Yongchang Wei

The prognostic value of long noncoding RNAs in prostate cancer: a systematic review and meta-analysis

The abnormally expressed LncRNAs played irreplaceable roles in the prognosis of prostate cancer (PCa). Therefore, we conducted this systematic review and meta-analysis to summarize the association between the expression of LncRNAs, prognosis and clinicopathology of PCa. 18 eligible studies were recruited into our analysis, including 18 on prognosis and 9 on clinicopathological features. Results indicated that aberrant expression of LncRNAs was significantly associated with biochemical recurrence-free survival (BCR-FS) (HR = 1.55, 95%CI: 1.01-2.37, P < 0.05), recurrence free survival (RSF) (HR = 3.07, 95%CI: 1.07-8.86, P < 0.05) and progression free survival (PFS) (HR = 2.34, 95%CI: 1.94-2.83, P < 0.001) in PCa patients. LncRNAs expression level was correlated with several vital clinical features, like tumor size (HR = 0.52, 95%CI: 0.28-0.95, P = 0.03), distance metastasis (HR = 4.55, 95%CI: 2.26-9.15, P < 0.0001) and histological grade (HR = 6.23, 95% CI: 3.29-11.82, P < 0.00001). Besides, down-regulation of PCAT14 was associated with the prognosis of PCa [over survival (HR = 0.77, 95%CI: 0.63-0.95, P = 0.01), BCR-FS (HR = 0.61, 95%CI: 0.48-0.79, P = 0.0001), prostate cancer-specific survival (HR = 0.64, 95%CI: 0.48-0.85, P = 0.002) and metastasis-free survival (HR = 0.61, 95%CI: 0.50-0.74, P < 0.00001)]. And, the increased SChLAP1 expression could imply the worse BCR-FS (HR = 2.54, 95%CI: 1.82-3.56, P < 0.00001) and correlate with Gleason score (< 7 vs ≥ 7) (OR = 4.11, 95% CI: 1.94-8.70, P = 0.0002). Conclusively, our present work demonstrated that LncRNAs transcription level might be potential prognostic markers in PCa.The abnormally expressed LncRNAs played irreplaceable roles in the prognosis of prostate cancer (PCa). Therefore, we conducted this systematic review and meta-analysis to summarize the association between the expression of LncRNAs, prognosis and clinicopathology of PCa. 18 eligible studies were recruited into our analysis, including 18 on prognosis and 9 on clinicopathological features. Results indicated that aberrant expression of LncRNAs was significantly associated with biochemical recurrence-free survival (BCR-FS) (HR = 1.55, 95%CI: 1.01–2.37, P < 0.05), recurrence free survival (RSF) (HR = 3.07, 95%CI: 1.07–8.86, P < 0.05) and progression free survival (PFS) (HR = 2.34, 95%CI: 1.94–2.83, P < 0.001) in PCa patients. LncRNAs expression level was correlated with several vital clinical features, like tumor size (HR = 0.52, 95%CI: 0.28–0.95, P = 0.03), distance metastasis (HR = 4.55, 95%CI: 2.26–9.15, P < 0.0001) and histological grade (HR = 6.23, 95% CI: 3.29–11.82, P < 0.00001). Besides, down-regulation of PCAT14 was associated with the prognosis of PCa [over survival (HR = 0.77, 95%CI: 0.63–0.95, P = 0.01), BCR-FS (HR = 0.61, 95%CI: 0.48–0.79, P = 0.0001), prostate cancer-specific survival (HR = 0.64, 95%CI: 0.48–0.85, P = 0.002) and metastasis-free survival (HR = 0.61, 95%CI: 0.50-0.74, P < 0.00001)]. And, the increased SChLAP1 expression could imply the worse BCR-FS (HR = 2.54, 95%CI: 1.82-3.56, P < 0.00001) and correlate with Gleason score (< 7 vs ≥ 7) (OR = 4.11, 95% CI: 1.94-8.70, P = 0.0002). Conclusively, our present work demonstrated that LncRNAs transcription level might be potential prognostic markers in PCa.

MicroRNAs serve as a bridge between oxidative stress and gastric cancer (Review).

