[show abstract][hide abstract] ABSTRACT: To study the mechanisms in gambogic acid (GA) -induced JeKo-1 human Mantle Cell Lymphoma cell apoptosis in vitro.
The proliferation of GA-treated JeKo-1 cells was measured by CCK-8 assay and Ki-67 immunocytochemical detection. Apoptosis, cell cycle and mitochondrial membrane potential were measured by flow cytometric analysis. Caspase-3, -8 and -9 were detected by colorimetric assay. Bcl-2 and Bax were analyzed by Western blotting.
GA inhibited cell growth in a time- and dose- dependent manner. GA induces apoptosis in JeKo-1 cells but not in normal bone marrow cells, which was involved in reducing the membrane potential of mitochondria, activating caspases-3, -8 and -9 and decreasing the ratio of Bcl-2 and Bax without cell cycle arresting.
GA induced apoptosis in human MCL JeKo-1 cells by regulating Bcl-2/Bax and activating caspase-3, -8 and -9 via mitochondrial pathway without affecting cell cycle.
Chinese Journal of Cancer Research 04/2013; 25(2):183-191. · 0.45 Impact Factor
[show abstract][hide abstract] ABSTRACT: To date, case-control studies on the association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and follicular lymphoma have provided controversial results. To clarify the effect of MTHFR polymorphisms on the risk of follicular lymphoma, a meta-analysis of all case-control studies was performed. The fixed effects and random effects model showed that the C677T polymorphism was associated with a risk of follicular lymphoma among Caucasian populations, and A1298C polymorphism was associated with a risk of follicular lymphoma among Asian populations. Our pooled data suggest evidence for a major role of MTHFR polymorphisms in the carcinogenesis of follicular lymphoma.
[show abstract][hide abstract] ABSTRACT: To determine whether the use of idarubicin+cytarabine (IA) is more effective than the use of daunorubicin+cytarabine (DA) as induction chemotherapy for patients with newly diagnosed acute myeloid leukaemia.
A computer-based search was performed. Randomised trials comparing IA with DA as induction therapy for newly diagnosed AML were included in this meta-analysis. The primary outcome of interest for our analysis was survival (disease-free survival, event-free survival and overall survival); the secondary endpoint was complete remission.
Ten trials with 4,060 patients were eligible for this meta-analysis. Our pooled results suggest that IA is associated with a significant advantage in CR (RR = 1·23; 95% CI = 1·07-1·41, p = 0.004), EFS (HR = 0·64; 95% CI = 0·45-0·91, p = 0.013), and OS (HR = 0·88; 95% CI = 0·81-0·95, p = 0.02) but not in DFS (HR = 0·90; 95% CI = 0·80-1·00, p = 0.06). In the subgroup analysis, age had a significant interaction with OS and CR benefits.
Our analysis indicated that IA could improve the duration of overall survival compared to DA as induction therapy for young patients with newly diagnosed AML. Further study is needed to determine whether IA can produce clinical benefits in selected genetic or molecular subgroups of young AML patients.
PLoS ONE 01/2013; 8(4):e60699. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Autologous hematopoietic stem cell transplantation (AHSCT) has been tested for the treatment of patients with newly-diagnosed type 1 diabetes (1, 2), we reported here our experience with a young man who developed diabetic ketoacidosis (DKA) with coma at onset of the disease and achieved clinical remission by the regimen of AHSCT.
