Hallazgos tomográficos en paciente con osteosarcoma condroblástico mandibular recidivante de alto grado / Tomographic Findings in a Patient with Recurrent High - Grade Chondroblastic Osteosarcoma of the Jaw

Hallazgos de lesión expansiva que compromete la región hemifacial izquierda, con plano de clivaje sobre las estructuras adyacentes, que genera cambios líticos sobre la rama mandibular izquierda, en el cuerpo y la región del cóndilo mandibular. La lesión tiene un diámetro aproximado de 12,5 cm, con múltiples calcificaciones en su interior, que genera efecto de masa sobre las estructuras del piso de la boca y desvía la columna de la vía aérea en sentido dextroconvexo, sin evidenciar estenosis significativa(AU)

Effects of miR-143 on the migration and invasion of osteosarcoma cells by regulating MMP-13 expression / 中国骨伤

OBJECTIVE@#To explore the effect of miR-143 regulating matrix metalloproteinase(MMP)-13 expression on migration and invasion of osteosarcoma cells.@*METHODS@#The mouse osteosarcoma cell line 143B cells were cultured in 96-well plates, and blank group, negative group, positive group, and intervention group were set up. Then, the blank group did no treatment 50 μg miR-143 mimic was added to positive group, negative group added equal mimic NC (control sequence of miR-143 mimic), the intervention group was added 50 μg miR-143 mimic and 10 μg MMP-13 protein, all groups continued to culture for 3 to 6 hours, and finally the serum was aspirated to treat for half an hour. The protein expressions of miR-143 and MMP-13 in each group were measured by fluorescence quantitative PCR experiment and Western blot experiment, respectively, and the invasion and migration abilities of cells were measured by Transwell and scratch experiments.@*RESULTS@#The expression of MMP-13 protein in the positive group and the intervention group was significantly lower than that in the blank group, and the positive group was lower than the intervention group (P<0.05);The mean numbers of invasive cells in blank group, negative group, positive group and intervention group were (1 000.01±44.77), (959.25±46.32), (245.04±4.33), (634.06±33.78) cells/field, respectively;the scratch healing rate of the positive group and the intervention group was significantly lower than that of the blank group, and the positive group was lower than the intervention group (P<0.05).@*CONCLUSION@#MMP-13 is a target of miR-143, which can reduce the migration and invasion ability of osteosarcoma cells by inhibiting the expression of MMP-13.

Long-term effectiveness of uncemented allograft-prosthesis composite for reconstruction of bone defects after proximal femur tumor resection / 中国修复重建外科杂志

OBJECTIVE@#To investigate the long-term effectiveness of uncemented allograft-prosthesis composite (APC) for reconstruction of bone defects after proximal femur tumor resection.@*METHODS@#Between June 2007 and March 2014, 21 patients who underwent uncemented APC reconstruction of proximal femur after tumor resection were retrospectively evaluated. There were 9 males and 12 females with an average age of 33.2 years (range, 19-54 years). There were 9 cases of giant cell tumor of bone, 5 cases of osteosarcoma, 4 cases of osteoblastic osteosarcoma, 2 cases of chondrosarcoma, and 1 case of undifferentiated pleomorphic sarcoma. Thirteen cases of benign bone tumors were all classified as stage 3 by Enneking staging; and 8 cases of malignant bone tumors were classified as grade ⅡB in 7 cases and grade ⅡA in 1 case according to the American Joint Committee on Cancer (AJCC) staging system. Among them, 7 patients underwent reoperation after recurrence, and the rest were primary operations; 8 patients presented with pathological fractures. The preoperative Harris hip score (HHS) and American Musculoskeletal Tumor Society (MSTS) score was 40 (30, 49) and 9.1±3.5, respectively. The length of osteotomy was 80-154 mm, with an average of 110 mm. At 1 year after operation and last follow-up, HHS and MSTS scores were utilized to evaluate the function of hip joint; the gluteus medius strength score was used to evaluation of the hip abduction function. Image examinations were taken at 1, 3, 6, 9, and 12 months after operation and every year thereafter to assess the union of allograft-host bone interfaces. Intra- and post-operative complications were also recorded.@*RESULTS@#All patients were followed up 84-163 months (mean, 123.5 months). At 1 year after operation and last follow-up, the HHS and MSTS scores significantly improved when compared with the preoperative scores ( P<0.05). However, there was no significant difference in the HHS score, MSTS score, and gluteus medius strength score between the two time points after operation ( P>0.05). Image examination showed that all allograft-host bone interfaces achieved union after 5-10 months (mean, 7.6 months). At last follow-up, all patients had bone resorption, including 11 severe cases, 4 moderate cases, and 6 mild cases; the bone resorption sites included Gruen 1, 2, and 7 regions. Complications included 10 fractures and 1 prosthetic fracture. Local recurrence occurred in 3 patients and pulmonary metastasis in 3 patients.@*CONCLUSION@#Uncemented APC is a reliable method for the reconstruction of bone defects after proximal femur tumor resection. It has the good long-term effectiveness and possesses obvious advantages in the union at the bone-bone surface.

