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1.
Medicine (Baltimore) ; 100(34): e26681, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449453

RESUMO

RATIONALE: Recently, the number of osteosarcomas has been increasing in elderly patients due to human longevity. Lung metastases are the primary cause of death from osteosarcomas. Complete resection of lung metastases can prolong the survival. However, complete resection in elderly patients is often difficult due to high risk of operative complications. Computed tomography (CT) guided radiofrequency ablation (RFA) is a minimally invasive technique to destroy tumor nodules using heat. In this report, we present the first case older than 65 years applying RFA for lung metastases due to osteosarcoma. PATIENT CONCERNS: A 74-year-old male presented with 1-year history of heel pain. A conventional high-grade osteosarcoma in his calcaneus was diagnosed. Below-knee amputation was performed. However, lung metastases were found in both lungs 1 year after amputation. CT-guided lung RFA was chosen since surgical intervention for lung metastases was abandoned because of tumor multiplicity and medical comorbidities. A total of 18 lung metastases were treated by CT-guided RFA. The most frequent complication was pneumothoraxes in 4 of 8 (50%) procedures and chest tube drainage was required in 2 of these (2 of 8 (25%) procedures). DIAGNOSES: Six lung metastases of osteosaroma were found in both lungs at 1 year after surgery. INTERVENTIONS: CT-guided lung RFA was performed. A total of 18 lung metastases were treated in 8 lung RF procedures. OUTCOMES: The patient has been alive with disease for 5.5 years after the initial surgery. LESSONS: CT-guided lung RFA is effective for elderly patients with osteosarcoma lung metastases in spite of discouragement of lung metastasectomy due to multiplicity of metastases and medical-comorbidities.


Assuntos
Neoplasias Ósseas/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Osteossarcoma/patologia , Ablação por Radiofrequência/métodos , Idoso , Calcâneo/patologia , Humanos , Masculino , Radiografia Intervencionista , Tomografia Computadorizada por Raios X
2.
Hell J Nucl Med ; 24(1): 36-44, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33866337

RESUMO

OBJECTIVE: To evaluate the clinical utility of quantitative values obtained with bone single photon emission computed tomography/computed tomography (SPECT/CT) for primary bone neoplasms. SUBJECTS AND METHODS: Bone SPECT/CT scans of 23 patients with 19 benign bone neoplasms (5 osteoid osteomas, 4 bone giant cell tumor, 4 osteofibrous dysplasia, 3 intraosseous ganglion, 2 aneurysmal bone cyst, 1 intraosseous hemangioma) and 5 malignant bone neoplasms (2 osteosarcoma, 1 periosteal osteosarcoma, 1 malignancy in bone giant cell tumor, 1 Ewing sarcoma) were retrospectively analyzed with maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), mean SUV (SUVmean), metabolic bone volume (MBV), and total bone uptake (TBU) of primary lesions. RESULTS: Mean SUVmax of 19 benign and 5 malignant primary bone neoplasms were 6.89±3.26 (range 3.9-15.13) and 10.31±3.19 (5.0-13.45) respectively, with statistically significant difference (P=0.048). Mean SUVpeak of those were 5.87±2.83 (range 3.5-13.63) and 9.18±3.05 (4.09-12.03) respectively, with statistically significant difference (P=0.032). Mean SUVmean of those were 4.43±2.11 (range 2.59-9.37) and 7.13±2.90 (3.3-10.42) respectively, with statistically significant difference (P=0.027). Mean MBV of those were 22.0±30.0 (range 2.47-110.61) and 27.8±39.94 (8.59-99.24) respectively, with no statistically significant difference (P=0.72). Mean TBU of those were 80.64±94.57 (range 10.50-373.57) and 166.60±203.97 (28.68-528.13) respectively, with no statistically significant difference (P=0.17). CONCLUSION: Quantitative values obtained with bone SPECT/CT may serve as osteoblastic biomarkers for primary bone neoplasm.

3.
Case Rep Oncol ; 13(2): 829-834, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884526

RESUMO

We here report on 2 cases of monostotic Paget's disease of bone, one in the ilium and the other in the skull, including quantitative values obtained with bone single photon emission computed tomography/computed tomography (SPECT/CT), which were useful to evaluate the response to bisphosphonate treatment. The quantitative parameters determined with those findings were decreased, with the maximum standardized uptake value (SUV), peak SUV, mean SUV, metabolic bone volume, and total bone uptake in case 1 and case 2 reduced by 48.8 and 60.3%, 46.6 and 58.8%, 24.3 and 60.5%, 87.0 and 11.8%, and 90.2 and 55.8%, respectively, while TRACP-5B and alkaline phosphatase (ALP) were also reduced by 39.5 and 88.6% and by 53.7 and 78.1%, respectively. Quantitative SPECT/CT parameter decreases were correlated with TRACP-5B and ALP, indicating the usefulness of this modality to examine treatment response.

