No abstract

PurposeThe primary goal of the present study was to develop the nano-drug consisting of doxorubicin and exosome derived from mesenchymal stem cells, and to explore its effect on osteosarcoma in vitro.MethodsThe exosomes were isolated from bone marrow MSCs (BM-MSCs) by an Exosome Isolation Kit. The exosome-loaded doxorubicin (Exo-Dox) was prepared by mixing exosome with Dox-HCl, desalinizing with triethylamine and then dialyzing against PBS overnight. The nanoparticle tracking analysis (NTA) and transmission electron microscope (TEM) were used to characterize of the exosome and Exo-Dox. The cytotoxicity of Exo-Dox was determined by CCK-8 assay. Further, the cellular uptake of different drugs was analyzed using inverted fluorescence microscope and flow cytometry.ResultsThe typical exosome structures can be observed by TEM. After loading with doxorubicin, its size is larger than free exosome. Compared with the free Dox, the prepared Exo-Dox showed enhanced cellular uptake efficiency and anti-tumor effect in osteosarcoma MG63 cell line but low cytotoxicity in myocardial H9C2 cell line.ConclusionThe prepared Exo-Dox could be used as an excellent chemotherapeutic drug for treatment of osteosarcoma in vitro. Considering the tumor-homing feature of BM-MSCs, the Exo-Dox may be a good candidate for targeted osteosarcoma treatment in future study.

PURPOSE This trial aimed to assess the efficacy and safety of the paclitaxel plus fluorouracil regimen versus the cisplatin plus fluorouracil regimen in definitive concurrent chemoradiotherapy (dCRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS Patients with locally advanced ESCC were enrolled and randomly assigned to either the paclitaxel plus fluorouracil group or the cisplatin plus fluorouracil group. The patients in the paclitaxel plus fluorouracil group were treated with paclitaxel and fluorouracil one cycle per week in dCRT for five cycles followed by paclitaxel and fluorouracil one cycle per month in consolidation chemotherapy for two cycles. The patients in the cisplatin/5-fluorouracil group were treated with cisplatin and fluorouracil one cycle per month in dCRT for two cycles followed by two cycles in consolidation chemotherapy. The radiotherapy dose was 61.2 Gy delivered in 34 fractions. The primary end point was 3-year overall survival (OS). RESULTS Four hundred thirty-six patients with ESCC in six centers were recruited at a 1:1 ratio between April 2012 and July 2015. The median follow-up of the surviving patients was 48.7 months (interquartile range, 42.6-60.9). The 3-year OS was 55.4% in the paclitaxel plus fluorouracil group and 51.8% in the cisplatin plus fluorouracil group (hazard ratio, 0.905 [95% CI, 0.698 to 1.172]; P = .448). The 3-year progression-free survival was also not significantly different between the paclitaxel plus fluorouracil group and the cisplatin plus fluorouracil group (43.7% v 45.5%, respectively; hazard ratio, 0.973 [95% CI, 0.762 to 1.243]; P = .828). Compared with the cisplatin plus fluorouracil group, the paclitaxel plus fluorouracil group had significantly lower incidences of acute grade 3 or higher anemia, thrombocytopenia, anorexia, nausea, vomiting, and fatigue ( P < .05), but higher incidences of acute grade 3 or higher leukopenia, radiation dermatitis, and radiation pneumonitis ( P < .05). CONCLUSION The paclitaxel plus fluorouracil regimen did not significantly prolong the OS compared with the standard cisplatin plus fluorouracil regimen in dCRT in patients with locally advanced ESCC.

The inherent radioresistance and inaccuracy of localization of tumors weaken the clinical implementation effectiveness of radiotherapy. To overcome these limitations, hyaluronic acid-functionalized bismuth oxide nanoparticles (HA-Bi 2 O 3 NPs) were synthesized by one-pot hydrothermal method for target-specific computed tomography (CT) imaging and radiosensitization of tumor. After functionalization with hyaluronic acid, the Bi 2 O 3 NPs possessed favorable solubility in water and excellent biocompatibility and were uptaken specifically by cancer cells overexpressing CD44 receptors. The as-prepared HA-Bi 2 O 3 NPs exhibited high X-ray attenuation efficiency and ideal radiosensitivity via synergizing X-rays to induce cell apoptosis and arrest the cell cycle in a dose-dependent manner in vitro. Remarkably, these properties offered excellent performance in active-targeting CT imaging and enhancement of radiosensitivity for inhibition of tumor growth. These findings demonstrated that HA-Bi 2 O 3 NPs as theranostic agents exhibit great promise for CT imaging-guided radiotherapy in diagnosis and treatment of tumors.

No abstract

Epigenetic abnormalities play a vital role in the progression of ovarian cancer. Lysine-specific demethylase 1 (LSD1/KDM1A) acts as an epigenetic regulator and is overexpressed in ovarian tumors. However, the upstream regulator of LSD1 expression in this cancer remains elusive. Here, we show that epidermal growth factor (EGF) signaling upregulates LSD1 protein levels in SKOV3 and HO8910 ovarian cancer cells overexpressing both LSD1 and the EGF receptor. This effect is correlated with a decrease in the dimethylation of H3K4, a major substrate of LSD1, in an LSD1-dependent manner. We also show that inhibition of PI3K/AKT, but not MEK, abolishes the EGF-induced upregulation of LSD1 and cell migration, indicating that the PI3K/PDK1/AKT pathway mediates the EGF-induced expression of LSD1 and cell migration. Significantly, LSD1 knockdown or inhibition of LSD1 activity impairs both intrinsic and EGF-induced cell migration in SKOV3 and HO8910 cells. These results highlight a novel mechanism regulating LSD1 expression and identify LSD1 as a promising therapeutic target for treating metastatic ovarian cancer driven by EGF signaling.

The death-associated protein kinase 1 (DAPK1) gene is a candidate tumor suppressor (TSG) and the abnormal methylation of DAPK1 gene has been found in many carcinomas. The epigenetic changes of TSGs are now recognized as a mechanism contributing to the development of chronic myeloid leukemia (CML). To clarify the role of DAPK1 in CML, we examined the methylation status of DAPK1 in 49 patients with CML using methylation-specific polymerase chain reaction. The aberrant methylation of the DAPK1 gene was found in 25 of 49 (51.0%) CML cases, not in all controls. No correlation was found between DAPK1 gene methylation and the age, hematologic parameters, chromosomal abnormalities, the types and levels of bcr/abl transcripts of CML patients. However, correlation could be observed between the sex and the status of DAPK1 methylation in CML patients (R = 0.374, P = 0.008). Furthermore, there was a significant correlation between DAPK1 methylation and the stages of CML (R = 0.354, P = 0.013). The CML patients in accelerated phase (AP) and blast crisis (BC) had higher frequency of DAPK1 methylation than those in chronic phase (CP) (75.0% vs. 34.5%) (chi(2) = 7.776, P = 0.005). In one patient, the status of DAPK1 methylation became positive on the transition from CP to AP and BC. These results suggested that DAPK1 promoter methylation might play a significant role in the progression of CML.

No abstract