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1.
Ann Diagn Pathol ; 59: 151936, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35427924

RESUMO

INTRODUCTION: Fine needle aspiration cytology (FNAC) and core needle biopsy (CNB) can provide tissue samples for the diagnoses of bone and soft tissue tumors. We evaluated the diagnostic accuracy of FNAC and CNB, the usefulness of the image-guided needle procedures, and assessed whether a discordance can influence the prognosis. PATIENTS AND METHODS: We retrospectively examined the accuracy rates of FNAC and CNB procedures by analyzing results of 405 specimens of 389 patients. We evaluated the diagnostic accuracy of FNAC and CNB, compared the clinical effectiveness between the image-guided procedures and the blind procedures, and also compared survival rates between the true positive and the false negative cases for patients with high-grade malignant tumors. RESULTS: The accuracy rates of FNAC were 86.6% and 93.8% for CNB. In cases with non-palpable masses, there were significantly low sampling error rates in the image-guided procedure. There were no significant differences in progression-free-survival and overall survival rates in patients between the false negative and true positive cases. CONCLUSION: Both FNAC and CNB procedures had high accuracy rates. Limited to cases with no palpable masses, the image-guided procedure had a low sampling error rate and was an effective method for obtaining tissue samples.


Assuntos
Neoplasias de Tecidos Moles , Biópsia por Agulha Fina/métodos , Biópsia com Agulha de Grande Calibre , Humanos , Prognóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias de Tecidos Moles/diagnóstico
2.
Cancer Immunol Immunother ; 70(12): 3489-3499, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33893830

RESUMO

The characteristics of the tumor immune microenvironment remains unclear in liposarcomas, and here we aimed to determine the prognostic impact of the tumor immune microenvironment across separate liposarcomas subtypes. A total of 70 liposarcoma patients with three subtypes: myxoid liposarcoma (n = 45), dedifferentiated liposarcoma (n = 17), and pleomorphic liposarcoma (n = 8) were enrolled. The presence of tumor infiltrating lymphocytes (CD4+ , CD8+ , FOXP3+ lymphocytes) and CD163+ macrophages and expression of HLA class I and PD-L1 were assessed by immunohistochemistry in the diagnostic samples; overall survival and progression-free survival were estimated from outcome data. For infiltrating lymphocytes and macrophages, dedifferentiated liposarcoma and pleomorphic liposarcoma patients had a significantly higher number than myxoid liposarcoma patients. While myxoid liposarcoma patients with a high number of macrophages were associated with worse overall and progression-free survival, dedifferentiated liposarcoma patients with high macrophage numbers showed a trend toward favorable prognosis. Expression of HLA class I was negative in 35 of 45 (77.8%) myxoid liposarcoma tumors, whereas all dedifferentiated liposarcoma and pleomorphic liposarcoma tumors expressed HLA class I. The subset of myxoid liposarcoma patients with high HLA class I expression had significantly poor overall and progression-free survival, while dedifferentiated liposarcoma patients with high HLA class I expression tended to have favorable outcomes. Only four of 17 (23.5%) dedifferentiated liposarcomas, two of eight (25%) pleomorphic liposarcomas, and no myxoid liposarcoma tumors expressed PD-L1. Our results demonstrate the unique immune microenvironment of myxoid liposarcomas compared to other subtypes of liposarcomas, suggesting that the approach for immunotherapy in liposarcomas should be based on subtype.


Assuntos
Regulação para Baixo/imunologia , Lipossarcoma Mixoide/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/imunologia , Feminino , Antígenos HLA/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Imuno-Histoquímica/métodos , Lipossarcoma Mixoide/patologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Microambiente Tumoral/imunologia , Adulto Jovem
3.
Tohoku J Exp Med ; 248(2): 87-97, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31189751

RESUMO

Bone and soft tissue tumors are derived from mesenchymal cells, and they are hard to treat. Receptor-activator of nuclear factor-kappa B ligand (RANKL) is an essential cytokine for osteoclast differentiation and activation and is expressed on the surface of osteoblasts or stromal cells. In this study, to explore the potential of denosumab treatment for soft tissue tumors, we analyzed the expression profiles of RANKL mRNA in 425 tumor specimens of 33 histological types by real-time RT-PCR. Denosumab is a monoclonal antibody that prevents the binding of RANKL to receptor-activator of nuclear factor-kappa B (RANK). For comparison, the relative expression levels of RANK and osteoprotegerin (OPG) mRNAs were also measured. OPG functions as a soluble decoy receptor for RANKL. Higher expression levels of RANKL mRNA were detected in calcifying aponeurotic fibroma, fibrosarcoma, calcifying epithelioma, myositis ossificans, heterotopic calcification, giant cell tumor of the tendon sheath (GCTTS), and pigmented villonodular synovitis (PVNS), compared with the levels of other tumor types. Moreover, the expression levels of RANK mRNA were highest in GCTTS, followed by myositis ossificans and PVNS, whereas the expression levels of OPG mRNA were greatly varied among these histological types. We then analyzed RANKL protein expression by immunohistochemistry in 57 tumor specimens with higher expression levels of RANKL mRNA. RANKL-positive cells were detected in GCTTS, PVNS, myositis ossificans, heterotopic calcification, and calcifying aponeurotic fibroma. In conclusion, RANKL is expressed in subsets of soft tissue tumors with calcification, and denosumab is a potential therapeutic option for soft tissue tumors expressing RANKL.


