Inhibition of anlotinib-induced autophagy attenuates invasion and migration by regulating epithelial-mesenchymal transition and cytoskeletal rearrangement through ATG5 in human osteosarcoma cells

Abstract The cure rates for osteosarcoma have remained unchanged in the past three decades, especially for patients with pulmonary metastasis. Thus, a new and effective treatment for metastatic osteosarcoma is urgently needed. Anlotinib has been reported to have antitumor effects on advanced osteosarcoma. However, both the effect of anlotinib on autophagy in osteosarcoma and the mechanism of anlotinib-mediated autophagy in pulmonary metastasis are unclear. The effect of anlotinib treatment on the metastasis of osteosarcoma was investigated by transwell assays, wound healing assays, and animal experiments. Related proteins were detected by western blotting after anlotinib treatment, ATG5 silencing, or ATG5 overexpression. Immunofluorescence staining and transmission electron microscopy were used to detect alterations in autophagy and the cytoskeleton. Anlotinib inhibited the migration and invasion of osteosarcoma cells but promoted autophagy and increased ATG5 expression. Furthermore, the decreases in invasion and migration induced by anlotinib treatment were enhanced by ATG5 silencing. In addition, Y-27632 inhibited cytoskeletal rearrangement, which was rescued by ATG5 overexpression. ATG5 overexpression enhanced epithelial-mesenchymal transition (EMT). Mechanistically, anlotinib-induced autophagy promoted migration and invasion by activating EMT and cytoskeletal rearrangement through ATG5 both in vitro and in vivo. Our results demonstrated that anlotinib can induce protective autophagy in osteosarcoma cells and that inhibition of anlotinib-induced autophagy enhanced the inhibitory effects of anlotinib on osteosarcoma metastasis. Thus, the therapeutic effect of anlotinib treatment can be improved by combination treatment with autophagy inhibitors, which provides a new direction for the treatment of metastatic osteosarcoma.

Effect and mechanism of berberine-induced ferroptosis in osteosarcoma cells / 中国药房

OBJECTIVE To investigate the effect of berberine on ferroptosis in MG63 osteosarcoma cells and its mechanism. METHODS Using cells without drug treatment as control， the cell viability， proliferation， the related indexes of ferroptosis [nuclear proliferation associated-antigen （Ki67）， mitochondrial ultrastructure， ferric ion （Fe2+）， reactive oxygen species （ROS）， malondialdehyde （MDA）， and glutathione （GSH）]， the protein expression of signal transducer and activator of transcription 3 （STAT3）， tumor protein 53 （p53）， and solute carrier family 7 member 11 （SLC7A11） were detected after being treated with different concentrations of berberine. Cells were transfected with p53 siRNA and then assigned to the control group， p53 siRNA group， berberine group， and p53 siRNA+berberine group to explore the role of p53 in berberine-induced ferroptosis. After 24 h incubation with 10.0 μmol/L berberine， the protein expressions of p53 and SLC7A11， the levels of mitochondrial membrane potential， GSH， and MDA content were determined. Cells were transfected with STAT3 overexpressed plasmid and then assigned to the control group， berberine group， STAT3 group， and STAT3+berberine group to explore the effect of STAT3 on the regulation of the p53/SLC7A11 pathway. After 24 h incubation with 10 μmol/L berberine， the protein expressions of p-STAT3， STAT3， p53， and SLC7A11 were detected. RESULTS Compared with the control cell， the concentrations of 2.5， 5.0 and 10.0 μmol/L berberine could reduce the cell viability and expression of Ki67， and induce the morphological changes in ferroptosis-related mitochondria， increase the levels of Fe2+， ROS and MDA， and the protein expression of p53， reduce the level of GSH， the binding activity of STAT3 with DNA， and the protein expressions of p-STAT3 and SLC7A11； the above differences were statistically significant （P＜ 0.05 or P＜0.01）. Compared with the berberine group，significantly down-regulated p53 protein expression and MDA level， up-regulated SLC7A11 protein expression， and increased mitochondrial membrane potential and GSH level were observed in the p53 siRNA+berberine group （P＜0.01）. Compared with the berberine group， the protein expressions of p-STAT3， STAT3， and SLC7A11 in the STAT3+berberine group were significantly increased （P＜0.01）， while the protein expression of p53 was significantly decreased （P＜0.01）. CONCLUSIONS Berberine can induce the ferroptosis of MG63 cells by mediating STAT3/p53/SLC7A11 signaling pathway.