4.
Hell J Nucl Med ; 23(2): 133-137, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716404

RESUMO

OBJECTIVE: To evaluate the ability of quantitative values obtained with bone single photon emission computed tomography/computed tomography (SPECT/CT) to differentiate benign from malignant cartilaginous bone neoplasms. SUBJECTS AND METHODS: Bone SPECT/CT scans of 10 patients with 8 benign cartilaginous bone neoplasms (4 enchondromas, 1 periosteal chondroma, 1 osteochondroma, 1 bizarre parosteal osteochondromatous proliferation, 1 chondroblastoma) and 2 malignant cartilaginous bone neoplasms (1 periosteal chondrosarcoma, 1 chondrosarcoma) were retrospectively analyzed with maximum standardized uptake value (SUVmax), mean SUV (SUVmean), metabolic bone volume (MBV), and total bone uptake (TBU) of primary lesions. RESULTS: Mean SUVmax of 8 benign and 2 malignant cartilaginous bone neoplasms were 1.93±1.02 (range 0.59-3.41) and 6.07±0.86 (5.46-6.67), respectively with no overlap (P=0.028). Mean SUVmean of those were 1.24±0.71 (range 0.36-2.36) and 4.05±0.30 (3.84-4.26), respectively with no overlap (P=0.00036). Mean MBV of those were 7.17±4.19 (range 3.17-13.77) and 10.29±10.05 (3.19-17.4), respectively with no significant difference (P=0.74). Mean TBU of those were 9.22±8.31 (range 1.15-23.61) and 43.19±43.7 (12.26-74.13), respectively with no significant difference (P=0.47). CONCLUSION: Standardized uptake value obtained with bone SPECT/CT may be useful to differentiate benign from malignant cartilaginous bone neoplasms, thus helping the orthopedic surgeon towards the most appropriate treatment procedure.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Osso e Ossos/diagnóstico por imagem , Cartilagem/patologia , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Adolescente , Adulto , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
5.
Clin Orthop Relat Res ; 478(11): 2537-2547, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32297725

RESUMO

BACKGROUND: Clear cell chondrosarcoma is an extremely rare chondrosarcoma subtype; thus, its treatment outcomes and associated factors have not been widely studied. Knowing more about it is potentially important because clear cell chondrosarcomas are often misdiagnosed as other benign lesions and subsequently treated and followed inappropriately. QUESTIONS/PURPOSES: (1) What are the patient- and tumor-related characteristics of clear cell chondrosarcoma? (2) What proportion of patients with clear cell chondrosarcoma initially had a misdiagnosis or a misleading initial biopsy result? (3) What is the survivorship of patients with clear cell chondrosarcoma free from death, local recurrence, and distant metastasis, and what factors are associated with greater survivorship or a reduced risk of local recurrence? METHODS: Between 1985 and 2018, 12 Japanese Musculoskeletal Oncology Group (JMOG) hospitals treated 42 patients with a diagnosis of clear cell chondrosarcoma. All 42 patients had complete medical records at a minimum of 1 year or death, and were included in this multicenter, retrospective, observational study. No patients were lost to follow-up within 5 years of treatment but four were lost to follow-up greater than 5 years after treatment because their physicians thought their follow-up was sufficient. Clinical data were collected by chart review. The median (range) follow-up period was 69 months (2 to 392). In general, when a possibly malignant bone tumor was found on imaging studies, the histological diagnosis was made by biopsy before initiating treatment. Once the diagnosis had been made, the patients were treated by surgery only, complete resection if technically possible, because chondrosarcomas are known to be resistant to chemotherapy and radiotherapy. Unresectable tumors were treated with particle-beam radiation therapy. When patients with chondrosarcoma were referred after unplanned surgical procedures with inadequate surgical margins, immediate additional wide resection was considered before local recurrence developed. This diagnostic and treatment strategy is common to all JMOG hospitals and did not change during the study period. Primary wide resection was performed in 79% (33 of 42) patients, additional wide resection after initial inadequate surgery in 12% (five of 42), curettage and bone grafting in 5% (two of 42) patients, and radiotherapy was administered to 5% (two of 42). Surgical margins among the 40 patients who underwent surgery at JMOG hospitals were no residual tumor in 93% (37 of 42) of patients, microscopic residual tumor in 2% (one of 42), and macroscopic residual tumor or state after curettage or intralesional excision in 5% (two of 42). The oncological endpoints of interest were 5- and 10- year overall survival, disease-free survival, survival free of local recurrence, and survival free of distant metastases; these were calculated using the Kaplan-Meier method and compared using the log-rank test. Risk ratios with their respective 95% confidence intervals (CIs) were estimated in a Cox regression model. The Bonferroni adjustment was used for multiple testing correction. RESULTS: The sex distribution was 74% men and 26% women (31 and 11 of 42, respectively), with a mean age of 47 ± 17 years. Eighty one percent (34 of 42) of tumors occurred at the ends of long bones, and the proximal femur was the most common site accounting for 60% (25 of 42). The mean size of the primary tumors was 6.3 ± 2.7 cm. Definite pathologic fractures were present in 26% (10 of 42) and another 26% (10 of 42) had extraskeletal involvement. None had metastases at presentation. Twenty four percent (six of 25) tumors in the proximal femur were misdiagnosed as benign lesions and treated inadequately without biopsy. Twenty nine percent (10 of 35) patients had initial misdiagnoses by biopsy and core needle biopsies had a greater risk of resulting in inaccurate histological diagnoses. The study patients' 5- and 10-year overall survival rates were 89% (95% CI 74 to 96) and 89% (95% CI 74 to 96), respectively; 5- and 10- year disease-free survival rates 77% (95% CI 58 to 89) and 57% (95% CI 36 to 75), respectively; 5- and 10-year local recurrence-free survival rates 86% (95% CI 68 to 95) and 71% (95% CI 49 to 86), respectively; and 5- and 10-year distant metastasis-free survival rates 84% (95% CI 67 to 93) and 74% (95% CI 53 to 88), respectively. Notably, bone metastases (17%, seven of 42) were as common as pulmonary metastases (14%, six of 42); four patients developed both bone and pulmonary metastases. The difference between 10-year overall survival rates and 10-year disease-free survival indicated very late recurrence more than 5 years after the initial treatment. After controlling for multiple comparisons, the only factor we found that was associated with local recurrence-free survival was initial treatment (positive margin versus primary wide resection) (risk ratio 8.83 [95% CI 1.47 to 53.1]; p = 0.022 after the Bonferroni adjustment). Additional wide resection reduced the risk of local recurrence. CONCLUSIONS: The femoral head was the most common location of clear cell chondrosarcoma and had a high risk of misdiagnosis as common benign lesions that resulted in initial inadequate surgery and a consequent high risk of local recurrence. Immediate additional wide resection should be considered in patients who had initial inadequate surgery to reduce the risk of local recurrence. Because clear cell chondrosarcoma can recur locally or distantly in the bones and lungs in the long term, patients should be informed of the risk of very late recurrence and the necessity of decades-long with surveillance for local recurrence and lung and bone metastases. LEVEL OF EVIDENCE: Level IV, therapeutic study.


