diamide and Neoplasms

Many different non-hypoxic cell radiosensitizers have been identified over the years. Radiosensitization by these agents is mediated through a variety of mechanisms, including inhibition of repair (both enzymatic and chemical), modification in the DNA molecule, and perturbation and redistribution in the cell cycle. Recent clinical interest in the use of halogenated pyrimidines as radiosensitizers has prompted a number of questions requiring both laboratory and clinical research to maximize this therapeutic approach. Other radiosensitizers that alter cellular redox processes in different ways are discussed in the context of better understanding the cellular biochemical systems that are affected in aerobic radiosensitization. Advancement in the use of non-hypoxic cell sensitizers in radiation cancer treatment will most likely depend on a knowledge of the detailed biochemical mechanisms of these agents and how they might be used to exploit any subtle biochemical differences between tumor and normal tissue.

Topics: Animals; Bromodeoxyuridine; Buthionine Sulfoximine; Cell Survival; Cricetinae; Diamide; DNA Repair; Glutathione; Humans; Idoxuridine; In Vitro Techniques; Methionine Sulfoximine; Neoplasms; Radiation-Sensitizing Agents

The identification of self-renewing and multipotent neural stem cells (NSCs) in the mammalian brain holds promise for the treatment of neurological diseases and has yielded new insight into brain cancer. However, the complete repertoire of signaling pathways that governs the proliferation and self-renewal of NSCs, which we refer to as the 'ground state', remains largely uncharacterized. Although the candidate gene approach has uncovered vital pathways in NSC biology, so far only a few highly studied pathways have been investigated. Based on the intimate relationship between NSC self-renewal and neurosphere proliferation, we undertook a chemical genetic screen for inhibitors of neurosphere proliferation in order to probe the operational circuitry of the NSC. The screen recovered small molecules known to affect neurotransmission pathways previously thought to operate primarily in the mature central nervous system; these compounds also had potent inhibitory effects on cultures enriched for brain cancer stem cells. These results suggest that clinically approved neuromodulators may remodel the mature central nervous system and find application in the treatment of brain cancer.

Topics: Animals; Cell Survival; Cells, Cultured; Mice; Molecular Structure; Neoplasms; Neurons; Pharmaceutical Preparations; Sensitivity and Specificity; Stem Cells