RESUMO
Hepatocellular carcinoma (HCC) is the most common primary liver tumor worldwide. Current medical therapy for HCC has limited efficacy. The present study tests the hypothesis that human cerebral endothelial cell-derived exosomes carrying elevated miR-214 (hCEC-Exo-214) can amplify the efficacy of anti-cancer drugs on HCC cells. Treatment of HepG2 and Hep3B cells with hCEC-Exo-214 in combination with anti-cancer agents, oxaliplatin or sorafenib, significantly reduced cancer cell viability and invasion compared with monotherapy with either drug. Additionally, the therapeutic effect of the combination therapy was detected in primary tumor cells derived from patients with HCC. The ability of hCEC-Exo-214 in sensitizing HCC cells to anti-cancer drugs was specific, in that combination therapy did not affect the viability and invasion of human liver epithelial cells and non-cancer primary cells. Furthermore, compared to monotherapy with oxaliplatin and sorafenib, hCEC-Exo-214 in combination with either drug substantially reduced protein levels of P-glycoprotein (P-gp) and splicing factor 3B subunit 3 (SF3B3) in HCC cells. P-gp and SF3B3 are among miR-214 target genes and are known to mediate drug resistance and cancer cell proliferation, respectively. In conclusion, the present in vitro study provides evidence that hCEC-Exo-214 significantly enhances the anti-tumor efficacy of oxaliplatin and sorafenib on HCC cells.
RESUMO
BACKGROUND: Glenoid loosening, a common complication of shoulder arthroplasty, could relate to implant design and bone quality. However, the role of bone density has not been tested experimentally yet. In this study, tests on cadaveric specimens of varying bone density were performed to evaluate the effects of bone quality on loosening of typical anatomic glenoid implants. METHODS: Cadaveric scapulae scanned with a quantitative computed tomography scanner to determine bone mineral density (BMD) were implanted with either pegged or keeled cemented glenoid components and tested under constant glenohumeral load while a humeral head component was moved cyclically in the inferior and superior directions. Implant superior and inferior edge lifting, defined as displacement from the underlying bone, was measured with linear variable differential transducers until we reached 23,000 test cycles, and statistical testing was performed for differences in edge lifting due to implant design and related to periprosthetic BMD. RESULTS: Edge lifting was statistically significant at all time points, but on average, implant design had no effect. Lifting was highest in specimens in which BMD below the lifting edge was lower, with trends of increased displacement with decreased BMD. CONCLUSIONS: Implant lifting was greater in glenoids of lower bone density for both implant designs. This finding suggests that fixation failure will most likely occur in bone of lower density and that the fixation design itself may play a secondary role.
