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Objective@#To evaluate the impact of KIT D816 mutation on the salvage therapy in relapsed acute myeloid leukemia (AML) with t(8;21) translocation. @*Method@#The characteristics of the first relapsed AML with t(8;21) translocation from 10 hospitals were retrospectively collected, complete remission (CR2) rate after one course salvage chemotherapy and the relationship between KIT mutation and CR2 rate was analyzed. @*Results@#68 cases were enrolled in this study, and 30 cases (44.1%) achieved CR2. All patients received KIT mutation detection, and KIT D816 mutation was identified in 26 cases. The KIT D816 positive group had significantly lower CR2 compared with non-KIT D816 group (23.1% vs 57.1%, χ2=7.559, P=0.006), and patients with longer CR1 duration achieved significantly higher CR2 than those with CR1 duration less than 12 months (74.1% vs 31.9%, χ2=9.192, P=0.002). KIT D816 mutation was tightly related to shorter CR1 duration. No significant difference of 2 years post relapse survival was observed between KIT D816 mutation and non-KIT D816 mutation group. @*Conclusion@#KIT D816 mutation at diagnosis was an adverse factor on the salvage therapy in relapsed AML with t(8;21) translocation, significantly related to shorter CR1 duration, and can be used for prediction of salvage therapy response. KIT D816 mutation could guide the decision-making of salvage therapy in relapsed AML with t(8;21) translocation.
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Objective@#To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m2, 10 mg/m2 or 12 mg/m2 as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) .@*Methods@#A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m2) as induction chemotherapy in newly diagnosed patients of adult AML.@*Results@#Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m2 group, IDA 10 mg/m2 group and IDA 12 mg/m2 group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m2 group and IDA 12 mg/m2 group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m2 group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m2 was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m2 when compared with the IDA 8 mg/m2 was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×109/L in IDA 8 mg/m2 group, IDA 10 mg/m2 group and IDA 12 mg/m2 group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×109/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) .@*Conclusions@#For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m2 is clinically superior to IDA 8 mg/m2 and IDA 12 mg/m2 in favorable intermediate AML subgroup. However, idarubicin 12 mg/m2 is more suitable to adverse AML subgroup.
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Objective@#To evaluate efficacy of the BiRd regimen, a combination of clarithromycin, lenalidomide, and dexamethasone, in the treatment of patients with relapsed/refractory multiple myeloma (RRMM) .@*Methods@#Patients with RRMM treated with BiRd between September 11, 2013 and August 1, 2016 at six centers were included to evaluate overall survival rate (ORR) , clinical benefit rate (CBR) , progression-free survival (PFS) , overall survival (OS) , as well as adverse events.@*Results@#Of 30 patients with RRMM, 27 patients were evaluable, and ORR and CBR were 51.9% (14/27) and 66.7% (18/27) respectively, including 1 sCR (3.7%) , 3 CR (11.1%) , 3 VGPR (11.1%) , and 7 PR (25.6%) . In 13 patients with prior Rd, ORR and CBR were 38.5% (5/13) and 61.5% (8/13) respectively, of which 5 patients with ≥MR carried high-risk cytogenetic[ (e.g.17p- or t (4;14) ] together with at least one of other adverse-prognostic cytogenetic (e.g.13q- and/or 1q21+) . In 24 patients with prior bortezomib-based therapy, ORR and CBR were 45.8 and 62.5%, respectively. With a median follow-up time of 14.9 (range 1.0-33.8) months, the median PFS and OS were 12.0 (95%CI 11.6-12.4) and 27.6 (95%CI 15.1-40.1) months, respectively. The BiRd regimen was well tolerated.@*Conclusion@#The BiRd regimen is an effective and safety protocol for RRMM, including those carrying high-risk cytogenetic markers.
