Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 9.033
Filtrar
1.
Anticancer Res ; 41(4): 2111-2115, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813421

RESUMEN

BACKGROUND/AIM: It has been hypothesized that many, or even most cancers, utilize a unique immunomodulatory protein, called the progesterone induced blocking factor (PIBF) to allow spread of the cancer. Support for this concept has been provided by cancer cell line studies showing that PIBF is produced by these cancer cells and mifepristone suppresses this protein and inhibits proliferation of these cells. Furthermore, controlled murine studies with several spontaneous different types of cancer showed a clear beneficial effect of mifepristone over placebo control. Finally, there have been a variety of anecdotal reports showing efficacy of mifepristone in providing increased length and quality of life in patients with different types of advanced cancers. CASE REPORT: Single agent mifepristone was found to provide significant palliative benefit for a 51-year-old male whose metastatic advanced fibroblastic osteosarcoma progressed despite surgery, radiotherapy, multiagent chemotherapy, and targeted therapy. CONCLUSION: Thus, osteosarcoma can be added to the list of cancers, not necessarily associated with the classic nuclear progesterone receptor, that seem to respond to progesterone receptor antagonist therapy.


Asunto(s)
Neoplasias Óseas/tratamiento farmacológico , Mifepristona/administración & dosificación , Osteosarcoma/tratamiento farmacológico , Cuidados Paliativos/métodos , Administración Oral , Neoplasias Óseas/patología , Dolor en Cáncer/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Osteosarcoma/patología , Calidad de Vida , Tibia , Resultado del Tratamiento
2.
Anticancer Res ; 41(4): 1745-1751, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813378

RESUMEN

BACKGROUND/AIM: Osteosarcoma is the most frequent malignant bone tumor. Failure of first-line therapy results in poor prognosis of osteosarcoma. In the present report, we examined the efficacy of the combination of oral recombinant methioninase (o-rMETase) and docetaxel (DOC) on an osteosarcoma patient-derived orthotopic xenograft (PDOX) mouse model. MATERIALS AND METHODS: Osteosarcoma-PDOX models were established by tumor insertion within the tibia of nude mice. The osteosarcoma PDOX models were randomized into four groups (4-5 mice per group): control; o-rMETae alone; DOC alone; o- rMETase combined with DOC. The treatment period was 3 weeks. RESULTS: The combination of o-rMETase and DOC showed significant efficacy compared to the control group (p=0.03). In contrast, there was no significant efficacy of o-rMETase alone or DOC alone (p=0.65, 0.60, respectively). CONCLUSION: o-rMETase converted an osteosarcoma PDOX from DOC-resistant to -sensitive. This combination therapy may be effective against recalcitrant osteosarcoma and other recalcitrant cancers.


Asunto(s)
Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias Óseas/tratamiento farmacológico , Liasas de Carbono-Azufre/administración & dosificación , Docetaxel/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Osteosarcoma/tratamiento farmacológico , Tibia/efectos de los fármacos , Administración Oral , Adolescente , Animales , Neoplasias Óseas/patología , Humanos , Masculino , Ratones Desnudos , Osteosarcoma/patología , Proteínas Recombinantes/administración & dosificación , Tibia/patología , Ensayos Antitumor por Modelo de Xenoinjerto
3.
Anticancer Res ; 41(4): 1779-1784, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813382

RESUMEN

BACKGROUND/AIM: Osteosarcoma is a rare type of bone cancer that affects mostly children and adolescents. First-line chemotherapy for osteosarcoma has not been improved for many decades. Eribulin has been used to treat breast cancer and liposarcoma in the clinic. MATERIALS AND METHODS: A patient-derived orthotopic xenograft (PDOX) mouse model of osteosarcoma was established by tumor insertion within the tibia. This model more closely mimics osteosarcoma in clinical settings and was used to test the efficacy of eribulin. Tibia-insertion osteosarcoma PDOX mouse models were randomized into two groups: a control group (n=4) and an eribulin-treatment group (n=5). Mice were treated for fourteen days, four weeks after initial implantation. Tumor size and body weight were measured, and tumor histology was examined. RESULTS: Significant tumor growth inhibition (p=0.044) was observed in mice treated with eribulin compared to the control group. Histology demonstrated necrosis in the eribulin-treated tumors. There was no body-weight loss in the treated mice. CONCLUSION: Eribulin may be a clinically-effective, off-label chemotherapy for recalcitrant osteosarcoma that has failed first- and second-line therapy.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias Óseas/tratamiento farmacológico , Furanos/farmacología , Cetonas/farmacología , Osteosarcoma/tratamiento farmacológico , Tibia/efectos de los fármacos , Adolescente , Animales , Neoplasias Óseas/patología , Humanos , Masculino , Ratones Desnudos , Necrosis , Osteosarcoma/patología , Tibia/patología , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
4.
Int J Mol Sci ; 22(4)2021 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-33672879

RESUMEN

Osteosarcoma has a poor survival rate due to relapse and metastasis. Zoledronic acid (ZOL), an anti-resorptive and anti-tumor agent, is used for treating osteosarcoma. Delivery of ZOL to the target region is difficult due to its high binding affinity to bone minerals. This study developed a novel treatment for osteosarcoma by delivering ZOL to the target region locally and sustainably. In this study, we fabricated a novel bone substitute by loading ZOL on ß-tricalcium phosphate (ß-TCP). The ZOL-loaded ß-TCP (ZOL/ß-TCP) would be expected to express the inhibitory effects via both bound-ZOL (bound to ß-TCP) and free-ZOL (release from ZOL/ß-TCP). To explore the ability to release ZOL from the ZOL/ß-TCP, the amount of released ZOL was measured. The released profile indicates that a small amount of ZOL was released, and most of it remained on the ß-TCP. Our data showed that ZOL/ß-TCP could successfully express the effects of ZOL via both bound-ZOL and free-ZOL. In addition, we examined the biological effects of bound/free-ZOL using osteosarcoma and osteoclasts (target cells). The results showed that two states of ZOL (bound/free) inhibit target cell activities. As a result, ZOL/ß-TCP is a promising candidate for application as a novel bone substitute.


Asunto(s)
Fosfatos de Calcio/farmacología , Proliferación Celular/efectos de los fármacos , Osteoclastos/metabolismo , Osteosarcoma/metabolismo , Ácido Zoledrónico/farmacología , Animales , Sustitutos de Huesos/química , Sustitutos de Huesos/farmacocinética , Sustitutos de Huesos/farmacología , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacocinética , Diferenciación Celular/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Medios de Cultivo Condicionados/farmacología , Liberación de Fármacos , Humanos , Masculino , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Ratones Endogámicos C57BL , Osteosarcoma/patología , Ácido Zoledrónico/química , Ácido Zoledrónico/farmacocinética
5.
BMC Cancer ; 21(1): 210, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33648449

RESUMEN

BACKGROUND: A number of studies have linked positive Ki-67 expression with the prognosis of osteosarcoma (OS) patients. However, the results have been conflicting. To address this controversy, we conducted an analysis using a meta-analysis and a TCGA dataset to estimate the value of Ki-67 expression in the prognosis of OS. METHODS: A comprehensive search for relevant papers was conducted using NCBI PubMed, Embase, Springer, ISI Web of Knowledge, the Cochrane Library, and CNKI regardless of the publication year. The associations between Ki-67 expression and the clinical features and main prognostic outcomes of OS were measured. The TCGA dataset was also analyzed. The pooled odds ratio (OR) and its 95% confidential intervals (CIs) were utilized for statistical analysis. RESULTS: Overall, a total of 12 studies with 500 cases were included, and the results indicated that the expression of Ki-67 was significantly associated with Enneking stage (OR = 6.88, 95% CI: 2.92-16.22, p < 0.05), distant metastasis (OR = 3.04, 95% CI: 1.51-6.12, p < 0.05) and overall survival (OR = 8.82, 95% CI: 4.68-16.65, p < 0.05) in OS patients. Additionally, we observed no significant heterogeneity among all retrieved studies. Associations between Ki-67 expression and overall survival and disease-free survival of sarcoma were confirmed using the TCGA and Kaplan-Meier plotter datasets. CONCLUSION: The present study strongly suggests that positive Ki-67 expression was associated with Enneking stage, distant metastasis, and overall survival of OS, and it may be used as a potential biomarker to predict prognosis and guide clinical therapy for OS.


Asunto(s)
Antígenos de Neoplasias/análisis , Neoplasias Óseas/metabolismo , Antígeno Ki-67/análisis , Osteosarcoma/metabolismo , Antígenos de Neoplasias/biosíntesis , Antígenos de Neoplasias/genética , Neoplasias Óseas/genética , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Conjuntos de Datos como Asunto , Supervivencia sin Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Antígeno Ki-67/biosíntesis , Antígeno Ki-67/genética , Metástasis de la Neoplasia , Estadificación de Neoplasias , Osteosarcoma/genética , Osteosarcoma/mortalidad , Osteosarcoma/patología , Pronóstico , Sesgo de Publicación , Sarcoma/genética , Sarcoma/metabolismo , Sarcoma/mortalidad , Sarcoma/patología , Regulación hacia Arriba
6.
Anticancer Res ; 41(3): 1251-1259, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33788716

RESUMEN

BACKGROUND/AIM: Sorafenib, an oral multi-kinase inhibitor, has been shown to improve the outcome of patients with osteosarcoma (OS). However, the anti-OS effect and mechanism of sorafenib has not yet been fully understood. The main purpose of this study was to investigate the effect of sorafenib on apoptotic signaling and Nuclear Factor-κB (NF-κB)-mediated anti-apoptotic and metastatic potential in OS in vitro. MATERIALS AND METHODS: The effect of sorafenib on apoptotic signaling transduction, anti-apoptotic, and metastatic potential of OS U-2 cells was verified with flow cytometry, trans-well invasion/migration, and western blotting assay. RESULTS: Sorafenib induced the extrinsic and intrinsic apoptotic pathways. In addition, sorafenib reduced the invasion and migration ability of OS cells, induced NF-κB activation, and the expression of anti-apoptotic proteins and metastasis-associated proteins encoded by NF-κB target genes. CONCLUSION: Sorafenib led to stimulation of extrinsic/intrinsic apoptotic pathways and NF-κB inactivation in U-2 OS cells.


Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias Óseas/tratamiento farmacológico , FN-kappa B/antagonistas & inhibidores , Osteosarcoma/tratamiento farmacológico , Sorafenib/farmacología , Neoplasias Óseas/patología , Línea Celular Tumoral , Humanos , FN-kappa B/fisiología , Invasividad Neoplásica , Metástasis de la Neoplasia , Osteosarcoma/patología , Osteosarcoma/secundario
7.
Int J Mol Sci ; 22(4)2021 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-33670044

RESUMEN

Kallmann syndrome is the result of innate genetic defects in the fibroblast growth factor (FGF) regulated signaling network causing diminished signal transduction. One of the rare mutations associated with the syndrome alters the Sprouty (Spry)4 protein by converting the serine at position 241 into a tyrosine. In this study, we characterize the tyrosine Spry4 mutant protein in the primary human embryonic lung fibroblasts WI-38 and osteosarcoma-derived cell line U2OS. As demonstrated in a cell signaling assay, Spry4 gains the capability of inhibiting FGF, but not epithelial growth factor (EGF)-induced signaling as a consequence of the tyrosine substitution. Additionally, migration of normal embryonic lung fibroblasts and osteosarcoma-derived cells is potently inhibited by the tyrosine Spry4 variant, while an effect of the wildtype Spry4 protein is hardly measureable. Concerning cell proliferation, the unaltered Spry4 protein is ineffective to influence the WI-38 cells, while the mutated Spry4 protein decelerates the cell doubling. In summary, these data emphasize that like the other mutations associated with Kallmann syndrome the described Spry4 mutation creates a hyperactive version of a selective inhibitory molecule and can thereby contribute to a weakened FGF signaling. Additionally, the study pinpoints a Spry4 variation expanding the applicability of Spry4 in a potential cancer therapy.


Asunto(s)
Factor 2 de Crecimiento de Fibroblastos/farmacología , Péptidos y Proteínas de Señalización Intracelular/genética , Síndrome de Kallmann/genética , Mutación/genética , Proteínas del Tejido Nervioso/genética , Línea Celular , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Factor de Crecimiento Epidérmico/farmacología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Pulmón/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Osteosarcoma/patología , Fosforilación/efectos de los fármacos , Transducción de Señal , Tirosina/metabolismo
8.
Gene ; 782: 145537, 2021 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-33636294

RESUMEN

Detection of TCGA data revealed that WIPI1 is highly expressed in osteosarcoma cells. So we explore the mechanisms of WIPI1 affecting the proliferation of osteosarcoma cells through Affymetrix microarray analysis. Functional analysis of differentially expressed genes shows that the classical signaling pathways affecting tumor formation and development have changed significantly. By fitting analysis, it is speculated that the WIPI1 may function in the direction of osteosarcoma by regulating the expression of multiple cell cycle-related genes such as CDKN1A, CDK4 and CCND1. Therefore, the key genes are selected for RT-PCR and Western-blot verification. Combined with flow and other means, WIPI1 may affect the cell cycle and the osteosarcoma by regulating the expression of CDKN1A, CDK4 and CCND1. To verify the results, the effect of WIPI1 on cell proliferation was quantified by MTT, cell counts and nude mouse tumorigenicity assay. The results showed that WIPI1 promotes osteosarcoma cell proliferation.


Asunto(s)
Proteínas Relacionadas con la Autofagia/genética , Neoplasias Óseas/genética , Proliferación Celular/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/antagonistas & inhibidores , Proteínas de la Membrana/genética , Osteosarcoma/genética , Animales , Proteínas Relacionadas con la Autofagia/fisiología , Neoplasias Óseas/patología , Ciclo Celular/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Regulación Neoplásica de la Expresión Génica , Vectores Genéticos , Células HEK293 , Humanos , Lentivirus/genética , Proteínas de la Membrana/fisiología , Ratones Desnudos , Análisis de Secuencia por Matrices de Oligonucleótidos , Osteosarcoma/patología , Programas Informáticos , Transcriptoma
9.
J Clin Pathol ; 74(5): 321-326, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33589531

RESUMEN

AIMS: Osteosarcoma (OS) is the most common primary malignant tumour of the bone. However, further improvement in survival has not been achieved due to a lack of well-validated prognostic markers and more effective therapeutic agents. Recently, the c-Myc-phosphoribosyl pyrophosphate synthetase 2 (PRPS2) pathway has been shown to promote nucleic acid metabolism and cancer cell proliferation in malignant melanoma; phosphorylated mammalian target of rapamycin (p-mTOR) has been upregulated and an effective therapeutic target in OS. However, the p-mTOR-PRPS2 pathway has not been evaluated in OS. METHODS: In this study, the expression level of PRPS2, p-mTOR and marker of proliferation (MKI-67) was observed in a cohort of specimens (including 236 OS cases and 56 control samples) using immunohistochemistry, and the association between expression level and clinicopathological characteristics of patients with OS was analysed. RESULTS: PRPS2 protein level, which is related to tumour proliferation, was higher in OS cells (p=0.003) than in fibrous dysplasia, and the higher PRPS2 protein level was associated with a higher tumour recurrence (p=0.001). In addition, our statistical analysis confirmed that PRPS2 is a novel, independent prognostic indicator of OS. Finally, we found that the expression of p-mTOR was associated with the poor prognosis of patients with OS (p<0.05). CONCLUSIONS: PRPS2 is an independent prognostic marker and a potential therapeutic target for OS.


Asunto(s)
Neoplasias Óseas/enzimología , Neoplasias Femorales/enzimología , Osteosarcoma/enzimología , Ribosa-Fosfato Pirofosfoquinasa/análisis , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Neoplasias Óseas/cirugía , Proliferación Celular , Niño , Preescolar , Femenino , Neoplasias Femorales/mortalidad , Neoplasias Femorales/patología , Neoplasias Femorales/cirugía , Humanos , Inmunohistoquímica , Lactante , Antígeno Ki-67/análisis , Masculino , Recurrencia Local de Neoplasia , Osteosarcoma/mortalidad , Osteosarcoma/patología , Osteosarcoma/cirugía , Fosforilación , Serina-Treonina Quinasas TOR/análisis , Análisis de Matrices Tisulares , Resultado del Tratamiento
10.
Eur J Med Chem ; 214: 113203, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33530028

RESUMEN

A novel series of novel N-substituted (indole or indazole) benzamides were synthesized, and their anti-tumor properties were evaluated. The majority of tested compounds possessed moderate cytotoxicity, but inspiringly, we verified that active compound 5d presents an astonishing advantage by inhibiting the adhesion, migration, and invasion of osteosarcoma (OS) cells in vitro. Mechanistically, we confirmed 5d inhibited the migration ability of OS cells via the expression of genes related to adhesion, migration, and invasion. This effects of 5d suggest that it can be used as a potential chemotherapeutic drug to some aggressive and/or metastatic cancers, as well as in combination with other clinical anti-cancer drugs. In turn, this could enhance the therapeutic effect or reduce the risk of cell migration.