Gastric cancer (GC) remains one of the most prevalent tumors worldwide and affects human health due to its high morbidity and mortality. Mechanisms underlying occurrence and development of GC have been widely studied. Studies have revealed reactive oxygen species (ROS) generated by cells under oxidative stress (OS) are involved in gastric tumorigenesis, and modulate expression of microRNAs (miRs). As such, miRs have been shown to be associated with OS-related GC. Given the association of OS and miRs in development of GC, this review aims to summarize the relationship between miRs and OS and their role in GC development. Serving as a link between OS and GC, miRs may offer new approaches for gaining a more in-depth understanding of mechanisms of GC and may lead to the identification of new therapeutic approaches against GC.

Azelaic Acid Exerts Antileukemic Activity in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is an acute leukemia common in most adults; its prevalence intensifies with age. The overall survival of AML is very poor because of therapeutic resistance. Azelaic acid (AZA) is non-toxic, non-teratogenic, and non-mutagenic and its antitumor effect on various tumor cells is well established; Nonetheless, its therapeutic effects in AML cells are largely unknown. In this study, it was shown that AZA significantly inhibits the cell viability and induces apoptosis in AML cells in a dose-dependent manner. Additionally, AZA suppressed the expression of phosphorylated Akt, Jab1 and Trx, and this suppression was enhanced by treatment with Jab1 siRNA. Furthermore, AZA sensitized AML cells to Ara-c chemotherapy. The suppressive effect of AZA on tumor growth was examined in vivo by subcutaneously inoculated AML cells in a tumor model using nude mice. These findings indicate that AZA is useful as an effective ingredient in antineoplastic activity.

Jab1/Csn5-thioredoxin signaling in relapsed acute monocytic leukemia under oxidative stress

Purpose: High levels of ROS and ineffective antioxidant systems contribute to oxidative stress, which affects the function of hematopoietic cells in acute myeloid leukemia (AML); however, the mechanisms by which ROS lead to malignant transformation in relapsed AML-M5 are not completely understood. We hypothesized that alterations in intracellular ROS would trigger AML-M5 relapse by activating the intrinsic pathway. Experimental Design: We studied ROS levels and conducted c-Jun activation domain–binding protein-1 (JAB1/COPS5) and thioredoxin (TRX) gene expression analyses with blood samples obtained from 60 matched AML-M5 patients at diagnosis and relapse and conducted mechanism studies of Jab1′s regulation of Trx in leukemia cell lines. Results: Our data showed that increased production of ROS and a low capacity of antioxidant enzymes were characteristics of AML-M5, both at diagnosis and at relapse. Consistently, increased gene expression levels of TRX and JAB1/COPS5 were associated with low overall survival rates in patients with AML-M5. In addition, stimulating AML-M5 cells with low concentrations of hydrogen peroxide led to increased Jab1 and Trx expression. Consistently, transfection of ectopic Jab1 into leukemia cells increased Trx expression, whereas silencing of Jab1 in leukemia cells reduced Trx expression. Mechanistically, Jab1 interacted with Trx and stabilized Trx protein. Moreover, Jab1 transcriptionally regulated Trx. Furthermore, depletion of Jab1 inhibited leukemia cell growth both in vitro and in vivo. Conclusions: We identified a novel Jab1–Trx axis that is a key cellular process in the pathobiologic characteristics of AML-M5. Targeting the ROS/Jab1/Trx pathway could be beneficial in the treatment of AML-M5. Clin Cancer Res; 23(15); 4450–61. ©2017 AACR.

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.

A novel curcuminoid exhibits enhanced antitumor activity in nasopharyngeal carcinoma

Curcumin shows growth-inhibition against tumor cells through multi-target mechanisms. Nevertheless, the poor stability and pharmacokinetics considerably limit its clinical functions. Increased effort has been put into the chemical alteration of curcumin to find potential analogues with improved bioavailability and antitumor activities. In this study, the antitumor activity of a novel curcuminoid (B63) in nasopharyngeal carcinoma (NPC) was examined. The MTT and colony formation assays were used to detect NPC cell viability and proliferation. Flow cytometry was used to detect cell cycle distribution. The Annexin V/PI staining assay and cleavage PARP and cleavage caspase-3 expression were used to examine apoptosis. Western blotting was used to examine the protein expression of endoplasmic reticulum (ER) stress pathway markers, XBP-1, ATF-4 and CHOP. The suppressive effect of B63 on tumor growth was examined in vivo by subcutaneously inoculated NPC in a tumor model using nude mice. Treatment with B63 potentially caused growth inhibition and apoptosis in NPC cells in a dose- and time-responsive manner. Its antitumor effect was associated with the ER stress activation. Nevertheless, the same dose of curcumin did not activate ER stress. In addition, knockdown of Chop attenuated B63-induced cell viability inhibition, suggesting that the apoptotic pathway is ER stress-dependent. The tumor volume and weight were significantly reduced by pretreating the NPC cells with B63 before implantation in the in vivo mouse model. B63 exhibited a more potent antitumor action than curcumin in NPC. These observations on the novel compound B63 indicate a novel candidate for NPC therapy.

