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musculoskeletal metastasis - Top 30 Publications

Case report: vertebral foreign body granuloma mimicking a skeletal metastasis.

Intraosseous foreign body granuloma formation related to migrated surgical material is a rarely reported condition with variable imaging appearance. In this case report, we describe a foreign body granuloma that occurred in a lumbar vertebral body one level above a prior surgical fusion. The lytic appearance mimicked a skeletal metastasis in a 65-year-old patient with recently diagnosed renal cell carcinoma. To the best of our knowledge, this is the first reported case of a lumbar vertebral foreign body granuloma occurring distant from the site of surgery, indistinguishable from skeletal metastasis on radiologic examination.

microRNA-124 inhibits bone metastasis of breast cancer by repressing Interleukin-11.

Most patients with breast cancer in advanced stages of the disease suffer from bone metastases which lead to fractures and nerve compression syndromes. microRNA dysregulation is an important event in the metastases of breast cancer to bone. microRNA-124 (miR-124) has been proved to inhibit cancer progression, whereas its effect on bone metastases of breast cancer has not been reported. Therefore, this study aimed to investigate the role and underlying mechanism of miR-124 in bone metastases of breast cancer.

Mid- to long-term clinical outcome of giant cell tumor of bone treated with calcium phosphate cement following thorough curettage and phenolization.

Giant cell tumors of bone (GCTB) are intermediate and locally aggressive bone tumor. Calcium phosphate cement (CPC) is a bone void filler used in orthopaedic surgery. This study investigated the clinical outcome of GCTB treated with thorough curettage, phenolization, and CPC.

Isolated Right Atrial Mass in a Candidate of Coronary Bypass Grafting.

Hepatocellular carcinoma (HCC) is not uncommon neoplasm, and its occurrences with coronary artery disease (CAD) is more confronted by cardiac surgeon today. In most cases, when the HCC is detected, it has invaded to regional or distant sites. The most frequent location of HCC metastasis includes pulmonary system, musculoskeletal, lymphatic system, and central nervous system. Indeed, intra-atrial metastasis is a rare phenomenon and associated with poor outcome. We report a case of CAD with known HCC that referred for CABG before scheduling for hepatic tumor management. His severe typical chest pain, aggravated by mild activity so his abdominal pain is shadowed by chest pain. The abdominal ultrasound revealed a large mass in the left hepatic lobe. Chest x-ray was unremarkable. Routine preoperative transthoracic echocardiography (TEE) exhibits a large sessile mass in the right atrium. The patient underwent combined resection of right atrial mass and off-pump coronary artery bypass grafting. The most of HCC patients with RA involvement usually presenting with lengthy thrombus that continues from vascular invasion site to RA, however, as in our patient, isolated and sole metastasis to RA is an exceptional phenomenon in HCC. The clinical postoperative course was uneventful, and the patient discharged on the 10th day of operation. The six-month follow-up revealed no recurrence of right atrial mass when the patient completed his treatment by hepatic lobectomy and combined adjuvant chemotherapy.

Development and validation of a prognostic index to predict pulmonary metastasis of giant cell tumor of bone.

Giant cell tumor of bone (GCTB) is an intermittent tumor with a low probability of pulmonary metastasis. Our aim was to investigate the risk factors and establish a nomogram predictive model for GCTB pulmonary metastasis.

The Efficacy of Wide Resection for Musculoskeletal Metastatic Lesions of Renal Cell Carcinoma.

This study evaluated the outcome of wide resection for metastatic renal cell carcinoma (RCC) to the bone or soft tissue.

Epidemiology of soft tissue sarcomas in a university center in Hungary.

Our aim was to investigate the rare malignant soft tissue sarcomas responsible for 1.5% of all malignant tumors, to compare our epidemiological data from the patient population of the Department of Orthopaedics, Semmelweis University, to data described in the international literature for soft tissue tumors. We reviewed 595 cases of primary soft tissue sarcomas treated between 1994 and 2014 and compared results to international data from the literature. Our results were similar to those found in the international literature: mean age, mild male predominance, the most common sarcoma subgroups, the superficial and deep sarcoma ratio, low and high grade sarcoma ratio, the ratio of patients with a primary lung metastasis. Compared to other European data we found significantly longer patient referral to centers (3.6 months in case of superficial sarcomas, 8 months in case of deep localization) which surprisingly had no substantial effect on average tumor size (superficial: 5 cm, deep: 10.5 cm). This corresponds with data from the literature. The long delay period in patients' request of medical service draws attention to difficulties in differential diagnosis in this rare type of tumor, delays in referring patients to a center, and the lack of consultation. We recommend that the required investigations be performed in a musculoskeletal oncology center where this type of cancer is treated.