Assuntos
Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Condrossarcoma de Células Claras/mortalidade , Condrossarcoma de Células Claras/terapia , Adulto , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Diagnóstico Ausente , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
6.
Asian J Endosc Surg ; 13(1): 114-116, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30891893

RESUMO

Lipomas are often lightweight and small in size with few subjective symptoms. Giant lipomas are uncommon. We herein report a case involving a giant, deep-seated dumbbell-shaped intermuscular lipoma in the right thigh that extended into the pelvic region through the obturator foramen and caused obturator neuropathy. A 64-year-old man with numbness while walking was diagnosed with a 17 × 16-cm lipomatous tumor. He underwent radical surgery performed by a multidisciplinary team consisting of orthopedic and colorectal surgeons. High-definition magnified laparoscopic images of the deep pelvis confirmed that tumor had infiltrated the obturator nerve. The tumor was completely resected with the obturator nerve. Six months after surgical resection, the patient had no gait disturbance or evidence of recurrence. The laparoscopic approach for this kind of complicated deep pelvic surgery was safe and feasible when performed by colorectal surgeon with ample knowledge of the pelvic anatomy.


Assuntos
Lipoma/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Humanos , Laparoscopia , Lipoma/complicações , Lipoma/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Nervo Obturador/cirurgia , Doenças do Sistema Nervoso Periférico/etiologia , Neoplasias de Tecidos Moles/complicações , Neoplasias de Tecidos Moles/diagnóstico por imagem , Coxa da Perna , Tomografia Computadorizada por Raios X
7.
Int J Oncol ; 55(1): 167-178, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180533

