Disrupting YAP1-mediated glutamine metabolism induces synthetic lethality alongside ODC1 inhibition in osteosarcoma.

PURPOSE: Osteosarcoma, a highly malignant primary bone tumor primarily affecting adolescents, frequently develops resistance to initial chemotherapy, leading to metastasis and limited treatment options. Our study aims to uncover novel therapeutic targets for metastatic and recurrent osteosarcoma. METHODS: In this study, we proved the potential of modulating the YAP1-regulated glutamine metabolic pathway to augment the response of OS to DFMO. We initially employed single-cell transcriptomic data to gauge the activation level of polyamine metabolism in MTAP-deleted OS patients. This was further substantiated by transcriptome sequencing data from recurrent and non-recurrent patient tissues, confirming the activation of polyamine metabolism in progressive OS. Through high-throughput drug screening, we pinpointed CIL56, a YAP1 inhibitor, as a promising candidate for a combined therapeutic strategy with DFMO. In vivo, we utilized PDX and CDX models to validate the therapeutic efficacy of this drug combination. In vitro, we conducted western blot analysis, qPCR analysis, immunofluorescence staining, and PuMA experiments to monitor alterations in molecular expression, distribution, and tumor metastasis capability. We employed CCK-8 and colony formation assays to assess the proliferative capacity of cells in the experimental group. We used flow cytometry and reactive oxygen probes to observe changes in ROS and glutamine metabolism within the cells. Finally, we applied RNA-seq in tandem with metabolomics to identify metabolic alterations in OS cells treated with a DFMO and CIL56 combination. This enabled us to intervene and validate the role of the YAP1-mediated glutamine metabolic pathway in DFMO resistance. RESULTS: Through single-cell RNA-seq data analysis, we pinpointed a subset of late-stage OS cells with significantly upregulated polyamine metabolism. This upregulation was further substantiated by transcriptomic profiling of recurrent and non-recurrent OS tissues. High-throughput drug screening revealed a promising combination strategy involving DFMO and CIL56. DFMO treatment curbs the phosphorylation of YAP1 protein in OS cells, promoting nuclear entry and initiating the YAP1-mediated glutamine metabolic pathway. This reduces intracellular ROS levels, countering DFMO's anticancer effect. The therapeutic efficacy of DFMO can be amplified both in vivo and in vitro by combining it with the YAP1 inhibitor CIL56 or the glutaminase inhibitor CB-839. This underscores the significant potential of targeting the YAP1-mediated glutamine metabolic pathway to enhance efficacy of DFMO. CONCLUSION: Our findings elucidate YAP1-mediated glutamine metabolism as a crucial bypass mechanism against DFMO, following the inhibition of polyamine metabolism. Our study provides valuable insights into the potential role of DFMO in an "One-two Punch" therapy of metastatic and recurrent osteosarcoma.

Custom-made semi-joint prosthesis replacement combined ligament advanced reinforcement system (LARS) ligament reconstruction for the limb salvage surgery of malignant tumors in the distal femur in skeletal immature children.

Purpose: To explore the application of Custom-made Semi-joint prosthesis replacement combined with Ligament Advanced Reinforcement System (LARS) ligament reconstruction for the limb salvage surgery (LSS) of malignant tumors in the distal femur and provide selections for the LSS of malignant tumors in skeletal immature children. Methods: A total of 8 children with malignant tumors in the distal femur who underwent Custom-made Semi-joint prosthesis replacement combined LARS ligament reconstruction for LSS from January, 2018 until December, 2019 in our bone and soft tissue tumor center were retrospectively recruited. The prosthesis related complications, oncological prognosis and knee function were observed, and the surgical efficacy was comprehensively evaluated. Results: The average follow-up time was 36.6 months (30-50 months). The average osteotomy length was 13.2 cm (8-20 cm) according to the preoperative imaging results and the length of the customized prosthesis. Two years after operation, the average MSTS-93 score was 24.4 (16-29) which indicated good limb functions. The range of motion of the knee was 0°-120°, with an maximum average of 100°. At last follow-up, the average height of the children increased by 8.4 cm (6-13 cm), and the average limb shortening was 2.7 cm (1.8-4.6 cm). One patient had wound complications in the early postoperative period, wound scab fell off to form superficial ulcer, in whom debridement and suturing were performed. One patient developed hematogenous disseminated prosthesis infection 2 years after surgery, and the prosthesis is now in situ with anti-infection treatment. One patient developed pulmonary metastasis during follow-up, and received chemotherapy and targeted therapy with lesion well controlled. At the last follow-up, there was no local tumor recurrence or prosthesis loosening. Conclusion: Under the premise of appropriate case selection, customized semi-joint prosthesis replacement combined with LARS ligament reconstruction provides a new option for LSS in children with distal femur malignant tumors. LARS ligament reconstruction ensures the stability and range of motion of the knee joint, which maximally preserves the epiphysis of the tibia side and the growth function of the tibia side, reduces the complications of limb length inequality in the long term and creates conditions for limb lengthening or total joint replacement in adults.

Multi-omics analysis identifies osteosarcoma subtypes with distinct prognosis indicating stratified treatment.

Osteosarcoma (OS) is a primary malignant bone tumor that most commonly affects children, adolescents, and young adults. Here, we comprehensively analyze genomic, epigenomic and transcriptomic data from 121 OS patients. Somatic mutations are diverse within the cohort, and only TP53 is significantly mutated. Through unsupervised integrative clustering of the multi-omics data, we classify OS into four subtypes with distinct molecular features and clinical prognosis: (1) Immune activated (S-IA), (2) Immune suppressed (S-IS), (3) Homologous recombination deficiency dominant (S-HRD), and (4) MYC driven (S-MD). MYC amplification with HR proficiency tumors is identified with a high oxidative phosphorylation signature resulting in resistance to neoadjuvant chemotherapy. Potential therapeutic targets are identified for each subtype, including platinum-based chemotherapy, immune checkpoint inhibitors, anti-VEGFR, anti-MYC and PARPi-based synthetic lethal strategies. Our comprehensive integrated characterization provides a valuable resource that deepens our understanding of the disease, and may guide future clinical strategies for the precision treatment of OS.

Inhibition of sphingolipid metabolism in osteosarcoma protects against CD151-mediated tumorigenicity.

Osteosarcoma is the most common primary bone tumor, with a poor prognosis owing to the lack of efficient molecular-based targeted therapies. Previous studies have suggested an association between CD151 and distinct consequences in osteosarcoma tumorigenicity. However, the potential of CD151 as a therapeutic target has not yet been sufficiently explored. Here, we performed integrated transcriptomic and metabolomic analyses of osteosarcoma and identified sphingolipid metabolism as the top CD151-regulated pathway. CD151 regulates sphingolipid metabolism primarily through SPTCL1, the first rate-limiting enzyme in sphingolipid biosynthesis. Mechanistically, depletion of CD151 enhanced c-myc polyubiquitination and subsequent degradation. c-myc is vital for the transcriptional activation of SPTLC1. Functionally, sphingolipid synthesis and the SPTLC1 inhibitor, myriocin, significantly suppressed the clonogenic growth of CD151-overexpression cells. Importantly, myriocin selectively restrained CD151-high expression tumor growth in preclinical patient-derived xenograft models. Collectively, these data establish that CD151 is a key mediator of sphingolipid metabolism and provide a new approach to developing novel CD151-based targeted therapies for osteosarcoma.

O-arm-guided percutaneous microwave ablation and cementoplasty for the treatment of pelvic acetabulum bone metastasis.

