[Reversal of Drug Resistance in K562/ADM Cells Caused by RA and the Related Mechanisms].

OBJECTIVE: To investigate the effect of ursane triterpenoids 3ß,19α-dihydroxyursu-12-ene-23,28-dicarboxylic acid (Rotundioic acid, RA) on the sensitivity of adriamycin-resistant K562 cells (K562/ADM Cell) anti-tumor drug, and to explore the effect and mechanism of RA on the multidrug resistance of K562/ADM cells. METHODS: CCK-8 method was used to detect the effect of RA on the sensitivity of K562 cells and K562/ADM cells to anti-tumor drug. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression level of mRNA and the protein in K562 and K562/ADM cells, and the effect of RA on the expression of MDR1 mRNA and P-gp in K562/ADM cells was also detected; Western blot was used to detect the expression of p-JNK, p-p38 and p-ERK1/2 in K562/ADM cells. RESULTS: RA could increased the sensitivity of K562/ADM cells to adriamycin(the reversal factor was 1.61 times), the difference showed statistically significantly (P<0.05); the resistance factor of K562/ADM to ADM was 41.76 times. The expression of MDR1 mRNA in K562 cells was extremely low, and the protein product P-glycoprotein (P-gp) was almost not expressed; MDR1 mRNA and P-gp in K562/ADM cells were highly expressed; RA could down-regulate the expression levels of MDR1 and P-gp in K562/ADM cells. In addition, RA could upregulate the phosphorylation levels of p38 and ERK1/2 in K562/ADM cells, but it has no effect on the expression of p-JNK. CONCLUSION: RA may participate in the regulation of MAPK signaling pathway by upregulating the expression levels of p-p38 and p-ERK1/2 in K562/ADM cells, and thus inhibit the transcription and translation levels of MDR1, and finally reverse the multidrug resistance of leukemia cells.

[New Advances in the Treatment of Primary Central Nervous System Lymphoma--Review].

Primary central nervous system lymphoma (PCNSL) is a rare aggressive non-Hodgkin's lymphoma outside the lymph nodes. At present, high-dose chemotherapy based on methotrexate is the standard induction therapy for newly diagnosed PCNSL, but the effective therapy of relapse/refractory and elderly PCNSL is still unclear. With the progress of clinical trials, new drugs and combined treatment method appear constantly, such as rituximab and ibrutinib, the remission rate of refractory and relapsed patients increased, while lenalidomide showed a good activity in the maintenance treatment of elderly patients. This review summarized briefly the recent advances of research on immunocheckpoint inhibitors, immunoregulatory agents, bruton tyrosine kinase (BTK) and PI3K/AKT/mTOR pathway inhibitors.

[Research Progress on New Drug Therapy for Primary Immune Thrombocytopenic Purpura in Adults--Review].

Immune thrombocytopenia (ITP) is an immune disease characterized by an increased risk of hemorrhagic disease caused by a decrease in platelet count. At present, the first line, second-line treatment can not completely or maintain continuous remission of ITP. New treatments in recent research include stimulating platelet-producing drugs, Syk inhibitors, and molecular-targeted drugs, etc., which can play a role in key steps of the progression of the disease. Among them, new types of drugs that stimulate thrombopoiesis shows a better therapeutic prospects with a comparative mechanism and clinical research, Syk inhibitors have a unique role in the treatment of malignant diseases in blood system, and the transplantation of mesenchymal stem cells is a new treatment idea. These treatments show the potential to improve the quality of life in patients with ITP. In this review, the latest research progress of new therapeutic drugs for ITP is summarized briefly.

[Research Advances on the Pathogenesis of Primary Immune Thrombocytopenia--Review].

Abstract　Immune thrombocytopenia (ITP) is a complex autoimmune disease characterized by less than 100×109/L platelet count in peripheral blood. The pathogenesis of ITP is complex and has not been fully elucidated. Currently, researches on the pathogenesis of ITP mainly focus on the disorders of humoral immunity and cellular immunity. In recent years, some new progress has been made in the study of this pathogenesis, including the platelet clearance pathway that is not dependent on Fc γ R mediation, the metalloproteinase (ADAM) 10 that can regulate T and B cells, and the abnormal expression of micro RNA in genetic factors. Under the joint action of multiple factors, the imbalance of the immune system in the body leads to the occurrence of ITP. This article reviews the research progress on humoral immunity, cellular immunity and other possible new pathogenesis of ITP in recent years.

[Advances of Research on Application of Leukemia Xenotransplantation Model--Review].

Abstract　　Tumor xenograft model (PDTX) derived from leukemia patients is an animal model in which the leukemia cells or primary cell lines of patients are transplanted directly into immunodeficient mice.The emergence of nude mice and SCID mice opened early xenotransplantation, then the NSG, NOG mice and the improved model and humanized mice based on there mice significantly improves the success rate of transplantation. The late presented transplantation of leukemia LSC and transplantation of patient-derived and induced pluripotent stem cells obtained based on iPSC technology provide new insight for the anderstanding leukemia genesis and development, and the new type humanized mouse model with normal lymphatic hematopoietic reconstruction provides a new platform of leukemia cell therapy and immunotherapy for leukemia therapy. PDTX is an important platform for the study of the pathogenesis and drug resistance mechanism of leukemia, as well as the development of new drugs and individualized treatment. In this paper, the recent progress in the construction and application of models of immunodeficient mice and their models is reviewed.