Abstracts
Preclinical Experimental Chemotherapeutic Approachces for Treating Glioblastoma Multiform
Glioblastoma multiforme is the most common and most aggressive of the primary brain cancers, with a median survival rate of about one year. Standard treatment options include surgical resection, radiation therapy, and chemotherapy. Currently, the most effective of the approved chemotherapeutic agents used is a nitrosourea compound called carmustine [1]. When carmustine-impregnated wafers are implanted at the time of surgery the mean survival rate increases from 11.6 months to 13.9 months [2]. The identification of agents that may offer a more meaningful increase in mean survival rate than that demonstrated by carmustine was the object of this research project. Carmustine and five other compounds (berberine, curcumin, caffeic acid phenethyl ester, abscisic acid, and Primiplex™ 19) were used both independently and in various combinations to treat glioblastoma multiforme cells (cell line DBTRG-05MG). The effects on both mono-layers and multicellular tumor spheroid models were examined. Although none of the compounds was significantly successful in inhibiting cell proliferation or inducing apoptosis independently at low concentrations, several of the compounds (especially curcumin) were highly effective when used in conjunction with carmustine in the preclinical assessment.
Experimental Studies of Cyclopamine, Curcumin, Berberine on Treating Glioblastoma Multiforme
Glioblastoma multiforme (GBM) is a malignant tumor that arises from the supportive tissue of the brain. The supportive tissue of the brain consists of three types of cells which include astrocytes, oligodendrocytes, and epidymal cells;
these cells are collectively called glial cells. Gliomas can either be classified as low grade, that being, grades I and II which are slowly growing or high grade, grades III and IV which are rapidly growing. Increasing evidence now suggests that primary and secondary GBM might be two distinct diseases that may possibly evolve through different genetic pathways. The treatment of patients with glioblastoma becomes one that requires a combination of surgery, radiotherapy, and chemotherapy. Chemotherapy is usually an essential therapeutic tool that is offered to the patients diagnosed with GBM. The current course of drug that are being used as chemotherapants are drugs that do not differentiate between normal cells and GBM cells thus leading to the many adverse effects of chemotherapy. The approach that is utilized within this study is one that uses drugs that will for one only attack proliferating cells and have also been shown to have little or no adverse effect on the individuals and their normally dividing cells. The pathways that were chosen to be attacked are Sonic hedge hog (Shh) pathway, NF-KB pathway (nuclear Factor Kappa B), and the mtor pathway. Phytochemicals such as cyclopamine, berberine, and curcumin were chosen to treat GBM. The method used for this research was culturing cells as tumor spheroids. These spheroids were formed by preventing the cells fro attaching to plate by placing 1 ml of agarose within the wells, this forced the cells to clump and as a result form spheroids. Spheroids give a better ideas of how drugs would treat actual tumors as they resemble actual tumors.