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BACKGROUND: A clear classification of the subtype and grade of soft tissue sarcoma is important for predicting prognosis and establishing treatment strategies. However, the rarity and heterogeneity of these tumors often make diagnosis difficult. In addition, it remains challenging to predict the response to chemotherapy and prognosis. Thus, we need a new method to help diagnose soft tissue sarcomas and determine treatment strategies in conjunction with traditional methods. Genetic alterations can be found in some subtypes of soft tissue sarcoma, but many other types show dysregulated gene expression attributed to epigenetic changes, such as DNA methylation status. However, research on DNA methylation profiles in soft tissue sarcoma is still insufficient to provide information to assist in diagnosis and therapeutic decisions. QUESTIONS/PURPOSES: (1) Do DNA methylation profiles differ between normal tissue and soft tissue sarcoma? (2) Do DNA methylation profiles vary between different histologic subtypes of soft tissue sarcoma? (3) Do DNA methylation profiles differ based on tumor grade? METHODS: Between January 2019 and December 2022, we treated 85 patients for soft tissue sarcomas. We considered patients whose specimens were approved for pilot research by the Human Biobank of St. Vincent's Hospital, The Catholic University of Korea, as potentially eligible. Based on this, 41% (35 patients) were eligible; 1% (one patient) was excluded because of gender mismatch between clinical and genetic data after controlling for data quality. Finally, 39 specimens (34 soft tissue sarcomas and five normal samples) were included from 34 patients who had clinical data. All tissue samples were collected intraoperatively. The five normal tissue samples were from muscle tissues. There were 20 female patients and 14 male patients, with a median age of 58 years (range 19 to 82 years). Genomic DNA was extracted from frozen tissue, and DNA methylation profiles were obtained. Genomic annotation of DNA methylation sites and hierarchical cluster analysis were performed to interpret results from DNA methylation profiling. A t-test was used to analyze different methylation probes. Benjamini-Hochberg-adjusted p value calculations were used to account for bias resulting from evaluating thousands of methylation sites. RESULTS: The most common histologic subtypes were liposarcoma (n = 10) and leiomyosarcoma (n = 9). The tumor grade was Fédération Nationale des Centres de Lutte Contre Le Cancer Grades 1, 2, and 3 in 3, 15, and 16 patients, respectively. DNA methylation profiling demonstrated differences between soft tissue sarcoma and normal tissue as 21,188 cytosine-phosphate-guanine sites. Despite the small number of samples, 72 of these sites showed an adjusted p value of < 0.000001, suggesting a low probability of statistical errors. Among the 72 sites, 70 exhibited a hypermethylation pattern in soft tissue sarcoma, with only two sites showing a hypomethylation pattern. Thirty of 34 soft tissue sarcomas were distinguished from normal samples using hierarchical cluster analysis. There was a different methylation pattern between leiomyosarcoma and liposarcoma at 7445 sites. Using the data, hierarchical clustering analysis showed that liposarcoma was distinguished from leiomyosarcoma. When we used the same approach and included other subtypes with three or more samples, only leiomyosarcoma and myxofibrosarcoma were separated from the other subtypes, while liposarcoma and alveolar soft-part sarcoma were mixed with the others. When comparing DNA methylation profiles between low-grade (Grade 1) and high-grade (Grades 2 and 3) soft tissue sarcomas, a difference in methylation pattern was observed at 144 cytosine-phosphate-guanine sites. Among these, 132 cytosine-phosphate-guanine sites exhibited hypermethylation in the high-grade group compared with the low-grade group. Hierarchical clustering analysis showed a division into two groups, with most high-grade sarcomas (28 of 31) separated from the low-grade group and few (3 out of 31) clustered together with the low-grade group. However, three high-grade soft tissue sarcomas were grouped with the Grade 1 cluster, and all of these sarcomas were Grade 2. When comparing Grades 1 and 2 to Grade 3, Grade 3 tumors were separated from Grades 1 and 2. CONCLUSION: We observed a different DNA methylation pattern between soft tissue sarcomas and normal tissues. Liposarcoma was distinguished from leiomyosarcoma using methylation profiling. High-grade soft tissue sarcoma samples showed a hypermethylation pattern compared with low-grade ones. Our findings indicate the need for research using methylation profiling to better understand the diverse biological characteristics of soft tissue sarcoma. Such research should include studies with sufficient samples and a variety of subtypes, as well as analyses of the expression and function of related genes. Additionally, efforts to link this research with clinical data related to treatment and prognosis are necessary. LEVEL OF EVIDENCE: Level III, diagnostic study.
