Figure 6.
KPT-330+CS imposes significant antitumor effect on primary malignant patient samples. (A) Viability assay on mononuclear cells obtained from primary patient tissue samples with malignancy following 48 hours of incubation with respective drug treatment. Plasma cells from patients with MM were obtained following CD138 sorting through positive selection. (B) Viability assay showing the effect of KPT-330, CS and KPT-330+CS on mononuclear cells obtained from peripheral blood of healthy donors without a flow cytometry proven diagnosis of malignancy, and tissue biopsies from the indicated tissue types from patients without a diagnosis of cancer per histopathologic review. Cells were treated with 0.5 µM KPT-330 and 3 mM CS as single agent or in combination for 48 hours. (C) Patient tumor samples derived from PDX (5 ovarian cancers and 2 gliomas) were treated ex vivo with KPT-330 and CS as single agents, or in combination. Ovarian tumor cells were treated with 0.6 µM KPT-330 and 0.6 mM CS as single agent or in combination. Glioma cells were treated with 0.1 µM KPT-330 and 0.3 mM CS as single agent or in combination. *P < .05 to P < .005; **P < .005 to P < .0005; ***P < .0005. Paired Student t test was used to compare all continuous variables. A P value of <.05 was considered statistically significant.BM, bone marrow; CLL, chronic lymphocytic leukemia; CMML, chronic myelomonocytic leukemia; LPL, lymphoplasmacytic lymphoma with IgG monoclonal gammopathy; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma; PBMC, peripheral blood mononuclear cell; PDX, patient-derived xenograft; TCL, T-cell lymphoma; WM, Waldenstrom macroglobulinemia.