Effect of Celastrus orbiculatus extract on proliferation and apoptosis of multiple myeloma cells and its mechanism / 中国药理学通报

Aim To explore the effeet of the extract of Celastrus orbiculatus extract on the proliferation anrl ap- optosis of multiple myeloma eells (U-1996) and its molecular mechanism.Methods The U-1996 eells were divided into normal control ( NC ) group, the southern snake vine extraet group, si-NC group, si- LINC00472 group, pcDNA-NC group, pcDNA- LINC00472 group, southern snake vine extraet + si-NC group,and southern snake vine extraet + si-LINC00472 group.Heal-time quantitative PCR was used to deteet LINC00472 expression, CCK-8 and flow cytometry to deteet eell proliferation and apoptosis, Western blot to deteet the expression levels of phosphorvlated phos- phatidvlinositol-3 -hydroxykinase (p-PI3K) and phos- phorylated protein kinase B ( p-Akt).Results After treated with Celastrus orbieulatus extract, the viability of U-1996 eells and the expression of p-PI3K and p- Akt were significantly reduced, the apoptotie rate and the expression of LINC0047 were significantly raised ( P < 0.05 ).After inhibiting the expression of LINC00472, the viability of U-1996 eells and the ex¬pression of p-PBK and p-Akt significantly inereased, the apoptotie rate and the expression of LINC0047 sig¬nifieantly deereased ( P <0.05 ).After overexpression of LINC00472, the viability of U-1996 eells and the ex¬pression of p-PI3K and p-Akt were signifieantly re- dueed, the apoptotie rate and the expression of LINC0047 significantly inereased ( P <0.05 ).Inhibi¬ting the expression of LINC0047 can reverse the effects of Celastrus orbiculatus extract on proliferation , apopto- sis and PI3K/AKT signaling pathway of U-1996 cells (P < 0.05 ).Conclusions Celastrus orbiculatus ex¬tract can inhibit the proliferation of multiple myeloma cells and induce apoptosis through up-regulating LINC00472 to inhibit PI3K/Akt signaling pathway.

Genetic haploidentical peripheral blood stem cell transplantation for treatment of myelodysplastic syndrome:a 2-year follow-up visit of 21 cases / 中国组织工程研究

BACKGROUND: In recent years, genetic haploidentical peripheral blood stem cell transplantation has been gradually improved, and haploid allogeneic hematopoietic stem cell transplantation has become an important treatment choice for malignant hematopoietic disease. OBJECTIVE: To observe the clinical efficacy of genetic haploidentical peripheral blood stem cell transplantation for myelodysplastic syndrome. METHODS: The clinical data of 21 myelodysplastic syndrome cases undergoing genetic haploidentical peripheral blood stem cell transplantation were retrospectively analyzed. Modified BU/CY+ATG administration was performed as a pretreatment strategy for haploidentical peripheral blood stem cell transplantation, and the combined use of cyclosporine A+mycophenolate mofetil+short-range methotrexate±basiliximab was adopted to prevent graft-versus-host disease (GVHD). RESULTS AND CONCLUSION: (1) The 21 cases were followed for an median of 333 days (22-1 222 days), with 76% (16/21) infection of granulocyte lack period, 100% (21/21) neutrophil reconstruction, the median implantation time of 12 days (7-17 days), 81% (17/21) platelet engraftment, and the median implantation time of 14 days (7-68 days). (2) The accumulative incidence of GVHD was 52.4% (11/21), including 29% (6/21) of acute GVHD and 24% (5/21) of chronic GVHD. The incidence of hemorrhagic cystitis was 38.1% (8/21). The recurrence rate after transplantation was 4.8% (1/21). (3) The 2-year non-relapse mortality was 48% (10/21), and the 2-year disease-free survival rate was 46.8%. These results show that in the absence of HLA-identical related donors and unrelated donor, genetic haploidentical peripheral blood stem cell transplantation is a safe, effective, feasible and alternative treatment option for myelodysplastic syndrome.