Outcomes of internal hemipelvectomy for pelvic tumors: a developing country's prospective.

Previously, external hemipelvectomy was the mainstay of treatment for pelvic tumors. However, with technological advancements, limb salvage procedures such as internal hemipelvectomy have emerged as a viable alternative. However, there is limited literature available on long-term outcomes and complications of internal hemipelvectomy, especially from developing countries. Therefore, the objective of this study was to share our experience of internal hemipelvectomy at a tertiary care center in a developing country.

Apatinib inhibits migration and invasion as well as PD-L1 expression in osteosarcoma by targeting STAT3.

The cure rate of osteosarcoma has not improved in the past 30 years. The new treatments and drugs is urgently needed, especially for metastatic osteosarcoma. Anti-angiogenesis therapy and immunotherapy has got promising anti-tumor effects in various tumors. It is hypothesised that combining checkpoint inhibitor immunotherapies with antiangiogenic treatment may have a synergistic effect and enhance the efficacy of both treatments. However, its underlying mechanism remain largely uninvestigated. To investigate the clinical significance of vascular endothelial growth factor receptor-2 (VEGFR2) and programmed death ligand-1 (PD-L1) in osteosarcoma, we analyzes their expression levels in 93 osteosarcoma specimens by immunohistochemistry. Meanwhile, we analyzes their correlation with the metastatic behavior and overall survival (OS). We also investigate the effects of Apatinib on migration and invasion of osteosarcoma cells and its underlying mechanism in vitro and in vivo. In our study, the positive rates of the VEGFR2 and PD-L1 expression are 64.5% (60/93) and 35.5% (33/93), respectively. A significant correlation is detected between VEGFR2 and PD-L1 expression (P = 0.009). Receiver-operating characteristic (ROC) curves analysis indicates the predictive value of the two markers in tumor metastasis, and both PD-L1 and VEGFR2 are negatively correlated with OS. Transwell assays reveals that VEGFR2 inhibition attenuates migration and invasion of osteosarcoma cells. Mechanistically, we demonstrate that Apatinib attenuates migration and invasion by suppressing epithelial-mesenchymal transition (EMT) and inactivating STAT3. Additionally, Apatinib reduces PD-L1 expression in osteosarcoma cells. Apatinib markedly weakens pulmonary metastatic potential of osteosarcoma in vivo. In conclusion, our study reveals a pro-metastatic functional mechanism for VEGFR2 in osteosarcoma. Furthermore, we demonstrate that Apatinib exerts anti-tumor effect not only through antiangiogenic effect, but also via suppressing immune escape, which may represent a potential therapeutic target for metastatic osteosarcoma.

Lesion magnetic susceptibility response to hyperoxic challenge: A biomarker for malignant brain tumor microenvironment?

Quantitative susceptibility mapping has been previously used to differentiate lesions in patients with brain tumors. The aim of this work was to characterize the response of magnetic susceptibility differences in malignant brain tumors and surrounding edema to hyperoxic and hypercapnic respiratory challenges.

MiRNA-210: A Current Overview.

microRNAs (miRNAs) are a group of highly conserved small non-coding RNAs that were found to enhance mRNA degradation or inhibit post-transcriptional translation. Accumulating evidence indicates that miRNAs contribute to tumorigenesis and cancer metastasis. microRNA-210 has been largely studied in the past several years and has been identified as a major miRNA induced under hypoxia. A variety of miR-210 targets have been identified pointing to its role, not only in mitochondrial metabolism, but also in angiogenesis, the DNA damage response, cell proliferation, and apoptosis. Based on earlier research findings, this review aims to provide a current overview on the involvement of miRNA-210 in biological processes and diseases.

Analysis of the Infiltrative Features of Chordoma: The Relationship Between Micro-Skip Metastasis and Postoperative Outcomes.

