Novel CD19-KIRS2/Dap12-BB CAR-T Treatment for 3 Patients with Relapsed and Refractory B-Cell Tumors / 中国实验血液学杂志

OBJECTIVE@#To investigate the safety and efficacy of novel CD19-KIRS2/Dap12-BB chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory B-cell malignancy (R/R BCM).@*METHODS@#Three patients with R/R BCM treated with novel CD19-KIRS2/Dap12-BB CAR-T cells from June 2020 to November 2020 were enrolled, including 1 case of B-cell acute lymphoblastic leukaemia (B-ALL) and 2 cases of non-Hodgkin's lymphoma (NHL), and the efficacy and adverse reactions were observed.@*RESULTS@#After CAR-T cells infusion, patient with B-ALL achieved complete remission (CR) and minimal residual disease (MRD) turned negative, and 2 patients with NHL achieved partial remission (PR). Grade 2 cytokine release syndrome (CRS) occurred in B-ALL patient, grade 1 CRS occurred in 2 NHL patients, and grade II to IV hematologic adverse reactions occurred in 3 patients, all of which were controllable and reversible. The progression-free survival (PFS) of the 3 patients was 143, 199, and 91 days, and overall survival (OS) was 282, 430, and 338 days, respectively.@*CONCLUSION@#The novel CD19-KIRS2/Dap12-BB CAR-T cells in treatment of 3 patients with R/R BCM have significant short-term efficacy and controllable adverse reactions, but the long-term efficacy needs to be further improved.

Effect of Hemoglobin on Efficacy of CAR-T Therapy in Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of hemoglobin (Hb) on the efficacy of chimeric antigen receptor T cell therapy (CAR-T) in patients with multiple myeloma (MM).@*METHODS@#From June 2017 to December 2020, 76 MM patients who received CAR-T therapy in the Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, with complete clinical data and evaluable efficacy, were selected as the research objects. According to the receiver operating characteristic (ROC) curve, the best cut-off value was obtained. The patients were divided into groups on the basis of Hb 105.5 g/L as the cut-off value. The age, sex, serum calcium, β2-microglobulin, serum creatinine, lactate dehydrogenase (LDH), and the influencing factors of CAR-T treatment efficacy in MM patients were analyzed.@*RESULTS@#Hb was an influencing factor of efficacy. Univariate analysis showed that Hb, LDH, and albumin affected the efficacy of CAR-T therapy. Multivariate analysis showed that Hb ( OR=1.039, 95% CI: 1.002-1.078) and LDH ( OR=1.014, 95% CI: 1.000-1.027) were the influencing factors for the efficacy of CAR-T therapy.@*CONCLUSION@#The efficacy of CAR-T therapy in MM patients with low Hb is poor, and Hb is a factor affecting the efficacy of CAR-T therapy.

Hepatoprotective activity of cis-(trans)-emodin-emodin dianthrone from Polygonum multiflorum Thunb / 药学学报

The cis-emodin-emodin dianthrone (compound 1) and trans-emodin-emodin dianthrone (compound 2) were extracted from Polygonum multiflorum Thunb. The protective effect and mechanism of compound 1 and compound 2 (emodin-emodin dianthrones) on acute liver injury induced by concanavalin A (ConA) in ICR mice was first investigated. The results indicated that emodin-emodin dianthrones at 1 mg·kg-1 significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level (P < 0.05). Emodin-emodin dianthrones also improved liver histopathological damage in liver-injured mice. The level of Bcl-2-associated X protein (Bax) mRNA in liver was significantly reduced by 1 mg·kg-1 of emodin-emodin dianthrones, while the level of B-cell lymphoma-2 (Bcl-2) mRNA expression was significantly increased (P < 0.05). The protective activity of compounds 1 and 2 against hepatocyte injury was further evaluated by hydrogen peroxide (H2O2)-induced hepatocyte injury. Compounds 1 and 2 significantly inhibited H2O2-induced hepatocyte injury and reduced the levels of ALT, AST, alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in cell culture. Compounds 1 and 2 also significantly improved the cell survival rate and decreased H2O2-induced oxidative stress in hepatocytes. Compound 1 (0.5 µmol·L-1) significantly increased the enzymatic activity of superoxide dismutase (SOD) in hepatocytes (P < 0.01), and 0.5 µmol·L-1 of compound 2 significantly decreased the intracellular reactive oxygen species (ROS), increased SOD enzyme activity, and glutathione (GSH) content (P < 0.01). Compounds 1 and 2 at 0.5 µmol·L-1 also inhibited hepatocyte apoptosis by increasing the protein expression ratio of Bcl-2/Bax (P < 0.05) and decreasing the protein expression ratio of cleaved caspase-3 and pro caspase-3 (P < 0.05). This study indicates that the emodin-emodin dianthrones from Polygonum multiflorum Thunb. have liver-protective activity. Compounds 1 and 2 exerted hepatoprotective effects by inhibiting apoptosis and oxidative stress. The study provides an important material basis for the hepatoprotective effect of commonly used amounts of Polygonum multiflorum Thunb.

Induction of apoptosis and mechanism of MDA-MB-231 cells by water extract of dandelion root / 中国药理学通报

Aim: To discuss the effects of water extract of dandelion root on the proliferation and apoptosis of human triple negative breast cancer cell line MDA-MB-231 and its mechanism. Methods: In this study, the cytotoxicity of dandelion root extract and the inhibition of MDA-MB-231 cell proliferation were detected by Alamar Blue method. Effects of water extracts of dandelion root on apoptosis of MDA-MB-231 cells were assessed by morphological observation, DAPI staining and flow cytometry; The mechanism of dandelion root water extract induced apoptosis of MDA-MB-231 cells was analysed by Western blot. Results: Extracts from various parts of dandelion were not cytotoxic; furthermore, 7.5 and 15 g · L-1 water extract of dandelion significantly inhibited the proliferation of MDA-MB-231 cells, and the cells showed obvious apoptotic characteristics. Flow cytometry further confirmed the aqueous extract of dandelion root could induce the apoptosis of MDA-MB-231 cells. In terms of molecular mechanism, the water extract of dandelion root decreased the expression of Bcl-2 protein in a concentration-dependent manner, while the expressions of Bax, p53, active c-PARP, caspase-8, caspase-9 and caspase-3 increased. Caspase-8 inhibitor (Z-IETD-FMK) and caspase-9 inhibitor (Z-LEHD-FMK) were able to reverse the proliferation inhibitory activity of dandelion water extract on MDA-MB-231 cells. Conclusions: The water extract of dandelion has a significant inhibitory effect on human triple negative breast cancer MDA-MB-231 cells, pointing to its potential clinical application value for the treatment of triple negative breast cancer.