ABSTRACT
Immunotherapy with tumor lysate-pulsed dendritic cells (DCs) is one of the breakthrough strategies used in the treatment of cancer. However, DC-based immunotherapies for osteosarcoma are limited. In the present study, preclinical studies of a C3H osteosarcoma mouse model (produced by subcutaneous injection of LM8 murine osteosarcoma cells) validated the concept that LM8 cell lysate-pulsed bone marrow-derived DCs may evoke a more potent immune response compared with DCs that have been matured using polyinosinic:polycytidylic acid (poly I:C). A cytotoxic T lymphocyte (CTL) response was established using two groups of C3H mice (n=9) with osteosarcoma; the treatment group consisted of LM8 cell lysate-pulsed DCs and the control group consisted of DCs matured using poly I:C. Each group was immunized with doses of 1×106 cells twice per week for 3 weeks. No difference in the expression of cluster of differentiation markers was identified in the two groups. DCs pulsed with LM8 cell lysate were associated with the increased induction of CTL activity. Serum interferon-γ levels were increased in mice that received DCs pulsed with LM8 cell lysate compared with that in the poly I:C-matured DC group (P<0.041). Serum interleukin-4 was decreased in the treatment group vs. the control group (P<0.033). A mixed lymphocyte reaction assay confirmed that LM8-DC immunotherapy may evoke a significant antigen-specific immune response in a mouse model. The present study reveals promising data on efficacy of a DC-based immunotherapy in the treatment of osteosarcoma; however, further clinical studies are warranted.
ABSTRACT
BACKGROUND: Chronic synovitis is a consequence of recurrent intraarticular hemorrhage in patients with hemophilia. Eventually, synovitis leads to degeneration of the articular cartilage, with serious consequences that impact the quality-of-life in hemophiliacs. The aim of our study was to investigate the short term clinical effects of intraarticular injection of the radionuclide preparation(32)P colloid ((32)P-labelled colloidal chromic phosphate suspension) on recurrent intraarticular hemorrhages in patients with hemophilic synovitis of the knee. MATERIALS AND METHODS: Patients who met the inclusion criteria (n = 22) were enrolled in an open-label study between October 2011 and September 2012.(32)P colloid was injected into the knee joint and patients were followed up over 6 months after treatment. Hemorrhage frequency, visual analog scale pain score, hospital for special surgery knee score, knee circumference, upper knee circumference, knee diameter, and knee range of motion (ROM) were compared before and after treatment with intraarticular(32)P colloid injection. RESULTS: In 24 knees evaluated in 22 participating patients, there was a significant reduction in the number of hemorrhages after(32)P colloid treatment, along with significant pain relief. However, there were no statistically significant changes in the degree of joint swelling, degree of muscle atrophy and knee ROM between the pre and post treatment evaluations. CONCLUSION: The frequency of joint hemorrhage in patients with hemophilic knee synovitis can be significantly reduced and local symptoms can be improved in the short term by intraarticular injection of(32)P colloid.
ABSTRACT
Intermittent high glucose (IHG), one of the general and important symptoms of patients with diabetes, has greater effect than sustained high glucose on the development of diabetic cardiovascular complications, in which endothelial dysfunction caused by oxidative stress is regarded as the initiation. However, no study investigated either the degree of endothelial DNA oxidation caused by IHG or the potential protective effects of antioxidants. In this study, DNA oxidation, including 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentration and comet assay, was studied in human umbilical vein endothelial cells (HUVECs) under IHG with or without treatment of Ginkgo biloba extract (EGb 761). We found that high glucose, especially IHG, increased reactive oxygen species generation, 8-OHdG content and oxidative DNA damage in HUVECs. These high glucose-induced oxidative stress could be suppressed by EGb 761 (25-100 microg/ml) in a dose-dependent manner through the improvement of total antioxidant capacity. Our results indicated that the presence of significant DNA oxidation in HUVECs exposed to high glucose, and especially higher in the cells in IHG conditions. EGb 761, an antioxidant herbal medicine, can remarkably alleviate endothelial DNA oxidation caused by IHG, which may provide a novel approach for endothelial protection in the presence of IHG.