Assuntos
Ligante RANK/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/genética , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia
4.
Cancer Sci ; 109(10): 3043-3054, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30133055

RESUMO

The association between the immune status within the tumor microenvironment and prognosis in synovial sarcoma is not well understood. We aimed to investigate the tumor immune microenvironment and analyze its prognostic impact for patients with synovial sarcoma. A total of 36 primary patients who were treated in our institution were retrospectively evaluated. Infiltration of lymphocytes (CD4+, CD8+, and FOXP3+), CD163+ macrophages, and expression of human leukocyte antigen (HLA) class I and programmed death ligand 1 (PD-L1) were evaluated by immunohistochemistry. Moreover, we investigated PD-L1 and programmed death ligand 2 (PD-L2) mRNA expression in 19 of the 36 cases, using real-time PCR. The Kaplan-Meier method was used to estimate overall survival and progression-free survival. Infiltration of lymphocytes and macrophages varied among the patients. Furthermore, the expression of HLA class I was negative or downregulated in 11 specimens. No PD-L1 expression was observed using immunohistochemistry. Moreover, although PD-L1 mRNA expression was observed in 18 of 19 specimens, the expression level was low. A higher infiltration of CD8+ or FOXP3+ lymphocytes in patients was associated with a favorable overall survival. In addition, a higher infiltration of CD163+ macrophages indicated a significantly worse overall and progression-free survival. Infiltration of CD4+ lymphocytes, HLA class I, PD-L1, and PD-L2 expression were not associated with patient prognosis. This represents the first report investigating the tumor immune microenvironment as a prognostic factor in synovial sarcoma, indicating that CD163+ macrophages are associated with tumor progression. Our results underscore the clinical significance of the tumor immune microenvironment in synovial sarcoma.


Assuntos
Biomarcadores Tumorais/imunologia , Linfócitos do Interstício Tumoral/imunologia , Macrófagos/imunologia , Sarcoma Sinovial/imunologia , Microambiente Tumoral/imunologia , Adolescente , Adulto , Idoso , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Biópsia , Linhagem Celular Tumoral , Criança , Intervalo Livre de Doença , Feminino , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Sarcoma Sinovial/mortalidade , Sarcoma Sinovial/patologia , Sarcoma Sinovial/cirurgia , Adulto Jovem
5.
World J Surg Oncol ; 15(1): 100, 2017 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-28494796

RESUMO

BACKGROUND: A solitary fibrous tumour (SFT) is an unusual neoplasm typically found in soft tissues. Although SFTs can arise in the bones, they very rarely arise in the vertebral arch. Here, we describe a case of a SFT that arose in the vertebral arch of the first lumbar (L1) spinal vertebrae and mimicked osteosarcoma. CASE PRESENTATION: A 49-year-old woman presented with a 2-month history of lower back pain and a lumbar region mass. Magnetic resonance imaging demonstrated a heterogeneously enhanced mass in the L1 vertebral arch. The patient received neoadjuvant chemotherapy, followed by a surgical procedure comprising an anterior spinal fusion and en bloc resection. Histologically, our initial diagnosis was osteosarcoma. The postoperative course was uneventful, and the patient received adjuvant chemotherapy. However, the tumour metastasised to the lung 5 years after the first surgery, and a second surgery was performed for lung tumour resection. The histology of the metastatic lung tumour appeared similar to that of the malignant SFT, and the specimen from the first surgery was re-examined. Immunohistochemically, the tumour was positive for STAT6. Reverse transcription-polymerase chain reaction revealed a NAB2-STAT6 fusion gene, thus confirming our final diagnosis of malignant SFT. The patient died of disease progression 8 years after the first surgery; however, there was no evidence of local recurrence. CONCLUSIONS: Malignant SFT in the vertebral arch is extremely rare and very difficult to distinguish histologically an osteoid from lace-like collagen. STAT6 immunostaining is useful for distinguishing malignant SFTs from other neoplasms. Although it is difficult to completely resect a SFT arising from the spine, we demonstrated the feasibility of an en bloc resection of spinal tumours arising from posterior elements, without local recurrence.


