RESUMO
BACKGROUND/AIM: The aging population is expected to increase the occurrences of bone sarcoma (BS) and soft tissue sarcoma (STS). Carbon ion radiotherapy (CIRT) is reported to be effective for BS and several STSs. However, the effect of CIRT on clinical outcomes, functional prognoses, and quality of life (QOL) in older patients who underwent CIRT has not been reported. Therefore, we aimed to evaluate the effect of CIRT on clinical outcomes, functional prognoses and QOL in older patients with BS or STS. PATIENTS AND METHODS: This retrospective cohort study included 235 patients aged >70 years with BS or STS who underwent CIRT. Overall survival (OS), cancer-specific survival (CSS), and local control (LC) were evaluated in chordoma and non-chordoma patients. Furthermore, factors associated with post-CIRT Toronto Extremity Salvage Score (TESS) and EuroQoL 5-dimension 5-level (EQ-5D-5L) index were assessed. RESULTS: The overall 5-year LC, OS, and CSS rates were 81%, 62%, and 76%, respectively. In the chordoma and non-chordoma groups, the 5-year LC, OS, and CSS rates were 84%, 72%, and 87%; and 77%, 47%, and 60%, respectively. The mean post-CIRT TESS and EQ-5D-5L index were 75% and 0.71, respectively. The TESSs and EQ-5D-5L indices tended to be better among males, younger patients (<76 years old), patients with small tumor volumes, and patients with chordoma. CONCLUSION: CIRT is effective for older patients with BS, especially with chordoma, and STS with good LC and survival rates. Furthermore, post-treatment limb function and QOL were comparable with those of the other treatments and age groups.
Assuntos
Neoplasias Ósseas , Cordoma , Radioterapia com Íons Pesados , Osteossarcoma , Sarcoma , Masculino , Humanos , Idoso , Qualidade de Vida , Estudos Retrospectivos , Cordoma/radioterapia , Sarcoma/patologia , Radioterapia com Íons Pesados/efeitos adversos , Radioterapia com Íons Pesados/métodos , Osteossarcoma/etiologia , Neoplasias Ósseas/patologia , CarbonoRESUMO
PURPOSE: Limb salvage procedures for musculoskeletal tumors have inherent complications. Though most complications can be managed with retention of the reconstructions, occasionally salvaging these reconstructions is not possible. We evaluated the outcomes of patients undergoing rotationplasty after multiple failed revisions of limb salvage surgery and document the success rate of this "salvage" technique and the subsequent functional outcome of these patients. METHOD: Between January 1, 1999, and December 31, 2018, 14 patients (12 male and 2 female) with a median age of 24 years (11-51 years) underwent rotationplasty after multiple failed revisions of limb salvage surgery. Indication for rotationplasty was infection (10 patients), failed megaprosthesis (2 patients), unstable biological reconstruction (1 patient) and local recurrence (1 patient). The mean number of surgeries done before the patient underwent rotationplasty was 5 (range 2-7). RESULTS: One patient developed a vascular complication (venous congestion) immediately after rotationplasty and underwent an early amputation. The remaining 13 patients had no surgical complications. Mean Musculo Skeletal Tumor Society score in 13 evaluable patients was 26 (23-30). CONCLUSION: Our study demonstrates the utility of rotationplasty as a "salvage" procedure after multiple failed lower limb salvage surgeries. It offers good success rates, low rates of complications and good functional outcomes in carefully selected cases.
Assuntos
Neoplasias Ósseas , Neoplasias Femorais , Osteossarcoma , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Salvamento de Membro/métodos , Osteossarcoma/cirurgia , Osteossarcoma/etiologia , Osteossarcoma/patologia , Neoplasias Femorais/etiologia , Neoplasias Femorais/patologia , Neoplasias Femorais/cirurgia , Amputação Cirúrgica , Neoplasias Ósseas/cirurgia , Resultado do Tratamento , Estudos RetrospectivosRESUMO
With substantial improvement in survival in cancer patients, the risk of radiation-induced malignancy in previously irradiated areas is increasingly possible. Both radiation-induced sarcomas and papillary thyroid carcinomas (PTCs) are well documented in literature. However, radiation-induced synchronous malignancies are rare, are often misdiagnosed, and presents with diagnostic and therapeutic challenges due to paucity of literature and lack of available guidelines. Here, we report a case of radiation-induced synchronous mandibular osteosarcoma and PTC in a previously treated carcinoma of base tongue with concurrent chemoradiation. He initially presented with an oral cavity mass, and during the course of the treatment was incidentally diagnosed with a synchronous PTC. It also establishes the indolent course of PTC, which often goes undiagnosed till the presentation with regional nodal metastasis. This report, to the best of our knowledge, is the first reported case of synchronous radiation-induced OSM and PTC.
