Search

BackgroundSurgical resection and reconstruction for low-grade bone sarcoma in the metaphysis of the distal femur remain challenging. We hypothesized that 3D printing osteotomy guide plate could assist to accurately resect the tumor lesion and save the joint function.MethodsFrom January 2017 to August 2019, five patients diagnosed with low-grade bone sarcoma in the metaphysis of the distal femur were treated with hemicortical resection using 3D printing guide plate. Autologous bone graft was inactivated in a high-temperature water bath and re-implanted in situ fixed with plate and screw. Patients were followed up from 17 to 33 months. The Musculoskeletal Tumor Society Score was used to evaluate the joint function. X-ray was used to evaluate the bone union.ResultsOne patient was paracorticular osteosarcoma, and four cases had highly differentiated chondrosarcoma. All cases were involved in the metaphysis of the distal femur. Patients were followed up from 13 to 33 months, with an average of 23.6 months. There was neither post-operation infection, internal fixation loosening, nor fracture occurrence in any of the patients. The Musculoskeletal Tumor Society Score averaged at 28.1, while the International Society of Limb Salvage imaging score examination averaged 89.8%.ConclusionsHere, we demonstrate that the 3D printing osteotomy guide plate-assisted hemicortical bone resection is a beneficial strategy to effectively resect the primary low-grade malignant bone tumors in the metaphysis of the distal femur and retained satisfied joint function.

This study designs to investigate the role and potential mechanism of lncNRA HOTTIP in OS progression in vitro and in vivo. HOTTIP, PTBP1, and KHSRP expression levels were tested through qRT-PCR and western blot in OS tissues or cell lines. Cell proliferation was examined via CCK-8 and colony formation. Cell cycle and apoptosis were analyzed via flow cytometry analysis. The invasive and migratory abilities of OS cells were evaluated by transwell and wound-healing assays. The localization of HOTTIP in OS cells was determined by subcellular fractionation assay. RNA pull down and RNA immunoprecipitation were allowed to assess the interaction between HOTTIP and PTBP1. Xenograft tumor growth assay was employed to test the role of HOTTIP and KHSRP in OS progression. Our data demonstrated HOTTIP was upregulated in OS tissues. HOTTIP knockdown resulted in a suppression of OS cell proliferation, invasion and migration, as well as a promotion of OS cell apoptosis, while HOTTIP overexpression exhibited opposite effects. In mechanism, PTBP1 and KHSRP highly expressed in OS and HOTTIP was identified to interact with PTBP1 to promote KHSRP expression. Meanwhile, we found that overexpression of KHSRP or PTBP1, individually, can partially remove the repression of HOTTIP suppression for OS cell progression. Moreover, xenograft tumor growth assay revealed that HOTTIP knockdown significantly inhibited tumor growth, and this inhibitory effect was abolished by KHSRP overexpression. Collectively, these findings confirmed that HOTTIP facilitates OS cell proliferation, invasion and migration by binding to PTBP1 to promote KHSRP level. Abbreviation: LncRNA: long noncoding RNA; HOTTIP: HOXA distal transcript antisense RNA; KHSRP: KH-Type Splicing Regulatory Protein; qRT-PCR: quantitative real-time PCR; OS: osteosarcoma; OST: osteosarcoma tissues; ANT: adjacent normal tissue.

Introduction Emerging evidence has revealed the importance of long non-coding RNAs (lncRNAs) in carcinogenesis. The aim of this work was to investigate the roles of lncRNA growth arrest specific 5 (GAS5) in osteosarcoma (OS) progression. Methods Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to explore GAS5, microRNA-663a (miR-663a), and ras homolog family member B (RHOB) expression levels in OS tissues and cells. Moreover, cell counting kit-8 assay, wound-healing assay, and transwell invasion assay were conducted to investigate biological roles of GAS5 in OS progression. In addition, mechanisms underlying the functions of GAS5 in OS were investigated by bioinformatic analysis, luciferase activity reporter assay, and rescue experiments. Results The GAS5 expression level was significantly decreased in OS tissues and cells compared with normal tissues and cells, and could negatively regulate miR-663a expression. Moreover, we found RHOB expression can be negatively regulated by miR-663a. Overexpression of GAS5 and RHOB suppresses, while overexpression of miR-663a stimulates, OS cell proliferation, migration, and invasion in vitro. In summary, we revealed lncRNA GAS5 was a downregulated lncRNA in OS and impaired OS malignant behaviors. In addition, this regulation relied on miR-663a and its target gene, RHOB. Discussion To sum up, we showed lncRNA GAS5 regulates OS progression via regulating the miR-663a/RHOB axis.