RESUMO

Vascular endothelial growth inhibitor (VEGI; also referred to as TNFSF15 or TL1A) is involved in the modulation of vascular homeostasis. VEGI is known to operate via two receptors: Death receptor­3 (DR3) and decoy receptor­3 (DcR3). DR3, which is thus far the only known functional receptor for VEGI, contains a death domain and induces cell apoptosis. DcR3 is secreted as a soluble protein and antagonizes VEGI/DR3 interaction. Overexpression of DcR3 and downregulation of VEGI have been detected in a number of cancers. The aim of the present study was to investigate the effects of sodium valproate (VPA), a histone deacetylase inhibitor, in combination with hydralazine hydrochloride (Hy), a DNA methylation inhibitor, on the expression of VEGI and its related receptors in human osteosarcoma (OS) cell lines and human microvascular endothelial (HMVE) cells. Combination treatment with Hy and VPA synergistically induced the expression of VEGI and DR3 in both OS and HMVE cells, without inducing DcR3 secretion. In addition, it was observed that the combination of VPA and Hy significantly enhanced the inhibitory effect on vascular tube formation by VEGI/DR3 autocrine and paracrine pathways. Furthermore, the VEGI/VEGF­A immune complex was pulled down by immunoprecipitation. Taken together, these findings suggest that DNA methyltransferase and histone deacetylase inhibitors not only have the potential to induce the re­expression of tumor suppressor genes in cancer cells, but also exert anti­angiogenic effects, via enhancement of the VEGI/DR3 pathway and VEGI/VEGF­A interference.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Hidralazina/farmacologia , Osteossarcoma/tratamento farmacológico , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/biossíntese , Ácido Valproico/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Neoplasias Ósseas/irrigação sanguínea , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Sinergismo Farmacológico , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Inibidores Enzimáticos/farmacologia , Epigênese Genética , Humanos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Osteossarcoma/irrigação sanguínea , Osteossarcoma/genética , Osteossarcoma/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Membro 25 de Receptores de Fatores de Necrose Tumoral/biossíntese , Membro 25 de Receptores de Fatores de Necrose Tumoral/genética , Transcrição Genética/efeitos dos fármacos , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética
8.
Int J Clin Exp Pathol ; 12(3): 1029-1034, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31933915

RESUMO

Nodular fasciitis (NF) is a self-limited tumorous lesion occurring in the upper as well as lower extremities. NF is composed of a proliferation of "primary culture"-like myofibroblastic cells with nuclear atypia and large nucleoli, thus mimicking sarcoma. NF harbors a promoter-swapping fusion gene containing the entire coding region of USP6 gene. Therefore, NF is a tumor with a fusion oncogene but self-limited. In order to explore why NF is self-limited, we examined whether myofibroblastic cells in NF express p16 protein, a gene product of CDKN2A gene and an inhibitor of cyclin-dependent kinase 4 (CDK4) as well as one of the hallmarks of cellular senescence. We immunohistochemically demonstrated strong and diffuse expression of p16 in myofibroblastic cells in 11 out of 15 cases of NF, and strong but partial expression in the remaining 4 of the cases. We also showed that 15 out of 15 cases of NF were immunohistochemically negative or only showed focal and faint immunopositivity for CDK4, murine double minute 2 (MDM2), and TP53 proteins. Furthermore, there were no significant changes in the copy number of CDKN2A, CDK4 and MDM2 genes, and no significant mutations in TP53, RB1, and CDKN2A genes in 1 case of NF selected. These data suggest a possible involvement in cell cycle arrest and presumed cellular senescence by p16 in myofibroblastic cells in NF. This may explain the self-limited as well as inflammatory nature of NF as a senescence-associated secretory phenotype.

9.
Pathol Res Pract ; 214(9): 1504-1509, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29970305

RESUMO

We experienced a case of primary malignancy in giant cell tumor of bone (GCTB), arising in the right femur and harboring H3F3A mutation. A 27-year-old Japanese male without any prior disease history complained of pain in his right hip joint and right lower limb. Radiological images revealed an osteolytic and multicystic lesion existing mainly at the proximal epiphysis of the right femur. Preoperative clinical diagnosis was GCTB, although irregular marginal sclerosis was an atypical radiographic finding for conventional GCTBs. Biopsy sample from the lesion revealed the coexistence of typical GCTB and undifferentiated high-grade round cell sarcoma. Despite of the wide local resection of the tumor with preoperative and postoperative chemotherapy, the patient died of multiple distant metastases of the tumor 9 months after the surgery. Since heterozygous H3F3A c. 103G>T (p. Gly34Trp) mutation was detected not only in the biopsy sample from the primary site with typical GCTB and high-grade sarcoma components but also in the resected material from the metastatic site with only pure high-grade sarcoma component, the tumor was considered originally derived from conventional GCTB and acquire malignant transformation to high-grade sarcoma. Thus, this is an extremely rare case of primary malignancy in GCTB and the first case report of primary malignancy in GCTB proved the presence of H3F3A mutation even in the sarcoma component.


Assuntos
Neoplasias Ósseas/patologia , Tumor de Células Gigantes do Osso/patologia , Histonas/genética , Neoplasias Primárias Múltiplas/patologia , Sarcoma/patologia , Adulto , Neoplasias Ósseas/genética , Transformação Celular Neoplásica/genética , Evolução Fatal , Fêmur/patologia , Tumor de Células Gigantes do Osso/genética , Humanos , Masculino , Mutação , Neoplasias Primárias Múltiplas/genética , Sarcoma/genética
10.
Anticancer Res ; 38(5): 2995-3000, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29715130

