Increase in tumor GADD153 mRNA level following treatment correlates with response to paclitaxel.
OBJECTIVE
We investigated the relationship between the basal and treatment-induced change in the tumor expression of the drug resistance gene MDR1 and the cellular injury response gene GADD153, and clinical response to paclitaxel treatment.


METHODS
MDR1 and GADD153 mRNA levels were measured by reverse transcriptase polymerase chain reaction (RT-PCR) in tumor samples obtained by fine needle aspiration biopsy from 14 patients before and 24 h after paclitaxel infusion.


RESULTS
There was no difference between responders and non-responders with respect to either the basal MDR1 mRNA level or the change in MDR1 mRNA level at 24 h after treatment (P = 0.464). Likewise, there was no difference in basal GADD153 mRNA level between responders and non-responders. However, there was a significantly greater increase in GADD153 mRNA at 24 h in responders compared with non-responders (P = 0.005). An increase in GADD153 mRNA level of 1.5-fold or higher predicted response with a sensitivity of 86% and a specificity of 100%.


CONCLUSIONS
An increase in GADD153 mRNA level reflects chemotherapy-induced damage sufficient to be manifest as a clinically detectable reduction in tumor volume. Measurement of the change in GADD153 mRNA level successfully identified patients destined to respond as early as 24 h post-treatment.
de las Alas
M M
MM
University of California San Diego, Cancer Center 0058, La Jolla 92093-0058, USA. mdelasal@ucsd.edu
Christen
R D
RD
Gately
D P
DP
Weiner
D E
DE
Benbatoul
K
K
Kirmani
S
S
D'Agostino
H R
HR
Plaxe
S C
SC
Darrah
D
D
McClay
E F
EF
Aebi
S
S
Howell
S B
SB
Los
G
G
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis*; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D022762:CCAAT-Enhancer-Binding Proteins; C497249:DDIT3 protein, human; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D051742:Transcription Factor CHOP; D017239:Paclitaxel