Xingmei Cao

Mycophenolate mofetil as a treatment for refractory idiopathic thrombocytopenic purpura

AbstractAim:To determine whether mycophenolate mofetil (MMF) has beneficial effects on refractory idiopathic thrombocytopenic purpura (ITP) and the corresponding cellular mechanism.Methods:Twenty refractory ITP patients resistant to corticosteroid and/or splenectomy and chemical therapy were given MMF 1.5-2.0 g/d orally for a 2 to 4-month period. Serum immunoglobulin was detected by rate nephelometry. Platelet-associated antibodies (PAIgG) were assayed by enzyme-linked immunosorbant assay. The immunophenotypic analysis was performed on a flow cytometer and cell apoptosis was detected with transferase mediated dUTP biotin nick end labeling (TUNEL) method.Results:Sixteen of the 20 (80%) patients had responses to MMF treatment; 9 (45%) achieved a complete response, 4 (20%) achieved a partial response, and 3 (15%) achieved a minor response. The therapeutic effects were found to be better in male patients than female patients. The number of CD3+ peripheral blood cells (PBCs) and CD4+ PBCs increased and the number of CD8+ PBCs decreased. The plasma level of IgG, IgM, IgA and platelet associated IgG (PAIgG) decreased in 86% of the patients. TUNEL assay showed that mycophenolate acid (MPA) 0.1 mmol/L induced apoptosis of peripheral blood mononuclear cells isolated from refractory ITP patients. The apoptosis rate was increased in male patients after treatment with MPA, but was unchanged in female patients.Conclusion:Therapy for a period of 8 to 16 weeks with mediandose of MMF was valuable for the treatment of refractory ITP.

Role of IL-17A rs2275913 and IL-17F rs763780 polymorphisms in risk of cancer development: an updated meta-analysis

Single nucleotide polymorphisms (SNPs) in the interleukin-17 (IL-17) gene have been shown to be correlated with susceptibility to cancer. However, various studies report different results of this association. The aim of the present work was to clarify the effects of IL-17A G197A (rs2275913) and IL-17F T7488C (rs763780) polymorphisms on cancer risk. We performed systematic searches of the PubMed and CNKI databases to obtain relevant publications. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the association of rs2275913 and rs763780 polymorphisms with cancer risk. Data were extracted from the selected studies, and statistical analysis was conducted using the STATA software. Our results indicated that rs2275913 and rs763780 polymorphisms significantly increase cancer risk, especially in gastric cancers. Subgroup analysis suggested the existence of a significant correlation between rs763780 polymorphism and cancer susceptibility in Caucasian populations. This updated meta-analysis confirms that rs2275913 and rs763780 polymorphisms are highly associated with increased risk for multiple forms of cancer.

A novel multi‐epitope vaccine from MMSA‐1 and DKK1 for multiple myeloma immunotherapy

The identification of novel tumour‐associated antigens is urgently needed to improve the efficacy of immunotherapy for multiple myeloma (MM). In this study, we identified a membrane protein MMSA‐1 (multiple myeloma special antigen‐1) that was specifically expressed in MM and exhibited significantly positive correlation with MM. We then identified HLA‐A*0201‐restricted MMSA‐1 epitopes and tested their cytotoxic T lymphocyte (CTL) response. The MMSA‐1 epitope SLSLLTIYV vaccine was shown to induce an obvious CTL response in vitro. To improve the immunotherapy, we constructed a multi‐epitope peptide vaccine by combining epitopes derived from MMSA‐1 and Dickkopf‐1 (DKK1). The effector T cells induced by multi‐epitope peptide vaccine‐loaded dendritic cells lysed U266 cells more effectively than MMSA‐1/DKK1 single‐epitope vaccine. In myeloma‐bearing severe combined immunodeficient mice, the multi‐epitope vaccine improved the survival rate significantly compared with single‐epitope vaccine. Consistently, multi‐epitope vaccine decreased the tumour volume greatly and alleviated bone destruction. The frequencies of CD4+ and CD8+ T cells was significantly increased in mouse blood induced by the multi‐epitope vaccine, indicating that it inhibits myeloma growth by changing T cell subsets and alleviating immune paralysis. This study identified a novel peptide from MMSA‐1 and the multi‐epitope vaccine will be used to establish appropriate individualized therapy for MM.

Association of Vitamin D Receptor Cdx-2 Polymorphism With Cancer Risk: A Meta-Analysis.

