Establishment And Characterization Of An Orthotopic Murine Model Of Mucosal Malignant Melanoma Of The Maxillary Sinus

Objective: To establish a stable and reliable orthotopic murine model of mucosal malignant melanoma of the maxillary sinus and these animal models were monitored for survival and tumor growth.Meanwhile,the degrees of tumor infiltration were observed under the Magnetic Resonance Imaging.The objective is to provide appropriate animal models for further study pathogenesis and therapeutic regimen of sinonasal malignancy.Method: After confirming the degree of anesthesia,we placed the mice in a prone position.B16 tumor cells were implanted in the right maxillary sinus of male nude mice via transcutaneous injection underneath the right infraorbital muscle groups,with the needle angled toward the right lateral wall of the maxillary sinus.According to the random number table method,24 female BALB/c nude mice were numbered and randomly divided into three groups,and each group include 8 nude mice.Group A(Blank control,n = 8): each mouse was injected with 100?l normal saline;Group B(Experimental control,n = 8):each mouse was injected with 100?l tumor cell suspensions which concentrations are 1106cells/ml;Group C(Experimental control,n = 8):each mouse was injected with 100?l tumor cell suspensions which concentrations are 5106cells/ml.After implanting tumor cell,we observed tumorigenicity,tumor-forming time,the tumor volume,the weight of mice,and the survival of mice.Meanwhile,the degrees of tumor infiltration were observed under the Magnetic Resonance Imaging.Statistical analysis was done with SPSS software.In the tumor volume studies and mice weight studies,data of tumor volume and the mice weight was expressed as mean ± standard deviation(`x ± s),an ANOVA was done to assess whether an overall difference existed between the mean volumes of the tumors and the mean weight of the mice growing from tumor cell suspensions of different concentrations.P<0.05 was considered to indicate a statistically significant difference.The survival of mice was revealed with Kaplan-Meier survival curves,and log-rank test was done to assess whether an overall difference existed between the survivals of the mice growing from tumor cell suspensions of different concentrations.P<0.05 was considered to indicate a statistically significant difference.Result :(1)16 female BALB/c nude mice are implanted successfully in experiment group,the achievement ratio is100%.The time of formatting orthotopic xenograft tumor nodule was 5-6days in the experimental group which was injected with 5105 cell,the median was 5 days;the time of formatting orthotopic xenograft tumor nodule was 6-8 days in the experimental group which was injected with1105 cell,the median was 8 days.(2)The tumor volume was directly correlated with the implanted tumor cell concentrations.Under the same time,the mice which was injected with 5105 cells formed larger tumor volume than the mice which injected with 1105cells(P<0.05).(3)The mice weight was directly correlated with the implanted tumor cell concentrations.Under the same time,the mice which was injected with5105 cells get lower weight than the mice which injected with1105cells(P<0.05).(4)Kaplan-Meier survival analysis revealed a statistically significant difference in survival when mice injected with5105 cells were compared with mice injected with 1105cells(P<0.05).The median survival time was 24 days in the experimental group which was injected with 5105 cell.The median survival time was 30 days in the experimental group which was injected with 1105 cells.(5)MRI was performed on sagittal,coronal and transverse position of the head and neck of the nude mice.It revealed that the tumor invaded right nasal cavity,right orbital cavity and the basilar region.Conclusion: We describe a successful model for mucosal malignant melanoma of the maxillary sinus with high successful rate.The disease progress of this orthotopic model resembled to the human mucosal malignant melanoma of the maxillary sinus.This model offers an experimental tool for further research of biological characteristics of sinonasal malignancy and the development of new effective therapeutic regimen.