Chordomas are very rare primary malignant bone tumors that arise commonly from the sacrum (50-60%) and clivus (25-35%). Chordomas have a high rate of recurrence. The authors confirmed a unique histologic infiltration pattern of chordomas that resembles a skip-metastatic lesion in normal tissue around tumor, which they named "micro-skip metastasis." This study aimed to examine the correlations between the clinicopathologic features of chordomas, including micro-skip metastasis, and the clinical outcomes, including overall survival, local recurrence-free survival, and distant metastasis-free survival.

Synovial sarcoma of the shoulder: A series of 14 cases.

Synovial sarcoma is a rare soft tissue sarcoma with poor long-term prognosis due to late recurrence and metastasis. Synovial sarcoma arises in less than 6% from the shoulder. As a result, there is limited information in the literature about synovial sarcoma of the shoulder (SSS).

Therapeutic effect of neoadjuvant chemotherapy combined with curettage to treat distal femoral osteosarcoma: A case report.

Osteosarcoma is the most common malignant bone tumor in children and adolescents. Metastasis occurs early, the mortality rate is high, and the tumor results in a tremendous physical, mental, and economic burden on patients. Therefore, the treatment of osteosarcoma has been important for orthopedic surgeons. However, treatment has always been a difficult problem globally.

Combined Vertebral Augmentation and Radiofrequency Ablation in the Management of Spinal Metastases: an Update.

Spinal metastases are the most commonly encountered tumour of the spine, occurring in up to 40% of patients with cancer. Each year, approximately 5% of cancer patients will develop spinal metastases. This number is expected to increase as the life expectancy of cancer patients increases. Patients with spinal metastases experience severe and frequently debilitating pain, which often decreases their remaining quality of life. With a median survival of less than 1 year, the goals of treatment in spinal metastases are reducing pain, improving or maintaining level of function and providing mechanical stability. Currently, conventional treatment strategies involve a combination of analgesics, bisphosphonates, radiotherapy and/or relatively extensive surgery. Despite these measures, pain management in patients with spinal metastases is often suboptimal. In the last two decades, minimally invasive percutaneous interventional radiology techniques such as vertebral augmentation and radiofrequency ablation (RFA) have shown progressive success in reducing pain and improving function in many patients with symptomatic spinal metastases. Both vertebral augmentation and RFA are increasingly being recognised as excellent alternative to medical and surgical management in carefully selected patients with spinal metastases, namely those with severe refractory pain limiting daily activities and stable pathological vertebral compression fractures. In addition, for more complicated lesions such as spinal metastasis with soft tissue extension, combined treatments such as vertebral augmentation in conjunction with RFA may be helpful. While combined RFA and vertebral augmentation have theoretical benefits, comparative trials have not been performed to establish superiority of combined therapy. We believe that a multidisciplinary approach as well as careful pre-procedure evaluation and imaging will be necessary for effective and safe management of spinal metastases. RFA and vertebral augmentation should be considered during early stages of the disease so as to maintain the remaining quality of life in this patient population group.

BMPR2 and HIF1-α overexpression in resected osteosarcoma correlates with distant metastasis and patient survival.

Bone morphogenetic protein receptor 2 (BMPR2) and hypoxia-inducible factor 1-α (HIF1-α) existed abnormal expression in several types of cancer. However, their expressions and related roles in osteosarcoma are largely unknown.

An acetabular-preserving procedure for pelvic giant cell tumor involving partial acetabulum.

The management of pelvic giant cell tumors (GCTs) involving the acetabulum remains a challenge for surgeons on how to balance the relative benefits of minimizing recurrence and maintaining postoperative hip function. The present study was to present and evaluate the clinical indications, operative technique, and outcomes of pelvic GCTs involving partial acetabulum treated with multiplanar osteotomy and reconstruction of autogenous femoral head bone grafts combined with cementless total hip arthroplasty (THA).

A Subpopulation of Stromal Cells Controls Cancer Cell Homing to the Bone Marrow.

