Human TOP1 (DNA topoisomerase 1) ELISA Kit

Purpose: Prospective-retrospective assessment of the TOP1 gene copy number and TOP1 mRNA expression as predictive biomarkers for adjuvant irinotecan in stage II/III colon cancer. Experimental Design: Formalin-fixed, paraffin-embedded tissue microarrays were obtained from an adjuvant colon cancer trial (PETACC3) where patients were randomized to 5-fluorouracil/folinic acid with or without additional irinotecan. TOP1 copy number status was analyzed by fluorescence in situ hybridization (FISH) using a TOP1/CEN20 dual-probe combination. TOP1 mRNA data were available from previous analyses. Results: TOP1 FISH and follow-up data were obtained from 534 patients. TOP1 gain was identified in 27% using a single-probe enumeration strategy (>= 4 TOP1 signals per cell) and in 31% when defined by a TOP1/CEN20 ratio >= 1.5. The effect of additional irinotecan was not dependent on TOP1 FISH status. TOP1 mRNA data were available from 580 patients with stage III disease. Benefit of irinotecan was restricted to patients characterized by TOP1 mRNA expression > third quartile (RFS: HRadjusted, 0.59; P = 0.09; OS: HRadjusted, 0.44; P = 0.03). The treatment by TOP1 mRNA interaction was not statistically significant, but in exploratory multivariable fractional polynomial interaction analysis, increasing TOP1 mRNA values appeared to be associated with increasing benefit of irinotecan. Conclusions: In contrast to the TOP1 copy number, a trend was demonstrated for a predictive property of TOP1 mRNA expression. On the basis of TOP1 mRNA, it might be possible to identify a subgroup of patients where an irinotecan doublet is a clinically relevant option in the adjuvant setting of colon cancer. (C) 2015 AACR.

Salicylic acid (SA) is a small phenolic molecule with hormonal properties, and is an essential component of the immune response. SA exerts its functions by interacting with protein targets; however, the specific cellular components modulated by SA and critical for immune signal transduction are largely unknown. To uncover cellular activities targeted by SA, we probed Arabidopsis protein microarrays with a functional analog of SA. We demonstrate that thimet oligopeptidases (TOPs) constitute a class of SA-binding enzymes. Biochemical evidence demonstrated that SA interacts with TOPs and inhibits their peptidase activities to various degrees both in vitro and in plant extracts. Functional characterization of mutants with altered TOP expression indicated that TOP1 and TOP2 mediate SA-dependent signaling and are necessary for the immune response to avirulent pathogens. Our results support a model whereby TOP1 and TOP2 act in separate pathways to modulate SA-mediated cellular processes.