Assuntos
Neoplasias Ósseas , Carcinoma Papilar , Osteossarcoma , Neoplasias da Glândula Tireoide , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/patologia , Carcinoma Papilar/radioterapia , Humanos , Masculino , Osteossarcoma/diagnóstico , Osteossarcoma/etiologia , Câncer Papilífero da Tireoide/diagnóstico , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapiaRESUMO
Background: Osteosarcoma (OS) is the most common primary bone sarcoma in childhood. High-dose methotrexate, doxorubicine, cisplatin, and/or ifosfamide combinations are used as standard treatment in chemotherapy and could cause serious toxicity. Another alternative chemotherapy protocol is consisting of epirubicin, ifosfamide, and cisplatin (ECI), which we use in our center. The aim of this study was to evaluate the patients with OS who were treated with ECI protocol, retrospectively. Methods: Forty-three patients with OS diagnosed at our center between December 1995 and September 2017 were evaluated retrospectively. Results: The mean follow-up period was 31 months (5-145 months). Recurrence was detected in 15 of 43 patients. When the factors affecting relapse are examined, recurrence was higher in patients who were older than 10 years at the time of diagnosis, upper extremity involvement, osteoblastic, and chondroblastic subgroups, but there was no statistically significant difference. Five-year and 10-year overall survival rates were 67.4% and 58.9%, and event-free survival rates were 54% and 47.3%, respectively. While 5-year overall survival rate was 86.7% in nonrecurrent cases, this rate was 40.9% in recurrent cases and this difference was statistically significant (p = 0.023). Just two patients died because of the toxicity. Conclusion: The prognosis of OS is still poor in relapse cases, so the choice of chemotherapy for neoadjuvant and adjuvant therapy is vital. When the risk of toxicity is also considered, the first step of ECI protocol is seen as a preferable treatment option because the survival rates are similar to the literature.
Assuntos
Neoplasias Ósseas , Osteossarcoma , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/etiologia , Criança , Cisplatino/uso terapêutico , Humanos , Ifosfamida/uso terapêutico , Metotrexato , Recidiva Local de Neoplasia/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Osteossarcoma/etiologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: Increasing evidences suggest dysfunctions of microRNAs (miRNAs) are playing important part in tumors. Therefore, the role of miR-802 in osteosarcoma (OS) was exploited. The object was to evaluate the effect of miR-802 and verify its influence on p27 Kip1 (p27) in OS. METHODS: RT-qPCR experiment was used to detect miR-802 and p27 expression in OS tissues and cells. We explored the function of miR-802 through Transwell assays. The phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase pathway and epithelial-mesenchymal transition (EMT) was detected by Western blot assays. Luciferase assay was used to testify the target of miR-802. RESULTS: MiR-802 expression was elevated in OS, which was related to poor clinical outcome in OS patients. MiR-802 overexpression promoted OS migration, invasion and EMT. Further, p27 is a direct target of miR-802. P27 elevation counteracted the promotion effect of OS on EMT, migration and invasion induced by miR-802. In addition, miR-802 overexpression inactivated PI3K/AKT pathway via targeting p27 in OS. CONCLUSION: MiR-802 promoted the progress of EMT, migration and invasion in OS via targeting p27. This newly identified miR-802/p27/PI3K/AKT axis may represent potential targets for OS.