Background Invasion and metastasis of synovial sarcoma is the leading cause of death in patients. Epithelial mesenchymal transition (EMT) accelerates tumor cell invasion and metastasis. MiR-9 promotes tumor metastasis by inducing EMT. However, the role of miR-9 in synovial sarcoma is still not clear. Methods Overexpression or knockdown of miR-9 in human synovial sarcoma (HSS) cell lines was carried out by miR-9 mimics or miR-9 inhibitors transfection. Cell proliferation, apoptosis, migration and invasion were detected using MTS and colony formation assays, flow cytometry, wound healing and transwell assays, respectively. Luciferase reporter assay was applied to study the interaction between miR-9 and CDH1. Nude mice xenograft model was established, and immunohistochemistry staining assessed Ki-67 level. The related mRNA and protein expression levels were evaluated by qRT-PCR and Western blotting. Results The bioinformatics analyses and luciferase reporter assay showed that miR-9 can target CDH1 3′-UTR. Moreover, miR-9 could induce EMT of HSS cells via targeting CDH1. The negative regulation of miR-9 on CDH1 expression was also confirmed in a mouse xenograft model of synovial sarcoma. Furthermore, miR-9 was observed to induce HSS cell proliferation, migration and invasion and inhibit apoptosis. MAPK/ERK and Wnt/β-catenin signal pathways were activated by the miR-9 overexpression in HSS cells, and then further enhancing tumorigenesis of HSS, which was further confirmed in the mouse model. Conclusion MiR-9 induces EMT by targeting CDH1, and activates MAPK/ERK and Wnt/β-catenin signal pathways, thus promoting HSS tumorigenesis.

Background: Surgical resection and reconstruction for low grade bone sarcoma in the metaphysis of the long bone remains challenging. We hypothesize that 3D printing osteotomy guide plate could assist to accurately resect the tumor lesion and save the joint function without higher recurrence rate. Methods: From January 2017 to August 2019, ten patients with low-grade malignant bone tumor in metaphysis of the limbs were treated with hemicortical resection using 3D printing guide plate and biological reconstruction. Results: Four patients were paracorticular osteosarcoma, five cases had highly differentiated chondrosarcoma, and one case was a chondromyxoid fibroma. Two of the cases involved the proximal humerus, while eight cases involved the distal femur. There was neither post-operation infection, internal fixation loosening, nor fracture occurrence in any of the patients. The Musculoskeletal Tumor Society score averaged at 27.1, while the International Society of Limb Salvage imaging score examination averaged 87.8%. Conclusions: Here, we demonstrate that the 3D printing osteotomy guide plate assisted hemicortical bone resection is a beneficial strategy to effectively resect the primary low-grade malignant bone tumors in the metaphysis of long bone and restore excellent joint function.

Xinyu Yao, Xianan Li, Yi Luo, Xuezheng Xu, Jianfan Liu, Jie Bu Department of Orthopaedics, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, People’s Republic of ChinaCorrespondence: Jie Bu Email bujie_0731@yeah.netIntroduction: Emerging evidence has revealed the importance of long non-coding RNAs (lncRNAs) in carcinogenesis. The aim of this work was to investigate the roles of lncRNA growth arrest specific 5 (GAS5) in osteosarcoma (OS) progression.Methods: Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to explore GAS5, microRNA-663a (miR-663a), and ras homolog family member B (RHOB) expression levels in OS tissues and cells. Moreover, cell counting kit-8 assay, wound-healing assay, and transwell invasion assay were conducted to investigate biological roles of GAS5 in OS progression. In addition, mechanisms underlying the functions of GAS5 in OS were investigated by bioinformatic analysis, luciferase activity reporter assay, and rescue experiments.Results: The GAS5 expression level was significantly decreased in OS tissues and cells compared with normal tissues and cells, and could negatively regulate miR-663a expression. Moreover, we found RHOB expression can be negatively regulated by miR-663a. Overexpression of GAS5 and RHOB suppresses, while overexpression of miR-663a stimulates, OS cell proliferation, migration, and invasion in vitro. In summary, we revealed lncRNA GAS5 was a downregulated lncRNA in OS and impaired OS malignant behaviors. In addition, this regulation relied on miR-663a and its target gene, RHOB.Discussion: To sum up, we showed lncRNA GAS5 regulates OS progression via regulating the miR-663a/RHOB axis.Keywords: lncRNA, GAS5, miR-663a, RHOB, osteosarcoma