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Background: Three-dimensional (3D)-printed customized implants can be fabricated and utilized for all bones with massive bone defects. The main safety issues with 3D-printed implants made of Ti6Al4V alloy are related to the release of metal debris and residual powder. In this study, we investigated the perioperative titanium concentrations in whole blood and peri-implant fluid samples of patients who underwent limb salvage surgery with a 3D-printed Ti6Al4V implant. Methods: Nineteen patients who underwent limb salvage surgery with 3D-printed Ti6Al4V implants were divided into two groups: the serial samples group and the follow-up group. To observe metal distribution and clearance in the body, serial samples of blood and peri-implant fluid from the surgical drain were prospectively collected for five patients in the serial samples group. For the remaining 14 patients who were followed up for more than a year, blood samples were collected only once. Results: In the serial samples group, the mean baseline titanium concentration was 0.78 µg/L (range, 0.1-2.2 µg/L): 3 patients showed peak concentration before the third postoperative month, while 2 patients still showed an increasing pattern at this point. Total titanium mass in the surgical drain showed a wash-out phenomenon in a week, with a significant uniform decrease (p = 0.04). In 14 patients in the follow-up group, the mean titanium concentration in the whole blood was 10.8 µg/L (range, 0.3-36.6 µg/L). For the 14 patients with a long-term follow-up, the aluminum and vanadium concentrations were all negligible. Conclusions: Whole blood titanium concentrations were higher after surgery using 3D-printed implants than after that using conventional orthopedic implants, but markedly lower than in patients with implant failure. None of the patients developed serious clinical adverse effects during follow-up.
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Salvamento de Membro , Titânio , Humanos , Próteses e Implantes , LigasRESUMO
Sarcomas are rare and heterogeneous mesenchymal neoplasms originating from the bone or soft tissues, which pose significant treatment challenges. The current standard treatment for sarcomas consists of surgical resection, often combined with chemo- and radiotherapy; however, local recurrence and metastasis remain significant concerns. Although immunotherapy has demonstrated promise in improving long-term survival rates for certain cancers, sarcomas are generally considered to be relatively less immunogenic than other tumors, presenting substantial challenges for effective immunotherapy. In this review, we examine the possible opportunities for sarcoma immunotherapy, noting cancer testis antigens expressed in sarcomas. We then cover the current status of immunotherapies in sarcomas, including progress in cancer vaccines, immune checkpoint inhibitors, and adoptive cellular therapy and their potential in combating these tumors. Furthermore, we discuss the limitations of immunotherapies in sarcomas, including a low tumor mutation burden and immunosuppressive tumor microenvironment, and explore potential strategies to tackle the immunosuppressive barriers in therapeutic interventions, shedding light on the development of effective and personalized treatments for sarcomas. Overall, this review provides a comprehensive overview of the current status and potential of immunotherapies in sarcoma treatment, highlighting the challenges and opportunities for developing effective therapies to improve the outcomes of patients with these rare malignancies.
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Vacinas Anticâncer , Sarcoma , Masculino , Humanos , Sarcoma/tratamento farmacológico , Sarcoma/patologia , Imunoterapia , Microambiente Tumoral , Vacinas Anticâncer/uso terapêuticoRESUMO
As a high-grade soft-tissue sarcoma (STS), undifferentiated pleomorphic sarcoma (UPS) is highly recurrent and malignant. UPS is categorized as a tumor of uncertain differentiation and has few options for treatment due to its lack of targetable genetic alterations. There are also few cell lines that provide a representative model for UPS, leading to a dearth of experimental research. Here, we established and characterized new cell lines derived from two recurrent UPS tissues. Cells were obtained from UPS tissues by mincing, followed by extraction or dissociation using enzymes and culture in a standard culture environment. Cells were maintained for several months without artificial treatment, and some cell clones were found to be tumorigenic in an immunodeficient mouse model. Interestingly, some cells formed tumors in vivo when injected after aggregation in a non-adherent culture system for 24 h. The tissues from in vivo study and tissues from patients shared common histological characteristics. Pathways related to the cell cycle, such as DNA replication, were enriched in both cell clones. Pathways related to cell-cell adhesion and cell-cell signaling were also enriched, suggesting a role of the mesenchymal-to-epithelial transition for tumorigenicity in vivo. These new UPS cell lines may facilitate research to identify therapeutic strategies for UPS. [BMB Reports 2023; 56(4): 258-264].