AbstractVitamin D receptor (VDR) Cdx-2 polymorphism (rs11568820) has been indicated to be associated to cancer susceptibility. However, published studies reported mixed results. This meta-analysis was conducted to get a more accurate estimation of the association between Cdx-2 polymorphism and cancer risk.We identified 25 independent studies with a total of 34,018 subjects published prior to March 2015. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the susceptibility to cancer. Separate analyses were conducted on features of the population such as ethnicity, source of controls, and cancer types.Meta-analysis results showed that Cdx-2 polymorphism significantly increased cancer risk in the homozygous model in overall analysis. According to the further stratified analysis, significant association was found between Cdx-2 variant and cancer risk in American-Africans in the homozygous, recessive, and dominant comparison models. However, no significant associations were found in Caucasians and Asians. When stratified by different cancer types, significant association was observed between Cdx-2 variant and an increased risk of colorectal cancer in the homozygous, recessive, and dominant models. In addition, ovarian cancer susceptibility increased based on the homozygous and dominant comparison models.Our study indicated that VDR Cdx-2 polymorphism was associated with an increased cancer risk, particularly in American-Africans, colorectal, and ovarian cancers. However, other factors may impact on the association. Further multicenter studies are needed to confirm the effects of Cdx-2 polymorphism on cancer susceptibility.

Comparison of porcine anti‐human lymphocyte globulin and rabbit anti‐human thymocyte globulin in the treatment of severe aplastic anemia: a retrospective single‐center study

To compare the safety and efficacy of porcine antilymphocyte globulin (pALG) and rabbit antithymocyte globulin (rATG) in treating severe aplastic anemia (SAA).

Association Between Interleukin-10-3575T>A (rs1800890) Polymorphism and Cancer Risk

BACKGROUND Previous studies investigated the associations of interleukin-10 (IL-10) polymorphisms with different types of cancer, indicating an influence on cancer risk. IL-10-3575T>A (rs1800890) has been studied concerning a potential implication in terms of some cancer site risks, but the results from single studies are contradictory. METHODS Eligible articles were identified by a search of the PubMed, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) databases until November 30, 2014. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the cancer risk by cancer sites, ethnicity, and other study features. RESULTS We identified 15 published studies to research the link of the IL-10-3575T>A polymorphism with cancer risk. Our meta-analysis indicated that the IL-10-3575T>A polymorphism has a significant association with decreased melanoma risk in the heterozygote model (OR=0.67, 95% CI=0.49-0.92, p=0.02) and dominant model (OR=0.70, 95% CI=0.52-0.95, p=0.01), but increased diffuse large B-cell lymphoma (DLBCL) risk in all the different genetic models. CONCLUSION Our analysis suggests that the IL-10-3575T>A mutation may associate with melanoma and DLBCL and exert a differential effect in different cancer sites. However, other factors may influence the association, and large-scale multicenter with adequate methodological quality studies are needed to confirm the impact on cancer susceptibility.

Screening of novel immunostimulatory CpG ODNs and their anti-leukemic effects as immunoadjuvants of tumor vaccines in murine acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is a common malignant disease and a major cause of mortality due to recurrent disease. Immunotherapy is a promising strategy for eradicating minimal residual disease and thus preventing the relapse of leukemia. Apart from stem cell transplantation, CpG oligodeoxynucleotides (ODNs) are excellent candidates for the immunotherapy of leukemia. However, the number of usable CpG ODNs is limited. In this study, we tested a panel of CpG ODNs and obtained three CpG ODN sequences with strong immunostimulatory activity by comparing their capacity to activate lymphocytes. The data revealed that the flanking bases, the spacing of individual CpG motifs and polyguanosine ends, contribute to the immunostimulatory activity of a CpG ODN. In the immunotherapy of murine leukemia with the novel ODN as the adjuvant, we found that CpG Seqs 14 and 19 were effective in the treatment of a leukemia model by prolonging survival span, augmenting natural killer cell and CTL cytotoxicity, as well as increasing the number of long-term survivors. The ability of CpG ODN to induce both strong innate and adaptive anti-leukemic immune activity could render it an appropriate agent for therapeutic applications in acute leukemia. This study demonstrates the feasibility of active immunotherapy with CpG ODNs in patients with acute leukemia and thus represents a potential alternative therapeutic strategy for eradicating residual disease which is resistant to conventional cytoreductive treatment.