RESUMO

BACKGROUND: Osteoscopy is a minimally-invasive endoscopic technique for inspecting lesions inside bone marrow cavities. We describe the feasibility of osteoscopic surgery of giant cell tumor of bone (GCTB) in order to preserve the proximal fibula, and thereby achieve immediate recovery and avoid complications. PATIENTS AND METHODS: Five patients with GCTB in the proximal fibula were treated using osteoscopic curettage with adjuvants (argon plasma coagulation and cementation). Functional outcome was evaluated by knee stability, Musculoskeletal Tumor Society (MSTS) rating, and Tegner score. Oncological outcome was evaluated for local recurrence and pulmonary metastasis. RESULTS: Regarding functional outcome, knee instability was negative in all cases. Mean MSTS rating was 100%. Tegner scores were the same as those prior to surgery. Neither local recurrence nor pulmonary metastasis were found. CONCLUSION: Osteoscopic surgery is feasible for immediate and complete recovery, and can improve quality of life for patients with GCTB of the proximal fibula with satisfactory oncological outcome.


Assuntos
Neoplasias Ósseas/cirurgia , Endoscopia/métodos , Tumor de Células Gigantes do Osso/cirurgia , Procedimentos Ortopédicos/métodos , Adolescente , Adulto , Feminino , Fíbula/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Resultado do Tratamento
11.
Cureus ; 10(11): e3655, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30723654

RESUMO

We report here a case of periosteal sarcoma in a 10-year-old female, along with quantitative values obtained with bone single photon emission computed tomography/computed tomography (SPECT/CT), which were useful to evaluate treatment response to preoperative chemotherapy. Pretreatment radiograph images of the lower leg showed cortical thickening eroded by a broad-based soft-tissue mass without the involvement of the underlying cortex, while computed tomography (CT) revealed a small juxtacortical mass with thick calcification and periosteal reaction. In magnetic resonance imaging (MRI), the mass showed hypointensity in the inner part and isointensity in the outer part in T1-weighted images, while the inner part showed hypointensity and the outer part hyperintensity in T2-weighted images. Bone SPECT/CT results indicated the focal and intense uptake of the mass. Following neoadjuvant chemotherapy (NAC), radiograph and MRI results revealed a slight increase in size, with growing calcification. Although visual inspection of the bone SPECT/CT findings showed nearly the same amount of focal uptake, quantitative parameters determined with those findings were decreased, with maximum standardized uptake value (SUV), peak SUV, mean SUV, metabolic bone volume (MBV), and total bone uptake (TBU) reduced by -20.7%, -22.0%, -12.6%, -33.5%, and -41.9%, respectively. The excision biopsy at the surgery showed a pathological grade 1 (non-complete response) after NAC, including a more than 20% of cell necrosis part. The quantitative bone SPECT/CT was considered to reflect treatment response in this case.

12.
Pathol Res Pract ; 213(10): 1315-1321, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28645808

RESUMO

We experienced a 38-year-old Japanese male with t(10;19) CIC-DUX4 -positive undifferentiated small round cell sarcoma in the deep abdominal wall. Three months before his first visit to our hospital, he noticed a mass in his right abdominal wall. Computed tomography on admission revealed a solid abdominal tumor 70×53mm in size and multiple small tumors in both lungs. The biopsy of the abdominal tumor revealed undifferentiated small round cell sarcoma, suggestive of Ewing sarcoma. Under the clinical diagnosis of Ewing-like sarcoma of the abdominal wall with multiple lung metastases, several cycles of ICE (ifosfamide, carboplatin and etoposide) therapy were performed. After the chemotherapy, the lung metastases disappeared, while the primary lesion rapidly grew. Additional VDC (vincristine, doxorubicin and cyclophosphamide) therapy was carried out without apparent effect. Although the surgical removal of the primary lesion was done, peritoneal dissemination and a huge metastatic liver tumor appeared thereafter. The patient died of disease progression two months after the surgery. The total clinical course was approximately one year, showing that the tumor was extremely aggressive. The tumor cells of the surgical specimen were positive for CD99, WT1, calretinin, INI1, ERG and Fli1 by immunohistochemistry. Fusion gene analyses using the frozen surgical material revealed negativity for EWSR1-Fli1, EWSR1-ERG and t(4;19) CIC-DUX4 fusions, but positivity for t(10;19) CIC-DUX4 fusion. Thus, we made a final pathological diagnosis of t(10;19) CIC-DUX4-positive undifferentiated small round cell sarcoma. To our knowledge, this is the 13th case of t(10;19) CIC-DUX4 undifferentiated small round cell sarcoma with precise clinicopathological information. Especially in our case, two types of t(10;19) CIC-DUX4 fusion transcripts were observed, both of which are in-frame and novel.