Objective: This study aims to evaluate the indications, safety, and efficacy of microwave ablation combined with cementoplasty under O-arm navigation for the treatment of painful pelvic bone metastasis. Methods: We retrospectively collected data from 25 patients with acetabulum bone metastasis who underwent microwave ablation combined with cementoplasty. All patients underwent percutaneous microwave ablation combined with cementoplasty under O-arm navigation. The postoperative follow-up included evaluations of pain, quality of life, function, the incidence of bone cement leakage, and the presence of perioperative complications. Pain and quality of life were evaluated using the visual analog scale (VAS) and the QLQ-BM22 quality of life questionnaire for patients with bone metastases, respectively. The functional scores were calculated using the MSTS93 scoring system of the Bone and Soft Tissue Oncology Society. Results: There were 10 males and 15 females with an average age of 52.5 ± 6.5 years, all 25 patients received percutaneous procedures, and no technical failure occurred. Major complications, including pulmonary embolism, vascular or nervous injury, hip joint cement leakage, and infection, were not observed in the current study. Pain regression was achieved in 24 of 25 patients. The mean VAS scores significantly decreased to 3.4 ± 1.0, 2.5 ± 1.2, and 1.2 ± 0.6 points at 1 week, 1 month, and 3 months after the procedure, respectively, compared with 7.0 points before the procedure (P < .05). The mean QLQ-BM22 score significantly decreased to 36.2 ± 4.9, 30 ± 5.6, and 25.4 ± 2.3 points at 1 week, 1 month, and 3 months after the procedure, respectively, compared with 55.8 points before the procedure (P < .05). The preoperative Musculoskeletal tumour society (MSTS) functional score of 25 patients was 18.5 ± 5.3 points, and MSTS score was 20.0 ± 3.0, 21.4 ± 4.9, and 22.8 ± 2.3 at 1 week, 1 month, and 3 months after the procedure, respectively (P < .05). The average bone cement injection volume was 8.8 ± 4.6 ml. Conclusion: The use of O-arm-guided percutaneous microwave ablation combined with cementoplasty for the treatment of pelvic metastases could quickly and significantly alleviate local pain, prevent pathological fracture, and improve the quality of life of patients with reduced complications.

Feasibility and preliminary efficacy of tantalum components in the management of acetabular reconstruction following periacetabular oncologic resection in primary malignancies.

BACKGROUND: The aim of the study was to investigate the feasibility and preliminary efficacy of tantalum components utility in the reconstruction of acetabular defects following periacetabular oncologic resection of primary malignancies. METHODS: We prospectively collected a consecutive of 15 cases that were treated with tantalum components for acetabular reconstruction after periacetabular oncologic resection from January 2018 to December 2018. The cohort included 8 male and 7 female patients, with a mean age of 47.6 years (range, 33 to 67 years). Pathology types: chondrosarcoma (n = 9), malignant bone giant cell tumor (n = 3) and osteosarcoma (n = 3). Clinical outcomes, functional and radiographic results were recorded in detail for analysis. RESULTS: Patients received planned oncologic resection and tantalum components reconstruction without casualty; they were followed up with a mean of 39.7 months (35-45 months). The mean operation time was 4.0 h (3.0-6.0 h), and the mean blood loss was 1260 ml (800-2200 ml). Functional outcomes were assessed by MSTS-93 scale, with an average of 21.8 (12.0-26.0 scores), among which 3 cases were excellent, 11 were good and 1 was fair. The mean Harris Hip Score was 79.1scores (46.0-92.0 scores) at 1-year follow-up postoperatively. 3(3/15, 20.0%) cases experienced postoperative complications: 2 cases with hip dislocation received closed reduction under general anesthesia and were fixed with hip joint abduction braces for 6 weeks; one case had a superficial infection and received debridement with a delayed wound healing. Oncologic prognosis: one case relapsed at 8-month follow-up and received hemi-pelvic amputation; and another osteosarcoma patient experienced relapse with pulmonary metastasis and received further chemotherapy. No prosthetic loosening, displacement or fracture occurred during the follow-up period. CONCLUSION: Preliminary results suggested that the use of tantalum components in the management of acetabular reconstruction following periacetabular oncologic resection provided reasonable improvement on functional outcomes and early stability of the prostheses. Porous tantalum components are conducive to bony ingrowth, which is a potential alternative to various existing reconstruction techniques to achieve better functional outcomes.

PLCD1-Induced DNA Damage Inhibits the Tumor Growth via Downregulating CDKs in Chondrosarcoma.

