The AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) modulates cellular energy metabolism, and promotes mitochondrial proliferation and apoptosis. Previous studies have shown that AICAR has anticancer effects in various cancers, however the roles of AMPK and/or the effects of AICAR on osteosarcoma have not been reported. In the present study, we evaluated the effects of AICAR on tumor growth and mitochondrial apoptosis in human osteosarcoma both in vitro and in vivo. For in vitro experiments, two human osteosarcoma cell lines, MG63 and KHOS, were treated with AICAR, and the effects of AICAR on cell growth and mitochondrial apoptosis were assessed by WST assays, TUNEL staining, and immunoblot analyses. In vivo, human osteosarcoma-bearing mice were treated with AICAR, and the mitochondrial proliferation and apoptotic activity in treated tumors were assessed. In vitro experiments revealed that AICAR activated AMPK, inhibited cell growth, and induced mitochondrial apoptosis in both osteosarcoma cell lines. In vivo, AICAR significantly reduced osteosarcoma growth without apparent body weight loss and AICAR increased both mitochondrial proliferation and apoptotic activity in treated tumor tissues. AICAR showed anticancer effects in osteosarcoma cells through an AMPK-dependent peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)/mitochondrial transcription factor A (TFAM)/mitochondrial pathway. The findings in this study strongly suggest that AICAR could be considered as a potent therapeutic agent for the treatment of human osteosarcoma.

BackgroundChronic expanding hematoma is a rare entity resulting from trauma or surgery. This condition usually occurs in soft tissue, such as the trunk or extremities, while chronic expanding hematoma arising from bone has not been reported previously. We describe an unusual case of a huge intraosseous chronic expanding hematoma arising from the ilium, which had grown over a 40-year period following hip surgeries.Case presentationA 57-year-old Japanese woman presented with a 1.5-year history of right hip pain. She had a history of bilateral developmental dysplasia of the hip and had undergone bilateral arthroplasties in childhood. A physical examination revealed a large, firm, immobile mass at her right ilium. Based on radiographic findings, a type of slow-growing bone tumor was suspected, and an incisional biopsy was performed. A histopathologic examination revealed large amounts of old clotted blood within the lesion, and the capsule of the lesion was composed of dense, fibrous, connective tissue. There was no evidence of neoplasia, and chronic expanding hematoma was suspected. The lesion was resistant to conservative treatment, and so we performed an internal hemipelvectomy (including the capsule of the mass) and a reconstruction by hip transposition 2.5 years after the incisional biopsy. There was no recurrence of chronic expanding hematoma at the most recent follow-up of 1 year and 8 months postoperatively.ConclusionsA chronic expanding hematoma is characterized by its persistence and increasing size more than 1 month after the trauma or surgical event suspected of causing hemorrhage. To the best of our knowledge, this is the first report of chronic expanding hematoma arising from bone. We performed internal hemipelvectomy and hip transposition, and there has so far been no recurrence. This disease may be considered a differential diagnosis for bone tumor when the patient has a history of surgery or trauma, regardless of how many years have passed since the index event.

An infant boy underwent hip disarticulation for infantile fibrosarcoma immediately after birth. His rehabilitation began when he was 4 mos old and involved training with his left (residual) leg. He could stand with support at 12 mos. His initial prosthesis fitting was performed at the age of 13 mos. He could stand and walk with support at 15 mos of age and could walk with no additional support and go up and down stairs at 2 yrs. A single-axis prosthetic knee joint was introduced at the age of 2 yrs 3 mos. His first gait using a hip prosthesis was successful, and his prosthesis was replaced at appropriate intervals with no major problems. The authors believe that the key to achieving a successful prosthetic gait in children is good communication among the medical team, which should comprise an orthopedic doctor, rehabilitation doctor, nurse, physical therapist, prosthetist/orthotist, and the patient's parents.