Assuntos
Neoplasias Abdominais/genética , Biomarcadores Tumorais/genética , Diferenciação Celular , Cromossomos Humanos Par 10 , Cromossomos Humanos Par 19 , Fusão Gênica , Proteínas de Fusão Oncogênica/genética , Sarcoma de Células Pequenas/genética , Neoplasias Abdominais/química , Neoplasias Abdominais/patologia , Neoplasias Abdominais/terapia , Adulto , Biomarcadores Tumorais/análise , Biópsia , Western Blotting , Progressão da Doença , Evolução Fatal , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sarcoma de Células Pequenas/química , Sarcoma de Células Pequenas/secundário , Sarcoma de Células Pequenas/terapia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
13.
Immunobiology ; 222(5): 738-750, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28190533

RESUMO

C5-deficient mice usually present moderate neutrophil activation during the initiation phase of acute inflammation. Conversely, C5a receptor (C5aR)-deficient mice show unusually excessive activation of neutrophils. We identified the ribosomal protein S19 (RP S19) polymer, which is cross-linked at Lys122 and Gln137 by transglutaminases in apoptotic neutrophils, as a second C5aR ligand during the resolution phase of acute inflammation. The RP S19 polymer promotes apoptosis via the neutrophil C5aR and phagocytosis via the macrophage C5aR. To confirm the roles of the RP S19 polymer, we employed a carrageenan-induced acute pleurisy mouse model using C57BL/6J mice with a knock-in of the Gln137Glu mutant RP S19 gene and replaced the RP S19 polymer with either an S-tagged C5a/RP S19 recombinant protein or the RP S19122-145 peptide monomer and dimer (as functional C5aR agonists/antagonists) and the RP S19122-145 peptide trimer (as a functional C5aR antagonist). Neutrophils and macrophages were still present in the thoracic cavities of the knock-in mice at 24h and 7days after carrageenan injection, respectively. Knock-in mice showed structural organization and severe hemorrhaging from the surrounding small vessels of the alveolar walls in the lung parenchyma. In contrast to the RP S19122-145 peptide monomer and trimer, the simultaneous presence of S-tagged C5a/RP S19 and the RP S19122-145 peptide dimer completely improved the physiological and pathological acute inflammatory cues. The RP S19 polymer, especially the dimer, appears to play a role at the resolution phase of carrageenan-induced acute pleurisy in C57BL/6J model mice.


Assuntos
Carragenina/efeitos adversos , Pleurisia/imunologia , Pleurisia/metabolismo , Polímeros , Proteínas Ribossômicas/farmacologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Quimiotaxia de Leucócito/efeitos dos fármacos , Quimiotaxia de Leucócito/imunologia , Complemento C5a/imunologia , Complemento C5a/metabolismo , Modelos Animais de Doenças , Imunoglobulina G/imunologia , Imunoglobulina G/farmacologia , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Transgênicos , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Monócitos/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Fagocitose/efeitos dos fármacos , Fagocitose/imunologia , Pleurisia/induzido quimicamente , Pleurisia/tratamento farmacológico , Polímeros/química , Receptor da Anafilatoxina C5a/agonistas , Receptor da Anafilatoxina C5a/antagonistas & inibidores , Receptor da Anafilatoxina C5a/metabolismo , Proteínas Ribossômicas/química , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/imunologia
14.
Auris Nasus Larynx ; 44(4): 484-488, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27523716

RESUMO

We herein report the case of a patient presenting with myxofibrosarcoma (MFS) who underwent treatment with surgery, proton beam therapy (PBT), and pazopanib. A 64-year-old male was diagnosed with MFS, which ranged from the posterior neck to the shoulder. Surgery was performed as an initial treatment; however, the primary tumor recurred 83 months after the initial treatment. We, therefore, administered PBT. Although most of the recurrent tumor disappeared after PBT, multiple lung metastases were identified 3 months after the completion of PBT. We initiated antiangiogenic treatment with pazopanib. Although long-term survival was achieved with the treatments, the patient suffered from a skin ulcer and soft tissue necrosis and eventually died of general prostration caused by infection, and complicated by pneumonia. Although PBT and pazopanib were effective for treating the local recurrence and lung metastases of MFS, respectively, clinicians must be cognizant of the fact that the combination of high-dose irradiation and angiogenesis inhibitors, even in nonconcurrent cases, can result in a severe skin ulcer and soft tissue necrosis.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Fibrossarcoma/terapia , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias Pulmonares/terapia , Mixoma/terapia , Terapia com Prótons/efeitos adversos , Pirimidinas/efeitos adversos , Úlcera Cutânea/induzido quimicamente , Sulfonamidas/efeitos adversos , Desbridamento , Evolução Fatal , Fibrossarcoma/diagnóstico por imagem , Fibrossarcoma/secundário , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Mixoma/diagnóstico por imagem , Necrose/induzido quimicamente , Úlcera Cutânea/terapia , Infecções dos Tecidos Moles , Tomografia Computadorizada por Raios X
15.
Pathol Int ; 65(9): 468-75, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26126783