Characterization of Cell Subsets Associated With Prognosis of Osteosarcoma Based on Single-Cell Sequencing Data / 中国医学科学院学报

Objective To explore the cell subsets and characteristics related to the prognosis of osteosarcoma by analyzing the cellular composition of tumor tissue samples from different osteosarcoma patients.Methods The single-cell sequencing data and bulk sequencing data of different osteosarcoma patients were downloaded.We extracted the information of cell samples for dimensionality reduction,annotation,and cell function analysis,so as to identify the cell subsets and clarify the cell characteristics related to the prognosis of osteosarcoma.The development trajectory of macrophages with prognostic significance was analyzed,and the prognostic model of osteosarcoma was established based on the differentially expressed genes of macrophage differentiation.Results The cellular composition presented heterogeneity in the patients with osteosarcoma.The infiltration of mononuclear phagocytes in osteosarcoma had prognostic significance(P=0.003).Four macrophage subsets were associated with prognosis,and their signature transcription factors included RUNX3(+),ETS1(+),HOXD11(+),ZNF281(+),and PRRX1(+).Prog_Macro2 and Prog_Macro4 were located at the end of the developmental trajectory,and the prognostic ability of macrophage subsets increased with the progression of osteosarcoma.The prognostic model established based on the differentially expressed genes involved in macrophage differentiation can distinguish the survival rate of osteosarcoma patients with different risks(P<0.001).Conclusion Macrophage subsets are closely related to the prognosis of osteosarcoma and can be used as the key target cells for the immunotherapy of osteosarcoma.

Research progress in the mechanism and treatment of osteosarcoma / 中华医学杂志(英文版)

Osteosarcoma (OS) is the most common primary malignant bone tumor that more commonly occurs in children and adolescents. The most commonly used treatment for OS is surgery combined with chemotherapy, but the treatment outcomes are typically unsatisfactory. High rates of metastasis and post-treatment recurrence rates are major challenges in the treatment of OS. This underlines the need for studying the in-depth characterization of the pathogenetic mechanisms of OS and development of more effective therapeutic modalities. Previous studies have demonstrated the important role of the bone microenvironment and the regulation of signaling pathways in the occurrence and development of OS. In this review, we discussed the available evidence pertaining to the mechanisms of OS development and identified therapeutic targets for OS. We also summarized the available treatment modalities for OS and identified future priorities for therapeutics research.

Prognostic value and mechanism of long non-coding RNA DLEU1 in osteosarcoma / 中国骨伤