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Sarcoma , Camundongos , Animais , Sarcoma/tratamento farmacológico , Sarcoma/genética , Sarcoma/patologia , Linhagem Celular Tumoral , Diferenciação CelularRESUMO
PURPOSE: This study aimed to analyze characteristics, treatment, long-term outcomes, and prognostic factors for children, adolescents and young adults with rhabdomysosarcoma (RMS). METHODS: This retrospective historical study included 75 patients with RMS treated between 2002 and 2019. Clinical data and follow-up results were collected including all diagnosis, treatment and prognosis information. RESULTS: Patients median-age-at-diagnosis was 6 years. Embryonal and alveolar histology occurred in 51 (68.0%) and 21 (28.0%) patients, respectively. The tumors most frequently originated from parameningeal site (28.0%). Of 74 evaluable patients for treatment outcome, 60 (81.1%) achieved complete response for first-line treatment, of whom, 34 (56.6%) maintained complete response, 26 (43.3%; 23/26, local relapse) showed relapse. Of 40 patients with treatment failure, 16 and 6 occurred in parameningeal area and retroperitoneum/perineum, respectively. The 5-year progression-free survival (PFS) and overall survival (OS) were 45.0% and 64.5%, respectively. In multivariate analyses, parameningeal site (p = 0.027), no gross total resection (p = 0.047), and no radiation therapy (RT) (p < 0.001) for PFS; and parameningeal site (p < 0.001) and no RT (p = 0.010) for worse OS, were significant. The median PFS and OS from treatment failure date in 40 patients with primary treatment failure were 1.3 and 4.1 years, respectively. Of 26 patients with relapse, interval to relapse < 7 months, retroperitoneum/perineum site, TNM stages III/IIV, and no salvage RT were independently associated with OS. CONCLUSION: The importance of adequate local therapy was highlighted in RMS treatment. Treatment failure was largely a local failure. Whether as a component of initial or salvage treatment, RT could improve patients' survival.
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Rabdomiossarcoma Embrionário , Rabdomiossarcoma , Criança , Humanos , Adolescente , Adulto Jovem , Lactente , Estudos Retrospectivos , Recidiva Local de Neoplasia/terapia , Rabdomiossarcoma/patologia , Resultado do Tratamento , Prognóstico , Terapia Combinada , República da Coreia/epidemiologiaRESUMO
Background: A minimally invasive procedure for symptomatic pelvic bone metastasis is a feasible option for advanced cancer patients, and bone cement injection plays an essential role. Pulmonary embolism caused by thrombus, fat, or tumor emboli is a major complication related to bone cement injection, and increasing intraosseous pressure is a predisposing factor. This study aimed to quantify the degree of pressure change in the pelvic bone during percutaneous bone cement injection and investigate whether there is a significant decrease in intraosseous pressure when a decompressive route is additionally established. Methods: Bone cement injection into the acetabulum of swine pelvises by simulating the actual surgical procedure in terms of the injection method, bone cement, and surgical instruments was performed while recording the intraosseous pressure. Twenty swine pelvises were used and grouped into a decompression group and a non-decompression group. Bone cement injection and pressure measurement were conducted in the same way in both groups, but an additional decompressive route was established for each pelvis in the decompression group. Continuous variables were compared using the Mann-Whitney test. Results: The mean amount of injected bone cement was 19.8 mL and 20.3 mL and the mean speed of bone cement injection was 0.14 mL/sec and 0.12 mL/sec in the decompression group and the non-decompression group, respectively. The mean peak intraosseous pressures was 10.5 kPa with decompression and 37.8 kPa without decompression, and the difference was statistically significant (p < 0.01). Conclusions: Intraosseous pressure during bone cement injection into swine pelvises was similar to that during vertebroplasty or kyphoplasty. When the additional decompression route was established, the intraosseous pressure decreased to one third the level.
