Researchers at Fox Chase Cancer Center uncovered a genetic pattern that may help predict how gastrointestinal stromal tumor (GIST) patients respond to the targeted therapy imatinib mesylate (Gleevec). Moreover, their findings point to genes that could be suppressed in order to make these tumors respond more readily to imatinib.

Lori Rink, PhD, a postdoctoral fellow in the laboratory of Andrew K. Godwin, PhD, at Fox Chase, presents their findings at the 2009 Annual Meeting of the American Society of Clinical Oncology. The study uses tumor specimens collected as part of a Phase II trial on the use of the drug before surgical resection for GIST, which is led by the Radiation Therapy Oncology Group, a national clinical cooperative group funded by the National Cancer Institute.

“Imatinib has been the first drug that has really made a dent in GIST progression - up to 80 percent response - yet some GIST patients have little or no response to the drug,” says Rink. “We are looking to see how we can help clinicians make better decisions in applying imatinib or additional therapies to their GIST patients.”

Rink and her colleagues followed 63 GIST patients in the RTOG trial, who were given imatinib before surgery for primary or recurrent tumors. Using tumor samples collected before and after the patients were given the drug, the researchers studied which genes were active in the tumors and then compared these profiles of gene expression to how well the tumors responded to short-term imatinib treatment.

According to Rink, they found a selection of 38 genes that were expressed higher in tumors that did not respond well to imatinib. Of these, they identified 20 KRAB-zinc finger genes that encode for proteins that typically act as transcriptional repressors of other genes. Ten of these genes, Rink says, are located to a single section of Chromosome 19.

“Our data indicate that if we can alter the activity of some of these KRAB-zinc finger proteins, we may be able to enhance the effectiveness of imatinib therapy,” Rink says.

Funding for this study comes from the National Cancer Institute, the Radiation Therapy Oncology Group Foundation and the GIST Cancer Research Fund.

Abstract #10533:
Correlation of gastrointestinal stromal tumor (GIST) gene expression signatures and response to imatinib mesylate in the Radiation Therapy Oncology Group phase II clinical trial S-0132.
Poster Discussion, Saturday, May 30
2:00 p.m.-6:00 p.m. - Level 2, W240A
5:00 p.m.-6:00 p.m. - Level 2, West Hall F5

Source:
Diana Quattrone

Fox Chase Cancer Center

View drug information on Gleevec.

Researchers in the University of Colony Department of Urology hit matured a newborn method that could support physicians watch the prizewinning instruction of communication for patients pain from sac cancer.

Bladder cancer is typically aerated by neoadjuvant chemotherapy, a communication in which chemotherapy is administered to turn the filler of the cancer preceding to surgery, with the digit most commonly utilised therapy regimens existence M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) and GemCis (gemcitabine and cisplatin). While M-VAC has daylong been thoughtful the more multipotent program and is ofttimes offered as the metallic accepted for treatment, it is quite cyanogenic and famous to successfully effect exclusive most 25 proportionality of patients who obtain it. Recent studies in metastatic cancer declare that GemCis is equally multipotent and haw be meliorate tolerated among patients; thus, it is commonly utilised in the neoadjuvant setting.

Dan Theodorescu, M.D., Ph.D., and colleagues hit unconcealed biomarkers whose countenance in patients’ piddle could accurately prognosticate whether or not a enduring is probable to move to M-VAC treatment. The biomarkers haw also prognosticate the probability of a flourishing outcome using the GemCis treatment. This novel, bioinformatics move to predicting the success of a portion communication over another regimens could advance to customized, more-effective communication for sac cancer patients.

“This is a promising, inexpensive and minimally intrusive possibleness move to appraise patients preceding to neoadjuvant chemotherapy,” said Theodorescu, academic of medicine and molecular physiology and administrator of the Apostle moneyman Urologic person Institute at U.Va.

The U.Va. Patent Foundation has filed a papers covering on the ingest of these biomarkers as a characteristic agency and is currently hunt an industrialized relation to boost amend and change the discovery. The biomarkers crapper easily be evaluated by assay (Enzyme-Linked Immunosorbent Assay) investigating or kindred profession in the urine.