[show abstract][hide abstract] ABSTRACT: The aim of this study was to investigate the apoptosis-inducing effect of gambogic acid (GA) on Jurkat cells and its underlying signaling pathway. Apoptosis induced by GA and some inhibitors was assayed by Annexin V/PI doubling staining. The levels of caspase 3, caspase 8 and caspase 9 activated in living Jurkat cells were measured by flow cytometry. The expressions of caspase 3, caspase 9, p-JNK and P38 were detected by Western blot. The results showed that GA induced apoptosis of Jurkat cells in a dose-dependent manner. The positive cell number of activated caspase 3, caspase 8, caspase 9 and the levels of activated caspase 3, caspase 9, p-JNK, P38 increased after Jurkat cells were treated with GA. ROS, CaMKII, caspase 3, caspase 9, MAPKK, JNK1/2 and P38 inhibitors had some significant effect on GA-induced apoptosis. ROS, CaMKII, MAPKK, JNK1/2 and P38 inhibitors decreased the levels of activated caspase 3, caspase 9 by GA.ROS, CaMKII, MAPKK, JNK1/2 inhibitors decreased the levels of p-JNK by GA. ROS, CaMKII, MAPKK, P38 inhibitors decreased the levels of P38 by GA. It is concluded that GA induced apoptosis of Jurkat cells by activated caspases through activating of ROS-CaMKII-MAPKK-JNK/P38 pathway.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 06/2012; 20(3):587-91.
[show abstract][hide abstract] ABSTRACT: Autologous hematopoietic stem cell transplantation (AHSCT) has the potential to induce clinical remission in patients with newly diagnosed type 1 diabetes.
The objective of the study was to examine the impact of AHSCT on lymphocytes and pancreatic β-cell function.
This was a nonrandomized, open-label prospective study.
Thirteen patients with new onset of type 1 diabetes, 10 of them with diabetic ketoacidosis, were subjected to AHSCT with cryopreserved CD34(+) progenitor cells and followed up for 31-54 months.
The numbers of different subsets of lymphocytes and the levels of serum cytokines, islet antibodies, C-peptide, and plasma glycosylated hemoglobin were longitudinally measured.
The numbers of different subsets of lymphocytes, except for CD8(+) T cells, in the patients before AHSCT were significantly lower than those in controls. However, all lymphocytes gradually recovered after AHSCT, accompanied by decreased levels of serum autoantibodies, IL-1, IL-17, and TNF-α. After AHSCT, 11 of 13 patients required significantly reduced doses of insulin for adequate glycemic control, accompanied by reduced levels of glycosylated hemoglobin but increased C-peptide concentrations. Three patients achieved exogenous insulin independence for 7-54 months. The survival of remaining β-cells was associated positively with the preexisting β-cell function but negatively with preexisting autoantibodies (P < 0.05). The numbers of infused CD34(+) cells were positively correlated with the concentrations of serum IL-10, IL-4, TGF-β, and fasting C-peptide but negatively correlated with the levels of serum TNF-α and insulin doses after AHSCT (P < 0.05).
AHSCT modulated lymphocytes and preserved β-cell function in Chinese patients with new onset of type 1 diabetes and diabetic ketoacidosis.
The Journal of clinical endocrinology and metabolism 03/2012; 97(5):1729-36. · 6.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: Several trials have generated conflicting results about the results of high-dose chemotherapy followed by autologous stem cell transplantation (HDCT) for primary breast cancer. This meta-analysis summarizes the available evidence from all suitable studies.
Prospective, randomized trials with HDCT as a first-line therapy for primary breast cancer were included in this meta-analysis. The primary outcome of interest for our analysis was survival (disease-free survival and overall survival); secondary endpoints included treatment-related mortality (TRM) and second (non-breast) cancers. We used a median age of 47, a PR positive rate of 50% and a premenopausal rate of 70% as cutoff values to complete the subgroup analyses, which were pre-planned according to the prepared protocol.
Fourteen trials with 5747 patients were eligible for the meta-analysis. Compared with non-HDCT, non-significant second (non-breast) cancers (RR = 1.28; 95% CI = 0.82-1.98) and higher TRM (RR = 3.42; 95% CI = 1.32-8.86) were associated with HDCT for primary breast cancer. A significant DFS benefit of HDCT was documented (HR = 0.89; 95% CI = 0.79-0.99). No difference in OS (overall survival) was found when the studies were pooled (HR = 0.91; 95% CI = 0.82-1.00, p = 0.062). In subgroup analysis, age and hormone receptor status had a significant interaction with prolonged DFS and OS.