Mechanism of oxymatrine promoting the apoptosis of osteosarcoma MG63 cell line through mitophagy mediated by COX-2/PINK1/Parkin signaling pathway / 中国药房

OBJECTIVE To study the mechanism of oxymatrine inducing apoptosis of osteosarcoma MG63 cell line based on mitophagy mediated by cyclooxygenase-2 （COX-2）/PTEN-induced putative kinase-1 （PINK1）/Parkinson disease protein-2 （Parkin） signaling pathway. METHODS MG63 cells were treated with 2.0， 4.0， 8.0 mg/mL oxymatrine and 6 μmol/L 5-fluorouracil， then the apoptotic rate， the expression of apoptosis-related proteins [B-cell lymphoma-2 （Bcl-2）， Bcl-2 related X protein （Bax）]， the proportion of decrease in mitochondrial membrane potential， the level of mitophagy as well as the protein expressions of PINK1， Parkin， and microtubule-associated protein 1 light chain-3Ⅱ （LC3-Ⅱ） were detected. PINK1 small interfering RNA （siRNA） was adopted to intervene in the expression of PINK1， the cells were divided into control group， PINK1 siRNA group， oxymatrine group， and PINK1 siRNA+oxymatrine group； the protein expressions of PINK1， Parkin， and LC3-Ⅱ， the proportion of decrease in mitochondrial membrane potential （MMP） as well as apoptotic rate were detected. The lentivirus infection technique was used to overexpress COX-2， the cells were divided into control group， oxymatrine group， COX-2 group， and COX-2+oxymatrine group. The protein expressions of COX-2， PINK1， and Parkin， as well as the proportion of decrease in MMP were detected. RESULTS After being treated with oxymatrine， the apoptotic rate， the protein expressions of Bax， PINK1， Parkin， and LC3-Ⅱ， the level of mitophagy as well as the proportion of decrease in MMP were significantly increased （P＜0.05）， while the protein expression of Bcl-2 was significantly decreased （P＜0.05）. Compared with the oxymatrine group， the protein expressions of PINK1， Parkin， and LC3-Ⅱ， apoptotic rate and the proportion of decrease in MMP were significantly decreased in PINK1 siRNA+oxymatrine group （P＜0.05）. Compared with the oxymatrine group， the protein expression of COX-2 in the COX-2+oxymatrine group was increased significantly （P＜0.05）， while the protein expressions of PINK1 and Parkin as well as the proportion of 526087266@qq.com decrease in MMP were decreased significantly （P＜0.05）. CONCLUSIONS Oxymatrine can mediate the overactivity of mitophagy based on the PINK1/Parkin signaling pathway by inhibiting COX-2 expression， thus promoting the apoptosis of the MG63 osteosarcoma cell line.

Research progress on autocrine and paracrine regulation of osteosarcoma cell growth / 中国生物制品学杂志

@#Osteosarcoma(OS)is one of the most common malignant tumors in bone tissue,and its specific mechanism is not yet fully clear. Studies have shown that OS cells express different cytokines(CKs)and their receptors in the development stage of tumors,and enable them to grow autonomously and confer metastatic ability through autocrine and paracrine effects. In this regard,the most important CKs mainly includes insulin-like growth factor-1,transforming growth factor-β,chemokine 5 and interleukin-8,which can regulate the tumor microenvironment that is conducive to tumor growth,invasion and metastasis. This review summarizes the role and mode of action of CKs and their biological relevance to OS cells,hoping to provide effective new markers and therapeutic targets for clinical treatment of OS.

Synergistic effects of methotrexate and piperine on human osteosarcoma cell lines – An in-vitro study

Background: Osteosarcoma is a malignant cancer that effect bone and metastasizing to many vital organs such as lungs. There are many available drugs to treat the disease including tamoxifen, methotrexate (MTX), and cisplatin which have their own side effects and hurdles to become drugs of choice for the disease. On the other hand, introduction of herbal drugs as chemotherapeutic agents opened up new arena to potentiate the existing treatment by exhibiting synergy. Piperine (PPN) is widely used drug as anti-cancer agent as well as it has anti-inflammatory, analgesic properties, and also used in the treatment of abdominal pains, tuberculosis, arthritis, and respiratory illness. Aims and Objective: Thus, this study was designed to investigate the synergistic inhibitory potential of PPN and MTX on the MG63 osteosarcoma cell lines in vitro. Materials and Methods: The cell lines were cultured on DMEM medium and investigated for cytotoxicity of the drugs using MTT assay at 540 nm in UV. Three groups of cell lines administered with PPN, MTX, and PPN+MTX (1:1) in various concentrations and IC50 values were calculated based on the % cell viability graphs. Results: Results showed that the IC50 of PPN was 38.65, MTX was 123.98, and PPN+MTX was 15.13 proving the significant synergistic cytotoxic effect of PPN and MTX in inhibiting the proliferation of MG63 cell lines. Conclusion: Further research needs to be conducted in this field to elucidate the synergistic pathways in which PPN has shown a better anti-osteosarcoma effect when combined with MTX.

