Figure 6.
Figure 6. Patient-derived cells engrafted in NSG mice are sensitive to masitinib. (A) Pipeline for xenograft studies. WSU-DLCL2 cells were injected subcutaneously; mice were treated with vehicle or masitinib (50 mg/kg per day IP) for 12 days, and tumor growth was assessed by luminescence. (B) Representative images of bioluminescence signals from xenografted mice after 12 days of treatment with vehicle or masitinib. (C) Average of the tumor weight harvest from animals treated with masitinib (n = 6) or vehicle (n = 6). The P value was calculated using 2-tailed Student t test. (D) Representative images of immunohistochemistry analyses of tumors harvested from xenografted animals and stained for Ki67 and MYC. Scale bars, 100 μm. (E) Representation of the experiment design to assess the effect of masitinib and ibrutinib in a DH patient-derived xenograft model (patient 69487). Primary tumor cells were obtained from a de novo diagnosed DH lymphoma patient, engineered to express luciferase and injected in NSG mice. Six days after injection, animals were treated with vehicle, masitinib (50 mg/kg per day IP), or ibrutinib (12 mg/kg per day IP), and tumor growth was assessed by luminescence. (F) Images of bioluminescent signals in animals treated with masitinib, ibrutinib, or vehicle at days 6, 10, 14, 18, and 22. (G) Quantification of the bioluminescence signals in animals treated with masitinib, ibrutinib, or vehicle at days 6, 10, 14, 18, and 22. The signal (photons/sec) was normalized to the first day of treatment (day 6). Tumor growth is represented as the mean ± SEM of the luminescence signal for the indicated number of animals. P value was calculated using 2-tailed Student t test. Significant changes between untreated and ibrutinib or masitinib-treated mice at the different points are labeled with *P ≤ .05; **P ≤ .01; ****P ≤ .0001. (H) Representation of the experimental design to assess the effect of masitinib and ibrutinib in ABC-DLBCL patient-derived xenograft (patient 13796). (I) Representative images by ultrasound of the abdomens and liver autopsy of animals harboring ABC lymphoma and treated vehicle, ibrutinib, and masitinib for 2 months. The dotted lines were designed to highlight the tumor. (J) MYC expression in blood samples isolated from animals untreated or treated with ibrutinib or masitinib (n = 5 per group). P values were calculated using 2-tailed Student t test. Significant changes between untreated and ibrutinib or masitinib-treated mice are labeled with *P ≤ .05. (K) Survival analysis of animals bearing ABC-lymphoma (patient 13796) untreated or treated with ibrutinib (12 mg/kg per day IP) or masitinib (50 mg/kg per day IP).

Patient-derived cells engrafted in NSG mice are sensitive to masitinib. (A) Pipeline for xenograft studies. WSU-DLCL2 cells were injected subcutaneously; mice were treated with vehicle or masitinib (50 mg/kg per day IP) for 12 days, and tumor growth was assessed by luminescence. (B) Representative images of bioluminescence signals from xenografted mice after 12 days of treatment with vehicle or masitinib. (C) Average of the tumor weight harvest from animals treated with masitinib (n = 6) or vehicle (n = 6). The P value was calculated using 2-tailed Student t test. (D) Representative images of immunohistochemistry analyses of tumors harvested from xenografted animals and stained for Ki67 and MYC. Scale bars, 100 μm. (E) Representation of the experiment design to assess the effect of masitinib and ibrutinib in a DH patient-derived xenograft model (patient 69487). Primary tumor cells were obtained from a de novo diagnosed DH lymphoma patient, engineered to express luciferase and injected in NSG mice. Six days after injection, animals were treated with vehicle, masitinib (50 mg/kg per day IP), or ibrutinib (12 mg/kg per day IP), and tumor growth was assessed by luminescence. (F) Images of bioluminescent signals in animals treated with masitinib, ibrutinib, or vehicle at days 6, 10, 14, 18, and 22. (G) Quantification of the bioluminescence signals in animals treated with masitinib, ibrutinib, or vehicle at days 6, 10, 14, 18, and 22. The signal (photons/sec) was normalized to the first day of treatment (day 6). Tumor growth is represented as the mean ± SEM of the luminescence signal for the indicated number of animals. P value was calculated using 2-tailed Student t test. Significant changes between untreated and ibrutinib or masitinib-treated mice at the different points are labeled with *P ≤ .05; **P ≤ .01; ****P ≤ .0001. (H) Representation of the experimental design to assess the effect of masitinib and ibrutinib in ABC-DLBCL patient-derived xenograft (patient 13796). (I) Representative images by ultrasound of the abdomens and liver autopsy of animals harboring ABC lymphoma and treated vehicle, ibrutinib, and masitinib for 2 months. The dotted lines were designed to highlight the tumor. (J) MYC expression in blood samples isolated from animals untreated or treated with ibrutinib or masitinib (n = 5 per group). P values were calculated using 2-tailed Student t test. Significant changes between untreated and ibrutinib or masitinib-treated mice are labeled with *P ≤ .05. (K) Survival analysis of animals bearing ABC-lymphoma (patient 13796) untreated or treated with ibrutinib (12 mg/kg per day IP) or masitinib (50 mg/kg per day IP).

Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal