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Format: 04/24/2014
Format: 04/24/2014

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Philadelphia Examiner: Examiner Bio Allegheny General Hospital has been approved to use a drug that helps neurosurgeons extract tumors

Friday, May 7th, 2010

Allegheny General Hospital in Pittsburgh has been FDA approved for the use of an experimental drug called 5-aminolevunilic acid (5-ALA) that is used to illuminate and locate brain tumors using UV light. This drug and many other protoporphyrin-like compounds have been used to destroy cancer cells in photodynamic therapy in the past 30 years.

Remarkably, Allegheny General Hospital is only one of three hospitals in the world that are currently exploring the safety and efficacy of the drug of this oral fluorescent compound to illuminate and target gliomas, an aggressive form of brain cancer that arises in glial cells (support cells of neurons). Moreover, the US usually lags behind other countries in terms of approving medical protocols and experimental drugs in hospitals. Indeed, 5-ALA has already been approved in certain European countries while its approval is still pending in the US.

Gliomas claim the lives of an estimated 12,000 Americans each year and the incidence of gliomas are rapidly rising due to multitude of factors which include genetics, environmental factors and aging. Gliomas are classified as either low grade or high grade. While low grade gliomas are treatable with chemotherapy, high-grade gliomas may rapidly progress into progressive and often fatal tumors. The grade and type of gliomas depend on different surface markers/receptors the tumor may overexpress such that include isocitrate dehydrogenase 1 and 2, epidermal growth factor receptor, neurotrophin receptors and overactivation of the Akt in neoplastic gliomas and JNK pathways.

Treatment for gliomas typically involve a combination of radiation therapy, standard chemotherapy and surgery. Low grade gliomas with very well defined and confined visible borders are usually extracted with surgery by a well experienced neurosurgeon with high success. However, this is not typically the case with malignant gliomas as the extent of glioma proliferation and vascularization inside the brain cannot be determined with high accuracy. Sometimes a patient has to undergo several surgical procedures before the complete tumor mass is removed.

It is for these reasons that it is very important to know how the tumor is located, lodged into the brain matter and the extent of the tumor mass in order to do a successful resection which usually leads to a higher patient survival. The use of 5-ALA may solve this problem and it seems to work very well. Compared to normal tissue, 5-ALA is preferentially endocytosed (uptake) and metabolized by tumors to a fluorescent compound called a photoporphyrin whose structure is somewhat similar to that of chlorophyll, a pigment found in plants used in photosynthesis to extract energy from sunlight.

Tumors that adsorb this compound will fluoresce under UV light with a modified surgical microscope that contains a UV bulb to see the glowing tissue and guide the excision of the tumor. It is important to note that although UV itself can cause cancer, only the area of the brain containing the tumor is exposed during surgical extraction under very low doses of UV light.

As put by the words of Dr. Aziz, neurosurgeon of Allegheny General Hospital from the Department of Neurosurgery, "These tumors are often difficult because the lack of easily identifiable tumor margins under normal, direct vision of the operating field confounds the surgeon's attempts toward total resection. Any technique that would enhance our ability to more precisely determine these margins could make a significant difference for the patient. That is why we are so excited about investigating ALA as an adjunct to our conventional surgical approach. The preliminary experience with this innovative procedure has been extremely promising"

Finally, other promising alternative compounds/drugs that may be used in locating and destroying gliomas include the use of highly infrared adsorbing nanomaterials or magnetic nanoparticles to diagnose and treat brain tumors using a sophisticated technique termed thermal radiation therapy.

 

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