Role of incisional vacuum therapy in endoprosthetic bone reconstruction surgery / Papel da terapia a vácuo incisional em cirurgia de reconstrução óssea com endoprótese

ABSTRACT Reconstructive surgery with endoprostheses is the chosen method for treating bone malignancies. Postoperative infections are frequent complications, and their treatment involves prolonged hospital stays and antibiotic therapy. Among the advancements aimed at reducing the rate of postoperative infection, the use of incisional negative pressure therapy (iNPT) has shown promising results, with no reports in the literature regarding its use in patients with such conditions. Objective: To evaluate the effectiveness of iNPT in reducing postoperative complications in surgeries for resection of bone tumors associated with modular endoprosthesis reconstruction. Methods: Retrospective case series of 16 patients diagnosed with osteosarcoma, who underwent resection and reconstruction with endoprosthesis associated with iNPT during the postoperative period. Follow-up was performed for a period of six months, and the evaluated outcomes were the incidence of postoperative infection and complications of the surgical wound. Results: The use of iNPT for a postoperative period of seven days resulted in only three (18.7%) cases of postoperative infection. No cases of wound dehiscence, seroma formation, or hematoma at the surgical site were observed. Conclusion: The rate of surgical wound complications in our case series is lower than that reported in most of the literature, and iNPT appears to be an efficient way to reduce the rate of local complications in reconstructive surgeries with endoprosthesis after resection of bone malignancies. Level of Evidence III, Retrospective Study.

RESUMO A cirurgia reconstrutiva com endopróteses é o método escolhido no tratamento de malignidades ósseas. As infecções pós-operatórias são complicações frequentes, e seu tratamento envolve internações e antibioticoterapia prolongadas. Entre os avanços que visam reduzir a taxa de infecção pós-operatória, o uso da terapia com pressão negativa incisional (TPNi) vem mostrando resultados promissores, não havendo relatos na literatura de seu emprego em pacientes com tal quadro. Objetivo: Avaliar a eficácia da TPNi em reduzir complicações pós-operatórias em cirurgias de ressecção de tumores ósseos associadas à reconstrução com endopróteses modulares. Métodos: Série de casos retrospectiva de 16 pacientes diagnosticados com osteossarcoma, submetidos à ressecção e reconstrução com endoprótese associada à TPNi durante o pós-operatório. Foi realizado seguimento por um período de seis meses e os desfechos avaliados foram incidência de infecção pós-operatória e complicações da ferida operatória. Resultados: O uso da TPNi por um período pós-operatório de sete dias resultou em apenas três (18,7%) casos de infecção pós-operatória. Não foram observados casos em que ocorreu deiscência da ferida operatória, formação de seromas ou hematomas no sítio cirúrgico. Conclusão: A taxa de complicações de ferida operatória em nossa série de casos é menor que a da maior parte da literatura, e a TPNi parece ser uma forma eficiente de reduzir a taxa de complicações locais em cirurgias reconstrutivas com endoprótese após ressecção de malignidades ósseas. Nível de Evidência III, Estudo Retrospectivo.

LncRNA ZFAS1 contributes to osteosarcoma progression via miR-520b and miR-520e-mediated inhibition of RHOC signaling

ABSTRACT Objectives: We examined the expression of Lnc-ZFAS1 in osteosarcoma and comprehensively evaluated its effects on osteosarcoma in vitro and vivo. Moreover, we revealed the regulatory mechanism between Lnc-ZFAS1 and miR-520b/miR-520e-mediated RHOC and provided a novel clue for ameliorating osteosarcoma. Method: The expression of Long non-coding RNA Zinc Finger Antisense 1 (LncRNA ZFAS1) osteosarcoma tissues and normal tissues in the TCGA database was analyzed. Then, LncRNA ZFAS1 expression was further verified in clinical samples and osteosarcoma cell lines (U2OS and KHOS), as well as the human osteoblast cell line hFOB1.19 by qRT-PCR. Thereafter, LncRNA ZFAS1 was overexpressed or silenced to explore its effects on cell proliferation, apoptosis, migration, invasion, and Epithelial-Mesenchymal Transition (EMT). The fundamental mechanism through which Lnc-ZFAS1 affects osteosarcoma progression was further investigated and verified. Results: We found that LncRNA ZFAS1 was upregulated in osteosarcoma, and Lnc-ZFAS1 overexpression facilitated osteosarcoma cells proliferation, migration, invasion and EMT, while Lnc-ZFAS1 silence exerted reverse influence. Mechanistically, Lnc-ZFAS1 functionally acted as a sponger of microRNA-520b (miR-520b) and micro-RNA-520e (miR-520e) to up-regulate Ras Homologue C (RHOC). In addition, depleted Lnc-ZFAS1 restrained osteosarcoma cells proliferation, migration, and invasion, which could be rescued by RHOC overexpression. Lnc-ZFAS1 was upregulated in osteosarcoma and Lnc-ZFAS1 could exert promoted impact upon osteosarcoma cells proliferation, migration, invasion, and EMT in vitro. Conclusions: Lnc-ZFAS1 acted sponger of miR-520b and miR-520e to promote RHOC, indicating that Lnc-ZFAS1/miR-520b/RHOC and Lnc-ZFAS1/miR-520e/RHOC axes might serve as potential therapeutic strategies against osteosarcoma.

Computed tomography aspects of thoracic metastases from osteosarcoma: pictorial essay / Aspectos tomográficos das metástases torácicas de osteossarcoma: ensaio iconográfico

Abstract Osteosarcoma is the most common primary bone tumor, with a higher incidence in the second decade of life, and it often leads to pulmonary metastases. The most common pattern seen on computed tomography is one of multiple well-defined nodules in the lung parenchyma, often with calcifications. Because of the variety of presentations of pulmonary metastases in osteosarcoma, including atypical forms, knowledge of the computed tomography aspects of these lesions is important for characterizing and evaluating the extent of the disease, as well as for distinguishing metastatic disease from other benign or malignant lung diseases. This essay discusses the main tomographic findings of pulmonary metastases from osteosarcoma.

Resumo O osteossarcoma é o tumor ósseo primário mais comum, com maior incidência na segunda década de vida, sendo as metástases pulmonares achado frequente. O padrão tomográfico mais comum das metástases pulmonares de osteossarcoma é o de múltiplos nódulos bem definidos no parênquima pulmonar, frequentemente com calcificações. Em razão da multiplicidade de apresentações das metástases pulmonares do osteossarcoma, inclusive com formas atípicas, o conhecimento dos aspectos dessas lesões na tomografia computadorizada do tórax é importante para a caracterização e avaliação da extensão da doença, além de permitir a diferenciação entre doença metastática e outras doenças pulmonares benignas ou malignas. Este ensaio discute os principais achados tomográficos das metástases pulmonares de osteossarcoma.

Mesenchymal tumours of the head and neck: a 10-year institutional archival study / Tumores mesenquimales de cabeza y cuello: estudio de archivo institucional de 10 años de duración

Introduction: Histopathological characterisation of benign and malignant lesions of the head and neck in a systematic and coherent way is an essential part of Oral Pathology and Oral Medicine. Objective: To describe the frequency and histopathological profile of connective tissue tumours in the head and neck region reported in an Indian institute. Methods: A retrospective analysis was made of the 10-year records of reports of biopsy samples of patients maintained by the department of oral pathology showing histopathological diagnosis of connective tissue neoplasms. The data obtained was compiled for age, gender, site and histopathology of the lesions. Results: Majority of the tumours were benign and patients were found to be in the 2nd or 4th decade of life with female preponderance. The most common benign tumour was fibroma where buccal mucosa was the commonest location and malignant tumour was osteosarcoma where mandible was the commonest site. While fibromas were seen among general adult population, osteosarcomas were more in the males (7.2 percent) and in the younger population (< 20 years). The uncommon tumours among benign variety were leiomyoma and teratoma while in malignant category 1 case of undifferentiated sarcoma was reported. Conclusion: The findings in this study may be of help to oral and maxillofacial surgeons and general dentists in formulating diagnosis and rendering patient care in the existing local population(AU)

Introducción: La caracterización histopatológica de las lesiones benignas y malignas de cabeza y cuello de forma sistemática y coherente es una parte esencial de la Patología Oral y la Medicina Oral. Objetivo: Describir la frecuencia y el perfil histopatológico de los tumores del tejido conjuntivo de la región de cabeza y cuello notificados en un instituto indio. Métodos: Se realizó un análisis retrospectivo de los registros de 10 años de informes de muestras de biopsia de pacientes mantenidos por el departamento de patología oral que mostraban diagnóstico histopatológico de neoplasias del tejido conectivo. Se recopilaron los datos obtenidos en cuanto a edad, sexo, localización e histopatología de las lesiones. Resultados: La mayoría de los tumores eran benignos y los pacientes se encontraban en la 2ª o 4ª década de la vida, con preponderancia del sexo femenino. El tumor benigno más frecuente fue el fibroma, cuya localización más frecuente fue la mucosa bucal, y el tumor maligno fue el osteosarcoma, cuya localización más frecuente fue la mandíbula. Mientras que los fibromas se observaron entre la población adulta general, los osteosarcomas fueron más frecuentes en los varones (7,2 por ciento) y en la población más joven (< 20 años). Los tumores menos frecuentes en la variedad benigna fueron el leiomioma y el teratoma, mientras que en la categoría maligna se registró un caso de sarcoma indiferenciado. Conclusiones: Los hallazgos de este estudio pueden ser de ayuda para los cirujanos orales y maxilofaciales y los odontólogos generales en la formulación de diagnósticos y la prestación de atención al paciente en la población local existente (AU)

CT features of osteosarcoma lung metastasis: a retrospective study of 127 patients / Características tomográficas de metástase pulmonar de osteossarcoma: estudo retrospectivo com 127 pacientes

ABSTRACT Objective: Osteosarcoma lung metastases have a wide variety of CT presentations, representing a challenge for radiologists. Knowledge of atypical CT patterns of lung metastasis is important to differentiate it from benign lung disease and synchronous lung cancer, as well as to determine the extent of primary disease. The objective of this study was to analyze CT features of osteosarcoma lung metastasis before and during chemotherapy. Methods: Two radiologists independently reviewed chest CT images of 127 patients with histopathologically confirmed osteosarcoma treated between May 10, 2012 and November 13, 2020. The images were divided into two groups for analysis: images obtained before chemotherapy and images obtained during chemotherapy (initial CT examination). Results: Seventy-five patients were diagnosed with synchronous or metachronous lung metastases. The most common CT findings were nodules (in 95% of the patients), distributed bilaterally (in 86%), with no predominance regarding craniocaudal distribution (in 71%). Calcification was observed in 47%. Less common findings included intravascular lesions (in 16%), cavitation (in 7%), and the halo sign (in 5%). The primary tumor size was significantly greater (i.e., > 10 cm) in patients with lung metastasis. Conclusions: On CT scans, osteosarcoma lung metastases typically appear as bilateral solid nodules. However, they can have atypical presentations, with calcification being the most common. Knowledge of the typical and atypical CT features of osteosarcoma lung metastasis could play a key role in improving image interpretation in these cases.

RESUMO Objetivo: As metástases pulmonares do osteossarcoma têm uma grande variedade de apresentações tomográficas, o que é um desafio para os radiologistas. É importante conhecer os padrões tomográficos atípicos da metástase pulmonar para diferenciá-la de doença pulmonar benigna e câncer sincrônico de pulmão, bem como para determinar a extensão da doença primária. O objetivo deste estudo foi analisar as características tomográficas da metástase pulmonar do osteossarcoma antes da quimioterapia e durante a quimioterapia. Métodos: Dois radiologistas analisaram de modo independente as imagens de TC de tórax de 127 pacientes com osteossarcoma confirmado histopatologicamente, tratados entre 10 de maio de 2012 e 13 de novembro de 2020. As imagens foram divididas em dois grupos para a análise: imagens obtidas antes da quimioterapia e imagens obtidas durante a quimioterapia (TC inicial). Resultados: Setenta e cinco pacientes receberam diagnóstico de metástase pulmonar sincrônica ou metacrônica. Os achados tomográficos mais comuns foram nódulos (em 95% dos pacientes), distribuídos bilateralmente (em 86%), sem predominância de distribuição craniocaudal (em 71%). Observou-se calcificação em 47%. Alguns dos achados menos comuns foram lesões intravasculares (em 16%), escavação (em 7%) e o sinal do halo (em 5%). O tumor primário foi significativamente maior (> 10 cm) em pacientes com metástase pulmonar. Conclusões: Em imagens de TC, as metástases pulmonares do osteossarcoma tipicamente aparecem em forma de nódulos sólidos bilaterais. No entanto, podem ter apresentações atípicas, sendo a calcificação a mais comum. Conhecer as características tomográficas típicas e atípicas da metástase pulmonar do osteossarcoma pode ser fundamental para interpretar melhor as imagens nesses casos.

Ankle arthrodesis with intramedullary retrograde nail for bone tumors. preliminary results and surgical technique / Artrodese do tornozelo com cavilha intramedular retrógrada para tumores ósseos. resultados preliminares e técnica cirúrgica

ABSTRACT Objective Present the preliminary results of a case series using the surgical ankle arthrodesis technique with an intramedullary retrograde nail for bone tumors. Methods We present the preliminary data of 4 patients, 3 males and 1 female, with a mean age of 46,2 (range 32 to 58) years, with histology proven Giant Cell Tumour of bone in 3 and osteosarcoma in 1. The mean resection length of distal tibia was 11,75 (range 9 to 16) cm, and all the patients underwent reconstruction with a tibiotalocalcaneal arthrodesis with an intercalary allograft fixed by a retrograde intramedullary nail. Results Oncological follow-up evolved without evidence of local recurrence or disease progression in all patients. After a mean time of 69.5 (range 32 to 98 months), patients had a mean MSTS12 functional score of 82.5% (range 75 to 90). All tibial arthrodesis and diaphyseal osteotomy sites were fused within 6 months with a return to activities without complications related to coverage skin or infection. Conclusion No complications were recorded; all arthrodesis and diaphysial tibial osteotomy sites fused by 6 months, and the mean follow-up of those patients was 69,5 (range 32 to 988) months, with a mean functional MSTS score of 82,5% (range 75-90). Level of Evidence: IV; Retrospective Case Series.

RESUMO Objetivo Apresentar os resultados preliminares de uma série de casos utilizando a técnica cirúrgica de artrodese do tornozelo com haste intramedular retrógada para tumores ósseos. Métodos Apresentamos os dados preliminares de quatro pacientes, três homens e uma mulher, com idade média de 46,2 (variação de 32 a 58) anos, com histologia comprovada de tumor de células gigantes em três e osteossarcoma em um. O comprimento médio de ressecção da tíbia distal foi de 11,75 (variação de 9 a 16) cm, e todos os pacientes foram submetidos à reconstrução com uma artrodese tibiotalocalcaneana com um aloenxerto intercalar fixado por uma haste intramedular retrógrada. Resultados O acompanhamento oncológico evoluiu sem evidências de recidiva local ou progressão da doença, em todos os pacientes. Após um tempo médio de 69,5 (variação de 32 a 98 meses), os pacientes tiveram uma pontuação média funcional MSTS12 de 82,5% (variação de 75 a 90). Todos os locais de artrodese e osteotomia diafisária tibiais foram fundidos em 6 meses com retorno às atividades de vida diária sem complicações relacionadas à cobertura ou infecção. Conclusão Não foram registradas complicações; todos os locais de artrodese e osteotomia diafisária da tíbia fundiram-se em 6 meses, e o acompanhamento médio desses pacientes foi de 69,5 (variação de 32 a 988) meses, com uma pontuação média funcional MSTS de 82,5% (variação de 75-90). Nível de Evidência IV; Série de Casos Retrospectivos.

Efectividad de intervenciones fisioterapéuticas pre y posoperatorias en pacientes con osteosarcoma / Effectiveness of pre-and postoperative physiother-apy interventions in patients with osteosarcoma

ResumenIntroducción:La falta de información sobre la efectividad de intervenciones fisioterapéuticas en la rehabilitación de pacientes con osteosarcoma en Ecuador ha llevado a evaluaciones tardías, aumentando la agresividad de la enfermedad.Materiales y métodos:En la investigación se propuso analizar la eficacia de la intervención fisioterapéutica en las fases pre y posoperatoria, recopilando información de 35 artículos cien-tíficos mediante un enfoque documental e inductivo. La calidad metodológica se evaluó con la escala PEDro, garantizando una puntuación ≥7 para validar los estudios. Se utilizaron bases de datos como Redalyc, ProQuest, LILACS, Scopus, PubMed, SJR, Cochrane, Scielo y PEDro, aplicando estrategias de búsqueda con operadores booleanos.Resultados:En la fase pre y posoperatoria se realizan intervenciones fisioterapéuticas como masajes, estimulación nerviosa, acupuntura, crioterapia y ejercicio, mostraron beneficios sig-nificativos en la disminución del dolor, la fatiga, la ansiedad, la depresión, mejoran la movilidad y fortalecen la musculatura.Conclusión:La aplicación dentro de un enfoque multidisciplinario en pacientes con osteosar-coma dio como resultadobienestar y mejoría sintomática. Este estudio respalda la eficacia de la fisioterapia en el tratamiento integral, permitiendo la independencia de los pacientes post-tratamiento quirúrgico y protésico, destacando la importancia de implementar estas in-tervenciones desde las fases iniciales del diagnóstico

