Arthritis patients taking newer treatments do not have an overall increased cancer risk, research finds

ScienceDaily (May 27, 2011) — Newer biologic treatments, including infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia), golimumab (Simponi) and etanercept (Enbrel), used in patients with arthritis do not increase the risk of cancer, according to data from over 13,000 patients presented at the EULAR 2011 Annual Congress.

See Also:Health & MedicineArthritisBreast CancerCancerColon CancerCrohn's DiseaseOvarian CancerReferenceArthritisRheumatoid arthritisCOX-2 inhibitorPsoriasis

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Link between environment and genetics in triggering multiple sclerosis: Discovery points to personalized treatments

ScienceDaily (June 1, 2011) — Environmental and inherited risk factors associated with multiple sclerosis -- previously poorly understood and not known to be connected -- converge to alter a critical cellular function linked to the chronic neurologic disease, researchers with the UC Irvine Multiple Sclerosis Research Center have discovered.

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The findings, which appear in the online, open-access journal Nature Communications, suggest that a unifying mechanism may be responsible for multiple sclerosis and point to therapies personalized according to genetic factors.

"MS results from complex interactions between an individual's genetics and his or her environment," said study leader Dr. Michael Demetriou, a UCI neurologist and associate director of the Multiple Sclerosis Research Center. "Defining how these come together to induce the disease is critical for developing a cure. We've taken a giant first step toward understanding this."

Using blood samples from about 13,000 people, Demetriou and colleagues identified the way environmental factors -- including metabolism and vitamin D3, obtained through either sunlight exposure or diet -- interact with four genes (interleukin-7 receptor-alpha, interleukin-2 receptor-alpha, MGAT1 and CTLA-4) to affect how specific sugars are added to proteins regulating the disease.

Earlier work on mice by Demetriou revealed that changes in the addition of these specific sugars to proteins engender a spontaneous MS-like disease. They also found that N-acetylglucosamine (GlcNAc), a dietary supplement and simple sugar related to glucosamine, is able to suppress this process.

The current research shows that both vitamin D3 and GlcNAc can reverse the effects of four human MS genetic factors and restore the normal addition of sugars to proteins. "This suggests that oral vitamin D3 and GlcNAc may serve as the first therapy for MS that directly targets an underlying defect promoting disease," Demetriou said.

Virtually all proteins on the surface of cells, including immune and nervous system cells, are modified with complex sugars of variable lengths and composition. This adds information to proteins separate from that directly defined by the genome. The sugars interact with specific sugar-binding proteins on the cell, forming a molecular lattice that controls the clustering, signaling and surface expression of critical receptors and transporters, such as the T cell receptor and CTLA-4. Reducing sugar modification weakens the lattice and enhances growth and activity of immune system T cells in such a way that they increase neural degeneration -- a hallmark of MS.

Production of the complex sugars is regulated by both metabolic and enzymatic functions, the latter altered by genetic MS risk factors and vitamin D3. Demetriou pointed out that the MGAT1 genetic variant linked to MS increases or decreases the sugars attached to proteins depending on metabolism -- one possible explanation for why people with the same genetic risk factor may or may not develop MS.

These sugars have also been implicated in many other chronic diseases, such as diabetes and cancer, Demetriou added, so this work could open up entirely new areas of medicine.

Haik Mkhikian, Ani Grigorian, Carey F. Li, Hung-Lin Chen, Barbara Newton, Raymond W. Zhou, Sevan Torossian, Gevork Grikor Tatarian, Sung-Uk Lee, Christine Beeton, K. George Chandy and Zhaoxia Yu of UCI and Ken Lau, Erin Walker, Katherine A. Siminovitch and James W. Dennis of the Samuel Lunenfeld Research Institute in Toronto participated in the study, which received support from the National Institute of Allergy & Infectious Diseases and the National Multiple Sclerosis Society, among others.

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Higher doses of radiation in fewer treatments proved safe, effective for low-risk prostate cancer, study finds

ScienceDaily (June 2, 2011) — In a multicenter clinical trial, UT Southwestern Medical Center researchers have found that higher doses of stereotactic radiation therapy requiring fewer treatments are safe and effective for patients with low-to-intermediate-risk prostate cancer.

See Also:Health & MedicineMen's HealthProstate CancerUrologyBreast CancerCancerColon CancerReferenceMetastasisUrologyGliomaTumor suppressor gene

Results of the trial, available in the Journal of Clinical Oncology, showed that stereotactic body radiation therapy (SBRT), which delivers ultra-precise radiation, was effective in treating patients with localized prostate cancer in five 30-minute sessions every other day over two weeks. That compares to the typical radiation protocol for prostate cancer of 42 to 45 daily treatments administered over eight to nine weeks.

"We were trying to develop a fast, convenient, outpatient, non-invasive treatment," said Dr. Robert Timmerman, vice chairman of radiation oncology and professor of neurological surgery and senior author of the study. "In the low-risk population, there are a lot of good options, but none of them are altogether convenient. The most convenient treatment would finish quickly without the need for a prolonged recovery."

SBRT has been used in the last decade to treat patients with lung, liver and brain cancers. The current study tested whether high-potency treatments would work in a moving target like the prostate, which moves considerably due to normal bladder and bowel filling.

"We're trying to kill the prostate cancer, but without injuring the urethra, the bladder or the rectum," Dr. Timmerman said. "Each treatment had to be very potent in order to get the full radiation effect in only five treatments."

To avoid injury to healthy tissue, researchers used beams of radiation that were just millimeters larger than the target itself. That narrow scope helped avoid consequences such as rectal injury, impotence and difficulty urinating.

Prostate cancer is the most common cancer in men, with some 200,000 diagnosed each year in the U.S. About half of those who are treated undergo radiation therapy, typically for eight weeks. Not everyone is cured, however, because some tumors are resistant to radiation.

In the current clinical trial, researchers tested escalating doses for safety levels in 45 patients enrolled from November 2006 to May 2009. In a 90-day follow-up procedure, they looked at how much injury occurred in adjacent areas, including the rectum or urethra, and any changes to the patients' quality of life.

"There were a few more complications associated with higher doses, but they were fairly predictable and rarely severe," said Dr. Yair Lotan, associate professor of urology and a co-author of the study. "By giving these higher doses, we might be able to kill more resistant tumors with shorter treatments."

In the next stage of the clinical trial, a larger group of patients will be treated at one dosage level, and follow-up will be 18 months.

Other UT Southwestern researchers involved in this study were Dr. Paul DeRose, radiation oncology resident; Dr. Xian-Jin Xie, associate professor in the Harold C. Simmons Comprehensive Cancer Center; Jingsheng Yan, statistician; Dr. Ryan Foster, assistant professor of radiation oncology; Dr. David Pistenmaa, professor of radiation oncology; and Susan Cooley, senior research nurse in radiation oncology.

The study was supported by the Department of Defense.

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