HDCT has a benefit on DFS and OS compared to SDC in some special patients with high-risk primary breast cancer.
PLoS ONE 01/2012; 7(3):e33388. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Autologous haematopoietic stem cell transplantation (AHSCT) is a promising treatment for multiple sclerosis (MS) patients who have not adequately responded to conventional therapies. We retrospectively evaluated the safety and long-term clinical outcome of AHSCT in MS patients in China. Twenty-five patients with various types of MS were treated with AHSCT. Peripheral blood stem cells were derived by leukapheresis after mobilized with granulocyte colony-stimulating factor. Then CD34+ cell selection of the graft was performed and anti-thymocyte globulin was given for T-cell depletion, with the conditioning regimen BEAM adopted and early and late toxicities recorded. Long-term responses were evaluated by the expanded disability status scale (EDSS), progression-free survival and gadolinium-enhanced magnetic resonance imaging scans. 10, 7 and 8 patients experienced neurological improvement, stabilization and progression, respectively. The median EDSS scores observed over 1-year follow-up after transplantation (5.5-7.0) were consistently lower than the baseline (8.0). The progression-free survival rate was 74, 65 and 48% at 3, 6 and 9 years post-transplant. 58% cases (7/12) had active lesions at baseline and all turned to inactive status in the years of follow-up. 25% cases (3/12) experienced progression after transplantation but had no active lesions in MRI over the whole follow-up period. 17% cases (2/12) without active lesions at baseline progressed active lesions in MRI. The major early toxicity resulted in fever and late toxicity caused transplantation-related mortality due to severe pneumonia and varicella-zoster virus hepatitis, respectively. AHSCT is a feasible treatment for severe MS and its long-term efficacy is favorable.
[show abstract][hide abstract] ABSTRACT: To study the relationship between polymorphism of genes XPA, XPC, XPD, XRCC1 and susceptibility to acute lymphoblastic leukemia (ALL) in a Chinese population.
Polymorphism were determined by a case-control study through matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry method of Mass-ASSAY platform in 114 confirmed ALL cases and 169 age- and sex-matched controls, so as to compare the relationship between different genotypes and ALL risk.
Multivariate logistic regression analysis revealed that individuals carrying at least one 23G variant allele (AG/GG genotypes) had a significantly increased risk for ALL (adjusted OR 2.02; 95%CI 1.08 - 3.78) compared with the wild-type genotype (23AA), and evidence that positive interactions between the polymorphisms in XPC C499T and XPA A23G might occur. Furthermore, individuals with both putative risk genotypes had a significantly higher risk (adjusted OR 5.60; 95%CI 1.57 - 19.90), compared with those with both wild-genotypes. By contrast, no significant association was observed between the XPD T751G, XRCC1 G399A, C194T polymorphism and ALL risk.
XPA A23G and XPC C499T polymorphism may contribute to the risk of developing ALL. There are significant combinations between XPC C499T and XPA A23G.
Zhonghua nei ke za zhi [Chinese journal of internal medicine] 10/2011; 50(10):859-62.
[show abstract][hide abstract] ABSTRACT: Previous evaluation of intracoronary autologous bone marrow-derived stem cell (BMSCs) therapy following ischemic heart disease (IHD) suggested improvement of cardiac functional parameters. We performed a meta-analysis to provide systematic assessment of the safety and efficacy of direct (intramyocardial or endomyocardial) BMSCs transplantation in patients with IHD.
Randomized controlled Trials (RCTs) were identified in the MEDLINE (approximately Oct. 2010), the Cochrane Central Register of Controlled Trials (Central) (approximately Oct. 2010), EMBASE (approximately Oct. 2010), and EBSCO (approximately Oct. 2010), reviews, and reference lists of relevant articles. Weighted mean difference (WMD) was calculated for changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic volumes (LVEDV and LVESV) by using a fixed effects model.