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Fraturas por Compressão , Cifoplastia , Embolia Pulmonar , Fraturas da Coluna Vertebral , Vertebroplastia , Humanos , Suínos , Animais , Cimentos Ósseos , Vertebroplastia/métodos , Pelve , Fraturas da Coluna Vertebral/cirurgia , Fraturas por Compressão/cirurgiaRESUMO
Lattice structures for implants can be printed using metal three-dimensional (3D)-printing and used as a porous microstructures to enhance bone ingrowth as orthopedic implants. However, designs and 3D-printed products can vary. Thus, we aimed to investigate whether targeted pores can be consistently obtained despite printing errors. The cube-shaped specimen was printed with one side 15 mm long and a full lattice with a dode-thin structure of 1.15, 1.5, and 2.0 mm made using selective laser melting. Beam compensation was applied, increasing it until the vector was lost. For each specimen, the actual unit size and strut thickness were measured 50 times. Pore size was calculated from unit size and strut thickness, and porosity was determined from the specimen's weight. The actual average pore sizes for 1.15, 1.5, and 2.0 mm outputs were 257.9, 406.2, and 633.6 µm, and volume porosity was 62, 70, and 80%, respectively. No strut breakage or gross deformation was observed in any 3D-printed specimens, and the pores were uniformly fabricated with < 10% standard deviation. The actual micrometer-scaled printed structures were significantly different to the design, but this error was not random. Although the accuracy was low, precision was high for pore cells, so reproducibility was confirmed.
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Osso e Ossos , Impressão Tridimensional , Porosidade , Próteses e Implantes , Reprodutibilidade dos Testes , Titânio/químicaRESUMO
Background: Interferon (IFN) consensus sequence binding protein (ICSBP) is a transcription factor induced by IFN-γ. We previously reported that ICSBP expression promotes osteosarcoma progression by enhancing transforming growth factor-ß signaling. In cancer cells, programmed death-ligand 1 (PD-L1) contributes to immune escape and may also be involved in tumor progression. Because IFN-γ induces the expression of both ICSBP and PD-L1, we explored the association between ICSBP and PD-L1 expression in terms of osteosarcoma progression. Methods: Three osteosarcoma cell lines (Saos2, U2OS, and 143B) were employed. Gene expression was measured by qRT-PCR, and protein levels were assessed by immunoblotting. PD-L1 expression was evaluated in cells overexpressing ICSBP and in ICSBP knockdown cells. The effects of PD-L1 expression on cell growth were examined by MTS assays, Incucyte analysis, soft agar assays, and three-dimensional (3D) culture. Cell cycle and apoptosis were evaluated by FACS analysis of cells stained with propidium iodide (PI) and annexin V/PI, respectively. The antitumor effects of PD-L1 knockdown without or with doxorubicin treatment were evaluated in vivo in nude mice bearing ICSBP-overexpressing 143B cell xenograft. The clinical relevance of PD-L1 and ICSBP expression was evaluated immunohistochemically using a human osteosarcoma microarray and through analysis of publicly available data using Gene Expression Profiling Interactive Analysis2. Results: ICSBP overexpression upregulated PD-L1 expression in all three cell lines, whereas ICSBP knockdown decreased the PD-L1 expression. PD-L1 knockdown attenuated the cell growth and reduced colony-forming capacity in both soft agar assays and 3D culture. PD-L1 knockdown increased apoptosis and induced G2/M arrest, which was associated with decreased expression of survivin, cyclin-dependent kinase 4 (CDK4), cyclin E, and cyclin D1 expression and increased the expression of p27, phosphorylated Cdc2, and phosphorylated Wee1. PD-L1 knockdown decreased the growth of tumor xenografts and increased the doxorubicin sensitivity of ICSBP-overexpressing 143B cells both in vitro and in vivo. PD-L1 was expressed in human osteosarcoma tissues, and its expression was moderately correlated with that of ICSBP in osteosarcoma patients. Conclusion: ICSBP regulates PD-L1 expression in osteosarcoma cells, and PD-L1 knockdown combined with doxorubicin treatment could represent a strategy for controlling osteosarcoma expressing ICSBP.
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PURPOSE: Due to low incidence, epidemiologic data of Ewing sarcoma in the Asian population are scarce. We aimed to examine the incidence pattern and outcome of patients with Ewing sarcoma in the Republic of Korea. MATERIALS AND METHODS: Data of patients with Ewing sarcoma diagnosed between 1999 and 2017 were obtained from the Korea Central Cancer Registry (KCCR). Incidence, clinical characteristics, and survival rates were analyzed and compared between different age groups. RESULTS: There were 788 cases (459 males, 329 females), with a median age at diagnosis of 20 years. The age-standardized rate of Ewing sarcoma was 1.01. The number of cases and incidence rates in each age group were as follows: children, 1.6; adolescents and young adults (AYA), 0.93; adults, 0.44; and elderly, 0.53. There were more male cases in children and the AYA group (p < 0.001). Extraskeletal tumors (p < 0.001), primary sites other than extremity (p=0.007), and presence of metastasis at diagnosis (p=0.031) were more frequent in the adults and elderly group. With a median survival time of 78 months, the 5-year overall survival (OS) rate of the entire cohort was 52%. Children fared best (5-year OS, 75%), and the 5-year OS of AYA patients (51%) approximated the OS of the entire cohort. A two-fold difference of 5-year OS was observed between adults and elderly patients (42% vs. 19%). On univariate and multivariate analyses, age ≥ 15 years and presence of metastasis were adverse prognostic factors. CONCLUSION: This was the first epidemiologic study of Ewing sarcoma using the KCCR data. With a similar incidence to other Asian countries, the survival rate was slightly lower than that of Euro-American cases. Collaborative clinical studies are necessary to improve the outcome of Ewing sarcoma in low-incidence populations.
