Long Noncoding RNA ADAMTS9-AS2 Inhibits the Proliferation, Migration, and Invasion in Bladder Tumor Cells.

BACKGROUND: Bladder tumor is the fifth most prevalent tumor in men, yet its pathogenesis remains to be fully identified. Albeit a host of long noncoding RNAs (lncRNA) are emerging as new players involved in bladder tumor, the functions of many lncRNAs are still enigmatic. Reports on the deluge of studies on lncRNA ADAMTS9-AS2 have been convincingly associated with various tumors, but without mention of its roles in bladder tumor. Therefore, the roles of ADAMTS9-AS2 in bladder tumor cells were explored in our study. MATERIALS AND METHODS: Quantitative real-time PCR assays and bioinformatic tools were applied in bladder tumor cells to identify the ADAMTS9-AS2 and ADAMTS9 expression. Western blot assays were performed to obtain the protein levels of bladder tumor related key molecules. CCK8, clonogenic assay, scratch wound healing, and transwell assays were separately applied to identify the functional roles of ADAMTS9-AS2 on proliferation, migration, and invasion in bladder tumor cells. RESULTS: First, ADAMTS9-AS2 downregulation in bladder tumor cells was identified. Overexpression and knockdown experiments showed that ADAMTS9-AS2 expression was positively related to ADAMTS9, which is in accordance with the results from GEO database. Second, ADAMTS9-AS2 contributed to the inhibition of proliferation, migration, and invasion in bladder tumor cells. Third, ADAMTS9-AS2 was linked with PI3K/AKT/mTOR pathway related-molecules, several key autophagy, and apoptotic proteins. CONCLUSION: Conjointly, our findings suggested that ADAMTS9-AS2 might function as a tumor suppressor to restrain the proliferation, migration, and invasion in bladder tumor cells. The potential mechanism of ADAMTS9-AS2 related to PI3K/AKT/mTOR signal pathway was further identified. Of note, we found that ADAMTS9-AS2 has a significant effect on several key autophagy and apoptotic proteins. Therefore, these observations will provide supportive evidence to ADAMTS9-AS2 as a potential biomarker in patients with bladder tumor.

Bone transport using the Ilizarov method for osteosarcoma patients with tumor resection and neoadjuvant chemotherapy.

BACKGROUND: Studies on the applications of bone transport using the Ilizarov method for osteosarcoma (OS) patients with surgical resection and neoadjuvant chemotherapy are rare. METHODS: A retrospective analysis was conducted in 10 patients with limb OS receiving limb-salvage treatment by Ilizarov method from 2007 to 2012 in our hospital. The general information, treatment outcomes and follow-up data of the patients were collected. RESULTS: The mean length of the transported fragment and the mean transport distance of the affected limb were both 14 cm. The mean time in the external fixator was 34.2 ±â€¯11.2 months (16-47 months) and the mean external fixation index (EFI) was 75 days/cm. The mean follow-up time was 68.6 ±â€¯26.6 months (37-103 months). Seven patients underwent additional operations to treat the postoperative complications, and the mean number of operation was 1.7 times. Only one patient underwent amputation due to tumor relapse and all patients survived without tumor. The limb-salvage rate was 90%. At the time of external fixator removal, the ASAMI-bone score was good in 66.7% of patients and the ASAMI-function score was fair in 66.7% of cases. The mean MSTS score was 18.6 ±â€¯3.2 (n = 9). At 10 months after fixator removal, both the ASAMI-bone score and ASAMI-function score were both excellent in 80% and good in 20% cases, and the mean MSTS score was further improved to 27.2 ±â€¯1.11 (n = 5). CONCLUSION: Bone transport using the Ilizarov method can achieve good therapeutic effectiveness in the limb-salvage treatment for OS patients with neoadjuvant chemotherapy as long as the complications can be timely recognized and well managed.

Hippo/YAP signaling pathway is involved in osteosarcoma chemoresistance.