OBJECTIVE@#To investigate the prognostic value and mechanism of long non-coding RNA DLEU1(LncRNA DLEU1) in osteosarcoma.@*METHODS@#The tissue samples and clinical data of 86 patients with osteosarcoma treated by orthopaedic surgery in our hospital from January 2012 to December 2014 were retrospectively collected. The expression of LncRNA DLEU1 in pathological tissues was detected by qRT-PCR, then the patients were divided into high and low expression of LncRNA DLEU1 groups. Osteosarcoma cell line HOS was divided into two groups, down-regulated expression group (si-DLEU1 group) and negative control group (si-NC group). LncRNA DLEU1 siRNA and negative control sequence were transfected by Lipofectamine 3000. Chi-square test was used to analyze the relationship between the expression of LncRNA DLEU1 and the clinicopathological factors of osteosarcoma. Kaplan-Meier method was used to compare the difference of the overall survival rate of osteosarcoma patients between the high and low expression groups of LncRNA DLEU1. The risk factors affecting the overall survival rate of osteosarcoma were analyzed by single factor and multifactor analysis. The number of invasive cells in the two groups was determined and compared by Transwell assay.@*RESULTS@#The expression of LncRNA DLEU1 in osteosarcoma tissue was higher than that in adjacent tissues (P<0.001). The expression of LncRNA DLEU1 in human osteosarcoma cell lines (MG-63, U-2 OS, and HOS) was significantly higher than that in human osteoblast line hFOB 1.19 (P<0.001). The expression of LncRNA DLEU1 was significantly correlated with Enneking stage (P<0.001), distant metastasis (P=0.016), and histological grade (P=0.028). The 1-year overall survival rate of the LncRNA DLEU1 high expression group was significantly higher than that of the low expression group (90.7% vs 60.5%, P<0.001). The 5-year overall survival rate of the LncRNA DLEU1 high expression group was significantly higher than that of the low expression group (32.6% vs 11.6%, P<0.001). Univariate analysis showed that Enneking stage (P<0.001), tumor size (P=0.043), distant metastasis (P<0.001), histological grade (P<0.001), and expression of LncRNA DLEU1 (P<0.001) were risk factors for overall survival of osteosarcoma patients. Multivariate analysis showed that high expression of LncRNA DLEU1 [HR=1.948, 95% CI(1.141, 3.641), P=0.012] and distant metastasis[HR=4.108, 95% CI(2.169, 7.780), P<0.001] were independent risk factors for overall survival of osteosarcoma patients. The number of invasive cells in si-DLEU1 group was significantly lesser than that in si-NC group(139±13 vs 357±31, P<0.001).@*CONCLUSION@#High expression of LncRNA DLEU1 is a molecular marker affecting the prognosis of osteosarcoma patients. Downregulation of LncRNA DLEU1 can inhibit the invasion of osteosarcoma cells.

Mutation characteristics of osteosarcoma: a single center study of 64 cases using next-generation sequencing / 中华病理学杂志

Objective: To investigate the distribution and characteristics of gene mutations in osteosarcoma, and to analyze the frequency and types of detectable mutations, and to identify potential targets for individualized treatment of osteosarcoma. Methods: The fresh tissue or paraffin-embedded tissue samples of 64 cases of osteosarcoma that were surgically resected or biopsied and then subject to next generation sequencing, were collected from Beijing Jishuitan Hospital, China from November 2018 to December 2021. The tumor DNA was extracted to detect the somatic and germline mutations using targeted sequencing technology. Results: Among the 64 patients, 41 were males and 23 were females. The patient age ranged from 6 to 65 years with a median age of 17 years, including 36 children (under 18 years old) and 28 adults. There were 52 cases of conventional osteosarcoma, 3 cases of telangiectatic osteosarcoma, 7 cases of secondary osteosarcoma, and 2 cases of parosteosarcoma. The detection rate of gene mutations was overall 84.4% (54/64). There were 324 variations in 180 mutated genes, including 125 genes with copy number variations, 109 single nucleotide variants, 83 insertions or deletions, and 7 gene fusions. The most common mutated genes were TP53, VEGFA, CCND3, ATRX, MYC, RB1, PTEN, GLI1, CDK4 and PTPRD. Among them, TP53 had the highest mutation rate (21/64, 32.8%), single nucleotide variant was the main mutation type (14/23, 60.9%), and 2 cases carried the TP53 germline mutation. VEGFA and CCND3 showed copy number amplification simultaneously in 7 cases. Conclusions: The high-frequency mutation of TP53 suggests that it plays an important role in the pathogenesis and development of osteosarcoma. VEGFA, CCND3 and ATRX are mutated genes in osteosarcoma and worthy of further studies. Combination of pathologic diagnosis and next generation sequencing with clinical practice can guide individualized treatment for patients with refractory, recurrent and metastatic osteosarcoma.

miR-125b-5p inhibits proliferation and migration of osteosarcoma cells by negatively regulating RAB3D expression / 南方医科大学学报

