As a defense mechanism in prostate cancer cells, the fatty acid s

As a defense mechanism in prostate cancer cells, the fatty acid synthesis pathway harnesses

its oxidizing power for improving the redox balance despite conditions of extreme hypoxia, potentially altering Cu-ATSM hypoxia selectivity.

Methods: Human prostate tumor-cultured cell lines (PC-3, 22Rv1, LNCaP and LAPC-4), were treated with a fatty acid synthase (FAS) inhibitor (C75, 100 mu M) under anoxia. The 64 Cu-ATSM uptake in these treated cells and nontreated anoxic cells was then examined. Fatty acid synthase expression level in each cell line was subsequently quantified by ELISA. An additional study was performed in PC-3 cells to examine the relationship between the restoration of 64 Cu-ATSM hypoxia selectivity and the concentration of C75 (100, 20, 4 or 0.8 mu M) administered to the cells.

Results: Inhibition of fatty acid synthesis

with C75 resulted in a significant increase MCC950 in vivo in (CU)-C-64 -ATSM retention in prostate tumor cells in vitro under anoxia over 60 min. Inhibition studies demonstrated higher uptake values of 20.9 +/- 3.27%, 103.0 +/- 32.6%, 144.2 +/- 32.3% and 200.1 +/- 79.3% at 15 min over control values for LAPC-4, PC-3, LNCaP and 22Rv1 cells, respectively. A correlation was seen (R-2 =.911) with FAS expression plotted against percentage change in Cu-64-ATSM uptake with C75 treatment.

Conclusions: PD-1/PD-L1 Inhibitor 3 cell line Although Cu-ATSM has clinical relevance in the PET imaging of hypoxia in many tumor types, its translation to the imaging of prostate cancer may

be limited by the overexpression of FAS associated with prostatic malignancies. (C) 2008 Elsevier Inc. All rights reserved.”
“Template switching between copackaged human immunodeficiency virus type 1 (HIV-1) genomic RNAs is genetically silent when identical RNAs are copackaged but yields recombinants when virions contain two distinct RNAs. Sequencing has revealed that errors at retroviral recombination junctions are infrequent, suggesting that template switching is not intrinsically mutagenic. Here, we tested the hypothesis that template MG-132 ic50 switching may instead contribute to replication fidelity. This hypothesis predicts that reverse transcription of a single-copy gene will be more error prone than replication in the presence of a second copy. To test this, HIV-1-based vectors containing both lacZ and the puromycin resistance marker were expressed either alone or with an excess of an “”empty”" vector lacking lacZ and puro. This resulted in virions with either RNA homodimers or haploid genomes with only a single lacZ-puro RNA. In untreated cells, lacZ inactivation rates suggested that haploid vector reverse transcription was slightly more error prone than that of homodimerized pseudodiploid vectors. Haploid reverse transcription was at least threefold more error prone than pseudodiploid-templated synthesis when slowed by hydroxyurea treatment or stopped prematurely with zidovudine.

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