Search

Dan Guo,1,2 Peipei Xu,1 Dangui Chen,1 Lili Wang,1 Yudi Zhu,1 Yifan Zuo,1 Bing Chen1 1Department of Hematology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210093, People’s Republic of China; 2Department of Hematology, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, People’s Republic of ChinaCorrespondence: Bing ChenDepartment of Hematology, Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210093, People’s Republic of ChinaEmail chenbing2004@126.comIntroduction: The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increase risk of transformation to acute myeloid leukemia (AML). Daunorubicin (DNR) is an indispensable drug for the treatment of MDS and AML. However, its side effects including cardiac toxicity and bone marrow suppression severely limit clinical application. Many researches reported high expression of CD123 antigen on high-risk MDS cells, so we constructed a novel drug delivery system comprising daunorubicin-loaded CdTe QDs conjugated with anti-CD123 mAbs (DNR-CdTe-CD123) to develop targeted combination chemotherapy for MDS.Methods: CdTe conjugated antiCD123 through amide bond, co-loaded with DNR with electrostatic bonding. Then, we determined characterization and release rate of DNR-CdTe-CD123. The therapeutic effect and side effect of drug delivery system were evaluated through in vitro and in vivo experiments.Results: CdTe showed appropriate diameter and good dispersibility and DNR was loaded into CdTes with high encapsulation efficiency and drug loading. The maximum drug loading and encapsulation efficiency were 42.08 ± 0.64% and 74.52 ± 1.81%, respectively, at DNR concentration of 0.2mg/mL and anti-CD123 mAbs volume of 5ul (100ug/mL). Flow cytometry (FCM) showed that CD123 antigen was highly expressed on MUTZ-1 cells, and its expression rate was 72.89 ± 10.67%. In vitro experiments showed that the inhibition rate and apoptosis rate of MUTZ-1 cells treated with DNR-CdTe-CD123 were higher than those in the other groups (P< 0.05). Compared with the other groups, the level of apoptosis-related protein (P53, cleaved caspase-9, Bax and cleaved caspase-3) were upregulated in DNR-CdTe-CD123 group (P< 0.05). In vivo experiments, DNR-CdTe-CD123 can effectively inhibit the tumor growth of MDS-bearing nude mice and reduce the side effects of DNR on myocardial cells.Conclusion: The system of DNR-CdTe-CD123 enhances the therapeutic effects and reduce the side effects of DNR, thus providing a novel platform for MDS treatment.Keywords: myelodysplastic syndrome, daunorubicin, CdTe, anti-CD123 monoclonal antibody, drug delivery system

The miR17-92 family is found to be aberrantly expressed and associated with clinicopathological characteristics in patients with various cancers, including digestive system cancers. However, its prognostic value is not yet established. Therefore, we performed a systematic review and meta-analysis to investigate the association between miR17-92-family expression and clinical outcomes in digestive system cancers. We searched the PubMed, Web of Science, Embase, and CNKI (Chinese) databases to retrieve eligible studies up to June 30, 2018. Prognostic data and clinicopathological features of overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were extracted to evaluate correlations of the miR17-92 family with digestive system cancers. We used HRs to assess association between miR17-92-family expression and cancers prognosis. A total of 30 qualifying studies involving 4,056 subjects were included in this meta-analysis. Our results indicated that expression levels of miR17-92 can predict poor OS (HR 1.21, 95% CI 1.03–1.39; P=0). However, there was no relationship between the miR17-92 family and DFS (HR 0.86, 95% CI 0.6–1.11; P=0.170) or PFS (HR 1.37, 95% CI 0.83–1.91; P=0). Moreover, miR17-92 was related to TNM stage (III/IV vs I/II, HR 1.37, 95% CI 1.17–1.570; P=0.012), but there was no relationship between miR17-92 and metastasis (HR 1.64, 95% CI 1.34–1.95; P=0.491) or tumor size (≥5 cm vs