Assuntos
Neoplasias Ósseas/etiologia , Inibidor de Quinase Dependente de Ciclina p27/fisiologia , MicroRNAs/fisiologia , Osteossarcoma/etiologia , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Adolescente , Neoplasias Ósseas/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Osteossarcoma/patologia , Adulto JovemRESUMO
PURPOSE: No standard salvage regimen is available for relapsed or refractory sarcoma. We investigated the efficacy and toxicity of the vincristine, irinotecan, and temozolomide combination (VIT) for relapsed or refractory sarcomas of variable histology in children and young adults. MATERIALS AND METHODS: We retrospectively reviewed data from the relapsed or refractory sarcoma patients who were treated with VIT. The VIT protocol was given every 3 weeks as follows: vincristine, 1.5 mg/m2 intravenously on day 1, irinotecan, 50 mg/m2/day intravenously on days 1-5, and temozolomide, 100 mg/m2/day orally on days 1-5. RESULTS: A total of 26 patients (12 males) with various sarcoma histology were included in the study. Most common diagnosis was rhabdomyosarcoma (n=8) followed by osteosarcoma (n=7). Median age at the start of VIT was 18.5 years (range, 2.0 to 39.9). VIT was delivered as 2nd to 7th line of treatment, with 4th line most common (9/26, 34.6%). Median number of VIT courses given was 3 (range, 1 to 18). Of the 25 evaluable patients, there was two partial response (PR) and 11 stable disease (SD) with an overall control rate (complete remission+PR+SD) of 52%. PR was seen in one (50%) of the two evaluable patients with Ewing sarcoma and one (14.3%) of the seven patients with osteosarcoma. Overall survival and progression-free survival rates were 79.3% and 33.9% at 1 year, and 45.5% and 25.4% at 2 years, respectively. There was no treatment-related mortality. CONCLUSION: The VIT regimen was effective and relatively safe in our cohort of sarcoma patients.
Assuntos
Neoplasias Ósseas , Osteossarcoma , Sarcoma de Ewing , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/etiologia , Criança , Feminino , Humanos , Irinotecano/uso terapêutico , Masculino , Recidiva Local de Neoplasia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/etiologia , Estudos Retrospectivos , Sarcoma de Ewing/tratamento farmacológico , Temozolomida/uso terapêutico , Vincristina/efeitos adversos , Adulto JovemRESUMO
BACKGROUND/AIM: Recurrent osteosarcoma is recalcitrant with poor response rates to first-line chemotherapy due to heterogeneity and metastatic potential. This disease requires novel drug discovery and precision treatment. MATERIALS AND METHODS: The osteosarcoma patient-derived orthotopic xenograft (PDOX) mouse model mimics the clinical disease and has identified effective clinically-approved drugs and experimental agents, especially drug combinations, that hold much clinical promise. RESULTS: Effective treatment for drug-resistant osteosarcoma includes regorafenib, as monotherapy, and temozolomide-irinotecan, trabectedin-irinotecan, sorafenib-everolimus, sorafenib-palbociclib, and olaratumab-doxorubicin-cisplatinum, as combinations. CONCLUSION: The PDOX model can be used to improve the outcome of osteosarcoma patients, including individualized, precision therapy.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Ósseas/patologia , Descoberta de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Osteossarcoma/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/etiologia , Modelos Animais de Doenças , Suscetibilidade a Doenças , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Humanos , Camundongos , Terapia de Alvo Molecular , Osteossarcoma/tratamento farmacológico , Osteossarcoma/etiologia , Medicina de Precisão/métodosRESUMO
BACKGROUND: Circular RNAs (circRNAs), a class of noncoding RNAs (ncRNAs), may modulate gene expression by binding to miRNAs. Additionally, recent studies show that circRNAs participate in some pathological processes. However, there is a large gap in the knowledge about circDOCK1 expression and its biological functions in osteogenic sarcoma (OS). METHODS: Differentially expressed circRNAs in OS cell lines and tissues were identified by circRNA microarray analysis and quantitative real-time PCR (qRT-PCR). To explore the actions of circDOCK1 in vivo and in vitro, circDOCK1 was knocked down or overexpressed. To assess the binding and regulatory associations among miR-339-3p, circDOCK1 and IGF1R, we performed rescue experiments, RNA immunoprecipitation (RIP), RNA pulldown assays and dual-luciferase assays. Moreover, we performed apoptosis assays to reveal the regulatory effects of the circDOCK1/miR-339-3p/IGF1R axis on cisplatin sensitivity. RESULTS: CircDOCK1 expression remained stable in the cytoplasm and was higher in OS tissues and cells than in the corresponding controls. Overexpression of circDOCK1 increased oncogenicity in vivo and malignant transformation in vitro. In the U2OS and MG63 cell lines, circDOCK1 modulated tumor progression by regulating IGF1R through sponging of miR-339-3p. Additionally, in the U2OS/DDP and MG63/DDP cell lines, cisplatin sensitivity was regulated by circDOCK1 via the miR-339-3p/IGF1R axis. CONCLUSIONS: CircDOCK1 can promote progression and regulate cisplatin sensitivity in OS via the miR-339-3p/IGF1R axis. Thus, the circDOCK1/miR-339-3p/IGF1R axis may be a key mechanism and therapeutic target in OS.
