scholarly journals Clinicopathological significance and impact on outcomes of the gene expression levels of IGF-1, IGF-2 and IGF-1R, IGFBP-3 in patients with colorectal cancer: Overexpression of the IGFBP-3 gene is an effective predictor of outcomes in patients with colorectal cancer

2017 ◽  
Vol 13 (5) ◽  
pp. 3958-3966 ◽  
Author(s):  
Naoto Yamamoto ◽  
Takashi Oshima ◽  
Kazue Yoshihara ◽  
Toru Aoyama ◽  
Tsutomu Hayashi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Expression Levels ◽  
Clinicopathological Significance ◽  
Gene Expression Levels ◽  
Igfbp 3

Correlation of messenger RNA expression patterns of ERCC1, TS, EGFR, and VEGFR2 with KRAS and BRAF mutational status in advanced colorectal cancer: Implications for targeted therapies.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 383-383
Author(s):  
Martin K. H. Maus ◽  
Craig Stephens ◽  
Stephanie H. Astrow ◽  
Peter Philipp Grimminger ◽  
Dongyun Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Mrna Expression ◽  
Advanced Colorectal Cancer ◽  
Expression Patterns ◽  
Mrna Levels ◽  
Expression Levels ◽  
Mutational Status ◽  
Mrna Expression Levels ◽  
Gene Expression Levels

383 Background: Gene expression levels of ERCC1, TS, EGFR and VEGFR2 may have predictive value for the personalized use of standard chemotherapeutics as well as agents targeting the EGFR and VEGF pathways and the efficacy of EGFR directed monoclonal antibodies like panitumumab and cetuximab has been confirmed to be dependent on wt KRAS and wt BRAF in patients with advanced colorectal cancer. We investigated the correlations between KRAS/BRAF mutational status and the mRNA expression levels of these genes. Methods: Formalin-fixed paraffin-embedded tumor specimens from 600 patients with advanced colorectal adenocarcinoma were microdissected and DNA and RNA was extracted. Specifically designed primers and probes were used to detect 7 different base substitutions in codon 12 and 13 of KRAS, V600E mutations in BRAF and the expression levels of ERCC1, TS, EGFR and VEGFR2 by RT-PCR. Results: Mt KRAS tumors had significantly lower TS and EGFR gene expression levels compared with wt KRAS (p<0,001), whereas mt BRAF tumors showed significantly increased TS and EGFR mRNA levels compared to wt BRAF (p<0,001). Mt BRAF tumors showed significantly higher mRNA levels than mt KRAS tumors (p<0,001). ERCC1 and VEGFR2 mRNA levels were significantly down-regulated in mt KRAS specimen (p<0,001), but showed no significant correlation with BRAF mutational status. Conclusions: KRAS and BRAF mutations are associated with opposite mRNA expression levels for TS and EGFR. Recently, resistance to BRAF inhibition in mt BRAF colorectal tumors has been shown in preclinical models to be associated with up-regulation of EGFR. Our data suggests that BRAF mutants are associated with high EGFR levels at the time of diagnosis, and not necessarily part of an acquired mechanism of resistance. Significantly lower mRNA expression levels of VEGFR2 in mt KRAS tumors may explain lower response to angiogenesis inhibition seen in the TML study.

5-fluorouracil related gene expression levels in primary colorectal cancer and corresponding liver metastases

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 3568-3568 ◽  
Author(s):  
H. Kuramochi ◽  
K. Hayashi ◽  
K. Uchida ◽  
D. Shimizu ◽  
D. Vallboehmer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Liver Metastases ◽  
Related Gene ◽  
Primary Colorectal Cancer ◽  
Expression Levels ◽  
Gene Expression Levels

Molecular determinants of capecitabine efficacy in colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3606-3606
Author(s):  
D. Vallbohmer ◽  
H. Kuramochi ◽  
D. Shimizu ◽  
K. D. Danenberg ◽  
J. N. Nielsen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Single Agent ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Expression Levels ◽  
Cox 2 ◽  
Gene Expression Levels