AbstractIntroduction:The lack of information on the effectiveness of physiotherapy interventions forthe rehabilitation of patients withosteosarcoma in Ecuador has led to late evaluationsof this disease, increasing its aggressiveness. Materials and methods: The research aimed to analyze the effectiveness of the physiotherapy intervention in the pre-and postoperative phases, compiling information from 35 scientific ar-ticles through a documentary and inductive approach. Methodological quality was evaluated with the PEDro scale, guaranteeing a score ≥7 to validate the studies. Databases such as Re-dalyc, ProQuest, LILACS, Scopus, PubMed, SJR, Cochrane, Scielo, and PEDro were used, ap-plying search strategies with Boolean operators.Results: In the pre-andpostoperative phases, physiotherapeutic interventions such as mas-sage, nerve stimulation, acupuncture, cryotherapy, and exercise showedsignificant benefits in reducing pain, fatigue, anxiety, and depression, improving mobility,and strengthening mus-cles.Conclusion: Amultidisciplinary approach in patients with OS improved patientwell-being and symptoms. This study supports the effectiveness of physiotherapy in comprehensive treat-ment, allowing patients to become independentafter surgical and prosthetic treatment, high-lighting the importance of implementing these interventions from the initial phases of diagno-sis.

Quiste óseo aneurismático: diferencias diagnósticas con el osteosarcoma telangiectásico. Reporte de caso / Aneurysmal bone cyst: diagnostic differences with telangiectatic osteosarcoma. A case report

Introducción: los síntomas, signos y hallazgos imagenológicos e histológicos del quiste óseo aneurismático (QOA) y el osteosarcoma telangiectásico (OT) son similares, por lo que constituyen uno de los diagnósticos diferenciales más difíciles de establecer.Presentación del caso: mujer de 19 años que asistió al servicio de urgencias de un hospital de cuarto nivel de atención en Bogotá por dolor en la cadera izquierda, donde se identificó lesión lítica en el cuello del fémur y se remitió a consulta externa. Tres días después, la paciente regresó al servicio de urgencias por dolor en la cadera izquierda e incapacidad funcional. Mediante radiografía y resonancia magnética, se identificó fractura transcervical de la cadera en el lugar de la lesión lítica, por lo que se sospechó la presencia de QOA u OT. La paciente fue llevada a cirugía y se realizó biopsia por congelación, confirmando el diagnóstico de QOA; por lo tanto, se realizó curetaje y fresado de la lesión, reducción y fijación de la fractura con sistema DHS (dynamic hip screw), y aplicación de injerto y cemento óseo. Cuatro días después del procedimiento, la paciente fue dada de alta. En el seguimiento a los ocho meses, se evidenció recuperación completa de la funcionalidad de la cadera y ausencia de dolor.Conclusión: en pacientes en los que hay una alta sospecha de este tipo de lesiones óseas, es importante realizar un estudio histopatológico para confirmar el diagnóstico de QOA u OT, e instaurar un tratamiento adecuado y oportuno, que sin duda contribuirá a un mejor pronóstico, particularmente en términos de supervivencia

Introduction: Symptoms, signs, imaging and histological findings of aneurysmal bone cyst (ABC) and telangiectatic osteosarcoma (TO) are similar, which makes them one of the most difficult differential diagnoses. Case presentation: A 19-year-old woman attended the emergency department of a quaternary care hospital in Bogotá, Colombia, due to pain in the left hip. A lytic lesion in the femur was identified and the patient was referred to the outpatient clinic. Three days later, the patient returned to the emergency department with left hip pain and functional disability. By means of X-ray and MRI, a transcervical fracture of the hip was identified at the site of the lytic lesion, so the presence of ABC or TO was suspected. The patient was taken to surgery and a frozen section biopsy was performed, confirming the diagnosis of ABC. Consequently, curettage and reaming of the lesion were undertaken, followed by reduction and fixation of the fracture using the DHS (dynamic hip screw) system, and application of bone grafting and bone cement. Four days after the procedure, the patient was discharged. A follow-up at eight months showed complete recovery of hip functionality and absence of pain.Conclusion: In patients with a high suspicion of this type of bone lesions, it is important to perform a histopathological study to confirm the diagnosis of ABC or TO, and to establish an adequate and timely treatment, which will undoubtedly contribute to a better prognosis, particularly in terms of surviva

Research Progress of 3D Printing Technology for Perioperative Treatment of Osteosarcoma / 肿瘤防治研究

The anatomical site of osteosarcoma is generally complex. Hence, it is difficult to accurately remove osteosarcoma and retain important nerves and blood vessels around the tumor, as well as repair and reconstruct bone defects after osteosarcoma resection. 3D printing technology can "tailor" the "bone defect" after removing the irregular osteosarcoma to achieve a good therapeutic effect of limb reconstruction. This study reviews the application of 3D printing technology in the preoperative, intraoperative, and postoperative reconstruction of osteosarcoma and bone tissue engineering scaffolds. Thus, this study systematically analyzes the advantages and suggestions of 3D printing technology based on the characteristics of 3D printing to put forward references for the accurate treatments of osteosarcoma in the future.

