Showing papers by "Luke Whitesell published in 1993"

Tumoricidal activity of benzoquinonoid ansamycins against prostate cancer and primitive neural malignancies

Abstract: The invention provides methods and compositions for treating selected human malignancies including use of certain ansamycin benzoquinones.

Terminal neuroendocrine differentiation of human prostate carcinoma cells in response to increased intracellular cyclic AMP (hormone-refractory/pp60 c-src /multipotential)

Abstract: Recent clinicopathologic studies have shown that many prostatic andenocarcinomas express focal neuroendocrine differentiation and that neuroendocrine differentiation is most apparent in advanced anaplastic tumors. While studying growthregulatory signal transduction events in human prostate carcinoma cell lines, we found that in two of four cell lines, the androgen-sensitive line LNCaP and the highly metastatic androgenindependent line PC3M, elevation of cAMP through addition of cAMP analogues or phosphodiesterase inhibitors induced a markedly neuronal morphology. Also in LNCaP cells ultrastructural analysis showed that cAMP induced the appearance of neurosecretory cell- like dense-core granules. Phenotypic analysis of untreated LNCaP and PC3M calls shoved that both cell lines express markers of the neural crest including S100, cromogranin A, pp60 c-src , and neuron-specific enolase as well as the epithelial marker KSl/4 and stagespecific embryonic antigen 4. In PC3M cells, cAMP markedly elevated neuron-specific enolase protein and caused an increase in the specific activity of the neuroendocrine marker pp60 c-src , and in both cell lines expression of KS1/4 and stage-specific embryonic antigen 4 was down-regulated. In addition to effects on lineage markers, cAMP treatment induced Gl synchronization, growth arrest, and loss of clonogenicity, indicating terminal differentiation. Our data provide direct evidence of plasticity in the lineage commitment of adenocarcinoma of the prostate. We have shown that cell-permeant cAMP analogies can induce terminal differentiation, suggesting that hydrolysisresistant cyclic nucleotides may present an additional approach to the treatment of advanced prostate cancer.

Use of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme a reductase as a modality in cancer therapy

Abstract: Methods of treating various cancers, such as prostatic adenocarcinoma, with inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG Co-A), such as lovastatin, are provided. Dosing ranges, schedules and toxicities are included.

Activite tumoricide des ansamycines benzoquinonoides contre le cancer de la prostate et les malignites neurales primitives

Abstract: Procedes et compositions pour le traitement de certains malignites chez l'homme, comprenant l'utilisation de certains ansamycine-benzoquinones.