Clinical curative efficacy of inducing remission for the newly diagnosed aged AML patients by chemotherapy with IA and DA regimens / 中国实验血液学杂志

This study was aimed to explore the clinical efficacy and toxicity of idarubicin (IA regimen) and daunoru-bicin combined with cytarabine (DA regimen) for treating aged patients with AML as induction chemotherapy. The clinical data of 60 newly diagnosed AML aged patients treated with IA or DA regimen were analyzed retrospectively. IA regimen group included 22 patients (8 male and 14 females with median age of 66 yrs), while the DA regimen group included 38 patients (20 males and 18 females with median age of 64 yrs). The complete remission rate, total effective rate and adverse effects after one chemotherapy course were compared. The results showed that the CR rate in IA regimen group was 63.63%, which was significantly higer than that in DA regimen group (31.58%) (P < 0.05). The total effective rate was 63.63% and 36.84% respectively in IA and DA regimen groups, there was significant difference between the two groups (P < 0.05). Both the hematological and non-hematological adverse effects were observed and no difference was found in the two regimen groups, neither in myelosupression (P > 0.05), the major hematological adverse effects, nor in non-hematological adverse effects (P > 0.05). It is concluded that for aged AML patients, IA regimen can achieve a higher CR rate and higher total effective rate than that in DA regimen without increase of adverse effects after one induction chemotherapy course.

Changes of cell immunophenotypes after transformation from myeloproliferative disorders into acute myeloid leukemia / 中国实验血液学杂志

Some cases of myeloproliferative disorders (MPD) could be transformed into acute myeloid leukemia (AML), but the cell differentiation process of MPD into AML has not yet been observed in vivo. This study was aimed to reveal this differentiation process. The flow cytometry was used to analyse the immunophenotype of differentiated cells of 2 MPD cases who developed into AML in a short time. The reports showed that the different MPD-AML subclones are presented when the MPD cells that proliferate slowly in vivo become the AML blast cells that proliferate rapidly. It is concluded that understanding the process of MPD crisis will help the MPD-AML early diagnosis and treatment.

Immunogenetic diagnosis of large granular lymphocytic leukemia and therapy by sirolimus / 中国实验血液学杂志

This study was aimed to investigate the immunogenetic diagnosis of large granular lymphocytic leukemia (LGLL) and therapeutic efficacy of sirolimus, and to analysis 256 cases of LGLL reported at home and abroad within 2000 - 2010. Besides the routine examination of peripheral blood and classification of bone marrow cell morphology, the expression of T cell receptor variable region of β-chain (TCR BV), CD3, CD4 and CD8, as well as TCRαβ, TCRγδ were detected by flow cytometry; the RT-PCR was used to amplify and determine the TCR gene spectrotypes, and to analyze the clonality of abnormal cells. Sirolimus was first given to patients who did not gain efficacy from common agents. The results showed that lymphocytosis happened in all LGLL patients, but patients from West countries always displayed neutropenia while Chinese patients always displayed anemia. In 2 out of 4 patients from our hospital, the large granular lymphocytes (LGL) were difficult to be distinguished. In all 4 patients, almost all lymphocytes were CD3(+), CD8(+), and TCRα/β(+). TCR BV 24 gene family clones showed monoclonal TRBV 23, TRBV 20, TRBV 13.6, and TRBV 13.6, respectively. FCM results were consistent with those of RT-PCR. When 4 patients had been given sirolimus (6 mg first dose, 2 mg once a day) for about 1 week, hemoglobin level and reticulocyte count increased significantly without any serious side effects. It is concluded that the detection of specific lymphocyte monoclonal TCR BV 24 gene family by FCM contributes to the diagnosis of LGLL. Sirolimus is an effective agent without serious side effect for LGLL patients, especially for patients who cannot tolerate common drugs.

Role of nitro oxide in immunosuppressive effect of human mesenchymal stem cells on allogenic proliferative response of lymphocytes / 中国实验血液学杂志

The purpose of this study was to investigate the influence of nitro oxide (NO) from mesenchymal stem cells (MSC) on the proliferative responses of allogeneic lymphocytes and its mechanism. MSCs were isolated and cultured from human bone marrow. Selected surface antigens of MSCs were detected by flow cytometry and their morphologic characteristics were determined by microscopy. Mitomycin C-treated MSCs were plated in dishes and then mixed lymphocyte cultures (MLC) were set up. After 4 days, lymphocyte proliferation was determined by CCK-8 assays; NO secretion in coculture supernatant was determined by Griess reagent kit; the level of FOXP3 mRNA expression was detected by real-time quantitative PCR. The results indicated that in MSC/MLC coculture experiment, the lymphocyte proliferation decreased significantly with of IOD value 0.49+/-0.03, NO production increased obviously (21.05+/-1.14 micromol/L) and FOXP3 mRNA expression was increased [(1.56+/-0.34)%] as compared with MLC coculture without MSC. There were significant difference between these two groups. It is concluded that NO production in human MSC culture up-regulates FOXP3 mRNA expression and thus inhibits lymphocyte proliferation response.