Assuntos
Neoplasias Ósseas/etiologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Osteossarcoma/etiologia , RNA Circular/genética , Receptor IGF Tipo 1/genética , Proteínas rac de Ligação ao GTP/genética , Animais , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Cisplatino/farmacologia , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Camundongos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Interferência de RNA , Receptor IGF Tipo 1/metabolismo , Transdução de Sinais , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Purpose: To explore the effect of different anesthesia methods on emergence agitation (EA) and related complications in postoperative patients with osteosarcoma. Methods: According to the order of admission, 115 patients requiring osteosarcoma surgery treated in our hospital from January 2018 to December 2020 were selected as the research object and randomly divided into the control group (n = 57, accepted the general anesthesia with tracheal intubation) and the experimental group (n = 58, accepted the combined spinal-epidural anesthesia) to compare their anesthesia effect, incidence rates of agitation and complications, and other indexes. Results: In terms of the hemodynamic indexes (MAP, HR, and CVP values), both groups had lower ones at T 1 than at T 0, but the decline of the experimental group was generally lesser than that of the control group; at T 2, no statistical difference was shown within the experimental group's indexes when comparing with those at T 1, but the control group obtained a significant increase; at T 3 and T 4, both groups had their hemodynamic indexes increased, but such increase within the experimental group showed no statistical difference when comparing with those at T 0, while the control group achieved obviously higher values at T 4 than at T 0 (before the anesthesia); and the between-group difference in the hemodynamic indexes at T 1 and T 4 was significant. Compared with the control group, the experimental group achieved better VAS scores and anesthesia indexes and lower incidence rates of EA and complications such as the hypoxemia, cardiovascular response, delayed recovery, and headache. In addition, the differences in the incidence rates of hypotension and cognitive dysfunction between the two groups were not statistically significant. Conclusion: When comparing with tracheal intubation general anesthesia, the combined spinal-epidural anesthesia has a better effect in osteosarcoma surgery, with less hemodynamics influence on patients, reduced postoperative pain and stress reaction, and lowered incidence rates of postoperative EA and complications, which is worthy of wide application in clinical treatment.
Assuntos
Anestesia Epidural , Delírio do Despertar , Osteossarcoma , Anestesia Epidural/métodos , Anestesia Geral/efeitos adversos , Anestesia Geral/métodos , Delírio do Despertar/epidemiologia , Delírio do Despertar/etiologia , Humanos , Osteossarcoma/etiologia , Osteossarcoma/cirurgia , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologiaRESUMO
PURPOSE: To investigate the potential function of FAT10 in the development of osteosarcoma (OS) and its mechanism. METHODS: Relative level of FAT10 in OS specimens and cell lines was detected by qRT-PCR. The correlation between FAT10 level and clinical features of OS patients was assessed by χ2 test. After intervention of FAT10 in MG-63 and U2OS cells, changes of FAT10 level, cell viability, clonality and proliferative capacity were respectively detected by qRT-PCR, CCK-8, colony formation and EdU assay. Moreover, dynamic change of FAT10 in OS cells induced with pro-inflammatory factors was examined by qRT-PCR. Protein levels of FAT10, p-STAT1, p-STAT3 and p-STAT5 in OS cells induced with TNF-α were determined by Western blot. The JAK2 inhibitor AZ960 was used to further confirm the role of the JAK signaling in FAT10-regulated development of OS. RESULTS: FAT10 was upregulated in OS specimens and cell lines, which was correlated to tumor size, WHO grade and distant metastasis of OS patients. Knockdown of FAT10 inhibited viability, clonality and proliferative capacity of MG-63 and U2OS cells. FAT10 was time-dependently upregulated in OS cells stimulated with IFN-γ and TNF-α, which was dose-dependently downregulated by the treatment of AZ960. Protein levels of FAT10, p-STAT1, p-STAT3 and p-STAT5 in OS cells induced with AZ960 were remarkably downregulated. CONCLUSION: FAT10 is upregulated in OS samples, which stimulates the development of OS by activating the JAK/STAT signaling pathway.
