ABSTRACT
Osteosarcoma (OS) is the commonest primary malignant bone tumor in children and adolescents. However, chemotherapy resistance is a major challenge for the treatment of OS. Exosomes have been reported to serve an increasingly important role in different stages of tumor progression and chemotherapy resistance. The present study investigated whether exosomes derived from doxorubicinresistant OS cells (MG63/DXR) could be taken up in doxorubicinsensitive OS cells (MG63) and induce a doxorubicinresistant phenotype. MDR1, as the specific mRNA of chemoresistance, can be transferred by exosomes from MG63/DXR cells to MG63 cells. In addition, the present study identified 2,864 differentially expressed miRNAs (456 upregulated and 98 downregulated with foldchange >2.0, P<5x102, and FDR<0.05) in all three sets of exosomes from MG63/DXR cells and MG63 cells. The related miRNAs and pathways of exosomes involved in the doxorubicin resistance were identified by bioinformatic analysis. A total of 10 randomly selected exosomal miRNAs were dysregulated in exosomes from MG63/DXR cells relative to MG63 cells by reverse transcriptionquantitative PCR detection. As a result, miR1433p was found high expressed in exosomes from doxorubicinresistant OS cells compared with doxorubicinsensitive OS cells and upregulation of exosomal miR1433p abundance associated with the poor chemotherapeutic response to OS cells. Briefly, transfer of exosomal miR1433p confers doxorubicin resistance in osteosarcoma cells.
Subject(s)
Bone Neoplasms , Exosomes , MicroRNAs , Osteosarcoma , Humans , Bone Neoplasms/drug therapy , Bone Neoplasms/genetics , Doxorubicin/pharmacology , Exosomes/genetics , MicroRNAs/genetics , Osteosarcoma/drug therapy , Osteosarcoma/genetics , Drug Resistance, NeoplasmABSTRACT
OBJECTIVE: To evaluate the clinical outcomes of negative-pressure wound therapy (NPWT) for infection prevention following pelvic reconstruction after malignant bone tumor resection. METHODS: The study involved 82 patients who underwent pelvic reconstruction following en-bloc resection of malignant bone tumors between January 2003 and January 2016. Forty patients were treated with NPWT via implantation of vacuum-sealing drainage (VSD) materials into the pelvic cavity to prevent infection and wound problems (VSD group), and the remaining 42 patients underwent conventional treatment (control group). Study authors compared the inpatient length of stay, antibiotic use, drainage volume, time to wound closure, and infection rates between groups. Investigators also conducted cell cultures of the wound cavity washing fluid and hematoxylin-eosin staining for VSD materials to find recurrent tumor cells. RESULTS: In the VSD group, one patient (2.5%) had a superficial wound problem. In the control group, 18 patients (42.9%) had deep infection or wound problems. The VSD group had a significantly decreased infection rate, duration of antibiotic administration and inpatient stay, as well as increased wound healing compared with the control group (P < .05). Further, no tumor cells were observed in the VSD material or the wound cavity washing fluid. CONCLUSIONS: The application of NPWT with VSD material may be an effective and reliable method for preventing infection in patients who undergo pelvic reconstruction following malignant tumor resection.