Asunto(s)
Antineoplásicos/farmacología , Benzamidas/farmacología , Neoplasias Óseas/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico , Antineoplásicos/síntesis química , Antineoplásicos/química , Benzamidas/síntesis química , Benzamidas/química , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estructura Molecular , Osteosarcoma/metabolismo , Osteosarcoma/patología , Relación Estructura-Actividad , Células Tumorales Cultivadas
11.
BMC Cancer ; 21(1): 202, 2021 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-33639865

RESUMEN

BACKGROUND: In recent years, emerging studies have demonstrated critical functions and potential clinical applications of long non-coding RNA (lncRNA) in osteosarcoma. To further validate the prognostic value of multiple lncRNAs, we have conducted this updated meta-analysis. METHODS: Literature retrieval was conducted by searching PubMed, Web of Science and the Cochrane Library (last update by October 2, 2019). A meta-analysis was performed to explore association between lncRNAs expression and overall survival (OS) of osteosarcoma patients. Relationships between lncRNAs expression and other clinicopathological features were also analyzed respectively. RESULTS: Overall, 4351 patients from 62 studies were included in this meta-analysis and 25 lncRNAs were identified. Pooled analyses showed that high expression of 14 lncRNAs connoted worse OS, while two lncRNAs were associated with positive outcome. Further, analysis toward osteosarcoma clinicopathologic features demonstrated that overexpression of TUG1 and XIST indicated poor clinical parameters of patients. CONCLUSIONS: This meta-analysis has elucidated the prognostic potential of 16 lncRNAs in human osteosarcoma. Evidently, desperate expression and functional targets of these lncRNAs offer new approaches for prognosis and therapy of osteosarcoma.


Asunto(s)
Neoplasias Óseas/sangre , Osteosarcoma/sangre , ARN Largo no Codificante/sangre , ARN Neoplásico/sangre , Biomarcadores de Tumor , Neoplasias Óseas/genética , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Osteosarcoma/genética , Osteosarcoma/mortalidad , Osteosarcoma/patología , Pronóstico , Sesgo de Publicación
12.
Medicine (Baltimore) ; 100(6): e24471, 2021 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-33578541

RESUMEN

BACKGROUND: In osteosarcoma, the lung is the most common metastatic organ. Intensive work has been made to illuminate the pathogeny, but the specific metastatic mechanism remains unclear. Thus, we conducted the study to seek to find the key genes and critical functional pathways associated with progression and treatment in lung metastasis originating from osteosarcoma. METHODS: Two independent datasets (GSE14359 and GSE85537) were screened out from the Gene Expression Omnibus (GEO) database and the overlapping differentially expressed genes (DEGs) were identified using GEO2R online platform. Subsequently, the Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis of DEGs were conducted using DAVID. Meanwhile, the protein-protein interaction (PPI) network constructed by STRING was visualized using Cytoscape. Afterwards, the key module and hub genes were extracted from the PPI network using the MCODE and cytoHubba plugin. Moreover, the raw data obtained from GSE73166 and GSE21257 were applied to verify the expression differences and conduct the survival analyses of hub genes, respectively. Finally, the interaction network of miRNAs and hub genes constructed by ENCORI was visualized using Cytoscape. RESULTS: A total of 364 DEGs were identified, comprising 96 downregulated genes and 268 upregulated genes, which were mainly involved in cancer-associated pathways, adherens junction, ECM-receptor interaction, focal adhesion, MAPK signaling pathway. Subsequently, 10 hub genes were obtained and survival analysis demonstrated SKP2 and ASPM were closely related to poor prognosis of patients with osteosarcoma. Finally, hsa-miR-340-5p, has-miR-495-3p, and hsa-miR-96-5p were found to be most closely associated with these hub genes according to the interaction network of miRNAs and hub genes. CONCLUSION: The key genes and functional pathways identified in the study may contribute to understanding the molecular mechanisms involved in the carcinogenesis and progression of lung metastasis originating from osteosarcoma, and provide potential diagnostic and therapeutic targets.


Asunto(s)
Neoplasias Óseas/patología , Neoplasias Pulmonares/secundario , Osteosarcoma/patología , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/genética , Biología Computacional , Regulación Neoplásica de la Expresión Génica/genética , Redes Reguladoras de Genes/genética , Genes Relacionados con las Neoplasias/genética , Marcadores Genéticos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , MicroARNs/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Osteosarcoma/diagnóstico , Osteosarcoma/genética , Transducción de Señal/genética
13.
Expert Opin Drug Saf ; 20(4): 427-438, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33478264

RESUMEN

Introduction: Peri-operative chemotherapy is the backbone of treatment for patients with osteosarcoma. Methotrexate, cisplatinum, doxorubicin and ifosfamide are the main drugs used in chemotherapy regimens used for osteosarcoma.Areas covered: We have reviewed here the relevant literature related to the incidence and management of acute and late toxicities of systemic treatment used for the management of patients with osteosarcoma.Expert opinion: Early diagnosis and appropriate management of acute and late toxicities of chemotherapy is crucial for an efficient care of osteosarcoma patients. Although the incidence and management of chemotherapy-related acute toxicities are well known by most oncologists, the use of high doses of methotrexate have the potential to cause fatal toxicities and, therefore, needs careful monitoring. Moreover, the diagnosis of late toxicities is more challenging and requires long-term follow-up for an appropriate management.


Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias Óseas/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico , Animales , Antineoplásicos/efectos adversos , Neoplasias Óseas/patología , Quimioterapia Adyuvante/efectos adversos , Quimioterapia Adyuvante/métodos , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas , Humanos , Osteosarcoma/patología
14.
Int J Mol Sci ; 22(3)2021 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-33503899

RESUMEN

Telangiectatic osteosarcoma (TOS) is an aggressive variant of osteosarcoma (OS) with distinctive radiographic, gross, microscopic features, and prognostic implications. Despite several studies on OS, we are still far from understanding the molecular mechanisms of TOS. In recent years, many studies have demonstrated not only that microRNAs (miRNAs) are involved in OS tumorigenesis, development, and metastasis, but also that the presence in high-grade types of OS of cancer stem cells (CSCs) plays an important role in tumor progression. Despite these findings, nothing has been described previously about the expression of miRNAs and the presence of CSCs in human TOS. Therefore, we have isolated/characterized a putative CSC cell line from human TOS (TOS-CSCs) and evaluated the expression levels of several miRNAs in TOS-CSCs using real-time quantitative assays. We show, for the first time, the existence of CSCs in human TOS, highlighting the in vitro establishment of this unique stabilized cell line and an identification of a preliminary expression of the miRNA profile, characteristic of TOS-CSCs. These findings represent an important step in the study of the biology of one of the most aggressive variants of OS and the role of miRNAs in TOS-CSC behavior.


Asunto(s)
Neoplasias Óseas/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Osteosarcoma/genética , Transcriptoma , Biomarcadores , Biopsia , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Línea Celular Tumoral , Técnica del Anticuerpo Fluorescente , Humanos , Inmunohistoquímica , Osteosarcoma/metabolismo , Osteosarcoma/patología
15.
Braz J Med Biol Res ; 54(2): e9161, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33439936

RESUMEN

Patients with osteosarcoma (OS) usually have poor overall survival because of frequent metastasis. Long non-coding RNAs (lncRNAs) have been reported to be associated with tumorigenesis and metastasis. In this study, we investigated the expression and roles of lncRNA human histocompatibility leukocyte antigen (HLA) complex P5 (HCP5) in OS, aiming to provide a novel molecular mechanism for OS. HCP5 was up-regulated both in OS tissues and cell lines and high expression of HCP5 was associated to low survival in OS patients. Down-regulation of HCP5 inhibited cell proliferation, migration, and invasion, suggesting its carcinogenic role in OS. miR-101 was targeted by HCP5 and its expression was decreased in OS. The inhibitor of miR-101 reversed the impact of HCP5 down-regulation on cell proliferation, apoptosis, and metastasis in OS. Ephrin receptor 7 (EPHA7) was proved to be a target of miR-101 and had ability to recover the effects of miR-101 inhibitor in OS. In conclusion, lncRNA HCP5 knockdown suppressed cell proliferation, migration, and invasion, and induced apoptosis through depleting the expression of EPHA7 by binding to miR-101, providing a potential therapeutic strategy of HCP5 in OS.


Asunto(s)
Neoplasias Óseas , MicroARNs/metabolismo , Osteosarcoma , ARN Largo no Codificante/genética , Receptor EphA7/metabolismo , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos , Invasividad Neoplásica , Osteosarcoma/genética , Osteosarcoma/patología
16.
Anticancer Res ; 41(2): 719-730, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33517276

RESUMEN

BACKGROUND/AIM: The purpose of this study was to evaluate the effect of extracellular vesicles derived from canine M1-polarized macrophages (M1EVs) on canine tumor cells, such as D17 (osteosarcoma cells) and LMeC (melanoma cells). MATERIALS AND METHODS: Protein expression was determined by western blot analysis. Gene expression was determined by RT-qPCR. In addition, cell apoptosis was analyzed by Annexin V/PI staining. RESULTS: In the case of M1EV, the levels of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1ß were increased, and nitrate/nitrite levels were also increased. M1EV induced apoptosis of tumor cells by increasing caspase-3 and caspase-7 activation. In addition, M1EVs decreased expression of CCR4, Foxp3 and CTLA-4 in canine peripheral mononuclear cells cocultured with tumor cells. CONCLUSION: M1EV could be an effective anti-cancer therapeutic approach in melanoma and osteosarcoma and M1EVs can be used as immunomodulators in the tumor microenvironment for cancer treatment.


