Methylation signaling controls cancer growth

Nov. 28, 2013 — A study led by researchers at Boston University School of Medicine (BUSM) demonstrates a new mechanism involving a signaling protein and its receptor that may block the formation of new blood vessels and cancer growth. The findings are published in the December issue of Science Signaling.

Angiogenesis creates new blood vessels in a process that can lead to the onset and progression of several diseases such as cancer and age-related macular degeneration.

Vascular endothelial growth factor (VEGF) is a signaling protein produced by damaged cells, which binds to one of its receptors VEGFR-2, located on the surface of blood vessel cells. Once VEGF is bound to its receptor, it is activated and sends a biochemical signal to the inside of the blood vessel cell to initiate angiogenesis. There are currently multiple Federal Drug Administration-approved medications that target this process. However these medications are limited by insufficient efficacy and the development of resistance.

The researchers demonstrated that a biochemical process called methylation, which can regulate gene expression, also affects VEGFR-2, and this can lead to angiogenesis. Using multiple methods, the researchers were able to interfere with the methylation process of VEGFR-2 and subsequently block angiogenesis and tumor growth.

"The study points to the methylation of VEGFR-2 as an exciting, yet unexplored drug target for cancer and ocular angiogenesis, ushering in a new paradigm in anti-angiogenesis therapy," said Nader Rahimi, PhD, associate professor of pathology, BUSM, who served as the study's senior investigator.

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The above story is based on materials provided by Boston University Medical Center, via EurekAlert!, a service of AAAS.

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Researchers identify switch that controls growth of most aggressive brain tumor cells

Sep. 20, 2013 — Researchers at UT Southwestern Medical Center have identified a cellular switch that potentially can be turned off and on to slow down, and eventually inhibit the growth of the most commonly diagnosed and aggressive malignant brain tumor.

Findings of their investigation show that the protein RIP1 acts as a mediator of brain tumor cell survival, either protecting or destroying cells. Researchers believe that the protein, found in most glioblastomas, can be targeted to develop a drug treatment for these highly malignant brain tumors. The study was published online Aug. 22 in Cell Reports.

"Our study identifies a new mechanism involving RIP1that regulates cell division and death in glioblastomas," said senior author Dr. Amyn Habib, associate professor of neurology and neurotherapeutics at UT Southwestern, and staff neurologist at VA North Texas Health Care System. "For individuals with glioblastomas, this finding identified a target for the development of a drug treatment option that currently does not exist."

In the study, researchers used animal models to examine the interactions of the cell receptor EGFRvIII and RIP1. Both are used to activate NFκB, a family of proteins that is important to the growth of cancerous tumor cells. When RIP1 is switched off in the experimental model, NFκB and the signaling that promotes tumor growth is also inhibited. Furthermore, the findings show that RIP1 can be activated to divert cancer cells into a death mode so that they self-destruct.

According to the American Cancer Society, about 30 percent of brain tumors are gliomas, a fast-growing, treatment-resistant type of tumor that includes glioblastomas, astrocytomas, oligodendrogliomas, and ependymomas. In many cases, survival is tied to novel clinical trial treatments and research that will lead to drug development.

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Host genome controls skin microbiota and inflammation

Sep. 17, 2013 — Numerous recent studies linked gut microbiota with various diseases such as obesity or diabetes. Little is known, however, on how gut and skin microbiota composition is controlled. In a recent study published in the journal Nature Communications on 17 September, John Baines, Saleh Ibrahim and their colleagues of the Inflammation Research Excellence Cluster show that composition of skin microbiota is controlled by the host genome and that skin bacteria may have a greater influence on inflammatory diseases than previously thought. Their landmark findings will open the door to identify gene variants controlling skin microbiota and to define their link to various diseases such as skin inflammatory disorders.

The human body contains more bacteria than human cells. Most of these bacteria comprise the normal gut and skin microbiota. Susceptibility to chronic inflammatory diseases is determined by immunogenetic and environmental risk factors that include resident microbial communities. Whether these differences are of primary etiological importance or secondary to the altered inflammatory environment remains largely unknown.

The inflammation cluster research groups led by Saleh Ibrahim of the University of Lubeck, and John Baines of the MPI and CAU, correlated the genomic variations of hundreds of mice that partially develop skin inflammatory diseases with skin microbiota. They showed evidence for host gene-microbiota interactions contributing to disease risk in a mouse model of autoantibody-induced inflammatory skin disease. Furthermore they identified genetic loci contributing to skin microbiota variability, susceptibility to skin inflammation and their overlap. The majority of the identified microbiotal communities are characterized by reduced abundance being associated with increased disease risk, providing evidence of a primary role in protection from disease.

