Development of innovative more effective therapy is required for refractory osteosarcoma patients. We previously established that glycogen synthase kinase-3β (GSK- 3β) is a therapeutic target in various cancer types. In the present study, we explored the therapeutic efficacy of GSK-3β inhibition against osteosarcoma and the underlying molecular mechanisms in an orthotopic mouse model. Expression and phosphorylation of GSK-3β in osteosarcoma and normal osteoblast cell lines was examined, together with efficacy of GSK-3β inhibition on cell survival, proliferation and apoptosis and on the growth of orthotopically-transplanted human osteosarcoma in nude mice. We also investigated changes in expression, phosphorylation and co-transcriptional activity of β-catenin in osteosarcoma cells following GSK-3β inhibition. Expression of the active form of GSK- 3β (tyrosine 216-phosphorylated) was higher in osteosarcoma than osteoblast cells. Inhibition of GSK-3β activity by pharmacological inhibitors or of its expression by RNA interference suppressed proliferation of osteosarcoma cells and induced apoptosis. Treatment with GSK-3β-specific inhibitors attenuated the growth of orthotopic osteosaroma in mice. Inhibition of GSK-3β reduced phosphorylation at GSK- 3β-phospho-acceptor sites in β-catenin and increased β-catenin expression, nuclear localization and co-transcriptional activity. These results suggest the efficacy of GSK-3β inhibitors is associated with activation of β-catenin, a putative tumor suppressor in bone and soft tissue sarcoma and an important component of osteogenesis. Our study thereby demonstrates a critical role for GSK-3β in sustaining survival and proliferation of osteosarcoma cells, and identifies this kinase as a potential therapeutic target against osteosarcoma.

Background Of the biological reconstruction methods for malignant bone and soft tissue tumors, reconstruction with liquid nitrogen has the advantage of maintaining continuity on the distal side of the tumor bone site (pedicle freezing procedure; PFP). This method is expected to result in early blood flow recovery, with early union and low complication rate. The purpose of this study was to compare the outcomes of the PFP and free freezing procedure (FFP) in the lower extremities. Methods The study included 20 patients (12 men and 8 women) with frozen autografts (FFP, 13 cases; PFP, 7 cases). The mean age of the subjects was 36.3 years (range 11-79 years), and the mean follow-up period was 56.4 months (range 12-142 months). Results Final bone union occurred in 11 patients in the FFP group (84.6 %) and in 7 patients in the PFP group (100 %). The mean union period in patients who did not need additional surgery was 9.8 months (range 4-21 months) in the FFP group and 4.8 months (range 2-7 months) in the PFP group. Postoperative complications occurred in 8 cases: infection in 3 cases, fracture in 3 cases, and joint destruction in 2 cases. Six FFP patients, and 2 PFP patients (two cases of fracture), developed postoperative complications. Conclusions The union period was shorter and the rate of postoperative complications was lower with the PFP than with the FFP. We considered that early blood flow recovery might have led to the above results in the PFP.

The first aim of this study was to evaluate combination antiemetic therapy consisting of 5-HT3 receptor antagonists, neurokinin-1 receptor antagonists (NK-1RAs), and dexamethasone for multiple high emetogenic risk (HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting (CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV.

Purpose To preserve the joint structure in order to maintain good limb function in patients with osteosarcoma, we perform epiphyseal or metaphyseal osteotomy and reconstruction using frozen autografts that contain a tumour treated with liquid nitrogen. There are two methods of using liquid nitrogen-treated autografts: the free-freezing method and the pedicle-freezing method. The purpose of this study was to evaluate the results of intentional joint-preserving reconstruction using the free-freezing method and the pedicle-freezing method in patients with osteosarcoma.

