Using patient-derived xenograft models of colorectal liver metastases to predict chemosensitivity
| Autor: | Sohel M. Julovi, Aiqun Xue, Ross C. Smith, Anthony J. Gill, Jaswinder S. Samra, Thomas J. Hugh, Nick Pavlakis, K. M. Brown |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Male medicine.medical_specialty Colorectal cancer Pilot Projects Mice SCID 03 medical and health sciences Folinic acid Mice 0302 clinical medicine Mice Inbred NOD Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Animals Humans Aged Aged 80 and over business.industry Liver Neoplasms Cancer Middle Aged medicine.disease Endonucleases Xenograft Model Antitumor Assays Oxaliplatin Irinotecan DNA-Binding Proteins 030104 developmental biology Ki-67 Antigen Treatment Outcome Liver Fluorouracil Chemotherapy Adjuvant Drug Resistance Neoplasm 030220 oncology & carcinogenesis Immunohistochemistry Feasibility Studies Surgery Female ERCC1 business Colorectal Neoplasms medicine.drug |
| Zdroj: | The Journal of surgical research. 227 |
| ISSN: | 1095-8673 |
| Popis: | Background Few in vivo models for colorectal cancer have been demonstrated to show external validity by accurately predicting clinical patient outcomes. Patient-derived xenograft (PDX) models of cancer have characteristics that might provide a form of translational research leading to personalized cancer care. The aim of this pilot study was to assess the feasibility of using PDXs as a platform for predicting patient colorectal liver metastases responses, in this case by correlating PDX and patient tumor responses to either folinic acid, fluorouracil plus oxaliplatin or folinic acid, fluorouracil plus irinotecan-based regimens. Methods Sixteen patients underwent potentially curative resection of colorectal liver metastases, and tumors were grafted into NOD.CB17-Prkdcscid/Arc mice. Mice were divided into groups to determine relative tumor growth in response to treatment. Tumors were analyzed by immunohistochemistry for Ki67 and Excision repair cross-complementation group 1. Results An engraftment rate of 81% was achieved. Overall, there was a 67% positive match rate between eligible patient and PDX chemosensitivity profiles. There was a significant difference in relative decrease in Ki67 expression between sensitive/stable versus resistant PDXs for both treatment regimens. There was no statistically significant correlation between baseline ERCC1 expression and response to Oxaliplatin + 5-Fluorouracil in the PDXs. Conclusions This pilot study supports the feasibility of using PDX models of advanced colorectal cancer in larger studies to potentially predict patient chemosensitivity profiles. |
| Databáze: | OpenAIRE |
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