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Objective To evaluate the efficacy and safety of lenalidomide in a real-world clinical practice in Chinese patients with multiple myeloma (MM).Methods It was a prospective,multi-center,observational study.A total of 165 consecutive patients with MM treated with lenalidomide-based regimens were enrolled in 12 hospitals from June 2013 to November 2015.Relevant information was recorded,such as baseline clinical data,cytogenetic abnormalities,treatment regimens,and duration of treatment,safety,and survival.Results (1)There were 126 relapsed and refractory MM (RRMM) patients,25 newly diagnosed patients and 19 maintenance patients.The evaluable RRMM patients accounted for 120 cases,among which 74 cases(61.7％) reached the partial response (PR) or above,and a very good partial response (VGPR) in 16 patients (13.3％),a complete response (CR) in 14 cases (11.7％),a strictly complete response (sCR) in 4 cases (3.3％).Thus,a VGPR or above in 34 patients accounted for 28.3％.(2)The median follow-up was 13 months,the median time to progression 12 months.The median survival after receiving lenalidomide was 19 months,and the median overall survival (OS) was 62 months.(3) The univariate analysis in 120 RRMM patients suggested that prognostic factors for significant improvement in PFS included normal karyotype,international staging system (ISS) Ⅰ-Ⅱ,t(4;14) negative (detected by fluorescence in situ hybridization),non-bortezomib resistance and response to previous regimens.As to OS,nonbortezomib resistance,response to previous regimens and non-primary refractoriness were positive factors.Multivariate analysis showed that the response to previous regimens (PR or better) was an independent good prognostic factor for progress-free survival (PFS),non-bortezomib resistance and non-primary refractoriness for OS.(4) Grade 3 or 4 adverse events that occurred in more than 10％ of all enrolled patients were neutropenia (12.7％),leukocytosis (11.5％) and thrombocytopenia (12.7％).Owing to intolerance of toxic side effects,7 cases withdrew lenalidomide.Conclusions No matter what combination,regimens containing lenalidomide are effective to RRMM patients with overall response rate 61.7％,a time to progression 12 months and an overall survival 62 months.The toxicity is quite tolerable and manageable.In addition,the response to previous treatment (reached PR or above) is the independent good prognostic factor for PFS,non-bortezomib resistance and non-primary refractoriness for OS.Clinical trail registration Clinicaltrials.gov,NCT01947309
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Objective To explore the clinical efficacy and complications of transoral endoscopic peroral endo﹣scopic myotomy (POEM) for achalasia (AC). Methods 38 patients with AC received POEM treatment from January 2013 to January 2013 in our digestive endoscopy center. Procedure-related complications and gastroesophageal re﹣flux were observed, and ECKARDT score and the lower esophageal sphincter pressure changes were analysed. Results All patients underwent POEM successfully. No serious POEM-related complications were observed, bleed﹣ing, gas related complications were treated successfully by conservative treatment. Postoperative follow-up time was 10.4 months (range 9 to 12 months), the symptoms of all the patients were alleviated, ECKARDT score average from preoperative 8.7 points dropped to postoperative 1.2 points (P<0.01), esophageal sphincter pressure decreased sig﹣nificantly, mean pressure dropped from preoperative (33.40 ± 11.80) mmHg to postoperative (13.50 ± 4.30) mmHg (P< 0.01) and gas related complications occurred in 6 cases (15.78 %), esophageal reflux occurred rate total was 23.68%(9/38). Conclusion POEM is safe and effective for the treatment of AC, and has better long-term effect.
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Objective To evaluate the safety and efficacy of endoscopic implantation of self-expandable metallic stent (SEMs) for malignant colorectal obstruction. Methods A total of 108 patients who had undergone endoscopic SEMs implantation for malignant colonic obstruction from January 2011 to May 2014 were enrolled. The clinical suc-cess rates and the complications were reviewed. Results The clinical success rates were 92.59%(100/108). Abdomi-nal pain, perforation and bleeding were the most common post-procedure complications, the rates of which were 16.67% (18/108), 7.41% (8/108), 6.48% (7/108), respectively. The abdominal pain in most patients was self-reliev-ing except for 6 patients with perforation of colon. Patients with perforation were cured by emergency surgery. The 7 patients developing bleeding recovered themselves. Conclusion The success rate of endoscopic SEMs implantation is satisfactory in the study. As a bridge to surgery or a palliative care method, endoscopic SEMs implantation is effec-tive and safe for malignant colorectal obstruction.