BACKGROUND: Osteosarcoma is the most common bone malignancy in children and adolescents, and 20%-30% of the patients suffer from poor prognosis because of individual chemoresistance. The Hippo/yes-associated protein (YAP) signaling pathway has been shown to play a role in tumor chemoresistance, but no previous report has focused on its involvement in osteosarcoma chemoresistance. This study aimed to investigate the role of the Hippo/YAP signaling pathway in osteosarcoma chemoresistance and to determine potential treatment targets. METHODS: Using the Cell Titer-Glo Luminescent cell viability assay and flow cytometry analysis, we determined the proliferation and chemosensitivity of YAP-overexpressing and YAP-knockdown osteosarcoma cells. In addition, using western blotting and the real-time polymerase chain reaction technique, we investigated the alteration of the Hippo/YAP signaling pathway in osteosarcoma cells treated with chemotherapeutic agents. RESULTS: Mammalian sterile 20-like kinase 1 (MST1) degradation was increased, and large tumor suppressor kinase 1/2 (LATS1/2) total protein levels were decreased by methotrexate and doxorubicin, which increased activation and nuclear translocation of YAP. Moreover, YAP increased the proliferation and chemoresistance of MG63 cells. CONCLUSIONS: The Hippo/YAP signaling pathway plays a role in osteosarcoma chemoresistance, and YAP is a potential target for reducing chemoresistance.

Amputation Versus Limb-Salvage Surgery in Patients with Osteosarcoma: A Meta-analysis.

BACKGROUND: This meta-analysis compared survival and function in patients with limb osteosarcoma treated with limb-salvage surgery (LSS) versus amputation or rotationplasty. METHODS: Medline, Cochrane, EMBASE, and Google Scholar were searched until November 30, 2015 for studies reporting Musculoskeletal Tumor Society (MSTS) scores and survival rates in osteosarcoma patients. Differences between patients undergoing LSS versus ablative surgery were analyzed based on MSTS scores and postoperative survival rates. RESULTS: Of 1330 patients in the studies analyzed, 934 underwent LSS, and 662 were treated with amputation. A random-effects model was applied due to heterogeneity among studies (Q statistic = 1.829, I (2) = 0 %, p = 0.767). No difference was found in post-operative local recurrence rate between amputees and patients receiving LSS. The 5-year survival rate was significantly lower with amputation compared with LSS (OR 0.628; 95 % CI 0.431-0.913, p = 0.015). The 2-year survival rate was not different between amputation and LSS. In addition, amputees had lower MSTS scores than those undergoing LSS (difference in means = -4.46 %, 95 % CI 6.49-2.45 %, p < 0.001). CONCLUSIONS: LSS results in higher 5-year survival rates and better functional outcomes as indicated by MSTS scores in patients with limb osteosarcomas.

Controllable drug release and effective intracellular accumulation highlighted by anisotropic biodegradable PLGE nanoparticles.

Control of the stretching or compressing ratio of spherical nanoparticles (NPs) leads to a dramatic change in the shape and size of particles based on amphiphilic biodegradable poly(lactide-co-glycolide-b-ethylene glycol-b-lactide-co-glycolide) (PLGE) triblock copolymers. Drug release, endocytosis and intracellular accumulation tests on these anisotropic PLGE NPs show significantly enhanced properties in comparison with spherical NPs, indicating they are good candidates for drug delivery.

Effects of endostar combined multidrug chemotherapy in osteosarcoma.