Purpose: Typical genes for the treatment and diagnosis of high-grade chondrosarcoma are still in need. Our study aimed to explore the PLCD1 function in chondrosarcoma for further treatment. Materials and Methods: Our study collected the information of 49 patients in our department. The PLCD1 expression in our cohort was detected and was compared with the TCGA database. PLCD1 knockdown and overexpression cell lines were established stably. Cell viability assay and colony formation assay were performed for cell proliferation. Flow cytometry analysis was performed for cell cycle and apoptosis. Western blotting was performed for PLCD1-related protein expression. Animal xenografts were established to verify the effect of PLCD1 in high-grade chondrosarcoma. Results: Compared with the TCGA database, the relation between PLCD1 expression and the malignancy of chondrosarcoma was demonstrated. A lower PLCD1 expression was detected mainly in high-grade chondrosarcoma. PLCD1 overexpression in high-grade chondrosarcoma suppressed CDKs/cyclins and induced DNA damage causing cell cycle blocking and apoptosis. Antitumor effect of PLCD1 overexpression was verified in vivo. Conclusion: Lower PLCD1 was expressed in high-grade chondrosarcoma. Overexpressed PLCD1-induced DNA damage caused cell cycle blocking and apoptosis in vitro and in vivo. PLCD1 could be a novel target in high-grade chondrosarcoma for further drug development.

Correlation between Patient-Derived Xenograft Modeling and Prognosis in Osteosarcoma.

OBJECTIVE: To retrospectively analyze and compare the relationship between the success rate of patient-derived xenograft (PDX) modeling of osteosarcoma and prognosis (3-year overall survival rate and disease-free survival rate) and incidence of lung metastasis. METHODS: The sample group consisted of 57 osteosarcoma patients with definite pathological diagnoses from Shanghai General Hospital from 2015-2017. PDX models in 57 patients were analyzed by retrospective analyses. Among the patients currently inoculated, 20 were tumorigenic in the PDX model, and 37 were nontumorigenic. According to the tumorigenicity of PDXs, the corresponding osteosarcoma patients were divided into two groups. The effects of clinically related indicators on the model were retrospectively compared. The patients were followed, and the 3-year survival, 3-year disease-free survival (DFS), and lung metastasis rates were collected. The relationship between the modeling success and patient prognosis was investigated. RESULTS: In the chemotherapy-treated group, the PDX modeling success rate was 17.4%, and in the nonchemotherapy group, the success rate was 47.1%. The success of PDX modeling was related to whether patients received chemotherapy. The success rate of PDX modeling is significantly reduced after receiving chemotherapy. The 3-year overall survival rate of the PDX-grafted group was 49.23%, and that of the PDX-nongrafted group was 65.71%. There was a significant difference between the two groups, showing a strong negative correlation between the 3-year survival rate and the success rate of the PDX model. The 3-year disease-free survival rate of the PDX-grafted group was 29.54%. The 3-year DFS of the PDX-nongrafted group was 50.34%. There was a significant difference between the two groups. Lower grafted rates indicate a higher DFS rate. The incidence of lung metastasis in the PDX-grafted group was 32.4%, and that in the nongrafted group was 13.1%. There was a significant difference between the two groups. The successful establishment of the PDX model indicates that patients are more likely to have lung metastases. CONCLUSIONS: The success of PDX modeling often indicates poor prognosis (low 3-year overall survival rate and disease-free survival rate) and a greater possibility of lung metastasis. Therefore, PDX modeling in osteosarcoma patients can accurately predict the prognosis of patients and the risk of lung metastasis in advance to help us develop better therapeutic strategies.

Revision surgeries for tumor endoprostheses around the knee joint: a mid-long-term follow-up of 20 cases.