Surgical resection is the only treatment for chondrosarcomas, because of their resistance to chemotherapy and radiotherapy; therefore, additional strategies are crucial to treat chondrosarcomas. Peroxisome proliferator‐activated receptor gamma (PPAR γ) is a ligand‐activated transcription factor, which has been reported as a possible therapeutic target in certain malignancies including chondrosarcomas. In this study, we demonstrated that a nonsteroidal anti‐inflammatory drug, zaltoprofen, could induce PPAR γ activation and elicit anti‐tumor effects in chondrosarcoma cells. Zaltoprofen was found to induce expressions of PPAR γ mRNA and protein in human chondrosarcoma SW1353 and OUMS27 cells, and induce PPAR γ‐responsible promoter reporter activities. Inhibitory effects of zaltoprofen were observed on cell viability, proliferation, migration, and invasion, and the activity of matrix metalloproteinase‐2 (MMP2); these effects were dependent on PPAR γ activation and evidenced by silencing PPAR γ. Moreover, we showed a case of a patient with cervical chondrosarcoma (grade 2), who was treated with zaltoprofen and has been free from disease progression for more than 2 years. Histopathological findings revealed enhanced expression of PPAR γ and reduced expression of MMP2 after administration of zaltoprofen. These findings demonstrate that zaltoprofen could be a promising drug against the malignant phenotypes in chondrosarcomas via activation of PPAR γ and inhibition of MMP2 activity.

Background Low-grade myofibroblastic sarcoma (LGMS) is described as a distinct atypical myofibroblastic tumor often with fibromatosis-like features and predilection for the head and neck, especially the oral cavity and larynx. LGMS arising in the levator scapulae muscle is extremely rare. Case presentation A 69-year-old woman was admitted to our hospital because she noticed a hard mass in her left neck six months prior. Magnetic resonance images (MRI) showed a soft tissue tumor of the left levator scapulae muscle. A core needle biopsy showed cellular fascicles or a storiform growth pattern of spindle-shaped tumor cells with minimally atypia. Immunohistochemistry revealed focally positive for α-smooth muscle actin (α-SMA), negative for S-100, and a low-grade spindle cell sarcoma was suspected. Following a biopsy, the tumor was resected with a wide surgical margin. Immunohistochemical staining was a positive for vimentin and α-SMA and negative for desmin, CD34, nuclear β-catenin, and h-caldesmon. LGMS diagnosis was determined based on the histopathological findings. The patient was alive with no evidence of disease eight years after the surgery. Conclusions To the best of our knowledge, this is the first case report of LGMS arising in the levator scapulae muscle. In addition to the case report, 48 reports with 103 LGMS cases are reviewed and discussed. In previous reports of LGMS, there were 43 females and 60 males, with a mean age of 43.0 years (range, 2–75). There were 13 (12.6%) patients aged < 18 years, 67 (65.1%) patients aged 18 to 59 years, and 23 (22.3%) patients aged ≥60 years. The average tumor size was 4.4 cm (range: 0.4–22.0). The commonest sites of LGMS was the tongue. Tumor growth patterns were evaluated in 52 cases, and 44 cases (84.6%) showed infiltrative growth patterns. Local recurrence was 26.7%, and distant metastasis was 4.4%. Because of the locally aggressive feature, it is important to diagnose LGMS with biopsy and to excise the tumor with an adequately wide margin.

The incidence of SREs was significantly lower in NSCLC patients with better spinal stability as determined by SINS, which was a good prediction tool for SREs from bone metastasis. The lower incidence of SREs in EGFR-positive patients suggests tumor biology should be considered when predicting SREs.

We report 2 cases of late recurrence of osteosarcoma after 6 and 7 years. One patient had pulmonary metastasis, and the other had soft tissue recurrence. Both patients underwent complete resection and chemotherapy. The first patient achieved complete remission and remained disease-free 47 months later and had no limitation in his daily life. The second patient had a re-recurrence and underwent further resection and chemotherapy. He remained diseasefree 35 months later and could walk using a T-handled walking cane.Key words: neoplasm metastasis; neoplasm recurrence, local; osteosarcoma introduction Long-term survival of patients with osteosarcoma is 10% to 20% after surgical resection alone. With