cells during the Epithelial-Mesenchymal Transition (EMT). Sandra Peiro, a researcher from the IMIM Research Group on Epithelial-Mesenchymal Transition and Tumor Progression explains: "EMT is a process consisting of converting epithelial cells, the ones covering the internal and external surfaces of the body, into what are known as mesenchymal cells. In this process, the cells acquire a series of new characteristics that enable them to migrate and resist apoptosis (programmed cell death), self-regenerate and, finally, invade neighboring tissues and reach other areas of the body. When this process occurs at the tumor epithelial cells, the resulting mesenchymal cells can migrate and generate metastases."

The study shows that during the transformation into mesenchymal cells, DNA, folded in to chromatin cell, must then become reorganized to adapt to the now cell functions. Transcription factors Snail1, through LOXL2 is in charge of this transformation. Therefore, any mechanism that is able to block it would prevent Epithelial-Mesenchymal Transition and thus a metastasis. "Our research is basic, and therefore, our findings cannot be applied immediately, but the fact that LOXL2 is a key element in the process and an enzyme makes it a firm candidate to be a therapeutic target, since its activity can easily be inhibited or blocked with the right drugs," says Sandra Peiro.

Previous studies by this group had described, for the first time, that LOXL2 was present at the cell nucleus and played a key role in tumor development. These new outcomes show that the functions of the genome are found to go far beyond the simple DNA sequence and that, therefore, it is necessary to integrate all levels of regulation to understand genome regulation. Right now, the challenge for the researchers is to study how the genome is organized spatially during a vital process in the development of cancer as EMT.

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Red grapes, blueberries may enhance immune function

Sep. 17, 2013 — In an analysis of 446 compounds for their the ability to boost the innate immune system in humans, researchers in the Linus Pauling Institute at Oregon State University discovered just two that stood out from the crowd -- the resveratrol found in red grapes and a compound called pterostilbene from blueberries.

Both of these compounds, which are called stilbenoids, worked in synergy with vitamin D and had a significant impact in raising the expression of the human cathelicidin antimicrobial peptide, or CAMP gene, that is involved in immune function.

The findings were made in laboratory cell cultures and do not prove that similar results would occur as a result of dietary intake, the scientists said, but do add more interest to the potential of some foods to improve the immune response.

The research was published today in Molecular Nutrition and Food Research, in studies supported by the National Institutes of Health.

"Out of a study of hundreds of compounds, just these two popped right out," said Adrian Gombart, an LPI principal investigator and associate professor in the OSU College of Science. "Their synergy with vitamin D to increase CAMP gene expression was significant and intriguing. It's a pretty interesting interaction."

Resveratrol has been the subject of dozens of studies for a range of possible benefits, from improving cardiovascular health to fighting cancer and reducing inflammation. This research is the first to show a clear synergy with vitamin D that increased CAMP expression by several times, scientists said.

The CAMP gene itself is also the subject of much study, as it has been shown to play a key role in the "innate" immune system, or the body's first line of defense and ability to combat bacterial infection. The innate immune response is especially important as many antibiotics increasingly lose their effectiveness.

A strong link has been established between adequate vitamin D levels and the function of the CAMP gene, and the new research suggests that certain other compounds may play a role as well.

Stilbenoids are compounds produced by plants to fight infections, and in human biology appear to affect some of the signaling pathways that allow vitamin D to do its job, researchers said. It appears that combining these compounds with vitamin D has considerably more biological impact than any of them would separately.

Continued research could lead to a better understanding of how diet and nutrition affect immune function, and possibly lead to the development of therapeutically useful natural compounds that could boost the innate immune response, the researchers said in their report.

Despite the interest in compounds such as resveratrol and pterostilbene, their bioavailability remains a question, the researchers said. Some applications that may evolve could be with topical use to improve barrier defense in wounds or infections, they said.

The regulation of the CAMP gene by vitamin D was discovered by Gombart, and researchers are still learning more about how it and other compounds affect immune function. The unique biological pathways involved are found in only two groups of animals -- humans and non-human primates. Their importance in the immune response could be one reason those pathways have survived through millions of years of separate evolution of these species.

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Swallowing exercises shown to preserve function in head and neck cancer patients receiving radiation

AppId is over the quota
AppId is over the quota

A study from UCLA’s Jonsson Comprehensive Cancer Center (JCCC) has found that head and neck cancer patients receiving radiation as part of their treatment were less likely to suffer unwanted side effects such as worsening of diet, need for a feeding tube, or narrowing of the throat passage if they complied with a set of prescribed swallowing exercises called a swallow preservation protocol (SPP) during therapy.

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Among the research institutions NCI funds across the United States, it currently designates 67 as Cancer Centers. Largely based in research universities, these facilities are home to many of the NCI-supported scientists who conduct a wide range of intense, laboratory research into cancer’s origins and development. The Cancer Centers Program also focuses on trans-disciplinary research, including population science and clinical research. The centers’ research results are often at the forefront of studies in the cancer field.

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