Apoptotic mechanism of human leukemia K562/A02 cells induced by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin

The purpose of this study was to assess the induced apoptosis of self-assembled iron oxide magnetic nanoparticles (MNPs) co-loaded with daunorubicin (DNR) and 5-bromotetrandrin (Br Tet) (DNR/Br Tet-MNPs), acting as a drug depot system for the sustained release of the loaded DNR and BrTet, in the drug resistant human leukemia K562/A02 cells and further to explore potential mechanisms. After being incubated for 48 hours, K562/A02 cells were treated with DNR/Br Tet-MNPs or DNR and Br Tet in solution (DNR/Br Tet-Sol). Morphologic characteristics of K562/A02 cells were observed under a fluorescence microscope; cell apoptosis and intracellular accumulation of DNR were analyzed by FACS Calibur flow cytometry. Furthermore, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting analyses were performed to study the apoptosis associated gene transcription and protein expression, respectively. Typical apoptotic characteristics, including chromatin condensation and fragmentation of nuclei, were observed and a high rate of apoptosis was detected in K562/A02 cells treated with DNR/Br Tet-MNPs and DNR/Br Tet-Sol. Detection of relative fluorescence intensity of intracellular DNR demonstrated that intracellular DNR was higher in K562/A02 cells treated with DNR/Br Tet-MNPs than that of DNR/Br Tet-Sol. Further study demonstrated that both DNR/Br Tet-MNPs and DNR/Br Tet-Sol reduced the gene transcriptions and protein expressions of bcl-2 and survivin and enhanced that of bax and caspase 3. It is concluded that self-assembled DNR/Br Tet-MNPs, as one of the potential antitumor agents for hematologic malignancies, may effectively induce apoptosis of K562/A02 cells through elevating the ratio of bax/bcl-2, activating caspase 3, and inactivating survivin

Follicular dendritic cell sarcoma: a report of six cases and a review of the Chinese literature

<p>Abstract</p> <p>Goals</p> <p>The main purpose of this study is to broaden the clinicopathological spectrum and increase recognition of follicular dendritic cell sarcoma (FDCS) through analysis of the clinical and pathological features of 50 cases.</p> <p>Methods</p> <p>The clinicopathological features of total 50 cases of FDCS were analyzed including a review of 44 cases reported in Chinese literature before October 2009 and six original cases from the pathology files conducted by the authors.</p> <p>Results</p> <p>The youngest patient came under observation in this study is only seven years old. Including the cases contributed by the authors, our literary review indicated that male dominated the tumor cases (M: F = 3: 2). 28 cases (56%) present with this disease in extranodal sites. Tumor cells demonstrated positive staining for the follicular dendritic cell markers CD21 (47/49), CD35 (43/45), CD23 (20/23) and CD68 (23/25). In situ hybridization for Epstein-Barr virus-encoded RNA was performed in 10 cases. Nevertheless, EBV expression was absent in all these cases. The follow-up analysis of all cases shows that 26 (81.2%) patients were alive and disease free; 6 (18.8%) patients were alive with recurrent disease or metastasis; and nobody had died of this disease at the time of last follow-up.</p> <p>Conclusions</p> <p>The diagnosis of the FDCS is based on the findings of morphology and immunohistochemistry. The FDCS occurred in China should be viewed and treated as a low-grade sarcoma, and the role of the EBV in the pathogenesis of this tumor is still uncertain. There is a possibility that the tumor might be racial or geographic correlated, because most cases were reported from Eastern Asia area; it's particular the case of the liver or spleen tumor.</p

Synthesis and antitumor efficacy of daunorubicin-loaded magnetic nanoparticles

Jun Wang1, Baoan Chen1, Jian Chen1, Xiaohui Cai1, Guohua Xia2, Ran Liu1, Pingsheng Chen2, Yu Zhang3, Xuemei Wang31Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China 210009; 2Medical School, Southeast University, Nanjing; 3State Key Laboratory of Bioelectronics, Southeast University, Nanjing, China 210009Background: A promising approach to optimize the disposition of daunorubicin-loaded magnetic nanoparticles (DNR-MNPs) was developed to minimize serious side effects of systematic chemotherapy for cancer.Methods: The physical properties of DNR-MNPs were investigated and their effect on leukemia cells in vitro was evaluated by a standard WST-1 cell proliferation assay. Furthermore, cell apoptosis and intracellular accumulation of DNR were determined by FACSCalibur flow cytometry.Results: Our results showed that the majority of MNPs were spherical and their sizes were from 10 to 20 nm. The average hydrodynamic diameter of DNR-MNPs in water was 94 nm. The in vitro release data showed that the DNR-MNPs have excellent sustained release property. Proliferation of K562 cells was inhibited in a dose-dependent manner by DNR in solution (DNR-Sol) or by DNR-MNPs. The IC50 for DNR-MNPs was slightly higher than that for DNR-Sol. DNR-MNPs also induced less apoptosis in K562 cells than did DNR-Sol. Detection of fluorescence intensity of intracellular DNR demonstrated that DNR-MNPs could be taken up by K562 cells and persistently released DNR in cells.Conclusion: Our study suggests that optimized DNR-MNPs formulation possesses sustained drug-release and favorable antitumor properties, which may be used as a conventional dosage form for antitumor therapy.Keywords: daunorubicin, magnetic iron oxide nanoparticles, drug delivery system, target selection, K562 cell