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. Our 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, our 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, we 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 our 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

Lindsay M. De Biase, Ph.D., University of California Los Angeles
The role of microglial lysosomes in selective neuronal vulnerability
Synapses, the sites of signaling between neurons in the brain, play essential roles in learning, memory, and the health of neurons themselves. An enduring mystery is why some neurons are…
How the nervous system constructs internal models of the external world
As animals navigate their environments, they construct internal models of the external sensory world and use these models to guide their behavior. This ability to incorporate ongoing sensory stimuli into…
Xiaojing Gao, Ph.D., Stanford University
When Neural Circuits Meet Molecular Circuits: Quantitative Genetic Manipulation with Single-cell Consistency
Cells are the building blocks of our bodies. We get sick when the cells “misbehave”. The way modern gene therapies work is to introduce genes, fragments of DNA molecules that…
Rafiq Huda, Ph.D., Rutgers University
Conducting the orchestra of movement—functional role of striatal astrocytes in health and disease
Movement requires coordinated activity across a large brain-wide network. The striatum is a particularly important part of this circuit; it integrates motor-related information from many distinct brain regions to regulate…