BACKGROUND: Tumor endoprostheses of the knee joint after limb salvage surgery is associated with high rates of complications, which has introduced great challenges to a delayed revision surgery. The aim of the study was to summarize the failures, functional outcomes and prosthetic survival in revision tumor endoprostheses of the knee joint. METHODS: The clinical data of 20 patients with malignant tumors who received prosthetic revisions after limb salvage surgery from January, 2000 until January, 2018 were retrospectively reviewed. The cohort was constituted of 11 male and 9 female patients with a mean age of 34.1 years (range, 16 to 66 years). Infection cases received two-stage revisions after removing prostheses initially, while all other cases received one-stage revisions. Revision reasons and complications were well documented and analyzed. RESULTS: All patients received complete follow-up with a mean time of 64.7 months (range, 27 to 155 months). A total of 6 (6/20, 30.0%) patients experienced a second complication after revision surgery, of whom, one patient with deep infection experienced repeated infections after prosthetic revision and received amputation surgery; one patient revised of prosthetic fracture experienced an infection and received a second-stage infection revision; one case revised of prosthetic loosening had deep infection receiving anti-infective therapy with prostheses still in position; one case having wound complication healed after receiving two times of debridement surgery; one MBGCT patient experienced a second aseptic loosening 6 years after the initial loosening thus undergoing a second revision; a recurrent osteosarcoma patient died of pulmonary metastasis 3 years after revision surgery. Kaplan-Meier survival curve indicated a 5-year survival rate of initial prostheses was 75%. The Musculoskeletal Tumor Society (MSTS-93) score [20.9 (range, 15 to 27 scores)] at 1 year after revision surgeries was significantly improved (p < 0.001) when compared with the score [17.2 (range, 13 to 21 scores)] before revisions. CONCLUSION: Prosthetic mechanical problems, aseptic loosening and infections were primary reasons for revisions after tumor endoprostheses of the knee joint. Although revision surgeries were complicated while still associated with high risk of failure, which remains the remedy strategy for limb salvage and functional recovery in those patients.

Multicentre Study Using Machine Learning Methods in Clinical Diagnosis of Knee Osteoarthritis.

Knee osteoarthritis (OA) is one of the most common musculoskeletal disorders. OA diagnosis is currently conducted by assessing symptoms and evaluating plain radiographs, but this process suffers from the subjectivity of doctors. In this study, we retrospectively compared five commonly used machine learning methods, especially the CNN network, to predict the real-world X-ray imaging data of knee joints from two different hospitals using Kellgren-Lawrence (K-L) grade of knee OA to help doctors choose proper auxiliary tools. Furthermore, we present attention maps of CNN to highlight the radiological features affecting the network decision. Such information makes the decision process transparent for practitioners, which builds better trust towards such automatic methods and, moreover, reduces the workload of clinicians, especially for remote areas without enough medical staff.

Do reverse total shoulder replacements have better clinical and functional outcomes than hemiarthroplasty for patients undergoing proximal humeral tumor resection using devitalized autograft composite reconstruction: a case-control study.

OBJECTIVE: To compare the efficacy and prognosis of reverse total shoulder arthroplasty (rTSA) with shoulder hemiarthroplasty (SHA) using devitalized autograft or allograft composite reconstruction after proximal humeral tumor resection. METHODS: We retrospectively reviewed patients who underwent SHA (32) and rTSA (20) for tumor resections of the proximal humerus from January 2014 to July 2020. The clinical results included duration of the operation, intraoperative blood loss, bone union, visual analog scale (VAS) score, shoulder range of motion (ROM), American Shoulder and Elbow Surgeons (ASES) shoulder score, recurrence, and overall survival. RESULTS: Fifty-two patients were followed up for a mean of 30 months. Thirty-two patients were SHA with allograft-prosthetic composite (APC) reconstructions, while other 20 were rTSA with devitalized autograft-prosthetic composite reconstructions. At the end of the follow-up, 2 recurrence, 3 postoperative infections, and 4 subluxations occurred among the SHA patients. Two patients in the rTSA group had postoperative anterior dislocation and underwent revision surgery with surgical mesh, and 2 (2/20) had grade II scapular notching. The mean VAS score of the shoulder was 1.5 ± 0.8 in the rTSA group and 2.3 ± 1.2 in the SHA group (p < 0.05). The mean active forward flexion of the shoulder joint was 50.6 ± 6.0 in the SHA group and 100 ± 7.6 in the rTSA group (p < 0.05). The ASES shoulder score was 78 ± 3.0 in the rTSA group and 52 ± 5.6 in the SHA group (p < 0.05). The overall 3-year survival rate of all patients was 60.0%, and patients in the rTSA group showed better survival in terms of the mean 3-year OS than patients in the SHA group (p = 0.04). CONCLUSION: rTSA with devitalized autograft-prosthetic composite can offer a reasonable reconstruction of the shoulder joint after Malawer type I tumor resection. Compared with patients who underwent SHA, patients who underwent rTSA present good outcomes, a better range of motion, better bone union, and no increase in instability rate in the mid-term.

