Preliminary Exploration Of A New Preclinical Research Pattern Based On Tumor Animal Model

Preclinical researches can provide important evidences in solving clinical problems. In the viewpoint of historical development, the establishment of scientific and formal preclinical tumor animal models can lead to reliable and practical conclusions of cancer preclinical research.Here in this study presents a method of a new preclinical research pattern based on tumor animal models. According to translational medicine methods, the specific clinical problems were detailed into several experimental problems. Abiding to strict preclinical tumor animal experimental study of the specification, choose reasonable tumor model and overall design plan of experiment experiment; comprehensive evaluation of the conclusion of experiments, in order to answer clinical questions.We provided proofs initially on the feasibility of the model in two experiments.(1) The tumor suppression efficacy of intratumoral injection of paclitaxel liposome in H22mouse xenograft model was studied, to support the clinical application of intratumoral injection of liposomal paclitaxel in advanced cancer patients with local solid tumors. We established H22mouse subcutaneous xenograft tumor models, studied ultrasonograph features of intratumoral injection of paclitaxel liposome, compared the intravenous and intratumoral drug distribution with in vivo near infrared fluorescence, and found an optimal dosage and administration frequency with best antitumor effect. The safety was also considered. It is demonstrated that intratumoral injection of3mg/ml liposomal paclitaxel in the75mg/kg dose of weekly can reach95%tumor suppression rate, compared with intravenous administration in significant statistic differences (P<0.01). Intensified echo region can be detected by ultrasonography when injecting paclitaxel liposome intratumorally, ensuring that the drug distributed in the tumor. The in vivo near infrared fluorescence images displayed a sustained high drug concentration confined in tumor for24hr after intratumoral injection, while a gradually increasing and relatively low concentration of drug in tumor after intravenous injection. No obvious diabrosis or erosion of subcutaneous tissues and overall adverse effect was observed during intratumoral injection. So reasonable parameters were provided for further clinical application.(2) In vivo drug sensitive testing in nude mice bearing human gastric cancer primary tumor xenograft model to select chemotherapeutic regimens for postoperative gastric cancer patient, intact tumor block was applied in implantation to evaluate this notion. Personalized human gastric tumor xenograft model was established in nude mice using surgery excised tumor tissues. Compared the pathogenic and genetic features between xenograft and primary tumor. Observed the responses of these model to two chemotherapeutic agents, docetaxel and pemetrexed. As a result,95xenografts from all11patients of gastric cancer were transplanted successfully. Pathological comparison confirmed that no differences between xenografts and primary tumors while the therapeutic response exhibited differently between different drugs (P<0.05) and among different patients(P<0.05). In conclusion, applying personalized primary tumor xenograft model derived from freshly excised tumor in pre-clinic trails would potentially lead to a more effective customized chemotherapy.The above experiment results can provides a more scientific basis for clinical problem solving, indicating that this new pattern for tumor animal model based preclinical research is worthy of further studying.