Could cytokine release syndrome induce acute myelofibrosis in CD19 chimeric antigen receptor T cells therapy?

CAR-T cells therapy can give rise to most common and concerning two side effects - cytokine release syndrome (CRS) and neurotoxicity. But in our CD19 CAR-T cells therapy clinical trial, we observed 1 out of 17 patients with B-cell acute lymphoblastic leukemia (B-ALL) developed acute myelofibrosis(AMF) after grade IV CRS post to the CD19 CAR-T cells therapy. This finding suggests that the CAR-T cells therapy may have rare and serious AMF, which we should pay important attention to. Trial registration:NCT02968472. Registered 18 November 2016 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02968472.

Anti-tumor activities of active ingredients in Compound Kushen Injection.

Kushen (Radix Sophorae Flavescentis) has a long history of use for the treatment of tumors, inflammation and other diseases in traditional Chinese medicine. Compound Kushen Injection (CKI) is a mixture of natural compounds extracted from Kushen and Baituling (Rhizoma Smilacis Glabrae). The main principles of CKI are matrine (MT) and oxymatrine (OMT) that exhibit a variety of pharmacological activities, including anti-inflammatory, anti-allergic, anti-viral, anti-fibrotic and cardiovascular protective effects. Recent evidence shows that these compounds also produce anti-cancer actions, such as inhibiting cancer cell proliferation, inducing cell cycle arrest, accelerating apoptosis, restraining angiogenesis, inducing cell differentiation, inhibiting cancer metastasis and invasion, reversing multidrug resistance, and preventing or reducing chemotherapy- and/or radiotherapy-induced toxicity when combined with chemotherapeutic drugs. In this review, we summarize recent progress in studying the anti-cancer activities of MT, OMT and CKI and their potential molecular targets, which provide clues and references for further study.

[Inhibitory effect of N-terminal of p55PIK--regulatory subunit of phosphoinositide-3 kinase--on proliferation of gastric cancer cell line MGC803 and its mechanism].

BACKGROUND & OBJECTIVE: p55PIK is one of the regulatory subunits of phosphoinositide-3 kinase (PI3K). The unique 24 amino acids at N-terminal of p55PIK can bind Rb, and their ectopic expression may inhibit cell cycle progression. This study was to observe the effects of ectopic expression of the 24 amino acids at N-terminal of p55PIK (N24p55PIK) on cell proliferation and tumor growth of gastric cancer, and explore possible mechanism. METHODS: Plasmid pEGFPN24 was transfected into gastric cancer cell line MGC803 (MGC803/GFP-N24); pEGFPC1 was transfected into MGC803 cells as control (MGC803/pEGFPC1). Transient expression of GFP-N24 fusion protein was confirmed by Western blot. The growth of cell clones was determined by MTT assay. Effect of N24p55PIK overexpression on cell clonogenic ability was detected by colony formation assay. Tumorigenic capacity of MGC803/GFR-N24 cells was tested by tumorigenicity assay in nude mice. Influence of N24p55PIK on the expression of cell cycle protein Cyclin D1 was analyzed by Western blot. RESULTS: N24p55PIK was efficiently expressed in MGC803 cells, but the level of GFP-N24 fusion protein in MGC803/GFP-N24 cells was much lower than that of GFP in MGC803/pEGFPC1 cells. Compared with MGC803/pEGFPC1 cells, the growth of MGC803/GFP-N24 cells was suppressed and the cell doubling time was prolonged. The volume of MGC803/GFP-N24 cell colonies was smaller than that of MGC803/pEGFPC1 cell colonies. The tumorigenic capacity of MGC803 cells was decreased after transfection of pEGFPN24 in nude mice. The tumor weight and volume were (0.398+/-0.244) g and (408+/-268) mm(3) in MGC803/pEGFPN24 group, and were (0.763+/-0.193) g and (829+/-271) mm(3) in MGC803/pEGFPC1 group (P<0.05). The expression of Cyclin D1 was down-regulated in MGC803/GFP-N24 cells. CONCLUSIONS: Ectopic expression of N24p55PIK might inhibit tumor cell growth both in vitro and in vivo through decreasing the expression of Cyclin D1. The N24 peptide, derived from PI3K regulatory subunit p55PIK, may be a potential drug in antitumor treatment.