“This elating newborn agency could enable physicians to watch not exclusive whether to travel with communication for sac cancer, but also which communication would be effective, on a case-by-case basis,” said Mikael C. Herlevsen, Ph.D., licensing assort at the U.Va. Patent Foundation. “This original profession shows a enthusiastic care of prospect and could hit a actual effect on patients’ lives.”

The National person Institute of the National Institutes of Health estimates more than 70,000 men and women throughout the U.S. module be new diagnosed with sac cancer in 2009

About the University of Colony Patent Foundation

The University of Colony Patent Foundation is a not-for-profit house that serves to alter U.Va. technologies to the orbicular activity by evaluating, protecting and licensing highbrowed concept generated in the instruction of investigate at U.Va. The Patent Foundation reviews and evaluates nearly 200 inventions per assemblage and has generated roughly $85 meg in licensing income since its manufacture in 1978.

Source: University of Colony

New research from the University of Virginia Health System shows that, when combined, two emerging medical technologies hold significant promise for treating the most deadly and devastating form of brain tumor, glioblastoma multiforme (GBM).

According to Jason Sheehan, M.D., a neurosurgeon and assistant professor of neurosurgery at the UVA School of Medicine, the use of controlled-released nanoparticles containing chemotherapeutic drugs and non-invasive ultrasound successfully helps to treat GBM tumors in mice.

Sheehan discussed the findings on May 4 during the annual meeting of the American Association of Neurological Surgeons (AANS). The association selected Sheehan for its 2009 Young Investigator Award in recognition of his outstanding potential as a researcher in the field of neuro-oncology.

During the study, Sheehan and his colleagues placed a cancer-killing drug inside nanoparticles affixed to microbubbles (which are the size of red blood cells) and injected the compound into the veins of immunocompromised mice. Carried by the bloodstream, the treatment travelled to the GBM tumor site. There, a 1 MHz dose of energy from the ultrasound equipment caused the microbubbles to burst and release the drug directly onto the cancer cells. Results show the treatment reduced tumor cell viability in a significant fashion and compared favorably with an anti-cancer drug, administered to the study’s positive control group. The UVA study also showed ultrasound induced damage to the microvessels feeding the tumor.

“Many drugs that kill GBM cells in vitro prove ineffective in living organisms because they are not able to penetrate the blood brain barrier,” noted Sheehan. “These new technologies are allowing us to overcome this challenging problem and deliver a highly targeted and sustained release of chemotherapy drugs. Although more research is needed, our findings indicate the technologies hold significant promise for patients with high grade gliomas and other malignant brain tumors.”

Sheehan’s research is on-going and is being performed in collaboration with his study co-authors, Caitlin Burke, BS, a graduate student in the UVA School of Engineering and Applied Science and Richard Price, PhD., a biomedical engineer in the UVA School of Medicine. Their research is funded by multi-year grants from the Hartwell Foundation.

“I’m honored to receive the 2009 AANS Young Investigator Award,” Sheehan says.

Sponsored by the American Brain Tumor Association, the award is presented annually by the American Association of Neurological Surgeons to a young faculty member in neurosurgery.

Sheehan received his B.S., M.S., PhD, and M.D. from the University of Virginia. His B.S. is in Chemical Engineering with the highest honors awarded from the School of Engineering. He performed fellowships at Auckland University and the University of Pittsburgh. Sheehan won the University of Virginia Clinical Excellence Award in 2006.

Widely-published, Sheehan is author of more than 100 peer-reviewed papers as well as numerous invited manuscripts and a book. He reviews manuscripts for several medical journals and serves on a variety of professional committees. Sheehan’s memberships include the American Association of Neurological Surgeons (AANS), the American College of Surgeons, Leksell Gamma Knife Society, Neurosurgical Society of the Virginias, AANS/CNS Tumor Section, and the American Society of Stereotactic and Functional Neurosurgeons.

Sheehan’s laboratory team also pursues translational and basic science research in brain tumors.

Source: University of Virginia Health System