Assuntos
Neoplasias Ósseas/etiologia , Janus Quinases/fisiologia , Osteossarcoma/etiologia , Fatores de Transcrição STAT/fisiologia , Transdução de Sinais , Ubiquitinas/fisiologia , Neoplasias Ósseas/patologia , Humanos , Osteossarcoma/patologia , Células Tumorais CultivadasRESUMO
Interaction with surrounding healthy cells plays a major role in the growth and metastasis of osteosarcoma. In this study, we hypothesized that humoral factors, which do not require direct contact with cells, are involved in the interaction between osteosarcoma and the surrounding cells. We identified the humoral factor involved in the association between tumor cells and surrounding normal cells using a co-culture model and investigated the significance of our findings. When human osteosarcoma cells (MG63) and human mesenchymal stem cells (hMSCs) were co-cultured and comprehensively analyzed for changes in each culture group, we found that the expression of chemokine (CC motif) ligand 26 (CCL26) was significantly enhanced. We also analyzed the changes in cell proliferation in co-culture, enhanced interaction with administration of recombinant CCL26 (rCCL26), reduced interaction with administration of anti-CCL26 antibodies, changes in invasive and metastatic abilities. CCL26 levels, motility, and invasive capability increased in the co-culture group and the group with added rCCL26, compared to the corresponding values in the MG63 single culture group. In the group with added CCL26 neutralizing antibodies, CCL26 level decreased in both the single and co-culture groups, and motility and invasive ability were also reduced. In a nude mice lung metastasis model, the number of lung metastases increased in the co-culture group and the group with added rCCL26, whereas the number of tumors were suppressed in the group with added neutralizing antibodies compared to those in the MG63 alone. This study identified a possible mechanism by which osteosarcoma cells altered the properties of normal cells to favorably change the microenvironment proximal to tumors and to promote distant metastasis.
Assuntos
Neoplasias Ósseas/metabolismo , Quimiocina CCL26/metabolismo , Osteossarcoma/metabolismo , Transdução de Sinais , Microambiente Tumoral , Antineoplásicos Imunológicos , Neoplasias Ósseas/etiologia , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Quimiocina CCL26/antagonistas & inibidores , Quimiocina CCL26/genética , Técnicas de Cocultura , Imunofluorescência , Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Osteossarcoma/etiologia , Osteossarcoma/patologia , Transcriptoma , Microambiente Tumoral/genética , Proteínas rac de Ligação ao GTP/metabolismo , Quinases da Família src/metabolismoRESUMO
PURPOSE: This study aimed to illustrate the biological role of hsa_circ_0005721 in the development of osteosarcoma and the molecular mechanism. METHODS: hsa_circ_0005721 levels in 30 pairs of osteosarcoma and non-tumor tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Functional experiments were conducted to assess the influence of hsa_circ_0005721 on proliferative, metastatic and apoptotic rates of osteosarcoma cells. The downstream target of hsa_circ_0005721 and their co-regulatory mechanism in malignant development of osteosarcoma were analyzed by dual-luciferase reporter assay and rescue experiments, respectively. RESULTS: hsa_circ_0005721 was upregulated in osteosarcoma tissues and cell lines. Knockdown of hsa_circ_0005721 suppressed proliferative and metastatic rates of U-2OS and Saos-2 cells, and stimulated apoptosis. Serving as a ceRNA, hsa_circ_0005721 upregulated the linear transcript TEP1 by competitively binding miR-16-5p, thus exerting its biological functions in regulating osteosarcoma development. CONCLUSIONS: This study for the first time identified the upregulated hsa_circ_0005721 in osteosarcoma, which triggers the malignant development of osteosarcoma by upregulating the linear transcript TEP1.