Asunto(s)
Apoptosis , Neoplasias Óseas/patología , Vesículas Extracelulares/metabolismo , Macrófagos/metabolismo , Melanoma/patología , Osteosarcoma/patología , Neoplasias Cutáneas/patología , Animales , Neoplasias Óseas/metabolismo , Línea Celular Tumoral , Técnicas de Cocultivo , Perros , Melanoma/metabolismo , Osteosarcoma/metabolismo , Fenotipo , Transducción de Señal , Neoplasias Cutáneas/metabolismo , Microambiente Tumoral
17.
Exp Mol Pathol ; 118: 104596, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33347862

RESUMEN

Lysophosphatidic acid (LPA) signaling via LPA receptors (LPA1 to LPA6) exhibits a variety of biological responses. In tumor microenvironment, endothelial cells promote cancer cell functions. In this study, we investigated the roles of endothelial cells in the regulation of cell motile activity via LPA2 and LPA3 in human osteosarcoma MG-63 cells. In cell motility assay, the cell motile activity of MG-63 cells was markedly increased by the supernatants of endothelial F2 cells. MG-63 cell motility elevated by the supernatants was enhanced by GRI-977143 (LPA2 agonist) and reduced by (2S)-OMPT (LPA3 agonist). LPAR2 and LPAR3 expressions were increased in highly migratory MG63-CR7(F2) cells, which were generated from MG-63 cells by co-culture with F2 cell supernatants. MG63-CR7(F2) cell motility was stimulated by LPA treatment. In the presence of F2 cell supernatants, MG63-CR7(F2) cell motility was markedly enhanced by GRI-977143 and suppressed by (2S)-OMPT. Autotaxin (ATX) enzymatically converts lysophosphatidylcholine (LPC) to LPA. ATX expression was higher in MG63-CR(F2) cells than in MG-63 cells. MG63-CR7(F2) cell motility was markedly increased by LPC in comparison with MG-63 cells. In addition, MG63-CR(F2) cell motility was significantly stimulated by the supernatants of LPC treated F2 cells. The present results suggest that the activation of LPA signaling via LPA2 and LPA3 by endothelial cells is involved in the modulation of cell motile activity of MG-63 cells.


Asunto(s)
Neoplasias Óseas/patología , Movimiento Celular , Células Endoteliales/patología , Regulación Neoplásica de la Expresión Génica , Osteosarcoma/patología , Receptores del Ácido Lisofosfatídico/metabolismo , Apoptosis , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Proliferación Celular , Células Endoteliales/metabolismo , Humanos , Lisofosfolípidos/metabolismo , Osteosarcoma/genética , Osteosarcoma/metabolismo , Receptores del Ácido Lisofosfatídico/genética , Transducción de Señal , Células Tumorales Cultivadas
18.
Life Sci ; 268: 118925, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33358903

RESUMEN

AIMS: Osteosarcoma (OS) is an extremely malignant bone cancer with high incidence and rapid progression. This study aims to investigate the role and underlying mechanisms of MALAT1 and miR-485-3p in OS. MATERIALS AND METHODS: qRT-PCR and Western blotting were utilized to measure the levels of miR-485-3p, MALAT1, c-MET, AKT3, p-mTOR, mTOR, glycolysis-related proteins or migration-related proteins. Colony formation and transwell assay were used to test the roles of miR-485-3p, MALAT1, c-MET and AKT3 in cancer cell proliferation, migration and invasion. Dual luciferase assay was used to validate the interactions of miR-485-3p/c-MET, miR-485-3p/AKT3, and MALAT1/miR-485-3p. Glucose uptake assay and measurement of lactate production were employed to determine the glycolysis process. Mouse tumour xenograft model was used to determine the effect of shMALAT1 and miR-485-3p mimics on tumour growth and metastasis in vivo. KEY FINDINGS: miR-485-3p was decreased while c-MET, AKT3, and MALAT1 were increased in human OS tissues and cells. miR-485-3p bound directly to c-MET and AKT3 mRNAs and repressed OS cell glycolysis, proliferation, migration, and invasion through decreasing glycolysis-related proteins and migration-related proteins via inhibiting c-MET and AKT3/mTOR pathway. In addition, MALAT1 interacted with miR-485-3p and disinhibited c-MET and AKT3/mTOR signalling. Knockdown MALAT1 or overexpression of miR-485-3p restrained OS tumour growth and lung metastasis in vivo. SIGNIFICANCE: miR-485-3p suppresses OS glycolysis, proliferation, and metastasis via inhibiting c-MET and AKT3/mTOR signalling and MALAT1 acts as a sponge of miR-485-3p. MALAT1 and miR-485-3p may be the key regulators in OS progression, and potential molecular targets for future OS therapy.