Breast and prostate cancer cells home to the bone marrow, where they presumably hijack the hematopoietic stem cell niche. We characterize here the elusive premetastatic niche by examining the role of mesenchymal stromal cells (MSC) in cancer cell homing. Decreasing the number of MSC pharmacologically enhanced cancer cell homing to the bone marrow in mice. In contrast, increasing the number of these MSCs by various interventions including G-CSF administration diminished cancer cell homing. The MSC subpopulation that correlated best with cancer cells expressed stem, endothelial, and pericytic cell markers, suggesting these cells represent an undifferentiated component of the niche with vascular commitment. In humans, a MSC subpopulation carrying markers for endothelial and pericytic cells was lower in the presence of cytokeratin+ cells in bone marrow. Taken together, our data show that a subpopulation of MSC with both endothelial and pericytic cell surface markers suppresses the homing of cancer cells to the bone marrow. Similar to the presence of cytokeratin+ cells in the bone marrow, this MSC subpopulation could prove useful in determining the risk of metastatic disease, and its manipulation might offer a new possibility for diminishing bone metastasis formation.Significance: These findings establish an inverse relationship between a subpopulation of mesenchymal stromal cells and cancer cells in the bone marrow. Cancer Res; 78(1); 129-42. ©2017 AACR.

Carbon-fiber reinforced intramedullary nailing in musculoskeletal tumor surgery: a national multicentric experience of the Italian Orthopaedic Society (SIOT) Bone Metastasis Study Group.

Carbon fiber reinforced (CFR) implants have been proposed for the treatment of fractures or impending fractures of the long bones in the oncology patient. Aim of this study is to present the largest cohort of oncology patients operated by CFR nailing by the Italian Orthopaedic Society (SIOT) Bone Metastasis Study Group.

miR-216a inhibits osteosarcoma cell proliferation, invasion and metastasis by targeting CDK14.

Osteosarcoma (OS) has emerged as the most common primary musculoskeletal malignant tumour affecting children and young adults. Cyclin-dependent kinases (CDKs) are closely associated with gene regulation in tumour biology. Accumulating evidence indicates that the aberrant function of CDK14 is involved in a broad spectrum of diseases and is associated with clinical outcomes. MicroRNAs (miRNAs) are crucial epigenetic regulators in the development of OS. However, the essential role of CDK14 and the molecular mechanisms by which miRNAs regulate CDK14 in the oncogenesis and progression of OS have not been fully elucidated. Here we found that CDK14 expression was closely associated with poor prognosis and overall survival of OS patients. Using dual-luciferase reporter assays, we also found that miR-216a inhibits CDK14 expression by binding to the 3'-untranslated region of CDK14. Overexpression of miR-216a significantly suppressed cell proliferation, migration and invasion in vivo and in vitro by inhibiting CDK14 production. Overexpression of CDK14 in the miR-216a-transfected OS cells effectively rescued the suppression of cell proliferation, migration and invasion caused by miR-216a. In addition, Kaplan-Meier analysis indicated that miR-216a expression predicted favourable clinical outcomes for OS patients. Moreover, miR-216a expression was downregulated in OS patients and was negatively associated with CDK14 expression. Overall, these data highlight the role of the miR-216a/CDK14 axis as a novel pleiotropic modulator and demonstrate the associated molecular mechanisms, thus suggesting the intriguing possibility that miR-216a activation and CDK14 inhibition may be novel and attractive therapeutic strategies for treating OS patients.

Treatment strategies for central low-grade chondrosarcoma of long bones: a systematic review of the literature and meta-analysis.

The need for wide local excision (WLE) versus intralesional (IL) treatment of low-grade chondrosarcomas (CS) of the appendicular skeleton remains controversial. We sought to perform a systematic review and meta-analysis to compare different conventional types of surgical treatments for grade I CS in terms of: (1) rate of local recurrence (LR) and metastases, (2) functional outcome as measured by the Musculoskeletal Tumor Society (MSTS) score, (3) complication rate. Eighteen studies enrolling 695 patients met our criteria. Studies reported on WLE versus IL treatment (n = 7), and IL treatment with or without different adjuvants (N = 11). The LR rate was not significantly different between WLE and IL treatment (OR 2.31; 95% CI, 0.85-6.2; P = 0.1). On the contrary, complication rates were significantly lower in favor of IL treatment (OR 2.27; 95% CI, 0.07-0.72; P = 0.012). The mean reported MSTS score ranged from 21.8 to 28.2 for WLE and from 26.5 to 29.7 for IL treatment, with a significant difference in favor of IL treatment. IL treatment as an alternative to WLE does not greatly increase the risk of LR or metastasis and has lower complication rates with better functional scores. In light of the retrospective nature of the studies available, our findings should be interpreted with caution.