Assuntos
Neoplasias Ósseas/etiologia , Neoplasias Ósseas/patologia , Movimento Celular , Proliferação de Células , Osteossarcoma/etiologia , Osteossarcoma/patologia , RNA Circular/fisiologia , Proteínas de Ligação a RNA/fisiologia , Regulação para Cima , Humanos , Invasividade Neoplásica , Células Tumorais CultivadasRESUMO
We present the case of a 32-year-old man with a diagnosis of type-III osteogenesis imperfecta who developed a telangiectatic osteosarcoma in the proximal right tibia. An above-knee amputation was performed and after one-year follow-up, pulmonary metastatic lesions were detected on the thoracic CT scan. Palliative chemotherapy was proposed and to date the patient is still living and is under medical treatment. The association between osteogenesis imperfecta and osteosarcoma is rare. There are only ten confirmed reports of this unusual situation, but to our knowledge this is the first case reported with a telangiectatic osteosarcoma arising in this particular setting.
Assuntos
Neoplasias Ósseas , Osteogênese Imperfeita , Osteossarcoma , Adulto , Amputação Cirúrgica , Neoplasias Ósseas/etiologia , Humanos , Masculino , Osteogênese Imperfeita/complicações , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/etiologia , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: We aim to systematically review and summarize the demographics, clinical features, management strategies, and clinical outcomes of primary and radiation-induced skull-base osteosarcoma (SBO). METHODS: PubMed, Scopus, and Cochrane databases were used to identify relevant articles. Papers including SBO cases and sufficient clinical outcome data were included. A comprehensive clinical characteristic review and survival analysis were also conducted. RESULTS: Forty-one studies describing 67 patients were included. The median age was 31 years (male = 59.7%). The middle skull-base was most commonly involved (52.7%), followed by anterior (34.5%) and posterior (12.7%) skull-base. Headache (27%), exophthalmos (18%), and diplopia (10%) were common presenting symptoms. Sixty-eight percent of patients had primary SBO, while 25% had radiation-induced SBO. Surgery was the main treatment modality in 89% of cases. Chemotherapy was administered in 65.7% and radiotherapy in 50%. Median progression-free survival (PFS) was 12 months, and the overall 5-year survival was 22%. The five-year survival rates of radiation-induced SBO and primary SBO were 39% and 16%, respectively (P < 0.05). CONCLUSION: SBO is a malignant disease with poor survival outcomes. Surgical resection is the primary management modality, in conjunction with chemotherapy and radiotherapy. Radiation-induced SBO has a superior survival outcome as compared to its primary counterpart. Complete surgical resection showed a statistically insignificant survival benefit as compared to partial resection.
Assuntos
Osteossarcoma , Neoplasias da Base do Crânio , Base do Crânio , Humanos , Osteossarcoma/etiologia , Osteossarcoma/terapia , Intervalo Livre de Progressão , Resultado do TratamentoRESUMO
Osteosarcoma (OS) is the most common primary malignant bone tumour in adolescence. Lately, light-emitting diodes (LED)-based therapy has emerged as a new promising approach for several diseases. However, it remains unknown in human OS. Here, we found that the blue LED irradiation significantly suppressed the proliferation, migration and invasion of human OS cells, while we observed blue LED irradiation increased ROS production through increased NADPH oxidase enzymes NOX2 and NOX4, as well as decreased Catalase (CAT) expression levels. Furthermore, we revealed blue LED irradiation-induced autophagy characterized by alterations in autophagy protein markers including Beclin-1, LC3-II/LC3-I and P62. Moreover, we demonstrated an enhanced autophagic flux. The blockage of autophagy displayed a remarkable attenuation of anti-tumour activities of blue LED irradiation. Next, ROS scavenger N-acetyl-L-cysteine (NAC) and NOX inhibitor diphenyleneiodonium (DPI) blocked suppression of OS cell growth, indicating that ROS accumulation might play an essential role in blue LED-induced autophagic OS cell death. Additionally, we observed blue LED irradiation decreased EGFR activation (phosphorylation), which in turn led to Beclin-1 release and subsequent autophagy activation in OS cells. Analysis of EGFR colocalization with Beclin-1 and EGFR-immunoprecipitation (IP) assay further revealed the decreased interaction of EGFR and Beclin-1 upon blue LED irradiation in OS cells. In addition, Beclin-1 down-regulation abolished the effects of blue LED irradiation on OS cells. Collectively, we concluded that blue LED irradiation exhibited anti-tumour effects on OS by triggering ROS and EGFR/Beclin-1-mediated autophagy signalling pathway, representing a potential approach for human OS treatment.
