Correlations of Clinicopathological Factors with Protein Expression Levels of Thymidylate Synthase, Dihydropyrimidine Dehydrogenase and Orotate Phosphoribosyltransferase in Colorectal Cancer

Chemotherapy ◽  
2010 ◽  
Vol 56 (2) ◽  
pp. 120-126 ◽  
Author(s):  
Tetsuo Sumi ◽  
Kenji Katsumata ◽  
Akihiko Tsuchida ◽  
Tetsuo Ishizaki ◽  
Motohide Shimazu ◽  
...  
2019 ◽  
Vol 9 (3) ◽  
pp. 439-444 ◽  
Author(s):  
Mahshid Mohammadian ◽  
Shima Zeynali-Moghaddam ◽  
Mohammad Hassan Khadem Ansari ◽  
Yousef Rasmi ◽  
Anahita Fathi Azarbayjani ◽  
...  

Purpose: Dihydropyrimidine dehydrogenase (DPD) is the principal enzyme in the catabolism of fluoropyrimidine drugs including capecitabine. A recent report has suggested that oxaliplatin chemotherapy is associated with elevated DPD levels and chemoresistance pattern. As a newly developed chemotherapeutic agent, 17-allyloamino-17-demethoxy-geldanamycin (17-AAG) can be effective in combination therapy with oxaliplatin and capecitabine in colorectal cancer (CRC). DPD expression level can be a predictive factor in oxaliplatin and capecitabine-based chemotherapy. We evaluated DPD in mRNA and protein levels with new treatments: 17-AAG in combination with oxaliplatin and capecitabine in HT-29 and HCT-116 cell lines. Methods: Drug sensitivity was determined by the water-soluble tetrazolium-1 assay in a previous survey. Then, we evaluated the expression levels of DPD and its relationship with the chemotherapy response in capecitabine, oxaliplatin, and 17-AAG treated cases in single and combination cases in two panels of CRC cell lines. DPD gene and protein expression levels were determined by real-time polymerase chain reaction and western blotting assay, respectively. Results: DPD gene expression levels insignificantly increased in single-treated cases versus untreated controls in both cell lines versus controls. Then, the capecitabine and oxaliplatin were added in double combinations, where DPD gene and protein expression increased in combination cases compared to pre-chemotherapy and single drug treatments. Conclusion: The elevated levels of cytotoxicity in more effective combinations could be related to a different mechanism apart from DPD mediating effects or high DPD level in the remaining resistance cells (drug-insensitive cells), which should be investigated in subsequent studies.


Chemotherapy ◽  
2022 ◽  
pp. 1-10
Author(s):  
Cheng Yang ◽  
Na Xie ◽  
Zhifei Luo ◽  
Xiling Ruan ◽  
Yixin Zhang ◽  
...  

<b><i>Introduction:</i></b> We investigated the function of cell division cycle 6 (CDC6) on the prognosis in colorectal carcinoma (CRC). <b><i>Methods:</i></b> CDC6 protein expression levels in 121 patients with colorectal cancer and adjacent normal mucosa were detected by immunohistochemistry. <b><i>Results:</i></b> Compared to adjacent normal tissues, CDC6 mRNA level was overexpressed in CRC tissues. Moreover, CDC6 protein levels were expressed up to 93.39% (113/121) in CRC tissues in the cell nucleus or cytoplasm. However, there were only 5.79% (7/121) in normal mucosal tissues with nuclear expression. CDC6 expression was significantly correlated with TNM stage and tumor metastasis. The 5-year survival rate was lower in the high CDC6 expression group than the low group. After silencing of CDC6 expression in SW620 cells, cell proliferation was slowed, the tumor clones were decreased, and the cell cycle was arrested in G1 phase. In multivariate analysis, increased CDC6 protein expression levels in colon cancer tissues were associated with cancer metastasis, TNM stage, and patient survival time. <b><i>Conclusion:</i></b> CDC6 is highly expressed in CRC, and downregulation of CDC6 can slow the growth of CRC cells in vitro. It is also an independent predictor for poor prognosis and may be a useful biomarker for targeted therapy and prognostic evaluation.


Open Medicine ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. 226-230 ◽  
Author(s):  
Liu Tao ◽  
Li Jin ◽  
Li Dechun ◽  
Yang Hongqiang ◽  
Kou Changhua ◽  
...  

AbstractObjectiveTo explore the expression levels of galectin-3 in colorectal cancer and the association between galectin-3 and its clinical pathological parameters, as well as the prognosis of colorectal cancer patients.MethodsAn immunohistochemistry assay was used to test the expression levels of galectin-3 in cancer tissues of 61 colorectal cancer cases and in normal intestinal tissues adjacent to the cancer tissues of 23 cases. The associations between protein expression levels of galectin-3 and the clinicopathological features, such as age, sex, pathology type, lymphatic metastasis, and prognosis were also analyzed.ResultsThe positive rate of galectin-3 in cancer tissues was significantly higher than that of cancer-adjacent tissues: 62.5% (38/61) versus 13.0% (3/23) (P<0.05), respectively. Correlation was found between the protein expression of galectin-3 and the tumor size (P<0.05), as well as between the tumor differentiation (P<0.05) and Duke staging (P<0.05). The median progression-free survival times of patients with galectin-3 positive and negative expression were 19.2 and 35.1 months, respectively, with significant statistical difference (P<0.05).ConclusionGalectin-3 expression was correlated with the genesis and development of colorectal cancer and which could be used a biological marker for the prognosis of colorectal cancer patients.


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