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Objective To study the effects of bortezomib on the expression of NF-κB, IκB and P-gp of drug-resistant K562 cells induced by daunorubicin (K562/DNR), to explore the molecular mechanism of drug-resistant reverse. Methods The expression of NF-κB, IκB and P-gp in K562/DNR cells were detected when the cells had been treated with 100 μg/ml DNR only or together with 4 μg/L bortezomib for 12 h, 24 h and 36 h. The apoptosis rates were detected in each group respectively and the activity of NF-κB was detected by ELISA method. Results Compared with the control group, the expressions of NF-κB and P-gp in K562/DNR could be increased and IκB was decreased after being treated with DNR. When K562/DNR were cultured with bortezomib, the expressions of NF-κB and P-gp induced by DNR were significantly suppressed and IκB was increased. The activity of NF-κB were detected in different time points: (15.3±1.87) %[(23.8± 2.27) % in DNR group] at 12 h, (10.2±1.69) % [(25.4±1.98) % in DNR group] at 24 h, (6.08±2.53) % [(26.9±2.58) % in DNR group] at 36 h. There were a significant differences between DNR group and DNR+PS-341group. The apoptosis rates were increased in DNR+PS-341 group at different time points than those in DNRgroup, (35.23±5.15) % [(15.56±4.12) % in DNR group] at 12 h, (40.26±6.89) % [(17.25±2.89) % in DNR group] at 24 h, (43.58±7.69) % [(22.47±4.58) % in DNR group] at 36 h. The effccts showed the character of time-dependent pattern. Conclusion Bortezomib could downregulate the expressions of NF-κB and P-gp in K562/DNR, reverse the drug resistance and up-regulate the apoptotic rates in K562/DNR cells.
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Objective To investigate the effect of Helicobacter pylori infection on cell proliferation and apoptosis of gastric cancer cell line SGC 7901. Method SGC 7901 cells were incubated with 1 × 108,5 × 107,1 × 107,5 × 106 cfu / ml concentration gradient of the standard HP NCTC 11637 strains in vitro. Morphological changes of cells were observed at 24, 48, 72 hour, respectively. Cell proliferation inhibition rate were detected with MTT assay. Apoptosis were observed by flow eytometry and TUNEL analysis, mRNA expression of survivin were detected by RT-PCR, and survivin expression were determined by western blot. Results Cell proliferation inhibition rate was 54.5%, 58.9%, 67.6%, 72.9% with 1 × 108,5 × 107, 1 × 107,5 × 106 cfu / ml concentration gradient of the HP bacteria on the role of SGC 7901 cells at 72h, respectively. The rate of apoptosis after 72h detected by flow cytometry and TUNEL with HP concentration gradient of different bacteria were 42.51%, 45.67%,48.57%, 49.51% and 54.61%, 51.26%, 59.41%, 62.46.% Helieobacter pylori could significantly reduce mRNA and protein expression of survivin. These effects were strengthened as the concentration of Helicobacter pylori increased and the time extended. Conclusion H. Pylori infection may be through reducing the expression of survivin to inhibit cell proliferation and pro-mote apoptosis of SGC 7901 in vitro. Moreover, this effect was positive related with time and dose.
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Objective To understand the effect of curcumin and TSA on c-myc gene expression in human gastric cancer and to explore the dynamic balance of the histone acetylation / deacetylation in gene expression in gastric cancer and the significance of the regulation. Methods Gastric cancer cell line SGC-7901 and MGC803 were cultured,and then different concentrations of histone acetylase inhibitors curcumin and histone deacetylase inhibitor TSA were added,respectively.mRNA of c-myc expression wasdetected by RT-PCR. Results With increasing of the concentration of curcumin and redcuing of the TSA concentrations c-myc expression was inhibited (P