OBJECTIVE@#To investigate the inhibitory effect of miR-125b-5p on proliferation and migration of osteosarcoma and the role of RAB3D in mediating this effect.@*METHODS@#The expression level of miR-125b-5p was detected by qRT-PCR in a normal bone cell line (hFOB1.19) and in two osteosarcoma OS cell lines (MG63 and HOS). A miR-125b-5p mimic or inhibitor was transfected in the osteosarcoma cell lines via liposome and the changes in cell proliferation and migration were detected with EDU and Transwell experiments. Bioinformatic analysis was conducted for predicting the target gene of miR-125b-5p, and the expression level of RAB3D in hFOB1.19, MG63, and HOS cells was detected by Western blotting. In the two osteosarcoma cell lines transfected with miR-125b-5p mimic or inhibitor, the expression levels of RAB3D mRNA and protein in osteosarcoma cells were examined with qRT-PCR and Western blotting. The effects of RAB3D overexpression, RAB3D knockdown, or overexpression of both miR-125b-5p and RAB3D on the proliferation and migration of cells were assessed using EDU and Transwell experiments.@*RESULTS@#The two osteosarcoma cell lines had significantly lower expression levels of miR-125b-5p (P < 0.05). Bioinformatic analysis predicted that RAB3D was a possible target gene regulated by miR-125b-5p. In osteosarcoma cells, overexpression of miR-125b-5p significantly lowered the expression of RAB3D protein (P < 0.05); inhibiting miR-125b-5p expression significantly decreased RAB3D expression only at the protein level (P < 0.05) without obviously affecting its mRNA level. Modulation of miR-125b-5p and RAB3D levels produced opposite effects on proliferation and migration of osteosarcoma cells, and in cells with overexpression of both miR-125b-5p and RAB3D, the effect of RAB3D on cell proliferation and migration was blocked by miR-125b-5p overexpression (P < 0.05).@*CONCLUSION@#Overexpression of miR-125b-5p inhibits the proliferation and migration of osteosarcoma cells by regulating the expression of RAB3D at the post-transcriptional level.

Radiation-associated sarcomas of bone and soft tissue: a clinicopathological analysis of 46 cases / 中华病理学杂志

Objective: To investigate the clinical, imaging, histological, and molecular features and the differential diagnosis of radiation-associated sarcomas of bone and soft tissue. Methods: Forty-six cases of radiation-associated sarcomas of the bone and soft tissue in Beijing Jishuitan Hospital from January 2010 to January 2022 were retrospectively analyzed; and the imaging, histological features and immunophenotype were examined. Results: There were 33 females and 13 males, aged from 18 to 74 years, with a mean of 52 years. The most common site of radiation-associated sarcomas were the limbs and spine (15 cases), followed by the chest (9 cases). The primary diseases included epithelial tumors (15 breast cancer, 6 cervical cancer, and 5 bowel cancer), hematolymphoid tumors, bone and soft tissue tumors and infectious lesions. The latent period of radiation-associated sarcomas ranged from 2-22 years, with an average of 11.6 years. Histopathologically, the morphology was divergent from the primary tumor. The most common malignant tumor type was undifferentiated sarcoma (22 cases), followed by osteosarcoma (16 cases). The immunophenotype of radiation-related sarcoma was almost the same as the corresponding soft tissue sarcoma. Conclusions: Radiation-induced sarcoma has a wide range of primary tumor types and its imaging, morphology and immunohistochemical features are similar to those of the primary sarcoma of bone and soft tissue. Clinical correlation is often recommended for the differential diagnosis.

Reconstruction with Unconventional Endoprostheses after Resection of Primary Distal Femoral Bone Tumors: Implant Survival and Functional Outcomes / Reconstrução com endoprótese não convencional após ressecção de tumores ósseos primários de fêmur distal: sobrevida do implante e resultados funcionais

Abstract Objective To evaluate the survival time, the failure rate and its causes, and the functional results of cemented endoprostheses, with a polyethylene body, used after resection of primary bone tumors of the distal femur. Methods A retrospective study including 93 primary and 77 review procedures performed between 1987 and 2014. Survival was obtained by the Kaplan Meyer analysis, and the risk factors for implant failure were assessed through the Cox proportional risk model. The causes of endoprosthesis failure were classified according to Henderson et al. into five types: soft-tissue failure, aseptic loosening, structural fracture, infection, and tumor recurrence. The functional evaluation was performed using the functional classification system of the Musculoskeletal Tumor Society (MSTS) of bone sarcomas of the lower extremity, Brazilian version (MSTS-BR). Results Osteosarcoma was the most common diagnosis; 64.5% of the patients were younger than 20 years of age; the mean follow-up was of 124.3 months. The failure rate of the primary implant was of 54.8%, and the mean survival was of 123 months. The estimated survival of the primary implant was of 63.6%, 43.5%, 24.1%, and 14.5% in 5, 10, 15, and 20 years respectively. The most common cause of failure was type 2 (37.3%). Age ≤ 26 years and right side were risk factors for failure. The mean MSTS-BR score was of 20.7 (range: 14 to 27). Conclusion The results obtained for the failure rate and survival of the implant are in accordance with those of the literature, so the procedure herein studied is adequate and yields satisfactory functional results, even in the long term.

