In C. elegans, the Sma/Mab TGF␤ signaling pathway regulates body size and male tail patterning. SMA-9, the C. elegans homolog of Schnurri, has been shown to function as a downstream component to mediate the Sma/Mab TGF␤ signaling pathway in these processes. We have discovered a new role for SMA-9 in dorsoventral patterning of the C. elegans post-embryonic mesoderm, the M lineage. In addition to a small body size, sma-9 mutant animals exhibit a dorsal-to-ventral fate transformation within the M lineage. This M lineage defect of sma-9 mutants is unique in that animals carrying mutations in all other known components of the TGF␤ pathway exhibit no M lineage defects. Surprisingly, mutations in the core components of the Sma/Mab TGF␤ signaling pathway suppressed the M lineage defects of sma-9 mutants without suppressing their body size defects. We show that this suppression specifically happens within the M lineage. Our studies have uncovered an unexpected role of SMA-9 in antagonizing the TGF␤ signaling pathway during mesodermal patterning, suggesting a novel mode of function for the SMA-9/Schnurri family of proteins.

G-POEM is a technically feasible, safe, and successful procedure for the treatment of refractory gastroparesis. A further multicenter comparative study should be performed to compare this technique to laparoscopic pyloromyotomy.

specimen revealed a tumour mass with histologic features of pronounced osteogenesis and no more evidence of gctb. This case demonstrated a major tumour response to denosumab in the neoadjuvant setting, with a complete pathologic response.Is denosumab a breakthrough in the treatment of gctb? We reviewed the literature focusing on denosumab and gctb, and here we discuss the biggest questions related to the future management of gctb. GIANT CELL TUMOUR OF BONEAs one type of giant-cell-rich lesion of bone, gctb is characterized by the presence of numerous multinucleated osteoclast-type giant cells, and in this mesenchymal tumour, the mononuclear stromal cells are the neoplastic cell type 2 . The giant cells have been confirmed to express rankl and are responsible for the aggressive osteolytic nature of the tumour 3 . Although generally benign, atypical gctb may be associated with multiple local recurrences, multicentricity, pulmonary metastases, or lesions that cannot be removed surgically without causing substantial morbidity 4 . The World Health Organization therefore classifies gctb as "an aggressive, potentially malignant lesion" 5 .In the United States, gctb accounts for approximately 5% of all primary bone tumours and 20% of all benign bone tumours in adults 6 . About 50−60 new cases of gctb are managed by specialist health care services each year in the United Kingdom 7 . The disease is more common in China and India, where it constitutes approximately 20% of all primary bone tumours 5 . Giant cell tumour of bone occurs most commonly during the second to fourth decades of life (60%-75%) and has a maleto-female ratio in the range 1:1.2 to 1:1.5 2,5 . Most lesions develop in the long bones (75%-90%), with most cases (50%-65%) occurring near the knee 1,2,8 . Other frequent sites are the distal radius, proximal humerus, fibula, sacrum, and vertebral body (fewer than 3% of cases) 2,8 . In no reported case has gctb ABSTRACT Giant cell tumour of bone (gctb) is one type of giantcell-rich bone lesion characterized by the presence of numerous multinucleated osteoclast-type giant cells. Giant cells are known to express rankl (receptor activator of nuclear factor κB ligand) and are responsible for the aggressive osteolytic nature of the tumour. No available treatment option is definitively effective in curing this disease, especially in surgically unsalvageable cases. In recent years, several studies of denosumab in patients with advanced or unresectable gctb have shown objective changes in tumour composition, reduced bony destruction, and clinical benefit.Denosumab is a fully human monoclonal antibody that targets and binds with high affinity and specificity to rankl. Several large phase iii studies have shown that denosumab is more effective than bisphosphonates in reducing skeletal morbidity arising from a wide range of tumours and that it can delay bone metastasis. The relevant articles are reviewed here. The controversies related to the future use of denosumab in the treatment of gctb are discussed. KEY WORDSDenosuma...

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Perioperative TEAS at P6 may be an effective adjunct to the standard antiemetic drug therapy for the prevention of PONV after infratentorial craniotomy.