Correlation Between PD-1/CTLA-4 Expressions with C linicopathological Features and Prognosis of Osteosarcoma Patients / 肿瘤防治研究

Objective To explore the expression of PD-1 and CTLA-4 in osteosarcoma and their clinical significance. Methods Fifty-eight cases of osteosarcoma encountered from 2007 to 2016 were enrolled. The expression levels of PD-1 and CTLA-4 were detected through immunohistochemistry (EnVision method). Results PD-1 was positively expressed in 31 (53.4%) cases and negatively expressed in 27 (46.6%) cases. CTLA-4 was positively expressed in 19 (32.8%) cases and negatively expressed in 39 (67.2%) cases. A total of 12 (20.7%) cases were PD-1 and CTLA-4 double positive, whereas 20 (34.5%) cases were double negative, and 26 (44.8%) cases were single positive. The positive expression of PD-1 was correlated with neoadjuvant chemotherapy, tumor metastasis and relapse, and shortened survival time (P < 0.05). The positive expression of CTLA-4 was partly related with late Ennecking stage (P=0.051). Double positive expression was related to the highest tumor metastasis and relapse rates and the worst prognosis (P < 0.05), compared with double negative and single positive expression. Conclusion Positive expression of PD-1 and CTLA-4 in osteosarcoma is associated with worse prognosis, whereas double positive expression is associated with the highest tumor relapse and metastasis rates and shortest survival time. These results are potential valuable references for osteosarcoma immunotherapy.

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.

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.

Research progress on the role of non-coding RNA in chemotherapy resistance of osteosarcoma / 中华骨科杂志

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. With the emergence of chemotherapy resistance in recent years, the survival rate of osteosarcoma patients has reached a bottleneck. Therefore, exploration of its chemoresistance mechanism is one of the popular research directions currently. Non-coding RNA (ncRNA) is a class of RNA without the ability to encode proteins, which is classified into microRNA, long non-coding RNA, and circular RNA based on length and shape. With the development of high-throughput sequencing technology, there is increasing evidence that some non-coding RNAs are abnormally upregulated or downregulated in osteosarcoma cells and affect the response of osteosarcoma to four commonly used chemotherapeutic drugs (methotrexate, doxorubicin, cisplatin and ifosfamide) through mechanisms such as regulation of apoptosis, cell cycle, signaling pathways, intracellular drug concentration, and cellular autophagy. Therefore, thesenon-coding RNAs are expected to be novel targets for osteosarcoma treatment. In this paper, the current studies were searched and reviewed on the above three non-coding RNAs mediating chemoresistance in osteosarcoma, aiming to provide a reference for breaking the bottleneck of survival rate of osteosarcoma patients.

A new 3D-printed ankle fusion prosthesis for the treatment of osteosarcoma in the distal tibia: a case report / 中华骨科杂志

To report the short-term clinical outcome of three cases of distal tibial osteosarcoma treated with a novel 3D-printed ankle fusion prosthesis for limb preservation. The patients were admitted to the Department of Bone Tumor, Shanghai General Hospital from January 2020 to June 2021, with one male and two female cases, aged 18, 12, and 14 years, respectively, all diagnosed with distal tibial osteosarcoma (Ennecking stage IIb). A new self-designed ankle fusion prosthesis was used to perform osteosarcoma resection and prosthetic reconstruction of the distal tibia. The operation time, blood loss, postoperative American Orthopedic Foot and Ankle Society Score (AOFAS) and ankle range of motion were recorded. All the 3 patients successfully completed the operation and were followed up for 22 months, 18 months and 12 months, respectively. The operation time was 140 min, 110 min and 200 min, and the blood loss was 200 ml, 200 ml and 350 ml, respectively. At the last follow-up, the AOFAS were 86, 90 and 95 points, and the range of motion of ankle flexion and extension were 30°, 15° and 30°. There was no local recurrence or lung metastasis at the last follow-up. The novel 3D-printed ankle fusion prosthesis in the distal tibia is safe and effective for the reconstruction of bone defects after resection of osteosarcoma in the distal tibia, and the early postoperative function is satisfactory.