Eight RCTs with 307 participants were eligible. Compared with controls, direct BMSCs transplantation improved LVEF (8.4%, 95% CI, 6.49 to 10.31%; p < 0.01), reduced LVESV and LVEDV (-14.85 ml, 95% CI, -27.29 to -2.41 ml, p = 0.02 and -12.79 ml, 95% CI, -24.94 to -0.65 ml, p = 0.04, respectively).
This meta-analysis suggests that direct BMSCs transplantation is associated with moderate but significant improvements over regular therapy in cardiac functional parameters in patients with IHD, and supports conducting further RCTs of a higher quality.
[show abstract][hide abstract] ABSTRACT: Hematopoietic stem cell transplantation (HSCT) has been proposed as a novel therapy for multiple sclerosis (MS). CD4 + CD25 + regulatory T cells (Tregs) expressing Foxp3 play an important role in the maintenance of immune tolerance to self. Our study was conducted to confirm the efficiency of nonmyeloablative conditioning and syngeneic bone marrow transplantation (BMT) on experimental autoimmune encephalomyelitis (EAE) mice and to determine whether Tregs plays a role in the underlying mechanism.
EAE were induced in C57BL/6 mice and were randomly divided into 4 groups: the Conditioning group received the conditioning regimen, the Normal-EAE BMT group received conditioning and bone marrow (BM) grafts from normal mice, the EAE-EAE BMT group received conditioning and BM grafts from EAE mice and the EAE control group received no further therapy. The cumulative clinical score was used to assess the efficacy of the different treatments, and the proportion of Tregs in the spleen was measured by flow cytometry on day 40, 80 and 120 after BMT. Foxp3 mRNA expression was assessed by real-time PCR, and the expression of Foxp3 protein was tested by western blot on day 120 after BMT.
Conditioning and conditioning with BMT led to a significant clinical improvement on day 80 after BMT compared with EAE without further treatment. On day 120 after BMT, the clinical score of the Conditioning group showed no significant difference from that of the EAE control group, whereas BMT led to a further amelioration of the disease score. On day 80 and day 120 after BMT, the proportions of Tregs of the two BMT groups were significantly higher than that in EAE control group, whereas no statistically significant difference was found between the Conditioning group and the EAE control group. On day 120 after BMT, the Foxp3 mRNA level and Foxp3 protein expression was higher in the two BMT groups than in EAE control group or Conditioning group.
Nonmyeloablative conditioning could temporarily reverse already established EAE, but it was not sufficient for the induction of long-term EAE remission. Transplantation by BM cells from healthy or diseased donors was necessary and responsible for complete and long-time remission of EAE, and these beneficial effects may be the result of the induction of Tregs and the Treg-related factor Foxp3.
Restorative neurology and neuroscience 01/2011; 29(3):177-85. · 2.93 Impact Factor
[show abstract][hide abstract] ABSTRACT: To date, case-control studies on the association between methylenetetrahydrofolate reductase (MTHFR) C677T and childhood acute lymphoblastic leukemia have provided either controversial or inconclusive results. To clarify the effect of MTHFR C677T on the risk of childhood acute lymphoblastic leukemia, a meta-analysis of all case-control observational studies was performed. Heterogeneity (I(2)=65%, P<0.0001) for C677T among the studies was extreme. The random effects (RE) model showed that the 677T allele was not associated with a decreased susceptibility risk of childhood acute lymphoblastic leukemia compared with the C allele [OR=0.96, 95% confidence interval (CI) (0.88-1.04), P=0.34]. The contrast of homozygotes, recessive model and dominant model produced the same pattern of results as the allele contrast. Although MTHFR C677T was associated with increased risks of colorectal cancer, leukemia, and gastric cancer, our pooled data suggest no evidence for a major role of MTHFR C677T in the carcinogenesis of childhood acute lymphoblastic leukemia.