3606 Background: Capecitabine offers physicians a more convenient treatment for advanced colorectal cancer (CRC), with manageable toxicity and antitumor activity comparable to that of continuous-infusion therapies with 5-fluorouracil (5-FU). However, there are no validated and established predictive factors for clinical outcome of capecitabine efficacy in CRC. Therefore we investigated whether intratumoral mRNA expression levels of genes involved in the capecitabine/5-FU metabolism (cytidine deaminase (CDA), dihydropyrimidine dehydrogenase (DPD), folylpolyglutamate synthase (FPGS), gamma-glutamyl hydrolase (GGH), thymidine phosphorylase (TP), thymidylate synthase (TS)) and in angiogenesis (cyclooxygenase 2 (Cox-2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF)) are associated with the clinical outcome of patients with metastatic CRC treated with first-line capecitabine. Methods: Thirty-seven patients with metastatic CRC were enrolled in this study and treated with single agent capecitabine.The intratumoral mRNA levels of CDA, COX-2, DPD, EGFR, FPGS; GGH, TP, TS, and VEGF were assessed from paraffin-embedded tissue samples using laser-capture-microdissection methods and quantitative real-time PCR. Results: There were20 women and 17 men with a median age of 61 years (range 49–74). The median progression-free survival was 6.7 months (95% CI, 4.8–11.6 months), with a median follow up of 14.4 months (range: 1.3 to 18.7 months). Complete response was observed in 1 (3%), partial response in 6 (20%), stable disease in 14 (47%) and progressive disease in 9 (30%) patients (response was inevaluable in 7 patients). Higher gene expression levels of DPD were associated with resistance to capecitabine (P= 0.032; Kruskal-Wallis test). Patients with a lower mRNA amount of DPD (≤0.46) had a longer progression-free survival compared with patients that had a higher mRNA amount (8.0 vs. 3.3 months; adjusted P=0.048; log-rank test). Conclusions: This pilot study suggests that intratumoral gene expression levels of DPD may be useful to predict the clinical outcome of patients with metastatic CRC with first-line single agent capecitabine treatment. Our data are hypothesis generating and should be validated in larger and prospective clinical trials. [Table: see text]

scholarly journals 5-fluorouracil-related gene expression levels in primary colorectal cancer and corresponding liver metastasis

2006 ◽  
Vol 119 (3) ◽  
pp. 522-526 ◽  
Author(s):  
Hidekazu Kuramochi ◽  
Kazuhiko Hayashi ◽  
Kazumi Uchida ◽  
Satoru Miyakura ◽  
Daisuke Shimizu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Related Gene ◽  
Primary Colorectal Cancer ◽  
Expression Levels ◽  
Gene Expression Levels

Evaluation of 5-FU metabolism-relating enzyme gene expression levels using quantitative real-time RT-PCR from formalin fixed parafine embedded samples

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13034-13034
Author(s):  
M. Terashima ◽  
Y. Odashima ◽  
S. Ohtani ◽  
N. Soeta ◽  
F. Ohsuka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Real Time ◽  
Clinical Settings ◽  
Rt Pcr ◽  
Expression Levels ◽  
Ffpe Samples ◽  
Fresh Frozen ◽  
Gene Expression Levels

13034 Background: We have previously reported that tumors with high orotate phosphoribosil transferase (OPRT) and low dihydropyrimidine dehydrogenase (DPD) mRNA expression levels showed remarkable sensitivity to 5-fluorouracil (5-FU) by real-time RT-PCR using fresh frozen (FF) tumor samples. However, the use of fresh frozen samples has some limitations. The use of formalin fixed parafine embedded (FFPE) samples has great advantage to apply these technologies for clinical settings. In order to investigate the feasibility of real-time RT-PCR from FFPE samples to predict sensitivitiy to 5-fluorouracil (5-FU), we investigated the gene expression levels of 5-FU metabolism-relating enzymes by real-time RT-PCR from FFPE samples and compared the results from FF samples in gastric and colorectal cancer. Methods: FFPE samples and FF samples were obtained from 46 patients with gastric cancer and 29 patients with colorectal cancer. Gene expression levels of tymidylate synthase (TS), OPRT, thymidine phosphorylase (TP) and DPD were determined by quantitative real-time RT-PCR. In FFPE samples tumor tissue was obtained using laser captured microdissection (LCM). Tumor sensitivity to 5-FU was evaluated by in vitro ATP assay. Results: Gene expression levels of TS, TP, DPD determined from FFPE samples significantly correlated with those from FF samples. Although respective gene expression levels alone failed to show signifcianct correlation with the in vitro 5-FU sensitivity, statistically significant correlation was noted either from the samples of FF or FFPE in both gastric (FF: r = 0.660, FFPE: r = 0.780) and colorectal cancer (FF: r = 0.780, FFPE: r = 0.660), when OPRT/DPD mRNA ratio was applied for comparison with the results of 5-FU sensitivity. Thus, high OPRT/DPD ratio determined from FFPE samples resulted in high sensitivity to 5-FU. Conclusions: From these results, it is suggested that sensitivity to 5-FU is predictable by quantitative RT-PCR using FFPE samples. Measurement of 5-FU metabolism-relating enzyme gene expression level from FFPE samples appeared to be feasible for predicting 5-FU sensitivity and to have great advantage to apply the molecular predicting assay in clinical settings. [Table: see text]

scholarly journals Post-treatment recovery of suboptimal DNA repair capacity and gene expression levels in colorectal cancer patients

2014 ◽  
Vol 54 (9) ◽  
pp. 769-778 ◽  
Author(s):  
Jana Slyskova ◽  
Francesca Cordero ◽  
Barbara Pardini ◽  
Vlasta Korenkova ◽  
Veronika Vymetalkova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Dna Repair ◽  
Cancer Patients ◽  
Post Treatment ◽  
Repair Capacity ◽  
Expression Levels ◽  
Dna Repair Capacity ◽  
Colorectal Cancer Patients ◽  
Gene Expression Levels
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