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Objective To evaluate the efficacy of pegaspargase (PEG-ASP) combined with GEMOX regimen for the treatment of extranodal natural killer (NK) / T-cell lymphoma (ENKL),and to observe the changes of coagulation function.Methods 35 patients with histologically confirmed ENKL were enrolled from January 2010 to December 2014.All patients received 180 cycles of PEG-ASP combined with GEMOX chemotherapy and the efficacies were observed.The coagulation items such as prothrombin time (PT),activated partial thromboplastin time (APTT),fibrinogen (Fbg) and international normalized ratio (INR) were tested respectively on day 1st,day 8th and day 14th of every treatment cycle.Results Among 35 patients,11 patients (31.43 ％) were in stage Ⅰ-Ⅱ,and 24 patients (68.57 ％) were in stage Ⅲ-Ⅳ.All patients were subjected to 180 cycles of PEG-ASP combined with GEMOX chemotherapy,and each case was estimated to receive 6 cycles.The overall response (CR+PR) rate (ORR) was 71.43 ％ (25/35),the ORR was 81.82 ％ (9/11) in stage Ⅰ-Ⅱ group,and 66.67 ％ (16/24) in stage Ⅲ-Ⅳ group.The increased PT and APTT and decreased Fbg were observed on day 8th of the chemotherapy.The increased APTT and decreased Fbg were still observed on day 14th of the chemotherapy.Compared the data of patients one day before chemotherapy with healthy persons,the changes had statistical significance (P ＜ 0.05).Conclusions PEG-ASP combined with GEMOX regimen in the treatment of ENKL is safer and more effective compared with traditional chemotherapy,but the abnormal alternations of coagulation might be common during therapy.Dealing with the bleeding risk and supplement with plasma,PPSB or Fbg in time should be necessary.
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Objective To detect the significance of the SHP-1,p15 and SOCS-1 genes methylation status in the genesis and development of diffuse large B-cell lymphoma (DLBCL).Methods The methylation state of SHP-1,p15 and SOCS-1 genes CpG islands were measured by methylation-specific polymerase chain (MSP) reaction.Results The positive rates of aberrant methylation for SHP-1,p15 and SOCS-1 genes in 50 specimens of DLBCL were 96 ％ (48/50),52 ％ (26/50) and 56 ％ (28/50) respectively.In control group,however,15 specimens of benign lymph node proliferation showed no methylation in CpG island of SHP-1,p15 and SOCS-1 genes promoter.Conclusion Aberrant methylations of the SHP-1,p15 and SOCS-1 genes exist in the patients with DLBCL.The methylations of SHP-1,p15 and SOCS-1 genes may be associated with the occurrence and development of DLBCL.This study provides a theoretical basis of treatment methylation for DLBCL.
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Objective To investigate the effects of arsenic trioxide (AS2O3)on SOCS-1 gene methylation and expression of P-STAT3 in multiple myeloma (MM) cells.Methods MM cell lines U266 and CZ-1 were used as in vitro models.Methylation status of SOCS-1 gene was detected by the methylation specific PCR (MSP)while P-STAT3 protein expression was determined by Western blotting assay before and after AS2O3 treatment.Meanwhile growth inhibition and apoptosis of MM cells were determined by flow cytometry.Results Hypermethylation of SOCS-1 gene was observed in each MM cell line compared with wide type.After exposure to AS2O3,it was shown that SOCS-1 gene was demethylated obviously,meanwhile the expression level of P-STAT3 protein and cell proliferation was inhibited significantly in each cell line.The apoptosis rate was increased.When U266 and CZ-1 were treated with AS2O3 of 0,0.5,1.0,2.0 μmol/L respectively,the total cell apoptosisis ratio of U266 was 0.06％,0.56％,48.96％,61.07％ (X2 =9.19,P ＜ 0.05); and the total cell apoptosisis ratio of CZ-1 was 4.2％,,40.3％,,47.72％,,68.49％ (X2 =8.96,P ＜0.05 ).Conclusion AS2O3 could inhibit JAK/STAT signal transduction pathway by inducing SOCS-1 gene demethylation in MM cells which might be related to cell apoptosis.
