Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : Cell Therapeutics (CTIC) -- Ignore unavailable to you. Want to Upgrade?

To: Biomaven who wrote (199)	3/27/2004 3:03:51 PM
From: Biomaven	Respond to of 946

Note another possibility is to try to co-promote or acquire Vesanoid. From Erik's post on the Valuation thread reporting on a CTIC presentation: Expects to acquire still another product, which is supposed to add income to the P&L account already this year. This product is supposed to be synergistic with Trisenox, which of course will fit very well with the current sales structure. Trisenox has so many effects that it appears to be synergistic with a number of drugs (including Gleevec). Here's an extract on its synergies: Synergy of Arsenic with Other Agents Because of the many pathways involved in mediating the effects of arsenic, the potential exists for synergism with other agents to provide enhanced therapeutic benefits. As mentioned earlier, arsenic trioxide shows effects distinct from those of ATRA in APL cells and has clinical efficacy in patients with ATRA-resistant APL. The combination of ATRA and arsenic trioxide may be synergistic or antagonistic in vitro, whereas in vivo the combination or sequential use of the agents has been reported to accelerate tumor regression by enhancing both differentiation and apoptosis in some but not all of the models. Furthermore, combination therapy may allow for administration of lower doses of arsenic trioxide, minimizing toxicity and potential drug antagonism (27 , 29) . In human myeloid leukemia cells that express bcr-abl, arsenic trioxide treatment reduces bcr-abl levels and induces apoptosis. These effects appear to be independent of bcr-abl kinase activity, because they occur even when cells are pretreated with STI-571, a tyrosine kinase inhibitor specific for the bcr-abl tyrosine kinase. Furthermore, treatment with arsenic trioxide decreases proliferation of chronic myelogenous leukemia blasts but does not affect growth of peripheral CD34+ progenitor cells (114) . In contrast to these results, concurrent treatment with the combination of arsenic trioxide and STI-571 causes a greater apoptotic response than does treatment with either agent alone. Among the critical consequences of arsenic trioxide treatment was inhibition of the Akt kinase, important for growth and survival, and even greater inhibition of Akt in the presence of both agents (115) . Observations that perturbations in cellular methyl metabolism modulate the cytotoxicity of arsenic have led to the suggestion that methotrexate may act synergistically with arsenic trioxide. Folic acid supplementation abrogates the cytotoxic effects of arsenite. By causing a relative methyl insufficiency, methotrexate may potentiate the effects of arsenite in the presence of excess folic acid (116) . The combination of arsenic trioxide with IFN- has activity in adult T-cell leukemia cell lines, as well as clinically in patients (117 , 118) . Synergy between arsenic trioxide and IFN- was demonstrated using a colony forming unit-granulocyte/macrophage assay with mononuclear cells from six patients in the chronic phase of chronic myelogenous leukemia. Positive results from this study prompted additional investigation of these agents in combination, although there are few results to date (119) . Potential synergy of arsenic trioxide and vitamin C has been shown in vitro and in vivo by several groups (61 , 62 , 83 , 84) , and additional studies of the mechanism both in vitro and in the clinic appear warranted. Indeed, evidence for the potentiation by ascorbic acid of arsenic trioxide-induced cell death in multiple myeloma cells has been reported recently (61 , 84) . These results provided a basis for clinical trials under way to test the combined use of arsenic trioxide and ascorbic acid in refractory multiple myeloma. Furthermore, they suggest that ascorbic acid may be a successful adjuvant in other reduced glutathione-sensitive therapies. Ascorbic acid is not the only agent affecting intracellular redox to synergize with arsenic in vitro. The profound increases in arsenic sensitivity in vitro associated with glutathione depletion by buthionine sulfoximine suggest a need for experiments in animal models using this or related agents, as well. cancerres.aacrjournals.org