RESUMO

The aims of this study were: (i) to elucidate clinicopathological characteristics of pcCHS of long bones (L), limb girdles (LG) and trunk (T) in Japan; (ii) to investigate predictive pathological findings for outcome of pcCHS of L, LG and T, objectively; and (iii) to elucidate a discrepancy of grade between biopsy and resected specimens. Clinicopathological profiles of 174 pcCHS (79 male, 95 female), of L, LG, and T were retrieved. For each case, a numerical score was given to 18 pathological findings. The average age was 50.5 years (15-80 years). Frequently involved sites were femur, humerus, pelvis and rib. The 5-year and 10-year disease-specific survival (DSS) rates [follow-up: 1-258 months (average 65.5)] were 87.0% and 80.4%, respectively. By Cox hazards analysis on pathological findings, age, sex and location, histologically higher grade and older age were unfavorable predictors, and calcification was a favorable predictor in DSS. The histological grade of resected specimen was higher than that of biopsy in 37.7% (26/69 cases). In conclusion, higher histological grade and older age were predictors for poor, but calcification was for good prognosis. Because there was a discrepancy in grade between biopsy and resected specimens, comprehensive evaluation is necessary before definitive operation for pcCHS.


Assuntos
Neoplasias Ósseas/patologia , Condrossarcoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fêmur/patologia , Técnicas Histológicas , Humanos , Úmero/patologia , Japão , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Adulto Jovem
16.
Int J Oncol ; 46(5): 1994-2002, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25778932

RESUMO

The level of vascular endothelial growth inhibitor (VEGI) has been reported to be negatively associated with neovascularization in malignant tumors. The soluble form of VEGI is a potent anti-angiogenic factor due to its effects in inhibiting endothelial cell proliferation. This inhibition is mediated by death receptor 3 (DR3), which contains a death domain in its cytoplasmic tail capable of inducing apoptosis that can be subsequently blocked by decoy receptor 3 (DcR3). We investigated the effects of sodium valproate (VPA) and trichostatin A (TSA), histone deacetylase inhibitors, on the expression of VEGI and its related receptors in human osteosarcoma (OS) cell lines and human microvascular endothelial (HMVE) cells. Consequently, treatment with VPA and TSA increased the VEGI and DR3 expression levels without inducing DcR3 production in the OS cell lines. In contrast, the effect on the HMVE cells was limited, with no evidence of growth inhibition or an increase in the DR3 and DcR3 expression. However, VPA-induced soluble VEGI in the OS cell culture medium markedly inhibited the vascular tube formation of HMVE cells, while VEGI overexpression resulted in enhanced OS cell death. Taken together, the HDAC inhibitor has anti-angiogenesis and antitumor activities that mediate soluble VEGI/DR3-induced apoptosis via both autocrine and paracrine pathways. This study indicates that the HDAC inhibitor may be exploited as a therapeutic strategy modulating the soluble VEGI/DR3 pathway in osteosarcoma patients.


Assuntos
Células Endoteliais/patologia , Inibidores de Histona Desacetilases/uso terapêutico , Osteossarcoma/patologia , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Ácido Valproico/uso terapêutico , Linhagem Celular Tumoral , Células Endoteliais/metabolismo , Ensaio de Imunoadsorção Enzimática , Humanos , Ácidos Hidroxâmicos/uso terapêutico , Osteossarcoma/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Membro 6b de Receptores do Fator de Necrose Tumoral/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/imunologia
17.
Oncol Lett ; 7(6): 1826-1828, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24932240

RESUMO

Periosteal chondrosarcoma is an extremely rare low-grade malignant cartilaginous tumor arising from the external bone surface. Diagnosis of periosteal chondrosarcomas may be challenging, since this condition closely resembles periosteal chondromas. It has been reported that positron emission tomography (PET) is useful in distinguishing benign from malignant cartilaginous tumors using a maximum standardized uptake value (SUVmax) cut-off of 2.0 or 2.3. This report presents the case of a 40-year-old female with an 18-month history of a tender mass in the left distal femur. Radiological findings demonstrated periosteal buttressing. Magnetic resonance imaging (MRI) revealed a chondrogenic tumor of 3 cm in size developing from the external bone surface. It was difficult to differentiate periosteal chondrosarcoma from periosteal chondroma on the basis of size and the radiological and MRI findings. PET/computed tomography (CT) revealed abnormal linear uptake with an SUVmax of 2.7, indicating a malignant tumor. A diagnosis of periosteal chondrosarcoma was made, and wide resection was performed. Tumor histology was consistent with grade II chondrosarcoma. PET/CT is thus useful in differentiating periosteal chondrosarcoma from periosteal chondroma.

18.
Pathol Res Pract ; 209(12): 803-7, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23953591

RESUMO

Clear cell sarcoma is a unique tumor which has EWSR1-ATF1 or EWSR1-CREB1 fusion. Several patterns of EWSR1-ATF1 fusion are observed in clear cell sarcoma. Since type 5-7 fusions were reported recently, they are classified as type 1-7. We examined EWSR1-ATF1 and EWSR1-CREB1 fusions in a single case of clear cell sarcoma with lung metastasis in a 36-year-old Japanese man. As a result, we found only type 1 EWSR1-ATF1 fusion in the primary site, but 4 types of EWS-ATF1 fusion (type 1, 2, 5, 6) were detected in the metastatic site. These 4 types of fusion were completely identical to the recent report, but the case had the same fusion patterns in both primary and metastatic sites. In our case, increased splicing activity in the EWSR1-ATF1 fusion might be acquired at the metastatic site. There is another possibility that metastasis might develop through the increased splicing activity in the fusion.