Surgical resection and reconstructive techniques using autologous femoral head bone-grafting in treating partial acetabular defects arising from primary pelvic malignant tumors.

BACKGROUND: The aim of this study is to present and evaluate surgical resection and reconstructive techniques using autologous femoral head bone-grafting in treating partial acetabular defects arising from primary pelvic malignant tumors. METHODS: From January 2009 until January 2015, a total of 20 primary pelvic malignancy cases involving the acetabulum were retrospectively investigated. Surgical resections and reconstructions were conducted based on the type of the tumor with custom osteotomy guides and autologous femoral head bone-grafting. In all cases, prosthesis survival period, complication occurrence, and clinical outcomes data were collected and analyzed. RESULTS: Thirteen male and 7 female patients with an average age of 48 years old (range 23-69 years old) were followed for a median of 69 months (range 48-112 months). Of these cases, 17 included chondrosarcomas and 3 additional patients with a malignant giant cell tumor of bone (MBGCT) as proven by pathology. During follow-up, 3 cases of chondrosarcoma recurred (15%), of which two cases received hemi-pelvic amputation, 1 case of MBGCT relapsed and developed pulmonary metastases. Two cases of acetabular prosthesis with an impending dislocation received closed reduction followed by 6 weeks of hip abduction brace fixation. One case of prosthesis loosening was revised. In another case a deep infection occurred with debridement and prosthesis removal. Musculoskeletal Tumor Society 1993 (MSTS-93) score was utilized to conduct functional evaluation: 13 cases were good, 6 were average and one was poor. CONCLUSION: The precision of the osteotomies performed is likely crucial for this type of reconstructive strategy to be successful. The use of custom guides for acetabular osteotomies and femoral head reconstruction can improve functional outcomes with relatively low complications at the intermediate length of follow-up.

Antitumor activity of Raddeanin A is mediated by Jun amino-terminal kinase activation and signal transducer and activator of transcription 3 inhibition in human osteosarcoma.

Osteosarcoma is the most common primary malignant bone tumor. Raddeanin A (RA) is an active oleanane-type triterpenoid saponin extracted from the traditional Chinese herb Anemone raddeana Regel that exerts antitumor activity against several cancer types. However, the effect of RA on osteosarcoma remains unclear. In the present study, we showed that RA inhibited proliferation and induced apoptosis of osteosarcoma cells in a dose- and time-dependent way in vitro and in vivo. RA treatment resulted in excessive reactive oxygen species (ROS) generation and JNK and ERK1/2 activation. Apoptosis induction was evaluated by the activation of caspase-3, caspase-8, and caspase-9 and poly-ADP ribose polymerase (PARP) cleavage. RA-induced cell death was significantly restored by the ROS scavenger glutathione (GSH), the pharmacological inhibitor of JNK SP600125, or specific JNK knockdown by shRNA. Additionally, signal transducer and activator of transcription 3 (STAT3) activation was suppressed by RA in human osteosarcoma, and this suppression was restored by GSH, SP600125, and JNK-shRNA. Further investigation showed that STAT3 phosphorylation was increased after JNK knockdown. In a tibial xenograft tumor model, RA induced osteosarcoma apoptosis and notably inhibited tumor growth. Taken together, our results show that RA suppresses proliferation and induces apoptosis by modulating the JNK/c-Jun and STAT3 signaling pathways in human osteosarcoma. Therefore, RA may be a promising candidate antitumor drug for osteosarcoma intervention.

Evaluation of Quality of Life Using EORTC QLQ-BM22 in Patients with Bone Metastases after Treatment with Magnetic Resonance Guided Focused Ultrasound.

