Time-serial Assessment of Drug Combination Interventions in a Mouse Model of Colorectal Carcinogenesis Using Optical Coherence Tomography
| Autor: | Denise J. Roe, Ramireddy Bommireddy, Kyle J. Sprute, Natalia A. Ignatenko, R. Andrew Wall, Amber M. Luttman, Raymond B. Nagle, Edward R. Abril, Katrina Farrell, Chiu Hsieh Hsu, Eugene W. Gerner, Photini F. S. Rice, Jennifer K. Barton, Susan LeGendre-McGhee |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Oncology
medicine.medical_specialty Adenoma Colorectal cancer mouse model medicine.medical_treatment colorectal cancer Bioinformatics lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine Text mining Internal medicine sulindac medicine α-difluoromethylornithine Original Research 030304 developmental biology 0303 health sciences Chemotherapy Sulindac optical coherence tomography biology business.industry Cancer General Medicine lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease 3. Good health 030220 oncology & carcinogenesis Drug delivery biology.protein Cyclooxygenase business medicine.drug |
| Zdroj: | Cancer Growth and Metastasis Cancer Growth and Metastasis, Vol 2015, Iss Suppl. 1, Pp 63-80 (2015) Cancer Growth and Metastasis, Vol 8s1 (2015) |
| ISSN: | 1179-0644 |
| DOI: | 10.4137/cgm.s21216 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|