Leukemia research 12/2010; 34(12):1596-600. · 2.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: The effect of unrelated donor bone marrow transplantation (UBMT) and unrelated donor cord blood transplantation (UCBT) on the outcome of patients with hematological diseases remains controversial. We conducted a meta-analysis using data from controlled clinical trials comparing UCBT to UBMT in patients undergoing hematopoietic stem cell transplantation. Pooled comparisons of studies of UCBT and UBMT in children found that the incidence of chronic graft-versus-host disease (GVHD) was lower with UCBT (relative risk [RR]=0.41; 95% confidence interval [CI] (0.25, 0.68)), and the incidence of grades II-IV aGVHD was also significantly different (RR=0.69; 95% CI (0.55, 0.86)). The incidence of relapse was also lower with UCBT (RR=0.72; 95% CI (0.59, 0.87)). There was no difference in OS in children when studies were pooled (Hazard ratio [HR]=1.25; 95% CI (0.87, 1.78)). For adults, OS (HR=1.26; 95% CI (1.13, 1.40)) was statistically different. Thus, UCBT led to inferior outcomes than UBMT in adults.
Leukemia research 08/2010; 34(8):1018-22. · 2.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: Randomized controlled trials (RCTs) have reported conflicting results on the impact of high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT) as the first-line treatment for patients with aggressive non-Hodgkin lymphoma (NHL). We performed a systematic meta-analysis to assess the efficacy of HDCT compared to conventional chemotherapy in patients with aggressive NHL with regard to overall survival (OS) at 3 years. We gathered the data for our analysis from MEDLINE, EMBASE, Cochrane controlled trials register, Cochrane Library, and Science Citation Index (1/1990 to 11/2008) searches. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the random effect model. Fourteen RCTs were identified that were published in full text and included a total of 2,413 patients. There was evidence that HDCT showed decreased OS (HR 1.20, 95% CI 1.05-1.37, P=0.006) at 3 years when compared with conventional chemotherapy. The variation in OS probabilities between studies was not statistically significant (test for heterogeneity, Q=10.14, df=13, P=0.683). Thus, our meta-analysis showed that HDCT in aggressive non-Hodgkin lymphoma had decreased overall survival outcome compared with conventional chemotherapy.
Medical Oncology 04/2010; 28(3):822-8. · 2.14 Impact Factor
[show abstract][hide abstract] ABSTRACT: To explore the profiles of Th1, Th2, Th17 and Regulatory T (Treg) cells in patients with chronic idiopathic thrombocytopenic purpura (ITP).
Samples of peripheral blood were collected from 35 chronic ITP patients (21 in an active stage group, 5 in a non-remission stage group, 9 in a remission stage group) and also from 18 healthy subjects. Flow cytometry was used to measure the intracellular cytokines interferon (IFN)gamma, interleukin (IL)-4 and IL-17 so as to identify the Th1, Th2 and IL-17 cells. Treg cells were identified with CD(4)(+) CD(25)(+) Foxp3(+) cells and uncultured peripheral blood was used to measure the CD(4)(+) CD(+)(25) Foxp3(+) cells with flow cytometry. The concentrations of IFNgamma, IL-4, IL-17 and IL-10 in plasma specimens were detected with ELISA method and its correlation with peripheral platelets counts and megakaryocytes number was analyzed, respectively.