Isothiocyanates suppress the invasion and metastasis of tumors by targeting FAK/MMP-9 activity.

Isothiocyanates, which are present as glucosinolate precursors in cruciferous vegetables, have strong activity against various cancers. Here, we compared the anti-metastatic effects of isothiocyanates (benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC), and sulforaphane (SFN)) by examining how they regulate MMP-9 expression. Isothiocyanates, particularly PEITC, suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 activity and invasion in various cancer cell lines. By contrast, N-methyl phenethylamine, a PEITC analog without an isothiocyanate functional group, had no effect. A reporter gene assay demonstrated that BITC, PEITC, and SFN suppressed TAP-induced MMP-9 expression by inhibiting AP-1 and NF-κB in U20S osteosarcoma cells. All three compounds reduced phosphorylation of FAK, ERK1/2, and Akt. In addition, MMP-9 expression was downregulated by inhibiting FAK, ERK1/2, and Akt. Isothiocyanates-mediated inhibition of FAK phosphorylation suppressed phosphorylation of ERK1/2 and Akt in U2OS and A549 cells, along with the translocation of p65 and c-Fos, suggesting that isothiocyanates inhibit MMP-9 expression and cell invasion by blocking phosphorylation of FAK. Furthermore, isothiocyanates, abolished MMP-9 expression and tumor metastasis in vivo with the following efficacy: PEITC>BITC>SFN. Thus, isothiocyanates act as anti-metastatic compounds that suppress MMP-9 activity/expression by inhibiting NF-κB and AP-1 via suppression of the FAK/ERK and FAK/Akt signaling pathways.

IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease.

Interleukin 35 (IL-35) is a heterodimeric cytokine composed of IL-12p35 and Ebi3 subunits. IL-35 suppresses autoimmune diseases while preventing host defense to infection and promoting tumor growth and metastasis by converting resting B and T cells into IL-10-producing and IL-35-producing regulatory B (Breg) and T (Treg) cells. Despite sharing the IL-12p35 subunit, IL-12 (IL-12p35/IL-12p40) promotes inflammatory responses whereas IL-35 (IL-12p35/Ebi3) induces regulatory responses, suggesting that IL-12p35 may have unknown intrinsic immune-regulatory functions regulated by its heterodimeric partner. Here we show that the IL-12p35 subunit has immunoregulatory functions hitherto attributed to IL-35. IL-12p35 suppresses lymphocyte proliferation, induces expansion of IL-10-expressing and IL-35-expressing B cells and ameliorates autoimmune uveitis in mice by antagonizing pathogenic Th17 responses. Recapitulation of essential immunosuppressive activities of IL-35 indicates that IL-12p35 may be utilized for in vivo expansion of Breg cells and autologous Breg cell immunotherapy. Furthermore, our uveitis data suggest that intrinsic immunoregulatory activities of other single chain IL-12 subunits might be exploited to treat other autoimmune diseases.IL-12p35 is common to IL-35 and IL-12, which have opposing effects on inflammation. Here the authors show that the IL-12p35 subunit induces regulatory B cells and can be used therapeutically to limit autoimmune uveitis in mice.

Sclerostin: an Emerging Target for the Treatment of Cancer-Induced Bone Disease.

This review provides a summary of the current knowledge on Sost/sclerostin in cancers targeting the bone, discusses novel observations regarding its potential as a therapeutic approach to treat cancer-induced bone loss, and proposes future research needed to fully understand the potential of therapeutic approaches that modulate sclerostin function.

Resveratrol Regulates Colorectal Cancer Cell Invasion by Modulation of Focal Adhesion Molecules.

