ABSTRACT
Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.
ABSTRACT
Objective To discuss the effect of α-asarone on the expression level of Cyt-c,Smac,Caspase3 mRNA and protein in human esophageal carcinoma Eca-109 cell mitochondria. Methods The Eca-109 cells were cultured in vitro,and divided into the negative control group and the α-asarone treatment groups(final concentration:25,50,100 μg·mL-1).After 48 h,the morphological changes of Eca-109 cells were observed by fluorescence inversion microscope.The total RNA of cells were extracted by TRIzol method,the expressions of Cyt-c、Smac and Caspase3 were measured by RT-PCR and Western blotting. Results After Eca-109 cells were treated with different concentrations of α-asarone for 48 h,and obvious changes in the morphology were observed,the expressions of Cyt-c,Smac and Caspase3 genes and protein were increased significantly compared to the negative control group( P<0.05). Conclusion α-asarone can induce the human Eca-109 cells apoptosis by regulating expressions of mitochondrial apoptosis pathway correlation genes such as Cyt-c,Smac and Caspase3.