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Neoplasias Ósseas , Sarcoma de Ewing , Adolescente , Idoso , Criança , Feminino , Humanos , Incidência , Masculino , Sistema de Registros , Estudos Retrospectivos , Sarcoma de Ewing/epidemiologia , Taxa de Sobrevida , 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.
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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: In advanced cancer patients, pelvic bone metastasis often causes pain and gait disturbance. The use of percutaneous bone cement [polymethylmethacrylate (PMMA)] injection for pain management and strengthening in pelvic bone metastasis has rarely been reported. To evaluate this method, we aimed to determine surgical outcomes and complications over a long-term follow-up period using a large patient group. PATIENTS AND METHODS: We retrospectively collected data from 178 patients who underwent percutaneous cementoplasty for pelvic metastatic lesions, 201 in total. Surgical outcomes evaluated included pain reduction and improvement of ambulation. Mortality within 1 month after procedure and pulmonary embolism caused by thrombus, fat, tumor emboli, or bone cement were investigated as surgical complications. For long-term survivors, pain relapse and mechanical failure were analyzed. The mean follow-up period was 12.6 months, and there were 159 fatalities at last follow-up. RESULTS: The mean regional pain numerical rating scale scores decreased from 6.1 preoperatively to 2.4 1 month after procedure (p < 0.01). Gait function was maintained, worsened, and uncheckable in 68%, 24%, and 8% of patients, respectively, 1 month after procedure. Of long-term survivors followed up for > 12 months (n = 53), there were no significant changes in serial plain radiographs, and regional pain aggravation was observed in 9%. Pulmonary cement embolism and bone cement implantation syndrome was observed in 11% and 10%, respectively. However, all patients with these complications were asymptomatic. CONCLUSIONS: Percutaneous cement injection into the pelvis is a feasible and safe palliative surgical option for patients with advanced malignancy in terms of pain reduction and maintenance of ambulatory function under regional anesthesia.
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Neoplasias Ósseas , Cementoplastia , Ossos Pélvicos , Cimentos Ósseos/uso terapêutico , Neoplasias Ósseas/cirurgia , Humanos , Pelve , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The epidemiology of osteosarcoma in adolescents and young adults (AYA) remains unclear. We aimed to assess and compare the clinical features of osteosarcoma between AYA and other age groups. We retrieved osteosarcoma cases diagnosed between 1999 and 2017 from the Korea Central Cancer Registry. We compared survival trends and clinical characteristics between AYA and other age groups. AYA comprised 43.3% (1309/3022) of the osteosarcoma cases. Compared to other age groups, the male-to-female ratio was highest in AYA (1.61:1). The proportion of tumors located in an extremity was 80.3% in AYA, which was lower than in young children (92.5%) or pubertal children (93.8%) but higher than in adults (55.7%) or the elderly (47.5%). As for treatments, 71.2% of AYA received local treatment and systemic chemotherapy, and 28.8% received only local treatment (surgery: 261, radiotherapy: 9, surgery and radiotherapy: 5). The 5-year overall survival (OS) was lower in AYA (68%) than in young children (78%) or pubertal children (73%) but higher than in adults (47%) or the elderly (25%). When AYA were divided into five subgroups by age, patients aged 15-19 years constituted the largest proportion (45.4%, n = 594). Additionally, the proportion of patients with a non-extremity tumor increased in an age-dependent manner, from 10.3% in AYA aged 15-19 years to 35.3% in AYA aged 35-39 years. OS did not significantly differ among the different age subgroups of AYA. The clinical characteristics and OS of the AYA were more similar to those of children than to those of adults. There is a need for cooperation between pediatric and adult oncologists for effective osteosarcoma treatment in AYA.