Angiogenesis is closely related to tumor development and metastasis. Osteosarcoma is an angiogenesis-dependent tumor, and studies have shown that chemotherapy often induces angiogenesis. Endostatin is a broad spectrum angiogenesis inhibitor and, while pre-clinical trials have shown that the combination of endostatin with chemotherapy can enhance anti-tumor effects, this effect has not yet been shown in clinical trials. Here, we aimed to evaluate the clinical efficacy of endostar (ES, human recombinant endostatin) combined with chemotherapy in the treatment of osteosarcoma patients. A total of 116 newly diagnosed patients with osteosarcoma were enrolled in this study. All patients received 4cycles of chemotherapy with (54 cases) or without (62 cases) ES. ES was administered intravenously at a dose of 15mg/day for 2weeks during each cycle of chemotherapy. The tumors were removed by surgery after 2cycles of chemotherapy treatment, and their histologic response to chemotherapy was evaluated. Immunohistochemistry was used to measure VEGF and CD 31 expression. Chemotherapy increased VEGF expression and the presence of microvessels in osteosarcoma tissues compared with pre-chemotherapy. No significant difference was observed in the histologic response between the ES treatment and non-treatment groups. However, ES treatment significantly inhibited the chemotherapy-induced VEGF expression and presence of microvessels. The ES treatment did not affect the overall survival rate but did increase the event-free survival rate and decreased the occurrence of metastases. In conclusion, our results indicate that antiangiogenic therapy using ES has the potential to prevent the progression of metastases.

IL-17A stimulates the progression of giant cell tumors of bone.

PURPOSE: Giant cell tumors of bone (GCTB) exhibit aggressive bone lytic behavior. Studies have shown that interleukin 17A (IL-17A) is involved pathologic bone resorption in various skeletal disorders. Thus, we have investigated the role of IL-17A in GCTBs. EXPERIMENTAL DESIGN: We evaluated the progression of GCTBs using Campanacci grading and Enneking staging systems in 74 patients with GCTB. The expression of IL-17A and the IL-17A receptor A (IL-17RA) was assessed in GCTB tissues and in both multinucleated giant cells (MNGC) and stromal cells cultured in vitro using immunostaining and reverse transcription PCR (RT-PCR). The effects of IL-17A on the osteolytic activity of the MNGCs and the proliferation of the stromal cells were investigated using the "pit" formation and MTT assays, respectively. The effects of IL-17A on the expression of proosteolytic factors were examined in primary cultured MNGCs and stromal cells using RT-PCR, Western blotting, and gene expression microarrays. RESULTS: In GCTBs, we detected abundant levels of IL-17A, which were associated with tumor extension and grade. IL-17A is predominantly produced by MNGCs, whereas IL-17RA is expressed by both MNGCs and stromal cells in GCTBs. In the MNGCs, the IL-17A increased the mRNA expression of IL-17A and proosteolytic enzymes, and also enhanced osteolytic ability. In the stromal cells, the IL-17A stimulated cellular proliferation and the expression of proosteolytic factors, including RANKL through myc and STAT3, respectively. In addition, IL-17A stimulated in vivo tumor growth and the extent of angiogenesis in GCTBs. CONCLUSION: IL-17A stimulates the progression of GCTBs and might represent a useful candidate marker for progression and as a therapeutic target for GCTBs.

Down-regulation of long non-coding RNA TUG1 inhibits osteosarcoma cell proliferation and promotes apoptosis.

OBJECTIVE: To investigate the expression level of TUG1 and one of its transcript variants (n377360) in osteosarcoma cells and assess the role of TUG1 in proliferation and apoptosis in the U2OS cell line. METHODS: TUG1 and n377360 expression levels in patients with osteosarcomas and the U2OS human osteosarcoma cell line were evaluated using real-time quantitative PCR. U2OS cells were transected with TUG1 and n377360 siRNA or non-targeting siRNA. MTS was performed to assess the cell proliferation and flow cytometry was applied to analyze apoptosis. RESULTS: We found significantly higher TUG1 and n377360 expression levels in osteosarcoma tissues compared with matched non-tumorous tissues. In line with this, suppression of TUG1 and n377360 expression by siRNA significantly impaired the cell proliferation potential of osteosarcoma cells. Furthermore, inhibition of TUG1 expression significantly promoted osteosarcoma cell apoptosis. CONCLUSIONS: The overexpression of TUG1 and n377360 in osteosarcoma specimens and the functional role of TUG1 and n377360 regarding cell proliferation and apoptosis in an osteosarcoma cell line provided evidence that the use of TUG1 or n377360 may be a viable but an as yet unexplored therapeutic strategy in tumors that over express these factors.