Dose-enhanced combined priming regimens for refractory acute myeloid leukemia and middle-and-high-risk myelodysplastic syndrome: a single-center, retrospective cohort study

Objective To assess chemotherapeutic regimens for refractory acute myeloid leukemia (AML) and middle-and-high-risk myelodysplastic syndrome (MDS). Methods Between 2004 and 2014, 44 patients with refractory AML and 36 patients with MDS were treated with new priming regimens (CHAG, CHTG, CHMG, or CTMG), and 77 patients with refractory AML and 52 patients with MDS were treated with conventional priming regimens (CHG or CAG). This was a single-center retrospective analysis of remission, adverse event, mortality, and survival. The capacity of clinical features (including the expression of co-stimulatory molecule B7.1 on tumor cells) to influence survival was assessed by multivariate Cox regression. Results Complete and partial remission rates (RRs) were significantly higher in AML patients treated with new regimens compared to conventional ones (68.2% vs 13.6%, P<0.05). Complete and partial remission were also significantly higher in patients with MDS treated with new regimens (55.6% vs 19.4%, P<0.05). However, although survival advantages were observed in the first year, the new regimens did not significantly improve 3-year overall survival (P>0.05). Patients administered the new regimens experienced more severe and sustained myelosuppression (P<0.05), but no severe adverse events or treatment-related deaths were observed. The rate of non-hematological side effects did not differ significantly between treatment regimens (P>0.05). Both RR and B7.1 expression were significantly higher in patients with AML-M2 and M5 (P<0.05). Conclusion The new priming regimens improved the RR, lowered the recurrence rate, and improved survival in AML and middle-and-high-risk MDS, without significantly increasing adverse events.

Granulocyte colony stimulating factor priming chemotherapy is more effective than standard chemotherapy as salvage therapy in relapsed acute myeloid leukemia

INTRODUCTION AND OBJECTIVE To improve the complete remission (CR) rate of newly diagnosed acute myeloid leukemia (AML) patients and alleviate the severe side effects of double induction chemotherapy, we combined a standard regimen with granulocyte colony-stimulating factor (G-CSF) priming chemotherapy to compose a new double induction regimen for AML patients who failed to achieve CR after the first course. PATIENTS AND METHODS Ninety-seven patients with AML who did not achieve CR after the first course of standard chemotherapy were enrolled. Among them, 45 patients received G-CSF priming combined with low-dose chemotherapy during days 20-22 of the first course of chemotherapy, serving as priming group, 52 patients were administered standard chemotherapy again, serving as control group. RESULTS Between the two groups there were no differences in the French-American-British (FAB) classification, risk status, the first course of chemotherapy, blood cell count or blasts percentage of bone marrow before the second course. But the CR rate was significantly higher and the adverse effect was much lower in the priming group than the control group. Cox multivariate regression analysis showed that WBC level before the second course and the selection of the second chemotherapy regimen were two independent factors for long survival of patients. DISCUSSION These results elucidate that standard chemotherapy followed by G-CSF priming new double induction chemotherapy is an effective method for AML patients to improve CR rate and reduce adverse effects.

High-Intensity Chemotherapy is Associated with Better Prognosis in Young Patients with High-Risk Diffuse Large B-Cell Lymphoma: A 10-Year Single-Center Retrospective Cohort Study

Background Patients <60 years old with high-risk diffuse large B-cell lymphoma (DLBCL) receiving standard RCHOP(E) treatment display high relapse rates. Here, we compared this standard regimen to a high-intensity regimen in terms of recurrence and long-term survival. Material/Methods Newly diagnosed DLBCL patients <60 years old who were treated at the Second Hospital Affiliated with Xi’an Jiaotong University between January 2004 and December 2013 (n=198, 18–60 years) were included in the study. The high-intensity group included 107 patients (54.0%) who received >8 courses of chemotherapy (high-dose CHOP, CHOP-E, EPOCH, MAED, MMED, and HyperCVAD). The control group included 91 patients (46.0%) who received 6–8 courses of CHOP-based treatment. Response rate (RR), survival, relapse, and adverse effects were compared. Results Baseline characteristics of the patients were similar between the 2 groups. Median follow-up was 64.5 months. RR in the high-intensity and control groups was 88.8% and 84.6% (P=0.387), respectively; 5-year overall survival was 66.4% and 36.3% (P<0.001), respectively; 5-year progression-free survival was 56.1% and 28.6% (P<0.001), respectively; 5-year disease-free survival was 54.2% and 24.2% (P<0.001), respectively; and relapse rate during follow-up was 29.5% and 67.5% (P<0.001), respectively. There were no significant differences in adverse effects between the 2 groups. Conclusions High-intensity chemotherapy is associated with better prognosis of patients <60 years old with newly diagnosed high-risk DLBCL.