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Osteossarcoma/epidemiologia , Adolescente , Distribuição por Idade , Feminino , Humanos , Masculino , Osteossarcoma/diagnóstico , República da Coreia/epidemiologia , Análise de Sobrevida , Adulto JovemRESUMO
At the end of 2019, the cause of pneumonia outbreaks in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In February 2020, the World Health Organization named the disease cause by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). In response to the pandemic, the Korean Cancer Association formed the COVID-19 task force to develop practice guidelines. This special article introduces the clinical practice guidelines for cancer patients which will help oncologists best manage cancer patients during the COVID-19 pandemic.
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COVID-19 , Oncologia/normas , Neoplasias/terapia , Guias de Prática Clínica como Assunto , Ensaios Clínicos como Assunto , Detecção Precoce de Câncer , Humanos , Segurança do Paciente , República da CoreiaRESUMO
BACKGROUND: Three-dimensional (3D)-printing technology provides an advanced approach to pelvic bone tumor resection and reconstruction. However, only a few cases of pelvic bone tumor surgery using 3D-printing have been reported due to limited time since the introduction of the new implant. This study introduces pelvic bone tumor surgeries using 3D-printed bone-cutting guides and implants. METHODS: This single-center retrospective review included 12 patients who underwent malignant pelvic bone tumor surgeries using a 3D-printed bone-cutting guide and/or implant. Clinical information was collected regarding patient demographics, tumor characteristics, pathologic diagnosis, surgery details, and functional recovery. RESULTS: Type I internal hemipelvectomy was performed using 3D-printed bone-cutting guides for 4 patients that underwent cavitary bone tumor resection of the ilium. For 3 of these 4 patients, cavitary bone defects were filled with structural allobone graft precisely trimmed by the 3D-printed allograft-shaping guide (n = 1) and 3D-printed mesh-style titanium spacer (n = 2). For type II and III areas, one and two patients, respectively, underwent 3D-printing-assisted surgery. Five patients underwent type I, II, and III pelvic resection using 3D-printed cutting guides and reconstruction with 3D-printed implants. In all patients, independent gait was recovered except for a patient who underwent hindquarter amputation 4 months postoperatively because of local recurrence. CONCLUSIONS: This study provides preliminary, short-term data on the efficacy and safety of pelvic bone tumor surgery using 3D-printing.
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Ossos Pélvicos , Procedimentos de Cirurgia Plástica , Humanos , Recidiva Local de Neoplasia , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/cirurgia , Impressão Tridimensional , Estudos RetrospectivosAssuntos
Salvamento de Membro/métodos , Impressão Tridimensional , Próteses e Implantes , Desenho de Prótese/métodos , Adulto , Idoso , Aloenxertos , Ligas , Neoplasias Ósseas/cirurgia , Osso e Ossos/lesões , Diáfises/lesões , Diáfises/cirurgia , Feminino , Fêmur/lesões , Fêmur/cirurgia , Humanos , Úmero/lesões , Úmero/cirurgia , Masculino , Pessoa de Meia-Idade , Ossos Pélvicos/lesões , Ossos Pélvicos/cirurgia , Implantação de Prótese/métodos , Titânio , Adulto JovemRESUMO
Tight junction protein 1 (TJP1) is a membrane-associated cytosolic protein important for cell-cell communication in intercellular barriers in epithelial and non-epithelial cells. Here, we explored the functional involvement of TJP1 in non-epithelial tumors such as soft tissue sarcoma, especially in leiomyosarcoma (LMS). TJP1 expression in soft tissue sarcoma was analyzed in normal and tumor tissues as well as from public datasets such as the TCGA provisional dataset, in which TJP1 expression was compared with other subtypes such as undifferentiated sarcomas, and myxofibrosarcomas. SK-LMS-1 cell lines with reduced TJP1 expression showed attenuated anchorage-independent colony formation as well as reduced intercellular aggregation on non-coated culture plates compared with control as well as parental SK-LMS-1 cells. Transcriptome profiling following TJP1 knockdown in SK-LMS-1 cells suggested the involvement of several signaling pathways, including NF-κB pathway and growth factor receptor signaling. In addition, TJP1 downregulation induced enhanced response against anti-cancer agents, doxorubicin and gefitinib. Taken together, these results suggest that TJP1 contributes to sarcoma genesis and might be useful therapeutic target. KEY MESSAGES: ⢠TJP1 expression at RNA level higher in tumor than in normal tissues of sarcoma. ⢠Targeting TJP1 attenuates cell-cell aggregation and anchorage-independent growth. ⢠Targeting TJP1 is beneficial in anti-cancer therapy in LMS.
