Curcumin sensitizes human colorectal cancer to capecitabine by modulation of cyclin D1, COX‐2, MMP‐9, VEGF and CXCR4 expression in an orthotopic mouse model

2009 ◽  
Vol 125 (9) ◽  
pp. 2187-2197 ◽  
Author(s):  
Ajaikumar B. Kunnumakkara ◽  
Parmeswaran Diagaradjane ◽  
Preetha Anand ◽  
Harikumar B. Kuzhuvelil ◽  
Amit Deorukhkar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mouse Model ◽  
Cyclin D1 ◽  
Cxcr4 Expression ◽  
Human Colorectal Cancer ◽  
Orthotopic Mouse Model ◽  
Cox 2

scholarly journals Time-serial Assessment of Drug Combination Interventions in a Mouse Model of Colorectal Carcinogenesis Using Optical Coherence Tomography

2015 ◽  
Vol 8s1 ◽  
pp. CGM.S21216 ◽  
Author(s):  
Susan LeGendre-McGhee ◽  
Photini S. Rice ◽  
R. Andrew Wall ◽  
Kyle J. Sprute ◽  
Ramireddy Bommireddy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Rate ◽  
Optical Coherence Tomography ◽  
Mouse Model ◽  
Tumor Burden ◽  
Colorectal Carcinogenesis ◽  
Optical Coherence ◽  
Ki 67 ◽  
Tumor Number ◽  
Cox 2

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.

scholarly journals Establishment of an Endoscopy-Guided Minimally Invasive Orthotopic Mouse Model of Colorectal Cancer

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3007
Author(s):  
Chen Chen ◽  
Jens Neumann ◽  
Florian Kühn ◽  
Serene M. L. Lee ◽  
Moritz Drefs ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mouse Model ◽  
Minimally Invasive ◽  
Tumor Growth ◽  
Hepatic Metastases ◽  
Specific Cell ◽  
Local Tumor ◽  
Orthotopic Mouse Model ◽  
Endoscopic Score ◽  
Local Tumor Growth

Open orthotopic mouse models of colorectal cancer have disadvantages such as the requirement for advanced surgical skills or the trauma caused by laparotomy. To overcome these drawbacks, this study aimed to evaluate the establishment of a minimally invasive model using murine colonoscopy. CT26 and MC38 CRC cells of different concentrations were injected into BALB/C and C57BL/6J mice, respectively. Follow-up endoscopies were performed to assign an endoscopic score to tumor growth. Gross autopsy, histologic and immuno-histochemical evaluation, and immune scoring were performed. To describe the learning curve of the procedures, a performance score was given. Local tumor growth with colorectal wall infiltration, luminal ulceration, the presence of tumor-infiltrating lymphocytes, lympho-vascular invasion, and early spontaneous lymph node, peritoneal, and hepatic metastases were observed. The tumors showed cytoplasmic immuno-staining for CK20. Compared to the MC38/C57BL/6J model, tumorigenicity and immunogenicity of the CT26/BALB/C model were higher. Tumor volume correlated with the endoscopic score. This endoscopy-guided orthotopic mouse model is easy to learn and quick to establish. It features early metastasis and enables the study of interactions with the immune system. When specific cell concentrations and cell lines are applied, controlled local tumor growth and metastasis can be achieved within short observation periods.

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