Resumo Objetivo Avaliar o tempo de sobrevida, a taxa de falha e suas causas, e os resultados funcionais de endopróteses cimentadas, com corpo em polietileno, empregadas após ressecção de tumores ósseos primários do fêmur distal. Métodos Estudo retrospectivo, que incluiu 93 procedimentos primários e 77 de revisão, realizados entre 1987 e 2014. A sobrevida foi obtida pela análise de Kaplan Meyer, e os fatores de risco para falha do implante foram avaliados por meio do modelo de riscos proporcionais de Cox. As causas de falha da endoprótese foram classificadas segundo Henderson et al. em cinco tipos: falha de partes moles, soltura asséptica, fratura estrutural, infecção e recorrência do tumor. A avaliação funcional foi realizada por meio do sistema de classificação funcional da Musculoskeletal Tumor Society (MSTS) para sarcomas ósseos da extremidade inferior, versão brasileira (MSTS-BR). Resultados Osteossarcoma foi o diagnóstico mais comum; 64,5% dos pacientes tinham menos de 20 anos; e o seguimento médio foi de 124,3 meses. A taxa de falha do implante primário foi de 54,8%, e a sobrevida média foi 123 meses. A estimativa de sobrevida do implante primário foi de 63,6%, 43,5%, 24,1%, 14,5% em 5, 10, 15 e 20 anos, respectivamente. A causa de falha mais comum foi a do tipo 2 (37,3%). Idade ≤ 26 anos e lado direito foram fatores de risco para falha. A pontuação média no MSTS-BR foi de 20,7 (variação: 14 a 27). Conclusão Os resultados obtidos para a taxa de falha e o tempo de sobrevida do implante estão de acordo com os da literatura, de forma que o procedimento estudado é adequado e apresenta resultados funcionais satisfatórios, inclusive em longo prazo.

Cirugías ablativas por causas oncológicas. 17 años de experiencia en una Unidad Especializada del Estado Monagas, Venezuela / Ablative surgeries for oncological causes. 17 years experience in a Monagas specialized unit

Estudio retrospectivo, sobre pacientes a quienes se les practicó cirugías ablativas por causas oncológicas: un total de 76 casos, predominando en la serie: el sexo masculino, la segunda década de la vida y como motivo de consulta: aumento de volumen con un 73,5%, el osteosarcoma fue la neoplasia más frecuente con un 34%, la fractura patológica acompañó a los tumores en el 50% de los casos, el hueso más afectado fue el fémur, los estadios según Enneking predominantes fueron los II b y III. Se practicaron más cirugías en miembros inferiores, siendo la amputación transfemoral la más frecuente. La intención de los procedimientos fue predominantemente curativa con un 69% sobre las intenciones paliativas, se practicaron más amputaciones en niveles oncológicos radicales que amplias. Se obtuvo una sobrevida global de 53,4% a los dos años de seguimiento, el miembro fantasma estuvo presente como complicación por encima del 77% de los casos operados(AU)

Retrospective study on patients who underwent ablative surgeries for oncological causes: a total of 76 cases, predominantly in the series: male sex, second decade of life and as a reason for consultation: volume increase with 73,5%. Osteosarcoma was the most frequent neoplasm with 34%, pathological fracture accompanied the tumors in 50% of cases, the most affected bone was the femur, the predominant Enneking stages were IIb and III. More surgeries were performed on the lower limbs, with transfemoral amputation being the most frequent. The intention of the procedures was predominantly curative with 69% of the palliative intentions, more amputations were performed at radical oncological levels than extensive ones. An overall survival of 53.4% was obtained at two years of follow-up, the phantom limb was present as a complication in over 77% of operated cases.