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Antibióticos Antineoplásicos/farmacologia , Comunicação Celular/efeitos dos fármacos , Comunicação Celular/genética , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Leiomiossarcoma/genética , Proteína da Zônula de Oclusão-1/genética , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Proliferação de Células , Edição de Genes , Perfilação da Expressão Gênica , Inativação Gênica , Humanos , Janus Quinases/metabolismo , Leiomiossarcoma/tratamento farmacológico , Leiomiossarcoma/metabolismo , Leiomiossarcoma/patologia , NF-kappa B/metabolismo , RNA Interferente Pequeno/genética , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Transcriptoma , Proteína da Zônula de Oclusão-1/antagonistas & inibidoresRESUMO
OBJECTIVES: The histologic response to chemotherapy is an important prognostic factor in osteosarcoma. Thus, we attempted to develop an effective neoadjuvant regimen to achieve an improvement in histologic response. METHODS: Twenty-nine patients with a high-grade osteosarcoma received 2 courses of neoadjuvant chemotherapy non-randomly with either the MAP regimen (methotrexate 12 g/m2, cisplatin 120 mg/m2, and doxorubicin 75 mg/m2) or MAPI regimen (MAP plus ifosfamide 9 g/m2). We applied interval compression to MAPI by shortening the preoperative period to be aligned with that of MAP. Adjuvant chemotherapy was tailored according to the necrosis rate of resected tumor specimens. Necrosis rate, toxicity, and survival outcome were compared retrospectively between the 2 groups. RESULTS: The median interval between the beginning of neoadjuvant chemotherapy and surgery was 97.0 days in the MAPI group (17 patients) and 90.5 days in the MAP group (12 patients; p = 0.19). The good histologic response (>90% of necrosis) was observed in 71% of MAPI and in 42% of MAP (p = 0.12). Major toxicities of grade 3 or worse were not different between the 2 groups. The probability of 5-year progression-free survival and overall survival of the MAPI group were 74 and 83%, and those in the MAP group were 50 and 75%, showing no difference. CONCLUSIONS: Interval-compressed MAPI therapy given in a similar duration of the preoperative phase to that of conventional MAP therapy showed a marginal trend toward a better histologic response without a significant increase in major toxicities. Regarding the proportion of good histologic response, 71% is one of the highest values ever reported in the literature. The results warrant further testing in a prospective way in a larger cohort.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/diagnóstico , Osteossarcoma/tratamento farmacológico , Cuidados Pré-Operatórios , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medula Óssea/patologia , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/cirurgia , Criança , Esquema de Medicação , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Osteossarcoma/mortalidade , Osteossarcoma/cirurgia , Cooperação do Paciente , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Transforming growth factor-beta (TGF-ß) is a known tumor suppressor, which also exerts a tumor promoting activity at an advanced stage of cancer. Previously, we reported that expression of interferon consensus sequence-binding protein (ICSBP), also known as interferon regulatory factor-8, is positively correlated with TGF-ß type I receptor (TGF-ß RI) expression in osteosarcoma patient tissues. In this study, we demonstrated that ICSBP upregulated TGF-ß RI and induced epithelial-to-mesenchymal transition-like phenomena in human osteosarcoma cell lines. As determined by soft agar growth of osteosarcoma cells and xenografted mouse models, ICSBP increased tumorigenicity, which was reversed by ICSBP knock-down or a TGF-ß RI inhibitor. To test whether ICSBP directly regulates the promoter activity of TGF-ß RI, we performed a TGF-ß RI promoter assay, an electro mobility shift assay, and a chromatin immunoprecipitation assay. We observed that TGF-ß RI promoter was activated in ICSBP-overexpressing osteosarcoma cells. Exploiting serial deletions and mutations of the TGF-ß RI promoter, we found a putative ICSBP-binding site at nucleotides -216/-211 (GGXXTC) in the TGF-ß RI promoter. Our data suggest that ICSBP upregulates TGF-ß RI expression by binding to this site, causing ICSBP-mediated tumor progression in osteosarcoma cells. In addition, we found a positive correlation between ICSBP and TGF-ß RI expression in several types of tumors using the cBioportal database. SUMMARY: We demonstrated that interferon consensus sequence-binding protein upregulates transforming growth factor-beta type I receptor (TGF-ß RI) expression by binding to nucleotides -216/-211 (GGXXTC) in the TGF-ß RI promoter, which resulted in increased tumorigenicity and tumor progression in human osteosarcoma cells.