Assuntos
Morte Celular Autofágica , Neoplasias Ósseas/patologia , Luz/efeitos adversos , Osteossarcoma/patologia , Espécies Reativas de Oxigênio/metabolismo , Apoptose , Neoplasias Ósseas/etiologia , Neoplasias Ósseas/metabolismo , Movimento Celular , Proliferação de Células , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Osteossarcoma/etiologia , Osteossarcoma/metabolismo , Fosforilação , Células Tumorais CultivadasRESUMO
Background: There are few detailed reports on implant-associated sarcoma in dogs; however, loose implants, metal type, and infection have not been shown as specific risk factors for this condition. Case Description: A 14-year-old spayed female Labrador retriever was referred to our hospital with a main complaint of chronic right hind lameness after previous tibial fracture repair. On radiographs, rupture of the bone plate and screws with swelling of the surrounding soft tissue was observed, and osteosarcoma (OSA) was diagnosed after histopathological examinations. During amputation surgery, a plastic band was found associated with the implant. Conclusion: Veterinary surgeons should be aware of implant-associated OSA and refrain from using non-medical materials in the implants. Furthermore, they should recommend the removal of orthopedic implants after fracture repair.
Assuntos
Neoplasias Ósseas/veterinária , Doenças do Cão/diagnóstico , Osteossarcoma/veterinária , Complicações Pós-Operatórias/veterinária , Fraturas da Tíbia/veterinária , Animais , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/etiologia , Doenças do Cão/etiologia , Cães , Feminino , Osteossarcoma/diagnóstico , Osteossarcoma/etiologia , Complicações Pós-Operatórias/etiologia , Fraturas da Tíbia/complicações , Fraturas da Tíbia/cirurgiaRESUMO
AIM: To evaluate the activity and safety of the PD-1 antibody pembrolizumab in adult patients with advanced osteosarcoma. MATERIAL AND METHODS: The study was a single-arm, open-label, phase 2 trial in patients with unresectable, relapsed osteosarcoma. The primary endpoint was clinical benefit rate (CBR) at 18 weeks of treatment, defined as complete response, partial response, or stable disease using RECIST v1.1. The trial had a Simon´s two-stage design, and ≥ 3 of 12 patients with clinical benefit in stage 1 were required to proceed to stage 2. The trial is registered with ClinicalTrials.gov, number NCT03013127. NanoString analysis was performed to explore tumor gene expression signatures and pathways. RESULTS: Twelve patients were enrolled and received study treatment. No patients had clinical benefit at 18 weeks of treatment, and patient enrollment was stopped after completion of stage 1. Estimated median progression-free survival was 1.7 months (95% CI 1.2-2.2). At time of data cut-off, 11 patients were deceased due to osteosarcoma. Median overall survival was 6.6 months (95% CI 3.8-9.3). No treatment-related deaths or drug-related grade 3 or 4 adverse events were observed. PD-L1 expression was positive in one of 11 evaluable tumor samples, and the positive sample was from a patient with a mixed treatment response. CONCLUSION: In this phase 2 study in advanced osteosarcoma, pembrolizumab was well-tolerated but did not show clinically significant antitumor activity. Future trials with immunomodulatory agents in osteosarcoma should explore combination strategies in patients selected based on molecular profiles associated with response.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Osteossarcoma/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/etiologia , Neoplasias Ósseas/mortalidade , Terapia Combinada , Fluordesoxiglucose F18 , Perfilação da Expressão Gênica , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/efeitos adversos , Metástase Neoplásica , Estadiamento de Neoplasias , Osteossarcoma/diagnóstico , Osteossarcoma/etiologia , Osteossarcoma/mortalidade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Resultado do TratamentoRESUMO