These findings offer a promising potential for using those probiotic species for preventative and therapeutic treatment development. John Baines: "It appears that the skin flora is a phenotype that is partially controlled by the host genome variations. This in turn predisposes to the development of disease. The more we learn about these interactions, the more possibilities there will be for a better and more individualized treatment and prevention of skin inflammatory diseases.

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The above story is based on materials provided by Christian-Albrechts-Universitaet zu Kiel.

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Journal Reference:

1. Girish Srinivas, Steffen Moller, Jun Wang, Sven Kunzel, Detlef Zillikens, John F. Baines, Saleh M. Ibrahim. Genome-wide mapping of gene–microbiota interactions in susceptibility to autoimmune skin blistering. Nature Communications, 2013; 4 DOI: 10.1038/ncomms3462

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Exercise Controls Weight in White Girls Better Than in Black Girls: Study

AppId is over the quota
AppId is over the quota

WEDNESDAY, June 6 (HealthDay News) -- Exercise appears less likely to prevent obesity among black teenage girls than their white peers, a new study shows.

British researchers who gauged the effect of exercise on more than 1,100 girls, aged 12 to 14, surmised that black teen girls may be less sensitive than white teen girls to the effects of physical activity to prevent obesity.

"Higher levels of physical activity were associated with lower risk of obesity among white girls but not among black girls," wrote study authors James White and Russell Jago.

This is of concern because obesity rates are increasing at a greater rate among black teen girls than other U.S. youths, putting them at greater risk for heart disease, according to background information in the study. Black American girls were 80 percent more likely than white girls to be overweight in 2007-2010, the U.S. Department of Health and Human Services' Office of Minority Health reported. And about four out of five black American women are overweight or obese.

"At present, we don't know whether these differences can be attributed to genetics," said White, a researcher at Cardiff University in Wales. While other studies have found black girls consume more calories than white girls, he said this study took those differences into account, suggesting there may be other reasons. "These may be genetic, but we don't really know," he said.

However, at least one expert believes the study results may reflect lifestyle differences, which can be addressed, not just genetics.

White and Jago, of the University of Bristol in England, evaluated data on girls who participated in the long-running National Heart, Lung, and Blood Institute Growth and Health Study.

The researchers were looking at factors associated with obesity and the development of heart disease risk factors.

For this study, published in the June issue of the Archives of Pediatric and Adolescent Medicine, the research team focused on 538 black girls and 610 white girls for whom they had data on physical activity, obesity and other measures.

The girls' overall level of physical activity was measured for three days with a device that could detect frequency of movement and speed. Their TV viewing hours, height, weight, body-mass index (BMI), percent of body fat and daily calorie intake were also recorded. BMI, a calculation based on height and weight, is a reference used to determine obesity.

At age 12, the activity levels were higher in white girls than in black girls. The black girls had a higher BMI and body fat percentage, and ate more calories daily. They also watched more TV: The median -- meaning half watched more, half watched less -- was 44.3 hours a week for black girls vs. 24.5 for white girls.

Median daily caloric intake was slightly higher for black girls -- 1,912 vs. 1,906 for white girls.

At 12 years of age, 14 percent of the black girls were obese, compared to 4.3 percent of the white girls. At 14 years, 15.6 percent of the black girls and 5.1 percent of the white girls were obese.

That no link was found between physical activity levels and obesity among black girls is consistent with other research showing that fat-burning rates in response to physical activity are lower in black girls during puberty and adulthood than in whites.

Lifestyle issues, rather than genetics, may partly explain the results, said Pete McCall, an exercise physiologist with the American Council on Exercise.

Noting that black girls watch much more TV than white girls, he said, "That would be one area to change." They could shut off the TV and get exercise, "but the neighborhood may not be conducive," he said.

Parent education and income might affect the results, too, McCall speculated. More than half the parents of white girls had a college degree, but fewer than one-quarter of the black girls' parents did. The incomes of white girls' parents were higher, too.

"College education and income levels [of the parents] can play a role in the amount of physical activity a person gets," he added.

The authors noted that the black girls began menstruating earlier than the whites, which could also influence weight gain.

Encouraging black teen girls to exercise is still important, but different approaches may be needed to prevent obesity in black girls, the authors said.

"Our findings require replication before any real recommendations can be made," White said. "They do, however, suggest that black girls should be particularly attentive in controlling their caloric intake."

More information

To learn more about obesity and black Americans, visit the U.S. Office of Minority Health.

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