Assuntos
Neoplasias Pulmonares/secundário , Proteínas de Fusão Oncogênica/metabolismo , Sarcoma de Células Claras/secundário , Neoplasias de Tecidos Moles/patologia , Coxa da Perna/patologia , Adulto , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Proteínas de Fusão Oncogênica/genética , Sarcoma de Células Claras/genética , Sarcoma de Células Claras/metabolismo , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/metabolismo
19.
Int J Oncol ; 41(6): 2005-12, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22992985

RESUMO

Tumor cells express NKG2D ligands on their cell surface, which are the ligands of the activating receptor, NKG2D, that is expressed on the surface of NK cells. The binding of NK cells to tumor cells through the interaction of NKG2D and its ligands induces the cytolysis of the tumor cells. In the present study, we investigated the effects of hypoxia on the expression of NKG2D ligands on the surface of human osteosarcoma cells using three cell lines. To produce hypoxic and normoxic conditions, the osteosarcoma cell lines were cultured under 1 and 20% O2 conditions, respectively. The osteosarcoma cells expressed NKG2D ligands such as MHC class I-related chain molecules A and B (MICA and MICB) and the UL16-binding proteins 1, 2 and 3 (ULBP 1, 2 and 3). MICA was the most frequently expressed NKG2D ligand in the osteosarcoma cells. Hypoxia decreased the expression of cell surface MICA only without increasing the secretion of soluble MICA, which is produced by proteolytic cleavage of cell surface MICA. Hypoxia consistently decreased the susceptibility of the osteosarcoma cells to the cytotoxicity of the NK cells. Hypoxia induced the expression of hypoxia-inducible factor-1α (HIF-1α), and knockdown of the expression of HIF-1α using small interfering RNA increased the expression of cell surface MICA and concomitantly increased the level of soluble MICA. Hypoxia decreased the production of nitric oxide (NO) metabolites (nitrite and nitrate), thus, indicating a decreasing effect on NO production. However, a NO donor, NOC18, decreased the expression of cell surface MICA without any apparent effects on the expression of HIF-1α under both hypoxic and normoxic conditions. The present results indicate that hypoxia downregulates the expression of cell surface MICA without increasing the level of soluble MICA in a HIF-1α-dependent manner and suggest that the effects of hypoxia are not linked to the hypoxia-induced reduction of NO production.


Assuntos
Regulação Neoplásica da Expressão Gênica , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Osteossarcoma/genética , Osteossarcoma/metabolismo , Hipóxia Celular , Linhagem Celular Tumoral , Proliferação de Células , Citotoxicidade Imunológica/imunologia , Regulação para Baixo/genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Células Matadoras Naturais/imunologia , Ligantes , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Óxido Nítrico , Osteossarcoma/imunologia
20.
Oncol Rep ; 28(5): 1585-90, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22923031

RESUMO

Valproic acid, a histone deacetylase inhibitor, increases the expression of cell surface MHC class I-related chain molecules (MICs) A and B (MICA and B) in osteosarcoma cells and decreases their secretion of soluble MICA and MICB, which are produced by the proteolytic cleavage of cell surface MICs. Osteosarcoma cells have been reported to produce high levels of matrix metalloproteinase (MMP)-2 and -9. In this study, we investigated the involvement of MMP-2 and -9 in the inhibitory action of valproic acid (VPA) on the proteolytic cleavage of cell surface MICs using the U-2 OS and SaOS-2 osteosarcoma cell lines. VPA caused a marked decrease in the expression of MMP-9 mRNA in the U-2 OS and SaOS-2 cells and in the expression of MMP-2 mRNA in the U-2 OS cells, but only a slight decrease in the expression of MMP-2 mRNA in the SaOS-2 cells. The transfection of small interfering RNA (siRNA) for MMP-9 decreased the secretion of soluble MICA and MICB by both U-2 OS and SaOS-2 cells, but that of siRNA for MMP-2 did not. The present study therefore demonstrates that the downregulation of MMP-9 mRNA by VPA plays a role in the inhibitory action of VPA on the secretion of soluble MICA and MICB in osteosarcoma cells.


Assuntos
Antígenos de Histocompatibilidade Classe I/biossíntese , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Osteossarcoma/genética , Ácido Valproico/farmacologia , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Dipeptídeos/farmacologia , Regulação para Baixo , Humanos , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Proteínas de Membrana/biossíntese , Osteossarcoma/metabolismo , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno
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