Cyclooxygenase (COX)-2 immunoreactivity and relationship to p53 and Ki-67 expression in colorectal cancer

1999 ◽  
Vol 34 (2) ◽  
pp. 189-194 ◽  
Author(s):  
Kazuhiro Sakuma ◽  
Takahiro Fujimori ◽  
Kaoru Hirabayashi ◽  
Akira Terano
Keyword(s):  
Ki 67 ◽  
2015 ◽  
Vol 8s1 ◽  
pp. CGM.S21216 ◽  
Author(s):  
Susan LeGendre-McGhee ◽  
Photini S. Rice ◽  
R. Andrew Wall ◽  
Kyle J. Sprute ◽  
Ramireddy Bommireddy ◽  
...  

Optical coherence tomography (OCT) is a high-resolution, nondestructive imaging modality that enables time-serial assessment of adenoma development in the mouse model of colorectal cancer. In this study, OCT was utilized to evaluate the effectiveness of interventions with the experimental antitumor agent α-difluoromethylornithine (DFMO) and a nonsteroidal anti-inflammatory drug sulindac during early [chemoprevention (CP)] and late stages [chemotherapy (CT)] of colon tumorigenesis. Biological endpoints for drug interventions included OCT-generated tumor number and tumor burden. Immunochistochemistry was used to evaluate biochemical endpoints [Ki-67, cleaved caspase-3, cyclooxygenase (COX)-2, β-catenin]. K-Ras codon 12 mutations were studied with polymerase chain reaction-based technique. We demonstrated that OCT imaging significantly correlated with histological analysis of both tumor number and tumor burden for all experimental groups ( P < 0.0001), but allows more accurate and full characterization of tumor number and burden growth rate because of its time-serial, nondestructive nature. DFMO alone or in combination with sulindac suppressed both the tumor number and tumor burden growth rate in the CP setting because of DFMO-mediated decrease in cell proliferation (Ki-67, P < 0.001) and K-RAS mutations frequency ( P = 0.04). In the CT setting, sulindac alone and DFMO/sulindac combination were effective in reducing tumor number, but not tumor burden growth rate. A decrease in COX-2 staining in DFMO/sulindac CT groups (COX-2, P < 0.01) confirmed the treatment effect. Use of nondestructive OCT enabled repeated, quantitative evaluation of tumor number and burden, allowing changes in these parameters to be measured during CP and as a result of CT. In conclusion, OCT is a robust minimally invasive method for monitoring colorectal cancer disease and effectiveness of therapies in mouse models.


1998 ◽  
Vol 114 ◽  
pp. A671
Author(s):  
K. Sakuma ◽  
K. Hirabayashi ◽  
M. Ishida ◽  
T. Fujimori ◽  
A. Terano
Keyword(s):  
Ki 67 ◽  

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 502-502 ◽  
Author(s):  
In Kyu Lee ◽  
Hyung Jin Kim

502 Background: This study aimed to establish a correlation between the expression of cathepsin D; p53; Cox-2; EGFR; C-erbB2; Ki-67 protein and the prognosis of colorectal cancer patients. Methods: Tissue samples were collected from 266 patients who underwent surgery for colorectal cancer from January 2006 to December 2007. The expression of the six proteins was determined using immunohistochemical staining of paraffin-embedded tissue specimens. Results: Cathepsin D, p53, Cox-2, EGFR, C-erbB2, and Ki-67 expression was detected in 38.7%, 60.9%, 37.6%, 35.7%, 30.1%, and 74.4% of the samples, respectively. The expression of cathepsin D was significantly correlated with reduced cancer-free survival (p=0.036) and overall survival (p=0.003), whereas the expression of the other proteins could not be correlated. In a multivariate analysis, after adjusting for age, sex, and stage, cathepsin D expression was found to be an independent prognostic factor for a short overall survival(HR=8.55, 95% CI 1.07–68.49). Furthermore, patients with tumors expressing four or more of the proteins had a significantly decreased cancer-free survival rate (p=0.006) and overall survival rate (p=0.002), when compared with patients expressing fewer than four of the proteins Conclusions: In this study, the expression of CD was correlated with a poor prognosis in terms of the cancer-free survival and the overall survival rate. Importantly, the high hazard ratio (HR=8.55) associated with CD expression from the multivariate analysis, even after adjusting for the tumor stage, demonstrates its potential as an independent, single-gene prognostic factor. The expression of four or more of the examined proteins was significantly correlated with a poor prognosis, even after adjusting for the stage. Currently, the prognostic value of a single gene marker in CRCA is very controversial, but based on these results, we believe that the number of expressed genes/proteins may be helpful in identifying patients with both early-stage cancer and a potentially poor prognosis, which will help to determine if adjuvant chemotherapy is necessary.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kazim Husain ◽  
Domenico Coppola ◽  
Chung S. Yang ◽  
Mokenge P. Malafa

AbstractThe activation and growth of tumour-initiating cells with stem-like properties in distant organs characterize colorectal cancer (CRC) growth and metastasis. Thus, inhibition of colon cancer stem cell (CCSC) growth holds promise for CRC growth and metastasis prevention. We and others have shown that farnesyl dimethyl chromanol (FDMC) inhibits cancer cell growth and induces apoptosis in vitro and in vivo. We provide the first demonstration that FDMC inhibits CCSC viability, survival, self-renewal (spheroid formation), pluripotent transcription factors (Nanog, Oct4, and Sox2) expression, organoids formation, and Wnt/β-catenin signalling, as evidenced by comparisons with vehicle-treated controls. In addition, FDMC inhibits CCSC migration, invasion, inflammation (NF-kB), angiogenesis (vascular endothelial growth factor, VEGF), and metastasis (MMP9), which are critical tumour metastasis processes. Moreover, FDMC induced apoptosis (TUNEL, Annexin V, cleaved caspase 3, and cleaved PARP) in CCSCs and CCSC-derived spheroids and organoids. Finally, in an orthotopic (cecum-injected CCSCs) xenograft metastasis model, we show that FDMC significantly retards CCSC-derived tumour growth (Ki-67); inhibits inflammation (NF-kB), angiogenesis (VEGF and CD31), and β-catenin signalling; and induces apoptosis (cleaved PARP) in tumour tissues and inhibits liver metastasis. In summary, our results demonstrate that FDMC inhibits the CCSC metastatic phenotype and thereby supports investigating its ability to prevent CRC metastases.


2014 ◽  
Vol 25 ◽  
pp. ii75
Author(s):  
Tzilves Dimitrios ◽  
Patakiouta Frinda ◽  
Pilpilidis Ioannis ◽  
Lazaraki Georgia ◽  
Xiroy Persefoni ◽  
...  

2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Hennie MJ Roelofs ◽  
Rene HM te Morsche ◽  
Bjorn WH van Heumen ◽  
Fokko M Nagengast ◽  
Wilbert HM Peters

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