Asunto(s)
Neoplasias Óseas/patología , MicroARNs/genética , Osteosarcoma/patología , Proteínas Proto-Oncogénicas c-met/genética , ARN Largo no Codificante/genética , Animales , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Glucólisis/genética , Humanos , Masculino , Ratones Endogámicos BALB C , Osteosarcoma/genética , Osteosarcoma/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-met/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
19.
Cell Prolif ; 54(2): e12974, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33382511

RESUMEN

Signal transducer and activator of transcription 3 (STAT3) is one of seven STAT family members involved with the regulation of cellular growth, differentiation and survival. STAT proteins are conserved among eukaryotes and are important for biological functions of embryogenesis, immunity, haematopoiesis and cell migration. STAT3 is widely expressed and located in the cytoplasm in an inactive form. STAT3 is rapidly and transiently activated by tyrosine phosphorylation by a range of signalling pathways, including cytokines from the IL-6 family and growth factors, such as EGF and PDGF. STAT3 activation and subsequent dimer formation initiates nuclear translocation of STAT3 for the regulation of target gene transcription. Four STAT3 isoforms have been identified, which have distinct biological functions. STAT3 is considered a proto-oncogene and constitutive activation of STAT3 is implicated in the development of various cancers, including multiple myeloma, leukaemia and lymphomas. In this review, we focus on recent progress on STAT3 and osteosarcoma (OS). Notably, STAT3 is overexpressed and associated with the poor prognosis of OS. Constitutive activation of STAT3 in OS appears to upregulate the expression of target oncogenes, leading to OS cell transformation, proliferation, tumour formation, invasion, metastasis, immune evasion and drug resistance. Taken together, STAT3 is a target for cancer therapy, and STAT3 inhibitors represent potential therapeutic candidates for the treatment of OS.


Asunto(s)
Neoplasias Óseas/patología , Osteosarcoma/patología , Factor de Transcripción STAT3/metabolismo , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/metabolismo , Citocinas/genética , Citocinas/metabolismo , Resistencia a Antineoplásicos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/uso terapéutico , Humanos , Metástasis de la Neoplasia , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/metabolismo , Pronóstico , Isoformas de Proteínas/antagonistas & inhibidores , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/química , Factor de Transcripción STAT3/genética
20.
Biomed Pharmacother ; 134: 111155, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33370628

RESUMEN

Osteosarcoma (OS) is the most common type of bone malignant tumors. Clinical commonly used therapeutic drugs of OS treatment are prone to toxic and side effects, so it is very urgent to develop new drugs with low toxicity and low side effects. As a Chinese herbal medicine, Cardamonin (CAR) (C16H14O4) has inhibitory effects in various tumors. In the present study, we investigated the effects of CAR on OS cells in vitro and in vivo. We found that CAR inhibited cell proliferation, reduced migration, decreased invasion, and induced G2 / M arrest of OS cells. Notably, we demonstrated that CAR had no obvious effect on proliferation and apoptosis of normal cells. Besides, CAR repressed tumor growth of OS cells in xenograft mouse model. Mechanically, we found that CAR increased the phosphorylation level of P38 and JNK. In summary, our research validates that CAR may inhibit the proliferation, migration, and invasion of OS and promote apoptosis possibly by activating P38 and JNK Mitogen-activated protein kinase (MAPK) signaling pathway.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Neoplasias Óseas/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Chalconas/farmacología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Osteosarcoma/tratamiento farmacológico , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Apoptosis/efectos de los fármacos , Neoplasias Óseas/enzimología , Neoplasias Óseas/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Activación Enzimática , Femenino , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Osteosarcoma/enzimología , Osteosarcoma/patología , Fosforilación , Transducción de Señal , Ensayos Antitumor por Modelo de Xenoinjerto
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...