Tuesday, August 3, 2010
Fructose helps pancreatic cancer cells to multiply, UCLA study finds
WASHINGTON — Pancreatic tumor cells use fructose to divide and proliferate, U.S. researchers said Monday in a study that challenges the common wisdom that all sugars are the same.

Tumor cells fed both glucose and fructose used the two sugars in two different ways, the team at the University of California Los Angeles found.

They said their finding, published in the journal Cancer Research, might help explain other studies that have linked fructose intake with pancreatic cancer, one of the deadliest cancer types.

“These findings show that cancer cells can readily metabolize fructose to increase proliferation,” Anthony Heaney of UCLA’s Jonsson Cancer Center and colleagues wrote. “They have major significance for cancer patients given dietary refined fructose consumption, and indicate that efforts to reduce refined fructose intake or inhibit fructose-mediated actions may disrupt cancer growth.”

Americans take in large amounts of fructose, mainly in high-fructose corn syrup, a mix of fructose and glucose that is used in soft drinks, bread and a range of other foods. Politicians, regulators, health experts and the fructose industry have debated whether high-fructose corn syrup and other ingredients have been helping make Americans fatter and less healthy. Too much sugar of any kind not only adds pounds, but is also a key culprit in diabetes, heart disease and stroke, according to the American Heart Association. Several states, including New York and California, have weighed a tax on sweetened soft drinks, but the American Beverage Association has successfully opposed efforts to tax soda.

The industry has also argued that sugar is sugar. Heaney said his team found otherwise. They grew pancreatic cancer cells in lab dishes and fed them both glucose and fructose. Tumor cells thrive on sugar but they used the fructose to proliferate. “Importantly, fructose and glucose metabolism are quite different,” Heaney’s team wrote.

Los Angeles, California – July 21, 2010 – SiDMAP, LLC (www.sidmap.com), a privately held life-science company that provides metabolomics research services to the pharmaceutical and biotechnology industries and the academic biomedical research community worldwide, announced today results of a study conducted in collaboration with scientists at  Roche (Nutley, NJ), a leading pharmaceutical company, on a novel Roche drug for Type 2 diabetes.

The study, entitled “A Novel Approach for the Treatment of Type 2 Diabetes (T2D): Characterization of a Potent, Orally Active, Small Molecule Glycogen Synthase Activator,” was presented in Abstract 1389-P at the recently concluded American Diabetes Association (ADA), 70th Scientific Sessions, in Orlando, Florida.

Laszlo G. Boros, M.D., SiDMAP’s Chief Scientist, was SiDMAP’s lead investigator on the study. Andree R. Olivier, Ph.D., was lead investigator for Roche.

Using study methods designed by Dr. Boros in collaboration with Roche, the glycogen synthase activator GSA3 was administered to DIO mice (75 mg/kg), along with a stable isotope (non-emitting) glucose tracer. Subsequent laboratory analysis by SiDMAP of mouse tissue samples using the Company’s proprietary Stable Isotope Dynamic Metabolic Tracer technology demonstrated that GSA3 increased glycogen synthesis in mouse muscle and liver tissues, but the source of tracer-glucose in liver glycogen is primarily derived from an indirect pathway.

Dr. Boros said, “The purpose of the SiDMAP’s analysis of plasma and tissues from GSA3-treated DIO mice that had absorbed a stable isotope glucose tracer was to see if we could further validate Roche’s previous findings on the effects and mechanism of action of their potential T2D compound. The SiDMAP results were supportive of the previous Roche findings. The SiDMAP results also provided detailed pictures regarding glucose disposal mechanisms and system response using the highest scoring [U-13C6]-D-glucose tracer for TCA/pentose cycle and hepatic glucose production type clamp equivalent studies.”

As described in the study abstract, the SiDMAP findings, taken together with data on Roche GSA3 activator RO5289867, “provide evidence that direct pharmacological activation of GYS1 and GYS2 can lead to beneficial effects in whole body substrate metabolism and may be a viable approach for treating T2D and its co-morbidities.”

Dr. Olivier said, “The SiDMAP technology added value by giving Roche further confirmation and understanding of our compound’s mechanism of action, and enabled Roche to achieve its study objectives.”

According to Dr. Boros, “The precise and previously inaccessible flux map resulting from our in vivo study with Roche further support the use of Stable Isotope Dynamic Metabolic Profiling technology in the characterization of potential new drugs and their targets for Type 2 diabetes.”

The full text for Abstract 1389-P can be found at the following web address: http://ww2.aievolution.com/ada1001/index.cfm?do=cnt.page&pg=1009

About SiDMAP
SiDMAP, LLC is a metabolomics company that provides research services for drug discovery and development, biomedical research, and drug toxicology research. SiDMAP clients include global pharmaceutical companies, leading biotechnology companies, major academic research institutions and drug regulatory authorities.

Contact
Kate Hawkes, Manager, Business Development & Administration
SiDMAP, LLC
E-Mail Kate Hawkes, Phone:  310-478-1424, ext. 308

The new grant, funded by the National Institutes of Health / National Cancer Institute, provides support for metabolic profiling research in lung cancer. Shyam Biswal, Ph.D., Associate Professor at Johns Hopkins University, School of Medicine, in Baltimore, is Principal Investigator on the grant.
Entitled “Regulation of Tumorigenesis and Therapeutic Resistance by Nrf2 in Lung Cancer,” the grant will test the hypothesis that a gain in function of the gene transcription factor Nrf2 (Nuclear factor erythroid-2 related factor) promotes tumorigenesis in the presence of an oncogenic (cancer-causing) signal.

“SiDMAP opens new avenues for understanding and treating cancer by revealing the functional impact of known gene mutations on a complex hierarchy of metabolic reactions.” said Dr. Boros. He added, “SiDMAP is always glad to collaborate with top university investigators, such as our colleagues at Johns Hopkins, to accelerate research in the cancer field.”

Dr. Boros, a SiDMAP co-founder and Associate Professor at the UCLA School of Medicine, is a leading expert on the basic science and translational research applications of metabolomics, an evolving field of research focusing on metabolic changes associated with disease processes and response to drug treatment. Metabolomics studies are used by drug researchers to elucidate a drug’s mechanism of action (MOA) by identifying and measuring myriad metabolic changes that occur in cells and organs following drug administration. Metabolomics studies can also reveal early metabolic changes associated with increased potential for drug toxicity, and can be used to screen for cellular, animal model or patient phenotypes that respond more or less favorably to a particular drug. Metabolomics testing is also being used increasingly as a very precise tool for identifying novel drug targets, such as key enzymes that play critical roles in the function of metabolic pathways essential for the growth of cancer cells.

Dr. Boros and his research team at SiDMAP will collaborate with Dr. Biswal and his team at Johns Hopkins to determine whether a gain in Nrf2 function increases glucose metabolism via the pentose phosphate pathway and tricarboxlyic acid pathway—metabolic steps essential to tumorigenesis. The grant further seeks to determine if blocking Nrf2-dependent phosphate pathway enzymes inhibits growth of NSCLC cells and limits chemoresistance.

Use of SiDMAP’s proprietary stable-isotope dynamic metabolic profiling technology in the NIH/NCI-funded study at Johns Hopkins will help in understanding the regulation of lung tumorigenesis by a novel pathway and in developing a strategy for targeting this pathway to circumvent therapeutic resistance.

Contact

Kate Hawkes

Manager, Business Development & Administration
SiDMAP, LLC

Phone: 310-478-1424, ext. 308
khawkes@sidmap.com

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