OBJECTIVE: To reveal the alterations in quality of life (QOL) in bone metastases patients after magnetic resonance guided focused ultrasound (MRgFUS). METHODS: This retrospective study enrolled 26 patients diagnosed with bone metastases. Patients had various primary malignant tumors and tumor lesions in different locations. All patients received MRgFUS for bone metastasis. Each focal spot sonication pulse that was applied to create energy deposition lasted 20 s and was performed at a frequency of 1.05 MHz. The visual analog scale (VAS) was used to measure pain level and the EORTC QLQ-BM22 was applied to evaluate QOL for 12 months. The lower the QLQ-BM22 score, the better the QOL of patients. RESULTS: The painful site subscale of the EORTC QLQ-BM22 was observed without significant change. Significant reductions in the functional subscales were observed after therapy compared with the baseline. The functional interference was reduced significantly during the first 12 months. From the 2-month time point onwards, the pain characteristics subscale also decreased significantly. VAS scores had decreased by 40.8% 1 month after the operation and had decreased 10.9% compared with VAS scores preoperation. Scores for pain characteristics decreased by 28.8% after the operation and the scores were still down by 10.8% 1 year after the treatment. VAS scores indicated a significant reduction in pain over the course of the research until the 12-month time point follow-up compared with the baseline. CONCLUSION: MRgFUS therapy improved the QOL of patients with bone metastasis by relieving bone pain.

Palliative treatment of pelvic bone tumors using radioiodine (125I) brachytherapy.

BACKGROUND: Complete resection of pelvic bone tumors, especially recurrent and metastatic ones, is often impossible to achieve using conventional surgery. This study aimed to assess the benefits and adverse effects of computed tomography (CT)-guided radioiodine (125I) brachytherapy for inoperable recurrent and metastatic bone tumors of the pelvis. METHODS: This was a retrospective study of 22 patients with confirmed pelvic bone tumors (10 females and 12 males; 15-84 years; 21 with primary pelvic tumor and one with pelvic metastasis). CT-guided 125I brachytherapy was performed using 9-21 125I seeds (radioactivity of 0.5-0.7 mCi). Seed implantation was validated by postoperative CT scanning. Complications, pain, survival, and CT-estimated tumor size were carried out to evaluate the therapeutic benefits. RESULTS: Postoperative CT scans revealed satisfactory 125I seed implantation, and the radiation dose delivered to 90% of the target area (D90) was higher than the prescription dose (PD). No obvious complications were observed. Pain was reported by 19 of 22 patients, but 17 reported pain relief after implantation. Follow-up ranged 8-27 (median, 19) months. Tumor size was reduced in 11 patients within 1 month after surgery, nine patients showed no change, and tumor size increased in two patients. Finally, 1- and 2-year survival was 81.8 and 45.5%, respectively; 1- and 2-year local tumor control rates were 59.1 and 36.4%, respectively. CONCLUSIONS: 125I seed implantation significantly reduced bone tumor size and relieved pain, with a low complication rate. These findings suggest that 125I brachytherapy treatment could be a useful palliative approach for pelvic bone tumor treatment.

Comparison of Venous Thromboembolism after Total Artificial Joint Replacement between Musculoskeletal Tumors and Osteoarthritis of the Knee by a Single Surgeon.

The purpose of this study was to compare and evaluate the event of VTE (Venous Thromboembolism Event) after total artificial joint replacement between two groups diagnosed with either musculoskeletal tumors or osteoarthritis (OA) of the knee. From 2004 to 2014, a total of 1,402 patients (308 in tumor group, 1,094 in OA group) were involved in this study. The rate of asymptomatic DVT (Deep vein thrombosis) was significantly higher in tumor group when compared with OA group. Though both the incidence of symptomatic DVT and PE (Pulmonary embolism) were slightly higher in tumor group, no significant difference was detected. Tumor patients suffered an almost equal risk of VTE compared with OA patients except a higher rate of asymptomatic DVT after total artificial joint replacement. For patients with tumor, no significant association was observed between any potential risk factor and DVT.

Bioinformatics analysis of differentially expressed pathways related to the metastatic characteristics of osteosarcoma.

