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Surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF-MS) as a tool for molecular endpoint analysis of PX-12, a thioredoxin-1 inhibitor

Thioredoxin-1 is a redox protein upregulated in many cancers. Its functions include inhibition of apoptosis, increasing cellular growth and proliferation. It has been shown that cells displaying increased levels of Trx-1 have increased drug resistance. PX-12 is a Trx-1 inhibitor that shows anti-proloferative and cytotoxic activity in vitro and in vivo. We used surface enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF-MS) to measure plasma Trx-1 levels of patients treated with PX-12 as a side study of a phase-I trial. SELDI-TOF-MS was able to measure a decrease in plasma Trx-1 after PX-12 treatment semi-quantitatively. In addition, SELDI measured 57 other protein peaks in plasma; seven which were found in all plasma samples analyzed. One of these peaks was located at 13.86kDa and identified through LC-MS/MS sequencing to be a variant of Transthyretin. Further studies into these additional peaks are necessary to determine their biological importance in relation to Trx-1 and PX-12.

Identiferoai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/291852
Date January 2005
CreatorsTate, Wendy Rose
ContributorsPowis, Garth
PublisherThe University of Arizona.
Source SetsUniversity of Arizona
Languageen_US
Detected LanguageEnglish
Typetext, Thesis-Reproduction (electronic)
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.

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