The glycolytic-based metabolism of cancers promotes an acidic microenvironment that is responsible for increased aggressiveness. However, the effects of acidosis on tumour metabolism have been almost unexplored, and the metabolic adaptation of cancer cells to acidosis has never been compared with the metabolic response of normal cells. In this study, to pinpoint for the first time the different metabolic profiles between osteosarcoma (OS) cells and normal human fibroblasts (Fb) under short-term acidosis, we used capillary electrophoresis with time-of-flight mass spectrometry (CE-TOFMS). We also screened alterations of the epigenetic profiles – DNA methylation and histone acetylation – of OS cells and compared it with those of normal Fb. Using CE-TOFMS, we observed a significant metabolic difference associated with glycolysis repression (dihydroxyacetone phosphate), increase of amino acid catabolism (phosphocreatine and glutamate) and urea cycle enhancement (arginino succinic acid) in OS cells compared with normal Fb. Noteworthy, metabolites associated with chromatin modification, like UDP-glucose and N8-acetylspermidine, decreased more in OS cells than in normal Fb. Further, combined bisulfite restriction analysis (COBRA) and acetyl-H3 immunoblotting indicated an epigenetic stability in OS cells than in normal Fb, and OS cells were more sensitive to an HDAC inhibitor under acidosis than under neutral condition. Our data suggest that acidosis promotes a metabolic reprogramming that can contribute to the epigenetic maintenance under acidosis only in OS cells, and then the acidic microenvironment should be considered for future therapeutic approaches. The application of epigenetic modulators will be able to become an effectively therapeutic option to selectively target malignancies under the acidic microenvironment.
Limb salvage involving wide resection and reconstruction is now well established for managing musculoskeletal sarcomas. However, involvement of major nerves and vessels with a large volume of muscle and skin may result in a useless limb, contributing to depression and a low quality of life. We have been studying alternative treatments for musculoskeletal sarcoma since 1990, and have recently established a regime using photodynamic surgery with cells labelled with acridine orange, photodynamic therapy with cells treated similarly and radiodynamic treatment using the effect of X-rays on such cells. These techniques have been used after marginal or intralesional resection of tumours since 1999 and have enabled maintenance of excellent limb function in patients with sarcomas.
We studied the safety of external fixation during post-operative chemotherapy in 28 patients who had undergone distraction osteogenesis (17, group A) or vascularised fibular grafting (11, group B) after resection of a tumour. Four cycles of multi-agent post-operative chemotherapy were administered over a mean period of 14 weeks (6 to 27). The mean duration of external fixation for all patients was 350 days (91 to 828). In total 204 wires and 240 half pins were used. During the period of post-operative chemotherapy, 14 patients (11 in group A, 3 in group B) developed wire- and pin-track infection. A total of ten wires (4.9%) and 11 half pins (4.6%) became infected. Seven of the ten infected wires were in periarticular locations. External fixation during post-operative chemotherapy was used safely and successfully for fixation of a vascularised fibular graft and distraction osteogenesis in 27 of 28 patients. Post-operative chemotherapy for malignant bone tumours did not adversely affect the ability to achieve union or cause hypertrophy of the vascularised fibular graft and had a minimal effect on distraction osteogenesis. Only one patient developed osteomyelitis which required further surgery.
We describe a case of intraneural metastasis of a synovial sarcoma, the first published case of a metastasis of a soft-tissue sarcoma to a peripheral nerve.
We reviewed the results of 51 patients with benign bone tumours treated by curettage and implantation of calcium hydroxyapatite ceramic (CHA). The mean follow-up was 11.4 years (10 to 15.5). Post-operative fractures occurred in two patients and three had local recurrences; three had slightly limited movement of the adjacent joint and one had mild osteoarthritis. There were no allergic or neoplastic complications. In all cases, radiographs showed that the CHA was well incorporated into the host bone. Statistical analysis showed that absorption of the implanted CHA was greater in males (odds ratio, 6.2; 95% CI, 1.6 to 23.7) and younger patients (odds ratio, 0.6 for increase in age of 10 years; 95% CI, 0.91 to 0.99). However, the implanted CHA was not completely absorbed in any patient. We conclude that CHA is a useful and safe bone substitute for the treatment of benign bone tumours.