In this study, gene expression data of osteosarcoma (OSA) were analyzed to identify metastasis-related biological pathways. Four gene expression data sets (GSE21257, GSE9508, GSE49003 and GSE66673) were downloaded from Gene Expression Omnibus (GEO). An analysis of differentially expressed genes (DEGs) was performed using the Significance Analysis of Microarray (SAM) method. Gene expression levels were converted into scores of pathways by the Functional Analysis of Individual Microarray Expression (FAIME) algorithm and the differentially expressed pathways (DEPs) were then disclosed by a t-test. The distinguishing and prediction ability of the DEPs for metastatic and non-metastatic OSA was further confirmed using the principal component analysis (PCA) method and 3 gene expression data sets (GSE9508, GSE49003 and GSE66673) based on the support vector machines (SVM) model. A total of 616 downregulated and 681 upregulated genes were identified in the data set, GSE21257. The DEGs could not be used to distinguish metastatic OSA from non-metastatic OSA, as shown by PCA. Thus, an analysis of DEPs was further performed, resulting in 14 DEPs, such as NRAS signaling, Toll-like receptor (TLR) signaling, matrix metalloproteinase (MMP) regulation of cytokines and tumor necrosis factor receptor-associated factor (TRAF)-mediated interferon regulatory factor 7 (IRF7) activation. Cluster analysis indicated that these pathways could be used to distinguish between metastatic OSA from non-metastatic OSA. The prediction accuracy was 91, 66.7 and 87.5% for the data sets, GSE9508, GSE49003 and GSE66673, respectively. The results of PCA further validated that the DEPs could be used to distinguish metastatic OSA from non-metastatic OSA. On the whole, several DEPs were identified in metastatic OSA compared with non-metastatic OSA. Further studies on these pathways and relevant genes may help to enhance our understanding of the molecular mechanisms underlying metastasis and may thus aid in the development of novel therapies.

Gelsolin promotes cell growth and invasion through the upregulation of p-AKT and p-P38 pathway in osteosarcoma.

The gelsolin (GSN) has been involved in the regulation of tumor formation and development, but the biological role of GSN in the pathogenesis of osteosarcoma (OS) has not been well characterized. In this study, we show that high expression of GSN was observed in OS tissues and correlated with tumor size, advanced Enneking stage, and poor patient prognosis. Knockdown of GSN significantly inhibited cell proliferation and invasiveness in the OS cell lines. Furthermore, stable overexpression of GSN in OS cells resulted in a significant increase in cell growth and motility with the downregulation of p-AKT and p-P38 pathway. Finally, overexpression of GSN promoted growth of OS tumors in SCID mice. Taken together, these results provided the first evidence that GSN might contribute to OS cancer development and could be an attractive therapeutic target for patients with OS.

Gelfoam embolization or 125I seed implantation may be a more effective treatment than surgical treatment for giant benign sacral neurogenic tumors.

BACKGROUND: The goal of the present study was to assess the effects of computed tomography (CT)-guided iodine-125 (125I) seed implantation or gelatin sponge particle (GSP) embolization on patients with giant benign sacral neurogenic tumors. METHODS: A total of 24 cases with giant sacral neurogenic tumor were performed in a retrospective study between 2000 and 2012. Nineteen cases received surgical resection, and five cases received non-surgical treatment. In surgical group, patients with type III sacral tumor had received a combined anterior-posterior approach and patients with type IV were treated with simple anterior approach. In non-surgical group, CT-guided 125I seed implantation or GSP embolization was applied to occlude vessels. Besides, CT scanning or magnetic resonance imaging was used to assess the size and development of tumors. RESULTS: Two of the five patients were treated three times with GSP embolization, one had received GSP embolization combined with CT-guided 125I seed implantation, one case did not receive any treatment, and one patient was lost to follow-up. Patients in non-surgical group were followed up for 2-8 years. CONCLUSIONS: Our study suggested that CT-guided 125I seed implantation or GSP embolization treatment is very useful to slow down the development of giant benign sacral neurogenic tumors.

Inflammatory pseudotumor around metal-on-polyethylene total hip arthroplasty in patients with ankylosing spondylitis: description of two cases and review of literature.

Inflammatory pseudotumor has been commonly reported in patients undertaking total hip replacement (THR) for different reasons. The precise etiology of this biological reaction and whether the primary disease has an influence on pseudotumor formation remain unclear. There seems to be a consensus that metal ions and debris do play an important role during this process. Recently, however, compared to metal particles along, immune response induced by metal particles attracts more attention. We present two cases of pseudotumor who have accepted THR for ankylosing spondylitis (AS) and later required revision surgery and hindquarter amputation, respectively. By thorough literature review, we tried to investigate the association between inflammatory pseudotumors and immunology.