Assuntos
Neoplasias Ósseas/metabolismo , Regulação Neoplásica da Expressão Gênica , Fatores Reguladores de Interferon/metabolismo , Proteínas de Neoplasias/metabolismo , Osteossarcoma/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/biossíntese , Elementos de Resposta , Regulação para Cima , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Humanos , Fatores Reguladores de Interferon/genética , Proteínas de Neoplasias/genética , Osteossarcoma/genética , Osteossarcoma/patologia , Receptor do Fator de Crescimento Transformador beta Tipo I/genéticaRESUMO
OBJECTIVE: For symptomatic metastasis of the long bones, intramedullary nailing has been the most accepted fixation method. Intramedullary nailing has effective control of pain, perioperative bleeding, and local tumor progression by augmentation with bone cement around the nail. Here, we report the preliminary results of a new surgical implant that allows for simultaneous injection of bone cement while inserting a percutaneous, flexible intramedullary nail. MATERIALS AND METHODS: We performed palliative surgeries for long-bone metastasis using a multi-hole injection nail (MIN) with multiple side holes in the distal one third. When the nail tip entered the metastatic cancer lesion, the bone cement injection was started, and continued until the nail was completely seated. Ten patients with advanced cancer underwent palliative surgery using the new implant with simultaneous bone cement injection for humeral (n = 4), femoral (n = 4), and tibial (n = 2) metastases. RESULTS: The mean operative time was 42 min (range, 36-52 min). The mean length of the injection nail was 23.0 cm (range, 18.0-33.0 cm), and the mean volume of cement was 28.0 ml (range, 14.0-40.0 ml). Marked pain palliation (p < 0.001) and functional recovery (p = 0.01) were verified. The mean Musculoskeletal Tumor Society (MSTS) functional score improved significantly from 12.5 at 6 weeks preoperatively, to 24.9 postoperatively. No acute postoperative complications, including cement embolism, occurred. CONCLUSION: This minimally invasive surgical method with MIN could be useful for stabilization of long-bone metastases in patients with advanced cancer.
Assuntos
Cimentos Ósseos/uso terapêutico , Pinos Ortopédicos , Neoplasias Ósseas/secundário , Neoplasias Ósseas/cirurgia , Fêmur/cirurgia , Fixação Intramedular de Fraturas/métodos , Fraturas Espontâneas/cirurgia , Úmero/cirurgia , Tíbia/cirurgia , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Feminino , Fêmur/diagnóstico por imagem , Fraturas Espontâneas/diagnóstico por imagem , Humanos , Úmero/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Estudos Prospectivos , Tíbia/diagnóstico por imagem , Resultado do TratamentoRESUMO
The oncologic risk of ionizing radiation is widely known. Sarcomas developing after radiotherapy have been reported, and they are a growing problem because rapid advancements in cancer management and screening have increased the number of long-term survivors. Although many patients have undergone radiation treatment in Asian countries, scarce reports on post-radiation sarcomas (PRSs) have been published. We investigated the feature and prognostic factors of PRSs in an Asian population. The Eastern Asian Musculoskeletal Oncology Group participated in this project. Cases obtained from 10 centers were retrospectively reviewed. Patients with genetic malignancy predisposition syndrome, or who had more than one type of malignancy before the development of secondary sarcoma were excluded. Forty-two high-grade sarcomas among a total of 43 PRSs were analyzed. There were 29 females and 13 males, with a median age of 58.5 years; 23 patients had bone tumors and 19 had soft tissue tumors. The most common primary lesion was breast cancer. The median latency period was 192 months. There were no differences in radiation dose, latency time, and survival rates between bone and soft tissue PRSs. The most common site and diagnosis were the pelvic area and osteosarcoma and malignant fibrous histiocytoma for bone and soft tissue PRSs. The median follow-up period was 25.5 months. Five-year metastasis-free and overall survival rates were 14.5% and 16.6%, and 39.1% and 49.6% for bone and soft tissue PRSs. Survival differences depending on initial metastasis and surgery were significant in soft tissue sarcomas. Although this study failed to find ethnic differences, it is the largest review on PRS in an Asian population. As early recognition through long-term surveillance is a key to optimal management, clinicians should take efforts to understand the real status of PRS.