Bioinformatics-based identification of key genes CDC5L and related pathways in osteosarcoma and Ewing's sarcoma / 中国骨伤

OBJECTIVE@#Osteosarcoma(OS) and Ewing's sarcoma (EWS) are the two most common primary malignant bone tumors in children. The aim of the study was to identify key genes in OS and EWS and investigate their potential pathways.@*METHODS@#Expression profiling (GSE16088 and GSE45544) were obtained from GEO DataSets. Differentially expressed genes were identified using GEO2R and key genes involved in the occurrence of both OS and EWS were selected using venn diagram. Gene ontology and pathway enrichment analyses were performed for the ensembl. Protein-protein interaction (PPI) networks were established by STRING. Further, UCSC was used to predict the transcription factors of the cell division cycke 5-like(CDC5L) gene, and GEPIA was used to analyze the correlation between the transcription factors and the CDC5L gene.@*RESULTS@#The results showed that CDC5L gene was the key gene involved in the pathogenesis of OS and EWS. The gene is mainly involved in mitosis, and is related to RNA metabolism, processing of capped intron-containing pre-mRNA, mRNA and pre-mRNA splicing.@*CONCLUSION@#CDC5L, as a key gene, plays a role in development of OS and EWS, which may be reliable targets for diagnosis and treatment of these primary malignant tumors.

Bioinformatics Analysis on Key Genes and Immune Infiltration of Osteosarcoma / 中国医学科学院学报

Objective To screen the potential key genes of osteosarcoma by bioinformatics methods and analyze their immune infiltration patterns. Methods The gene expression profiles GSE16088 and GSE12865 associated with osteosarcoma were obtained from the Gene Expression Omnibus(GEO),and the differentially expressed genes(DEGs)related to osteosarcoma were screened by bioinformatics tools.Gene Ontology(GO)annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and analysis of immune cell infiltration were then carried out for the DEGs.The potential Hub genes of osteosarcoma were identified by protein-protein interaction network,and the expression of Hub genes in osteosarcoma and normal tissue samples was verified via the Cancer Genome Atlas(TCGA). Results A total of 108 DEGs were screened out.GO annotation and KEGG pathway enrichment revealed that the DEGs were mainly involved in integrin binding,extracellular matrix (ECM) structural components,ECM receptor interactions,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Macrophages were the predominant infiltrating immune cells in osteosarcoma.Secreted phosphoprotein 1(SPP1),matrix metallopeptidase 2(MMP2),lysyl oxidase(LOX),collagen type V alpha(II)chain(COL5A2),and melanoma cell adhesion molecule(MCAM)presented differential expression between osteosarcoma and normal tissue samples(all P<0.05). Conclusions SPP1,MMP2,LOX,COL5A2,and MCAM are all up-regulated in osteosarcoma,which may serve as potential biomarkers of osteosarcoma.Macrophages are the key infiltrating immune cells in osteosarcoma,which may provide new perspectives for the treatment of osteosarcoma.

A Bibliometric Analysis and Visualization of Current Research Trends in Chinese Medicine for Osteosarcoma / 中国结合医学杂志

BACKGROUND@#To illustrate the research framework, overall knowledge structure, and development trends of Chinese medicine (CM) treatment for osteosarcoma (OS) by using a bibliometric analysis and newly developed visualization tools.@*METHODS@#Research datasets were acquired from the Web of Science (WOS) database from January 1, 1980 to September 30, 2019. VOS viewer and Citespace software was used to analyze the data and generate visualization knowledge maps. Annual trends of publications, distribution of institutes, distribution of journals, citation and H-index status, co-authorship status, research hotspots and co-citation status were analyzed.@*RESULTS@#A total of 223 publications in the WOS database met the requirement. The number of published articles showed a rise but the citation frequency and the H-index of China were relatively low. The cooperation between the countries, institutes and authors were relatively weak. Most publications were basic researches. Most of the previous researches focused on basic mechanisms of CM in treating OS, and therapy and improvement of dosage form may become a frontier in this research field.@*CONCLUSIONS@#Compared with other fields, the field of CM treatment for osteosarcome is still in infancy. The distribution of researches is imbalanced and cooperation between countries, institutions and authors remains to be strengthened. Furthermore, basic research occupies an absolute dominant position, and the exploration of the molecular mechanism of CM in preventing and treating OS may become a key point in the future.