Reactive Oxygen Species-Mediated Tumor Microenvironment Transformation: The Mechanism of Radioresistant Gastric Cancer

Radioresistance is one of the primary causes responsible for therapeutic failure and recurrence of cancer. It is well documented that reactive oxygen species (ROS) contribute to the initiation and development of gastric cancer (GC), and the levels of ROS are significantly increased in patients with GC accompanied with abnormal expressions of multiple inflammatory factors. It is also well documented that ROS can activate cancer cells and inflammatory cells, stimulating the release of a variety of inflammatory cytokines, which subsequently mediates the tumor microenvironment (TME) and promotes cancer stem cell (CSC) maintenance as well as renewal and epithelial-mesenchymal transition (EMT), ultimately resulting in radioresistance and recurrence of GC.

Efficacy of Compound Kushen Injection in Combination with Induction Chemotherapy for Treating Adult Patients Newly Diagnosed with Acute Leukemia

We assessed the clinical effectiveness and safety of CKI (compound Kushen injection) plus standard induction chemotherapy for treating adult acute leukemia (AL). We randomly assigned 332 patients with newly diagnosed AL to control (n = 165, receiving DA (daunorubicin and cytarabine) or hyper-CVAD (fractionated cyclophosphamide, doxorubicin, vincristine, and dexamethasone)) or treatment (n = 167, receiving CKI and DA or hyper-CVAD) groups. Posttreatment, treatment group CD3+, CD4+, CD4+/CD8+, natural killer (NK) cell, and immunoglobulin (IgG, IgA, and IgM) levels were significantly higher than those of the control group (p < 0.05), and CD8+ levels were lower in the treatment group than in the control group (p < 0.05). Treatment group interleukin- (IL-) 4 and IL-10 levels were significantly higher compared to the control posttreatment (both p < 0.05) as were complete remission, overall response, and quality of life (QoL) improvement rates (p < 0.05). The control group had more incidences of grade 3/4 hematologic and nonhematologic toxicity (p < 0.05). Responses to induction chemotherapy, QoL improvement, and adverse events incidence between control group patients with acute myeloid leukemia and acute lymphocytic leukemia were not significantly different. CKI plus standard induction chemotherapy is effective and safe for treating AL, possibly by increasing immunologic function.

A hospital based retrospective study of factors influencing therapeutic leukapheresis in patients presenting with hyperleukocytic leukaemia

Therapeutic leukapheresis is a rapid and effective method to reduce early mortality of patients with hyperleukocytic leukaemia (HLL). However, few studies on factors influencing the efficiency have been reported. In this study, 67 cases who underwent leukapheresis were retrospectively analysed and factors related to the collection efficiency of leukapheresis (CEWBC) were also evaluated. Paired t test showed that there was a significant decrease in statistics of white blood cell (WBC) counts after apheresis. The results of two independent samples nonparametric test suggested that WBC counts, platelet (PLT) counts, haematocrit (HCT), hemoglobin (HGB), serum chlorine (Cl) and globulin (GLB) before leukapheresis correlated with the CEWBC. Multiple linear regression analysis with background stepwise variable selection indicated that only WBC and HCT before leukapheresis had an influence on CEWBC significantly. Kaplan-Meier analysis and Cox regression model indicated that lymphocyte (LY) and mean corpuscular hemoglobin (MCH) pre-apheresis as independent factors significantly affected the prognostic survival of patients with HLL. Moreover, platelets and red blood cell were contaminated in the product of leukapheresis. It is an urgent problem to be solved in order to realise higher efficacy and higher purity of WBC collection to improve the survival of patients with HLL through optimising instruments.