Uterine osteosarcoma has been reported, but it is an extremely rare tumor with highly aggressive behavior and poor prognosis. The pathogenesis of uterine osteosarcoma is not fully understood. Herein, we report on a high-grade uterine sarcoma with focal osteosarcomatous differentiation that developed from a long-standing MED12-mutated leiomyoma. A 47-year-old nulligravida woman, with known uterine leiomyoma presented with abdominal pain and distention. Imaging analyses revealed a tumor with a large cystic area in the uterine corpus and multiple metastases in intrapelvic and paraaortic lymph nodes, left ovary and left lung. With a clinical diagnosis of uterine sarcoma the patient underwent abdominal total hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy and removal of the left obturator lymph node. Despite postoperative chemotherapy and radiation therapy, the tumor progressed rapidly. She died 18 weeks after the surgery. Histopathologic examination identified a high-grade pleomorphic sarcoma in which focal osteoid production was observed. This high-grade sarcoma with focal osteosarcomatous differentiation was located within the uterine leiomyoma, and Sanger sequencing showed the identical MED12 L36R mutation in both the osteosarcomatous and leiomyomatous components supporting the shared origin of these two components. We, therefore, concluded that the high-grade sarcoma with osteosarcomatous differentiation arose from the transformation of the precedent leiomyoma.
Assuntos
Leiomioma/complicações , Sarcoma , Biomarcadores Tumorais/genética , Feminino , Humanos , Leiomioma/genética , Leiomioma/patologia , Complexo Mediador/genética , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Osteossarcoma/etiologia , Osteossarcoma/genética , Osteossarcoma/patologia , Sarcoma/etiologia , Sarcoma/genética , Sarcoma/patologia , Sarcoma/cirurgia , Neoplasias Uterinas/patologia , Útero/patologiaRESUMO
Esthesioneuroblastoma (ENB) is an uncommon sinonasal cancer of the olfactory neuroepithelium that is typically treated with surgical resection followed by radiation therapy. Radiation-induced intracranial osteosarcoma of the skull base is a rare but devastating long-term complication of radiation therapy in this region. Here, we present a case of an 82-year-old patient who developed radiation-induced osteosarcoma of the anterior skull base and paranasal sinuses 10 years after radiation therapy following resection of an ENB. Older patients may be at risk of developing this complication earlier and with a worse prognosis relative to younger patients. Treating physicians/surgeons should be aware of this devastating complication. Patients who are treated with high-dose radiation therapy in this region should be followed for many years.
Assuntos
Estesioneuroblastoma Olfatório/radioterapia , Cavidade Nasal , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Nasais/radioterapia , Osteossarcoma/etiologia , Neoplasias da Base do Crânio/etiologia , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Induzidas por Radiação/diagnóstico , Osteossarcoma/diagnóstico , Neoplasias da Base do Crânio/diagnósticoRESUMO
MicroRNAs (miRNAs) are a class of small (20-24 nucleotides), highly conserved, non-coding RNA molecules whose main function is the post-transcriptional regulation of gene expression through sequence-specific manners, such as mRNA degradation or translational repression. Since these key regulatory molecules are implicated in several biological processes, their altered expression affects the preservation of cellular homeostasis and leads to the development of a wide range of pathologies. Over the last few years, relevant investigations have elucidated that miRNAs participate in different stages of bone growth and development. Moreover, the abnormal expression of these RNA molecules in bone cells and tissues has been significantly associated with the progression of numerous bone diseases, including osteoporosis, osteosarcoma, osteonecrosis and bone metastasis, among others. In fact, miRNAs regulate multiple pathological mechanisms, including altering either osteogenic or osteoblast differentiation, metastasis, osteosarcoma cell proliferation, and bone loss. Therefore, in this present review, aiming to impulse the research arena of the biological implications of miRNA transcriptome in bone diseases and to explore their potentiality as a theragnostic target, we summarize the recent findings associated with the clinical significance of miRNAs in these ailments.