cortodoxone and Neoplasms

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

Cortiphen, a newly developed hormonal cytostatic ester of 11-desoxy-17 alpha-hydroxycorticosterone and chlorophenacyl, is described. It was studied in transplantable, spontaneous and induced tumors of 7 sites: hemoblastosis (5), hepatoma (3), mammary gland (5), lung (2), gastrointestinal tract (3), sarcoma (2) and melanoma. Practically all the tumors were shown to respond to cortiphen action. Among the antitumor effects of the drug were: long-term inhibition of tumor growth or tumor regression, contribution to longer survival, antimetastatic action and sustained action during repeated courses of administration. Cortiphen was found to interact with glucocorticoid receptors in both animal and human tumors. The role of the hormonal component of the drug's molecule in the realization of its antitumor effect is discussed.

Topics: Animals; Antineoplastic Agents; Corticosterone; Dogs; Drug Combinations; Drug Evaluation, Preclinical; Female; Humans; Male; Mice; Mice, Inbred Strains; Neoplasm Transplantation; Neoplasms; Neoplasms, Experimental; Nitrogen Mustard Compounds; Rats; Receptors, Glucocorticoid

Topics: Adrenal Cortex; Adrenal Cortex Hormones; Cortodoxone; Neoplasms