Reconstrução pélvica com aloenxerto ósseo após excisão de tumor / Pelvic reconstruction with allogeneic bone graft after tumor resection

Objetivos: A reconstrução pélvica após excisão de tumor é um desafio. Métodos: realizou-se um estudo retrospectivo para comparar os desfechos entre pacientes submetidos a cirurgia de reconstrução da pelve com aloenxerto ósseo após excisão em bloco de tumores pélvicos e pacientes submetidos apenas à excisão. Resultados: os pacientes sem reconstrução tiveram escores funcionais significantemente menores 3 meses (10 vs. 15, P = 0,001) e 6 meses após a cirurgia (18,5 vs. 22, P = 0,0024), menor tempo de hospitalização (16 dias vs. 40 dias, P < 0,001) e menor custo hospitalar (97.500 vs.193.000 yuans, P < 0,001) do que os que foram submetidos a reconstrução pélvica. Os escores funcionais foram similares 12 meses depois da cirurgia (21,5 vs. 23, P = 0,365) sem diferença na taxa de complicações entre os dois grupos (P > 0,05). Conclusões: A reconstrução pélvica com aloenxerto ósseo depois de cirurgia de tumores pélvicos é associada a desfechos cirúrgicos e funcionais satisfatórios. Outros estudos clínicos são necessários para explorar como selecionar o melhor método de reconstrução. Nível de Evidência IV, Séries de Casos.

Objectives: Pelvic reconstruction after tumor resection is challenging. Methods: a retrospective study had been performed to compare the outcomes between patients undergoing reconstructive surgery of the pelvis with allogeneic bone graft after en bloc resection of pelvic tumors and patients undergoing en bloc resection only. Results: Patients without reconstruction had significantly lower functional scores at 3 months (10 vs. 15, P = 0.001) and 6 months after surgery (18.5 vs. 22, P = 0.0024), a shorter duration of hospitalization (16 days vs. 40 days, P < 0.001), and lower hospital costs (97,500 vs. 193,000 RMB, P < 0.001) than those undergoing pelvic reconstruction. Functional scores were similar after 12 months of surgery (21.5 vs. 23, P = 0.365) with no difference in the rate of complications between the two groups (P > 0.05). Conclusions: pelvic reconstruction with allogeneic bone graft after surgical management of pelvic tumors is associated with satisfactory surgical and functional outcomes. Further clinical studies are required to explore how to select the best reconstruction method. Level of Evidence IV, Case Series.

Pelvic reconstruction with allogeneic bone graft after tumor resection.

OBJECTIVES: : Pelvic reconstruction after tumor resection is challenging. METHODS: A retrospective study had been preformed to compare the outcomes among patients who received pelvic reconstructive surgery with allogeneic bone graft after en bloc resection of pelvic tumors and patients who received en bloc resection only. RESULTS: Patients without reconstruction had significantly lower functional scores at 3 months (10 vs. 15, P = 0.001) and 6 months after surgery (18.5 vs. 22, P = 0.0024), a shorter duration of hospitalization (16 day vs. 40 days, P < 0.001), and lower hospitalization costs (97,500 vs. 193,000 RMB, P < 0.001) than those who received pelvic reconstruction. Functional scores were similar at 12 months after surgery (21.5 vs. 23, P = 0.365) with no difference in the rate of complications between the two groups (P > 0.05). CONCLUSIONS: : Pelvic reconstruction with allogeneic bone graft after surgical management of pelvic tumors is associated with satisfactory surgical and functional outcomes. Further clinical studies are required to explore how to select the best reconstruction method. Level of Evidence IV, Case Series.