Resveratrol, a safe and multi-targeted agent, has been associated with suppression of survival, proliferation and metastasis of cancer, however, the underlying mechanisms for its anti-cancer activity, particularly on cellular signaling during cancer cell migration still remain poorly understood. We investigated the invasion response of two human colorectal cancer (CRC) cells (HCT116 and SW480) to resveratrol and studied the effect of specific pharmacological inhibitors, cytochalasin D (CytD) and focal adhesion kinase-inhibitor (FAK-I) on FAK, cell viability and migration in CRC. We found that resveratrol altered cell phenotype of both CRC cells, reduced cell viability and the results were comparable to FAK-I and CytD. These effects of resveratrol were associated with marked Sirt1 up-regulation, FAK down-regulation, inhibition of focal adhesion and potentiation of effects by combinatorial treatment of resveratrol and inhibitors. Interestingly, inhibition of FAK with FAK-I or treatment with CytD suppressed resveratrol-induced Sirt1 up-regulation and markedly down-regulated FAK expression. Resveratrol or combination treatment with inhibitors significantly activated caspase-3 and potentiated apoptosis. Moreover, resveratrol suppressed invasion and colony forming capacity, cell proliferation, β1-Integrin expression and activation of FAK of cells in alginate tumor microenvironment, similar to FAK-I or CytD. Finally, we demonstrated that resveratrol, FAK-I or CytD inhibited activation of NF-κB, suppressed NF-κB-dependent gene end-products involved in invasion, metastasis, and apoptosis; and these effects of resveratrol were potentiated by combination treatment with FAK-I or CytD. Our data illustrated that the anti-invasion effect of resveratrol by inhibition of FAK activity has a potential beneficial role in disease prevention and therapeutic management of CRC.

Management of a Tibial Plafond Lung Cancer Metastasis Using an Intramedullary Hindfoot Fusion Nail.

Metastatic disease to the tibial plafond is rare with few reports in the literature. No consensus exists regarding surgical reconstruction of large structural defects of the ankle due to these lesions, as each treatment must be tailored to the individual patient's goals and prognosis. Cancer metastases pose a unique challenge to limb salvage as there is often bone loss and poor soft tissue quality combined with the need for postoperative adjuvant therapy. The goal of surgery is to obtain early weightbearing, pain relief, and a durable reconstruction that will outlive the patient. In this report, we present the case of an intraarticular fracture of the tibial plafond with severe bone loss due to a lung carcinoma metastasis. The patient was successfully treated with en bloc tumor excision, curettage, argon beam coagulation, tibiotalocalcaneal arthrodesis using an intramedullary hindfoot fusion nail, and bone cementation with postoperative chemotherapy and radiation. One year after surgery, the patient was able to bear full weight on the extremity without a brace or assistive device and had no pain in the ankle with no local tumor recurrence.

Degalactotigonin, a Natural Compound from Solanum nigrum L., Inhibits Growth and Metastasis of Osteosarcoma through GSK3β Inactivation-Mediated Repression of the Hedgehog/Gli1 Pathway.

Purpose: Agents extracted from natural sources with antitumor property have attracted considerable attention from researchers and clinicians because of their safety, efficacy, and immediate availability. Degalactotigonin (DGT), extracted from Solanum nigrum L, has anticancer properties without serious side effects. Here, we explored whether DGT can inhibit the growth and metastasis of osteosarcoma.Experimental Design: MTT, colony formation, and apoptosis assays were performed to analyze the effects of DGT on osteosarcoma cell viability in vitro The migration and invasion abilities were measured using a Transwell assay. Animal models were used to assess the roles of DGT in both tumor growth and metastasis of osteosarcoma. Gli1 expression and function were measured in osteosarcoma cells and clinical samples. After DGT treatment, Gli1 activation and the phosphorylation status of multiple cellular kinases were measured with a luciferase reporter and phospho-kinase antibody array.Results: DGT inhibited proliferation, induced apoptosis, and suppressed migration and invasion in osteosarcoma cells. DGT, injected intraperitoneally after tumor inoculation, significantly decreased the volume of osteosarcoma xenografts and dramatically diminished the occurrence of osteosarcoma xenograft metastasis to the lungs. Mechanistically, DGT inhibited osteosarcoma growth and metastasis through repression of the Hedgehog/Gli1 pathway, which maintains malignant phenotypes and is involved in the prognosis of osteosarcoma patients. DGT decreased the activity of multiple intracellular kinases that affect the survival of osteosarcoma patients, including GSK3β. In addition, DGT represses the Hedgehog/Gli1 pathway mainly through GSK3β inactivation.Conclusions: Our studies provide evidence that DGT can suppress the growth and metastasis of human osteosarcoma through modulation of GSK3β inactivation-mediated repression of the Hedgehog/Gli1 pathway. Clin Cancer Res; 24(1); 130-44. ©2017 AACR.