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Objective To explore the significance of the suppressor of cytokine signaling-1 (SOCS-1)gene methylation in the genesis, development and prognosis of diffuse large B-cell lymphoma (DLBCL).Methods The methylation state of CpG island in SOCS-1 gene were detected by methylation-specific polymerase chain reaction (PCR) and the level of SOCS-1 gene was measured by the real-time PCR. The clinical data of 30 patients with DLBCL were collected, and according to the international prognosis index (IPI), they were divided into low risk group and high risk group. Results Aberrant methylation of SOCS-1 in 17 DLBCL patients (56.7 %) were positive, however, in control group aberrant methylation was negative(P ＜0.01).The methylation level of DLBCL patients with positive SOCS-1 methylation was higher than that of patients with negative (P ＜0.05). Combined with the clinical data, the positive rate of methylation in patients with high level of serum LDH or the numbers of extra-nodal lesions＞l were significantly higher than that in patients with normal LDH level or the numbers of extra-nodal lesions ≤ 1, respectively. Hence, the positive rate of methylation in the high risk group of DLBCL was higher than that in the low risk group (P ＜0.05). Conclusion There were aberrant methylations of the SOCS-1 gene in the patients with DLBCL. The methylations of SOCS-1 can silence the gene expression, which indicates that SOCS-1 and its methylations play some role on genesis and development of DLBCL and can evaluate the prognosis of the patients with DLBCL.
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Objective To explore the possible relationship between alteration of cell cycle and JAK/STAT3 signal transduction pathway inhibition induced by arsenic trioxide (As_2O_3,) in myeloma cell lines U266 and RPMI8226 in vitro. Methods Multiple myeloma cell lines U266 and RPMI8226 were used as in vitro models. The influence of AS_2O_3 on myeloma cells were evaluated by MTT assay and flow cytometry. Meanwhile, methylation specific PCR and Western blotting were employed to detect the methylation status of gene SOCS-1 and protein expression level of P-STAT3 in these cells after AS_2O_3 treatment. Results AS_2O_3 significantly inhibited the growth of U266 and RPMI8226 cells in a dose-dependent manner. Furthermore, cell cycle was arrested at G0/G1 phase with inhibition of protein expression level of P-STAT3 and SOCS-1 gene demethylation after exposure to As_2O_3 for 72 h( r = 0. 85, P < 0.05). Conclusion AS_2O_3 could induce the alteration of cell cycle which might be related to JAK/STAT3 signal transduction pathway inhibition and SOCS-1 demethylation in myeloma cell lines. The study puts forward a new idea of AS_2 O_3 treatment in multiple myeloma.
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Objective To investigate clinical signifieances of serum levels of vascular endothelial growth factor (VEGF) in patients with diffuse large B-cell lymphoma (DLBCL) and to analyze the relationships with international prognostic index (IPI). Methods Serum levels of VEGF were measured by ELISA in 26 cases with newly diagnosed DLBCL and 9 cases with relapsed DLBCL. The clinical data of 26 patients were collected. According to the IPI, 26 patients were divided into two group: low risk group (IPI＜2) and moderate to high risk group (IPI≥2). Results Compared with the normal controls, newly diagnosed and relapsed DLBCL had significantly higher VEGF serum levels (P ＜0.01). In the patients responding to CHOP or RCHOP regimen a significantly decrease in VEGF serum levels occurred, while in the patients who did not achieve complete remission(CR) there was no significant decrease. Furthermore, pretreatment serum levels of VEGF were significantly lower in CR group than in partial remission (PR) and no remission (NR) group. In addition, serum levels of VEGF were significantly elevated in the high risk group than those at the low risk group(P＜0.01). Conclusion The serum levels of angiogenic factor VEGF are related to the development and progression of DLBCL. The VEGF combined with IPI can be used for evaluating the prognosis of DLBCL.