Giant cell tumor (GCT) of the bone is a relatively common primary bone tumor. Treatment with simple curettage often results in a high local recurrence rate. Tumor resection and reconstruction with prosthesis or an allograft has a low rate of local recurrence; however, the patient’s native joint function becomes significantly impaired. With the development and usage of aggressive curettage, it is a priority to treat GCT with a method that reduces the local recurrence rate and preserves the native joint. To evaluate the feasibility of treating GCT with aggressive curettage and cement filling using internal fixation and oral bisphosphonates, 16 patients with GCT of the bone located in the distal femur and treated in our department from January 2008 to June 2011, were followed up. The patients had received aggressive curettage, bone cement filling, internal fixation and oral administration of bisphosphonates.There were seven males and nine females in total, with a mean age of 38 years. All patients were carefully assessed prior to surgery in order to determine the integrity of the tumor cavity. Subsequently, patients were treated with aggressive curettage by high-speed burring and cementation with internal fixation, and were administered postoperative oral alendronate sodium tablets (10 mg/day) for two years. The median follow-up time was 25 months. None of the patients were lost to follow-up. No local recurrence or metastasis was observed in the last follow-up. The Enneking limb function score range of the affected limb was 24–29 (average, 26.7). At the last follow-up, all patients exhibited solid fixation without fracture of the subchondral bone in plain radiographs. Based on these data, we suggest that patients with distal femoral GCT may be treated with aggressive curettage and cement filling, with internal fixation and oral bisphosphonates. The advantages of this method are its safety and efficacy. However, the long-term outcomes require further investigation.

BackgroundThe combination of chemotherapeutic drugs with different pharmacological action has emerged as a promising therapeutic strategy in the treatment of cancers. Present study examines the antitumor potential of paclitaxel (PTX) and etoposide (ETP)-loaded PLGA nanoparticles for the treatment of osteosarcoma.ResultsThe resulting drug-loaded PLGA NP exhibited a nanosize dimension with uniform spherical morphology. The NP exhibited a sustained release profile for both PTX and ETP throughout the study period without any sign of initial burst release. The combinational drug-loaded PLGA NP enhanced the cytotoxic effect in MG63 and Saos-2 osteosarcoma cell lines, in comparison to either native drug alone or in cocktail combinations. Additionally, NPs showed an appreciable uptake in MG63 cells in a time-based manner. Co-delivery of anticancer drugs resulted in enhanced cell cycle arrest and cell apoptosis. The results clearly showed that combinational drugs remarkably improved the therapeutic index of chemotherapeutic drugs. The greater inhibitory effect of nanoparticle combination would be of great advantage during systemic cancer therapy.ConclusionTaken together, our study demonstrated that PTX-ETP/PLGA NP based combination therapy holds significant potential towards the treatment of osteosarcoma.

There is controversy regarding the impact of infection on long-term prognosis in osteosarcoma patients. Clinical trials and experiments relating to this field could bring reconsideration of immunotherapy for osteosarcoma. The clinical records were reviewed of 125 osteosarcoma patients with a mean follow-up of 5.1±3.9 years (range, 0.5-19.8 years), and a review of the literature was also carried out. Chronic localized infections (but not systemic infection) were determined in 6 patients (4.8%). Similar chemotherapeutic regimens (P=1.00) and histological reactions (P=0.65) were observed in patients with or without infection. Tumor location of proximal tibia (P=0.04) was more common in infected patients. More amputations (P<0.001) were necessitated in infected patients due to uncontrolled infection. The 5-year overall survival rate and event-free survival rate in infected patients were 100%, which were significantly higher than that of the non-infected patients, of whom the rates were 54 and 43% respectively (log-rank test: total survival, P=0.01; tumor-free survival, P=0.01). Distant metastasis was an independent risk factor for survival determined by Cox regression analysis (P<0.001, 95 confidence interval, 1.59-3.98). These findings suggested infection was likely to have positive effects on survival in osteosarcoma patients, however, underlying mechanisms remain to be elucidated. Reconsideration of the association of infection and survival in osteosarcoma patients will help to explore novel therapeutic routes and targets in these patients.