Melanoma is a human skin malignant tumor with high invasion and poor prognosis. The limited understanding of genomic alterations in melanomas in China impedes the diagnosis and therapeutic strategy selection. We conducted comprehensive genomic profiling of melanomas from 39 primary and metastatic formalin-fixed paraffin-embedded (FFPE) samples from 27 patients in China based on an NGS panel of 223 genes. No significant difference in gene alterations was found between primary and metastasis melanomas. The status of germline mutation, CNV, and somatic mutation in our cohort was quite different from that reported in Western populations. We further delineated the mutation patterns of 4 molecular subgroups (BRAF, RAS, NF1, and Triple-WT) of melanoma in our cohort. BRAF mutations were more frequently identified in melanomas without chromic sun-induced damage (non-CSD), while RAS mutations were more likely observed in acral melanomas. NF1 and Triple-WT subgroups were unbiased between melanomas arising in non-CSD and acral skin. BRAF, RAS, and NF1 mutations were significantly associated with lymph node metastasis or presence of ulceration, implying that these cancer driver genes were independent prognostic factors. In summary, our results suggest that mutational profiles of malignant melanomas in China are significantly different from Western countries, and both gene mutation and amplification play an important role in the development and progression of melanomas.

Highlights • MiR-488 suppressed migration, invasion and EMT of osteosarcoma cells. • ITGA6 abolished the suppressive influences of miR-488 on migration, invasion and EMT of osteosarcoma cells. • SNHG16 promoted migration, invasion and EMT of osteosarcoma cells by sponging miR-488. • ITGA6 abrogated the suppressive effects of sh-SNHG16 on migration, invasion and EMT of osteosarcoma cells., Background Osteosarcoma is a primary cause of cancer-associated death in children and adolescents worldwide. Long non-coding RNAs SNHG16 (lncRNA SNHG16) and integrin subunit-a 6 (ITGA6) are recently reported to be involved in the tumorigenesis of osteosarcoma by multiple mechanisms. However, the correlation between SNHG16 and ITGA6 in osteosarcoma remains undetermined. Methods Expression of miR-488, SNHG16 and ITGA6, as well as epithelial-mesenchymal transition (EMT) associated markers in osteosarcoma tissues and cell lines were examined by qRT-PCR or Western blotting. Effects of miR-488, SNHG16 and ITGA6 on cell migration, invasion were evaluated by wound-healing assay and transwell assay. Bioinformatics analysis and dual-luciferase reported assays were applied to assess the interaction among miR-488, SNHG16 and ITGA6. RNA immunoprecipitation (RIP) was also used to verify SNHG16 and miR-488 interaction. Finally, animal study was used to detect the effect of SNHG16 on osteosarcoma in vivo. Results SNHG16 and ITGA6 were significantly increased while miR-488 was decreased in osteosarcoma. ITGA6 was screened as a target gene of miR-488, and SNHG16 was sponged by miR-488 in osteosarcoma cells. MiR-488 overexpression and SNHG16 knockdown suppressed migration, invasion and EMT of osteosarcoma cells. Moreover, rescue assays proved that the influences of SNHG16 on osteosarcoma cells migration, invasion and EMT were dependent on miR-488 and ITGA6. In addition, the promotive effects of SNHG16 on osteosarcoma tumor growth and metastasis were further supported by xenograft tumor growth assay. Conclusion SNHG16 promoted migration, invasion and EMT of osteosarcoma by sponging miR-488 to release ITGA6.

Recent advances in the management of bone tumors have led to a significant increase in the survival rates of patients with malignant bone tumors. Thus, limb salvage surgery has gained importance for preserving limb function in the management of bone tumors. However, surgery presents unique difficulties in terms of the biomechanics and obtaining a soft-tissue cover, such as when the ankle is involved in the primary malignant bone tumor. We report a case of chondrosarcoma of the distal tibia treated with wide en bloc resection arthrodesis and reconstruction of the defect using distraction osteogenesis, which offers an effective alternative protocol for limb salvage. The patient has remained disease free for 3 years since the initial surgery and can maintain normal limb athletic function.