Bioinformatics analysis of differently expressed genes in osteoblastic sarcoma and screening of key genes / 中华肿瘤杂志

Objective: To screen the different expressed genes between osteosarcoma and normal osteoblasts, and find the key genes for the occurrence and development of osteosarcoma. Methods: The gene expression dataset GSE33382 of normal osteoblasts and osteosarcoma was obtained from Gene Expression Omnibus (GEO) database. The different expressed genes between normal osteoblasts and osteosarcoma were screened by limma package of R language, and the different expressed genes were analyzed by Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The protein interaction network was constructed by the String database, and the network modules in the interaction network were screened by the molecular complex detection (MCODE) plug-in of Cytoscape software. The different expressed genes contained in the first three main modules screened by MCODE were analyzed by gene ontology (GO) using the BiNGO module of Cytoscape software. The MCC algorithm was used to screen the top 10 key genes in the protein interaction network. The gene expression and survival dataset GSE39055 of osteosarcoma was obtained from GEO database, and the survival analysis was performed by Kaplan-Meier method. The data of 48 patients with osteosarcoma treated in the First Affiliated Hospital of Fujian Medical University from January 2005 to December 2015 were selected for verification. The expression of STC2 protein in osteosarcoma was detected by immunohistochemical method, and the survival analysis was carried out combined with the clinical data of the patients. Results: A total of 874 different expressed genes were identified from GSE33382 dataset, including 402 down-regulated genes and 472 up-regulated genes. KEGG enrichment analysis showed that different expressed genes were mainly related to p53 signal pathway, glutathione metabolism, extracellular matrix receptor interaction, cell adhesion molecules, folate tolerance, and cell senescence. The top 10 key genes in the interaction network were GAS6, IL6, RCN1, MXRA8, STC2, EVA1A, PNPLA2, CYR61, SPARCL1 and FSTL3. STC2 was related to the survival rate of patients with osteosarcoma (P<0.05). The results showed that the expression of STC2 protein was related to tumor size and Enneking stage in 48 cases of osteosarcoma. The median survival time of 25 cases with STC2 high expression was 21.4 months, and that of 23 cases with STC2 low expression was 65.4 months. The survival rate of patients with high expression of STC2 was lower than that of patients with low expression of STC2 (P<0.05). Conclusions: Bioinformatics analysis can effectively screen the different expressed genes between osteosarcoma and normal osteoblasts. STC2 is one of the important predictors for the prognosis of osteosarcoma.

GKK1032B from endophytic Penicillium citrinum induces the apoptosis of human osteosarcoma MG63 cells through caspase pathway activation / 中国天然药物

Chemical investigation of the culture extract of an endophytic Penicillium citrinum from Dendrobium officinale, afforded nine citrinin derivatives (1-9) and one peptide-polyketide hybrid GKK1032B (10). The structures of these compounds were determined by spectroscopic methods. The absolute configurations of 1 and 2 were determined for the first time by calculation of electronic circular dichroism (ECD) data. Among them, GKK1032B (10) showed significant cytotoxicity against human osteosarcoma cell line MG63 with an IC50 value of 3.49 μmol·L-1, and a primary mechanistic study revealed that it induced the apoptosis of MG63 cellsvia caspase pathway activation.

Osteosarcoma extraesquelético. Presentación de un caso / Extraskeletal osteosarcoma. Case report

El osteosarcoma extraesquelético es un tumor maligno de alto grado que representa menos del 2% de los sarcomas de partes blandas y que afecta principalmente a personas entre la quinta y sexta década de la vida. Típicamente el diagnóstico es tardío, con un período síntomas-diagnóstico extenso, >6 meses en comparación con el del osteosarcoma convencional. Comunicamos el caso de un hombre de 43 años que acudió con una tumoración en la región glútea y el muslo izquierdo de un año de evolución. Luego de estudios complementarios y una biopsia no concluyentes, se procedió a la resección quirúrgica del tumor con márgenes amplios. El estudio histológico de la pieza indicó osteosarcoma extraesquelético. El paciente tuvo una evolución muy buena, sin elementos de recidiva local ni compromiso a distancia luego de 20 meses de seguimiento. Nivel de Evidencia: IV

Extraskeletal osteosarcoma (EOS) is a high-grade malignant tumor that accounts for less than 2% of soft tissue sarcomas and mainly engages people between the fifth and sixth decade of life. It is typically of late diagnosis, with an extensive symptom-diagnosis period greater than 6 months compared to conventional osteosarcoma. We report the case of a 43-year-old patient who presented in our service with a 1-year-old tumor localized in the gluteal and left thigh region. After inconclusive paraclinical studies and biopsy, the tumor was surgically resected with wide margins and diagnosed as EOS after the histological analysis of the piece. The patient showed a very good clinical and paraclinical progression without signs of local or distant recurrence after 20 months of follow-up. Level of Evidence: IV