There were no statistically significant differences between any two of the three groups for the percentage of Th1 cells, Th17 cells and Th1/Th17 ratio. The percentage of Th2 cells was (1.01 +/- 0.88)% in active stage and (1.22 +/- 1.04)% in non-remission stage, being significantly decreased than those in remission stage (1.93 +/- 1.04)% (P < 0.05) and the controls (1.86 +/- 0.59)% (P < 0.05). Th1/Th2 ratio was 15.04 +/- 9.67 in active stage, 11.65 +/- 9.32 in non-remission stage, which were significantly higher than those in remission stage (7.17 +/- 5.38, P < 0.05) and the controls (7.02 +/- 3.01, P < 0.05). The percentage of Treg cells was (0.89 +/- 0.58)% in active stage and (1.46 +/- 1.27)% in non-remission stage, being significantly decreased than those in remission stage (6.41 +/- 1.86)% (P < 0.01) and the control (5.73 +/- 0.71)% (P < 0.01). There was no statistic difference between any two of the three groups for plasma IFNgamma and IL-17 level. The plasma IL-4 level was (2.25 +/- 2.05) ng/L in active stage and (2.33 +/- 2.14) ng/L in non-remission stage, being significantly decreased than those in remission stage (6.00 +/- 4.57) ng/L (P < 0.05) and the controls (5.54 +/- 4.00) ng/L (P < 0.05). The plasma IL-10 level was (5.07 +/- 4.10) ng/L in active stage and (5.66 +/- 4.35) ng/L in non-remission stage, being significantly decreased than those in remission stage (10.92 +/- 6.17) ng/L (P < 0.01) and the controls (14.21 +/- 7.31) ng/L (P < 0.01). The plasma level of IL-10 in patients in active stage was positively related to the platelet counts (r = 0.16, P = 0.03).
Deficiency of Treg cells might be one of mechanisms that cause immune regulation dysfunction in chronic ITP. Th17 cells might not play a role in the development of chronic ITP.
Zhonghua nei ke za zhi [Chinese journal of internal medicine] 03/2010; 49(3):213-6.
[show abstract][hide abstract] ABSTRACT: Molecular analyses such as fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) are demanded to improve diagnostic accuracy in addition to immunohistopathology of bone marrow (BM) trephine specimens. Conventional BM embedding method needs decalcification, and its procedure may impair tissue morphology and DNA quality. Here, we report an undecalcified method by which glycol methacrylate resin is polymerized at low temperature (4°C). Using this method, BM enzyme activity and antigenic determinants are well preserved, and moreover, DNA extracted from plastic embedding sections is suitable for PCR amplification and sequencing, FISH analysis can be well done because of the DNA integrity of BM sections. If working with BM trephine specimen, our protocol offers the possibility to combine superior morphology with modern molecular analysis.
Microscopy Research and Technique 03/2010; 73(11):1067-71. · 1.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: Treatment with autologous bone marrow transplantation (ABMT) can change the natural history of diabetes in patients with new-onset Type 1 diabetes (T1D). Effects of syngeneic bone marrow transplantation (syn-BMT) on diabetic nephropathy were studied in streptozotocin-induced diabetic mice. Diabetic mice received sibling's bone marrow on days 3, 10, 20, or 40 after T1D onset, respectively. Renal pathology, levels of oxidative stress, and the expressions of angiotensinogen (AGT), monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor beta 1 (Tgf-beta1) mRNA were investigated. Treatment with syn-BMT when disease was early-onset reduced mesangial area expansion and kidney enlargement; besides, if it is given on day 10, syn-BMT attenuated glomerular hypertrophy. Oxidative stress factors such as catalase (CAT) and superoxide radical anion O(2-) (O(2-)) were markedly maintained by syn-BMT compared to mice without treatment. In diabetic mice without treatment, renal AGT and MCP-1 mRNA were increased, while they were effectively suppressed by syn-BMT. But it showed no changes or even increment in Tgf-beta1 mRNA after syn-BMT. Syn-BMT, if applied when disease was early-onset, ameliorated diabetic renal injury. These preventive effects could be partly via maintaining oxidative stress and expression of AGT and MCP-1 in kidney in streptozotocin-diabetic mice.
[show abstract][hide abstract] ABSTRACT: For those patients who are not candidates for allogeneic stem cell transplantation (SCT) or who do not have an HLA-matched donor, it is unclear whether consolidation therapy with autologous SCT results in a survival benefit compared with further intensive post-remission non-myeloablative chemotherapy or no further therapy.