Diagnostic methods for detection of bone metastases.

Skeletal metastases are severe complications in the course of cancer, and they indicate a worse prognosis. The use of modern imaging techniques allows rapid diagnosis of bone metastases. Properly selected diagnostic imaging (scintigraphy, positron emission tomography, whole body MRI) allows us to evaluate the number of metastatic foci in the skeletal system. Complementary imaging examinations (X-ray, computed tomography, magnetic resonance imaging) determine the extent of metastasis and its character: osteolytic, osteoblast, mixed). Hypercalcaemia is a symptom of low specificity for metastatic bone disease (a result of osteolysis); nevertheless, it is a significant complication in oncological treatment and worsens the prognosis of the patient. A biopsy is the final stage of the diagnostic process, which allows us to assess cell and tissue changes. Guided biopsies are performed under the control of musculoskeletal imaging methods (CT, MRI) and they are the most promising tools in bone metastases diagnosis. The development of guided biopsy techniques has led to the conclusion that they should be standard in diagnosing bone metastases. Liquid biopsy (LB) seems to be the most promising diagnostic method for detection of bone metastases. LB based on tumour-specific DNA mutation gives an opportunity for early detection and assessment of the molecular heterogeneity of the overall disease.

Surgical management of pelvic Ewing's sarcoma in children and adolescents.

The present study describes a novel surgical strategy used to treat immature pelvic Ewing's sarcoma (ES), one made possible owing to the intrinsic structure of the skeletally immature pelvis. A total of 12 children and adolescents with open triradiate cartilage received limb-salvage surgeries following a diagnosis of pelvic ES. In total, 3 patients with iliac lesions (2 lesions with extension into the sacrum) received surgical tumor excisions and allograft reconstructions. Another 8 patients with periacetabular lesions received trans-acetabular osteotomies and allograft reconstructions. No reconstruction was performed on 1 patient following excision of a pubic lesion. The median follow-up time was 39 months. At the time of the final follow-up appointment, 9 patients exhibited no evidence of disease, 2 patients had slow progressive pulmonary metastasis, 1 patient exhibited local recurrence of the disease and 1 patient had succumbed to the disease 24 months after surgery. Complications included issues with wound healing in 1 patient, a discrepancy in leg length in another and a screw loosening in a further patient. The patients had a mean Musculoskeletal Tumor Society score of 26 points and a mean International Society of Limb Salvage radiographic score of 90.1%. The proposed surgical strategy for children and adolescents with pelvic ES in the present study could provide a feasible solution for acetabulum salvage and local tumor control.

BMPR2 promotes invasion and metastasis via the RhoA-ROCK-LIMK2 pathway in human osteosarcoma cells.

Bone morphogenetic protein receptor 2 (BMPR2) has been identified in several types of cancer. However, its role in osteosarcoma is largely unknown. We systematically investigated the role of BMPR2 in osteosarcoma cell lines, human tissue samples and xenograft models. The relationship between BMPR2 expression and osteosarcoma patients' survival was investigated by bioinformatics and clinical data. Wound healing assay and transwell assay were used to detect the changes of cell migration and invasion ability after BMPR2 transfection. In addition, downstream phosphoproteins were analyzed by iTRAQ-based phosphoproteomic analysis and verified by western blotting. In vivo, the effects of BMPR2 on the growth, formation and metastasis of 143B cells were observed by orthotopic transplantation of nude mice. Here, we demonstrated that BMPR2 expression was elevated in a majority of osteosarcoma tissues compared with normal bone tissue. Osteosarcoma patients with greater BMPR2 expressing level showed a poor overall survival. The depletion of BMPR2 in 143B cells markedly reduced the invasive capacity in vitro and metastatic potential in vivo. Mechanistically, we found that LIM domain kinase 2 (LIMK2) was phosphorylated and activated by BMPR2 and that this event was crucial for activation of the BMPR2-mediated signal pathway in osteosarcoma cells. Additionally, we demonstrated that BMPR2 could active LIMK2 through the RhoA/ROCK pathway and could also interact with LIMK2 directly. Taken together, our study revealed that BMPR2 functions as a prometastatic oncogene in vitro and in vivo with the activation of the RhoA-ROCK-LIMK2 pathway and may represent a potential therapeutic target for osteosarcoma.