scholarly journals UCHL1 Promotes Chemoresistance to 5-Fluoruracil Based Adjuvant Chemotherapy and is a Prognostic Marker for Stage II Colon Cancer Patients

Author(s):  
Liyuan Ma ◽  
Chaowen Wu ◽  
Lu Ding ◽  
Dong Yu ◽  
Xinrong Shi ◽  
...  

Abstract Background: 5-Fluoruracil based adjuvant chemotherapy after radical resection is recommended for stage II colon cancer patients with high risk of recurrence. Up to now, novel biomarkers still needed for better stratification for improving prognosis. Methods: Here we report that UCHL1 is an independent prognostic factor for stage II colon cancer patients and promotes chemoresistance both in vitro and in vivo. Results: Our study indicated that UCHL1 is significant up regulated in 96 pairs of stage II colon cancer patients who received postoperative 5-FU based chemotherapy. Stage II colon cancer patients with high UCHL1 expression showed high recurrence rate after chemotherapy. Multivariate Cox regression analysis showed that UCHL1 is an independent prognostic factor for overall survival (P=0.008) and disease-free survival (P=0.001). 5-FU based chemoresistance is examined in colon cancer cell lines (RKO and LoVo) with down regulation of UCHL1 by cytotoxicity test. Down regulation of UCHL1 exhibited decreased cell viability, elevated cell apoptosis rate, increased G2/M-phase and elevated level of cleaved caspase 3 and PARP when treated with 5-FU. Furthermore, the results in xenograft model are consistent with results in vitro.Conclusions: UCHL1 potentially contributing to identify recurrence risk and predict the benefit for postoperative 5-FU based adjuvant chemotherapy in stage II colon cancer patients.

2010 ◽  
Vol 21 (12) ◽  
pp. 2396-2402 ◽  
Author(s):  
A. Fariña-Sarasqueta ◽  
G. van Lijnschoten ◽  
E. Moerland ◽  
G.-J. Creemers ◽  
V.E.P.P. Lemmens ◽  
...  

2014 ◽  
Vol 20 (8) ◽  
pp. 2159-2168 ◽  
Author(s):  
Jeroen Dekervel ◽  
Daphne Hompes ◽  
Hannah van Malenstein ◽  
Dusan Popovic ◽  
Xavier Sagaert ◽  
...  

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 798-798
Author(s):  
Minki KIM ◽  
Daeyoun Won ◽  
Seong Taek Oh ◽  
In Kyu Lee

798 Background: Debates exist regarding the effectiveness of adjuvant chemotherapy for stage II colon cancer. This study aimed to investigate the current status of adjuvant chemotherapy and its impact on survival for Korean stage II colon cancer patients by analyzing the National Quality Assessment data. Methods: A total of 7880 patients who underwent curative resection for stage II colon adenocarcinoma between Jan 2011 and Dec 2014 in Korea were selected randomly as evaluation subjects for the quality assessment. The factors that influenced overall survival were identified. The high-risk group was defined as having at least one of the following: perforation/obstruction, lymph node harvest less than 12, lymphovascular/perineural invasion, positive resection margin, poor differentiation, or pathologic T4 stage. Results: The median follow-up period was 38 (1-63) months. Chemotherapy was a favorable prognostic factor for either the high- (HR 0.50 [0.40-0.62], p < 0.001) or low-risk group (HR 0.74 [0.61-0.89], p = 0.002) in multivariate analysis. This was also the case in patients over 70 years of age. The hazard ratio was significantly increased as the number of involved risk factors was increased in patients who didn’t receive chemotherapy. However, there was no survival difference between low-risk group patients and patients who only had 1 risk factor among patients who received adjuvant chemotherapy (HR 1.19 [0.93-1.52], p = 0.165). Adding oxaliplatin showed no difference in survival (HR 1.36 [0.91-2.03], p = 0.132). Conclusions: Adjuvant chemotherapy can be recommended for stage II colon cancer patients, but the addition of oxaliplatin to the regimen must be selective.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 421-421
Author(s):  
T. Dinh ◽  
P. Alperin ◽  
B. H. O'Neil

421 Background: The decision to treat stage II colon cancer patients with adjuvant chemotherapy involves assessment of life expectancy, risk for recurrent disease, and the potential benefit and likelihood of adverse effects from treatment. This is a challenging task, particularly for patients with pre-existing chronic illnesses such as diabetes, which may increase side effects and potentially lessen response to chemotherapy. Methods: We use the Archimedes Model to analyze cost effectiveness of adjuvant therapy in stage II colon cancer patients with pre-existing diabetes. The Archimedes Model is a large-scale, integrated mathematical model of human physiology, diseases, and healthcare systems, including pathways relating to diabetes, cardiovascular disease, and cancers of the breast, lung, and colon. The colon cancer model is built using the SEER, ACCENT databases and meta-analyses of clinical trials. Costs relating to colon cancer, diabetes and its complications are based on Medicare reimbursement rates. We simulate a trial in which stage II colon cancer patients are subjected to two treatment strategies: no treatment vs. adjuvant chemotherapy by FOLFOX regimen. We report incremental cost-effectiveness ratio (ICER), measured by cost per quality-adjusted life year (QALY) gained, of adjuvant therapy compared with no treatment. Results: Cost effectiveness is strongly dependent on a patient's tumor profile, age and duration of diabetes. For instance, adjuvant therapy saves ∼0.2 QALYs per person in stage IIA patients who are 75 and older and have been diagnosed with diabetes >10 years, at an ICER of >$150,000/QALY gained. In contrast, it saves 1.1 QALYs per person in stage IIB patients aged 60-65, recently diagnosed with diabetes, at an ICER of <$30,000/QALY gained. Results are sensitive to assumptions on efficacy and side effects of chemotherapy in diabetic patients, as well as cost of adjuvant therapy. Conclusions: The current study suggests that the decision to proceed with adjuvant chemotherapy requires careful assessment of severity of diabetes in stage II colon cancer patients with pre-existing diabetes. No significant financial relationships to disclose.


10.9738/cc131 ◽  
2013 ◽  
Vol 98 (2) ◽  
pp. 114-121 ◽  
Author(s):  
Satoshi Hatano ◽  
Hideyuki Ishida ◽  
Keiichiro Ishibashi ◽  
Kensuke Kumamoto ◽  
Norihiro Haga ◽  
...  

Abstract To identify risk factors for recurrence in patients with stage II colon cancer, Cox proportional hazards regression analysis was performed in 194 patients with stage II colon cancer who underwent curative surgery between April 1997 and December 2008. Thirteen clinical and pathologic factors, including use of fluoropyrimidine-based adjuvant chemotherapy in 113 of the patients (58.2%), were assessed. By multivariate analysis, only obstruction, perforation, and T4-level invasion were identified as independent risk factors affecting disease-free survival (DFS) (P &lt; 0.01). The 5-year DFS rate was 70.6% in patients with one or more risk factors (n = 68) and 96.0% in patients with no risk factors (n = 126) (P &lt; 0.01). These results suggest that obstruction, perforation, and T4-level invasion are suitable candidates for prediction of tumor recurrence in patients with stage II colon cancer. The oxaliplatin-based adjuvant chemotherapy, which has been reported to be effective in stage III colon cancer patients, may improve the prognosis in high-risk stage II colon cancer patients.


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