A meta-analysis evaluating autologous SCT versus further chemotherapy or no treatment for acute myeloid leukemia (AML) in first complete remission (CR1) was completed. The search used the following combined search terms in Medline, Embase, the Cochrane Controlled Trials Register, the Cochrane Library, the Web of Science and the China National Knowledge Infrastructure.
Overall, 13 studies of 12 randomized controlled trials were identified. Four studies were in pediatric patients and 9 were in adults. For adults, AML in CR1 compared with non-SCT, lower relapse and higher transplantation-related mortality were associated with autologous SCT, a significant disease-free survival benefit of autologous SCT was documented, and there was no difference in overall survival when studies were pooled. For pediatric AML in CR1, there were no differences in relapse, transplantation-related mortality, disease-free survival and overall survival. Significantly less survival from relapse impairment was found for autologous SCT.
Our results support the conclusion that autologous SCT should not be considered as the first-line post-remission therapy for AML patients in CR1.
[show abstract][hide abstract] ABSTRACT: This study was aimed to investigate the apoptosis-inducing effect of gambogic acid (GA) on K562 cell line and its mechanism. The K562 cells were treated with GA at different concentrations and times, the inhibition rates were detected by MTT assay. Apoptosis induced by GA was assayed by Annexin-V/PI doubling staining. The influence of GA on cell cycle was studied by propidium iodide method. The mitochondrial membrane potential was measured by JC assay. The levels of caspase 3, caspase 8 and caspase 9 activated by fluorescein in living K562 cells were measured by caspGLOW(TM) fluorescein staining kit. The results showed that after incubation with GA, K562 cell proliferation was dramatically inhibited in concentration- and time-dependent manners. K562/A02 cells need higher GA concentration (> 2 microg/ml) to show antiproliferative effect, compared with that of K562 cells (> 0.5 microg/ml). Apoptosis could be induced by GA but the influence on cell cycle was not significant. GA could decrease the mitochondrial membrane potential and increase the activated caspase 3, caspase 8, caspase 9 positive cell levels by 2.19%, -1.95%, 34.01% in 24 hr and 60.4%, 71.3%, 77.7% in 48 hr respectively. It is concluded that the GA can significantly inhibit the proliferation of K562 cells without influence on cell cycles. The GA triggers K562 cell apoptosis through both intrinsic and extrinsic pathways.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 12/2009; 17(6):1443-7.
[show abstract][hide abstract] ABSTRACT: Antifungal prophylaxis using fluconazole or itraconazole has been studied for many years but still no consensus has been reached regarding their safety and effectiveness. We performed a systematic meta-analysis to assess the efficacy of fluconazole compared to itraconazole in neutropenic patients with hematological malignancies. We gathered the data for our analysis from MEDLINE, EMBASE, Cochrane-controlled trials register, Cochrane Library, and Science Citation Index (1/1990 to 1/2009) searches. Risk ratio (RR) and 95% confidence intervals (CIs) were calculated using the random effect model. Nine RCTs were identified that were published in full text. Significantly, fewer patients were withdrawn from the studies due to the development of adverse effects with fluconazole prophylaxis when compared with itraconazole (RR 0.45, 95% CI 0.27-0.75, P=0.002). There were statistically significant differences regarding fungal infections (RR 1.34, 95% CI 1.08-1.67, P=0.009) and invasive fungal infections (RR 1.33, 95% CI 1.02-1.73, P=0.03) between the two educations. There were no statistically significant differences regarding overall mortality (RR 0.95, 95% CI 0.77-1.17, P=0.64), fungal-related mortality (RR 1.28, 95% CI 0.80-2.07, P=0.31), and proven fungal infections (RR 1.38, 95% CI 0.75-2.53, P=0.30). The analysis of published evidence reveals that itraconazole administration resulted in significantly fewer episodes of fungal infections and invasive fungal infections compared with fluconazole.
Medical Oncology 10/2009; 27(4):1082-8. · 2.14 Impact Factor