Brain Tumors

Evaluation of the Mechanism of Interaction between Temozolomide and TNFa in the Induction of Apoptosis
2005 Seed Grant
Bakhtiar Yamini, M.D.
The University of Chicago

Temozolomide is a standard chemotherapeutic agent used in conjunction with radiation therapy in the treatment of malignant brain tumors. Dr. Yamini’s lab’s work centers on a novel treatment of these tumors whereby Temozolomide is used to activate a known anticancer agent- tumor necrosis factor alpha (TNF)- that is injected directly into the tumor mass. In this combination strategy the Temozolomide and TNF work together to synergistically cause tumor cell killing. Although Temozolomide has been extensively studied for many years, their investigations demonstrate that this agent is working by a previously unreported mechanism to facilitate the killing of tumor cells by TNF. The experiments proposed in this project will specifically determine whether Temozolomide is blocking a known survival pathway in tumor cells thus allowing the TNF to kill them.

Malignant gliomas are the most common primary brain tumor in the United States and afflict patients in the prime of their lives. Standard treatment still centers on radiation and chemotherapy even though patient survival has not significantly changed in over 30 years. Newer treatment modalities such as gene therapy have had some success but have failed to uncover a ‘magic bullet’ . It is likely that a rationally devised, multimodal treatment approach will be necessary in this aggressive cancer. In this regard, Dr. Yamini’s lab have been studying a radiation and chemotherapy activated gene therapy strategy in an animal model. This project will investigate the mechanisms underlying the success seen in their animal experiments and, if successful, may well open up an important area of combination anti-tumor therapy for use in patients suffering from this devastating disease.

Other Grants

Rebekah C. Evans, Ph.D., Georgetown University
In Vivo and Ex Vivo Dissection of Midbrain Neuron Activity During Exercise
Exercise is important for the health of the body and the mind. Exercise promotes learning and reduces symptoms of brain-related diseases such as Parkinson’s disease and Alzheimer’s disease. However, it…
William J. Giardino, Ph.D. Stanford University
Deciphering the Neuropeptide Circuitry of Emotional Arousal in Narcolepsy
This research project aims to investigate the neural mechanisms of a specific type of brain cell called neuropeptide neurons within a region of the brain’s amygdala network called the bed…
Howard Gritton, Ph.D., University of Illinois
Attention Mechanisms Contributing to Auditory Spatial Processing.
Our world is composed of a rich mixture of sounds. We often process sounds including speech in the presence of many other competing auditory stimuli (e.g., voices in a crowded…
Nora Kory, Ph.D., Harvard University
Elucidating the Fates and Functions of Lactate in the Brain
The human brain requires significant energy to function. Despite accounting for only 2% of our body weight, the brain consumes a substantial 20% of the body’s energy, relying on a…