Background: Traditional Chinese medicine wogonin plays an important role in the treatment of leukemia. Recently, the application of drug-coated magnetic nanoparticles (MNPs) to increase water solubility of the drug and to enhance its chemotherapeutic efficiency has attracted much attention. Drugs coated with MNPs are becoming a promising way for better leukemia treatment. This study aimed to assess the possible molecular mechanisms of wogonin-coated MNP-Fe3O4 (Wog-MNPs-Fe3O4) as an antileukemia agent. Methods: After incubated for 48 h, the antiproliferative effects of MNPs, wogonin, or Wog-MNPs-Fe3O4 on K562/A02 cells were determined by methyl thiazolyl tetrazolium (MTT) assay. The apoptotic rates of K562/A02 cells treated with either wogonin or Wog-MNPs-Fe3O4 were determined by flow cytometer (FCM) assay. The cell cycle arrest in K562/A02 cells was determined by FCM assay. The elementary molecular mechanisms of these phenomena were explored by Western blot and reverse transcriptase polymerase chain reaction (RT-PCR). Results: With cell viabilities ranging from 98.76% to 101.43%, MNP-Fe3O4 was nontoxic to the cell line. Meanwhile, the wogonin and Wog-MNPs-Fe3O4 had little effects on normal human embryonic lung fibroblast cells. The cell viabilities of the Wog-MNPs-Fe3O4 group (28.64–68.36%) were significantly lower than those of the wogonin group (35.53–97.28%) in a dose-dependent manner in 48 h (P < 0.001). The apoptotic rate of K562/A02 cells was significantly improved in 50 μmol/L Wog-MNPs-Fe3O4 group (34.28%) compared with that in 50 μmol/L wogonin group (23.46%; P < 0.001). Compared with those of the 25 and 50 μmol/L wogonin groups, the ratios of G0/G1-phase K562/A02 cells were significantly higher in the 25 and 50 μmol/L Wog-MNPs-Fe3O4 groups (all P < 0.001). The mRNA and protein expression levels of the p21 and p27 in the K562/A02 cells were also significantly higher in the Wog-MNPs-Fe3O4 group compared with those of the wogonin group (all P < 0.001). Conclusions: This study demonstrated that MNPs were the effective drug delivery vehicles to deliver wogonin to the leukemia cells. Through increasing cells arrested at G0/G1-phase and inducing apoptosis of K562/A02 cells, MNPs could enhance the therapeutic effects of wogonin on leukemia cells. These findings indicated that MNPs loaded with wogonin could provide a promising way for better leukemia treatment.

Jie Ruan,1,* Peipei Xu,2,3,* Wei Fan,4 Qiaoling Deng,3 Mingxia Yu3 1Key Laboratory for Medical Molecular Diagnostics of Guangdong, Guangdong Medical University, Dongguan, Guangdong, 523808, China; 2Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450072, China; 3Department of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China; 4Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China *These authors contributed equally to this work Abstract: Epigenetic alteration of P16INK4a is conventionally thought to induce the initiation of carcinoma. However, the role of P16INK4a methylation in ovarian cancer still remains controversial. Therefore, we performed a meta-analysis to further elucidate the relationship between P16INK4a promoter methylation and ovarian cancer. A total of 24 studies, including 20 on risk, 10 on clinicopathological features, and 3 on prognosis, were included in our meta-analysis. Our results indicated that the frequency of P16INK4a methylation in cancer tissues was significantly higher than normal tissues and low malignant potential tumor tissues (odds ratio [OR] =5.01, 95%CI=1.55–16.14; OR =1.88, 95%CI=1.10–3.19, respectively), but similar to benign tissues (OR =1.18, 95%CI=0.52–2.65). Furthermore, P16INK4a promoter methylation was not strongly correlated with age, clinical stage, tumor differentiation, or histological subtype in patients with ovarian cancer. Additionally, survival analysis showed that patients with P16INK4a promoter methylation had a shorter progression-free survival in univariate and multivariate Cox regression models (hazard ratio =1.68, 95%CI=1.26–2.24; hazard ratio =1.55, 95%CI=1.15–2.08; respectively). In The Cancer Genome Atlas datasets, the methylation levels of seven out of nine CpG sites were significantly increased in the ovarian tumor tissues compared with the normal tissues. In conclusion, the present meta-analysis suggests that P16INK4a promoter methylation may be useful in distinguishing malignant cancer from healthy ovarian tissues, and it may be a potential predictive marker for prognosis in patients with ovarian cancer. Keywords: ovarian cancer, P16INK4a promoter methylation, TCGA datasets, meta-analysis