Assuntos
Neoplasias Ósseas/diagnóstico , Vértebras Lombares/patologia , Osteossarcoma/diagnóstico , Tumores Fibrosos Solitários/diagnóstico , Neoplasias Ósseas/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Vértebras Lombares/cirurgia , Pessoa de Meia-Idade , Osteossarcoma/cirurgia , Tumores Fibrosos Solitários/cirurgia
6.
Skeletal Radiol ; 45(12): 1747-1750, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27714415

RESUMO

Intravertebral cleft (IVC) is a common finding in osteoporotic compression fracture. However, since the vertebral collapse attributable to cancer metastasis is rarely associated with IVC, the phenomenon is generally considered as a sign of a benign lesion. In this study, we retrospectively reviewed the radiographs, computed tomography scans, and magnetic resonance images of 111 patients with spinal metastasis. Three cases (2.7 %) had IVC in the collapsed thoracic vertebral bodies (T7, T8, and T11) attributable to cancer metastasis. IVC alone is not necessarily an indicator of a benign vertebral collapse.


Assuntos
Fraturas por Compressão/diagnóstico por imagem , Metástase Neoplásica , Fraturas da Coluna Vertebral/diagnóstico por imagem , Idoso , Feminino , Fraturas por Compressão/etiologia , Fraturas Espontâneas/diagnóstico por imagem , Fraturas Espontâneas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas da Coluna Vertebral/etiologia
8.
BMC Cancer ; 14: 468, 2014 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-24965044

RESUMO

BACKGROUND: Diagnosing adipocytic tumors can be challenging because it is often difficult to morphologically distinguish between benign, intermediate and malignant adipocytic tumors, and other sarcomas that are histologically similar. Recently, a number of tumor-specific chromosome translocations and associated fusion genes have been identified in adipocytic tumors and atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDL), which have a supernumerary ring and/or giant chromosome marker with amplified sequences of the MDM2 and CDK4 genes. The purpose of this study was to investigate whether quantitative real-time polymerase chain reaction (PCR) could be used to amplify MDM2 and CDK4 from total RNA samples obtained from core-needle biopsy sections for the diagnosis of ALT/WDL. METHODS: A series of lipoma (n = 124) and ALT/WDL (n = 44) cases were analyzed for cytogenetic analysis and lipoma fusion genes, as well as for MDM2 and CDK4 expression by real-time PCR. Moreover, the expression of MDM2 and CDK4 in whole tissue sections was compared with that in core-needle biopsy sections of the same tumor in order to determine whether real-time PCR could be used to distinguish ALT/WDL from lipoma at the preoperative stage. RESULTS: In whole tissue sections, the medians for MDM2 and CDK4 expression in ALT/WDL were higher than those in the lipomas (P < 0.05). Moreover, karyotype subdivisions with rings and/or giant chromosomes had higher MDM2 and CDK4 expression levels compared to karyotypes with 12q13-15 rearrangements, other abnormal karyotypes, and normal karyotypes (P < 0.05). On the other hand, MDM2 and CDK4 expression levels in core-needle biopsy sections were similar to those in whole-tissue sections (MDM2: P = 0.6, CDK4: P = 0.8, Wilcoxon signed-rank test). CONCLUSION: Quantitative real-time PCR of total RNA can be used to evaluate the MDM2 and CDK4 expression levels in core-needle biopsies and may be useful for distinguishing ALT/WDL from adipocytic tumors. Thus, total RNA from core-needle biopsy sections may have potential as a routine diagnostic tool for other tumors where gene overexpression is a feature of the tumor.


Assuntos
Quinase 4 Dependente de Ciclina/genética , Neoplasias Lipomatosas/genética , Neoplasias Lipomatosas/patologia , Proteínas Proto-Oncogênicas c-mdm2/genética , Reação em Cadeia da Polimerase em Tempo Real , Adulto , Idoso , Biomarcadores Tumorais/genética , Biópsia com Agulha de Grande Calibre , Quinase 4 Dependente de Ciclina/metabolismo , Análise Citogenética , Feminino , Proteína HMGA2/genética , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Lipomatosas/diagnóstico , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Adulto Jovem
9.
Clin J Gastroenterol ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38853185

RESUMO

Rectal implantation cysts can occur at anastomotic sites after low anterior resection (LAR) for rectal cancer. Herein, we report a case of primary adenocarcinoma arising from a rectal implantation cyst after LAR for rectal cancer. A 70-year-old woman was referred to our hospital for diagnosis and treatment of a growing cystic lesion. She had LAR performed for rectal cancer 29 years previously and had a rectal implantation cyst detected 13 years previously. On the first visit to our hospital, serum CEA and CA19-9 levels were elevated, and computed tomography (CT) scans revealed a cystic lesion near the anastomosis. CT-guided biopsy revealed no cancer tissue in the cystic lesion. After that, the cystic lesion naturally shrank, and serum CEA and CA19-9 levels became normal. Follow-up included 3 monthly serum CEA and CA19-9 testing and 6 monthly CT scans. Two years later, serum CEA and CA19-9 levels were elevated again. Colonoscopy revealed an ulcerative lesion at the anastomotic site, in which adenocarcinoma was confirmed. Abdominoperineal resection with sacral resection was performed, and postoperative histopathological examination revealed a primary adenocarcinoma with mucinous component at the implantation cyst. Since rectal implantation cysts can become malignant after extended periods, clinicians need to be aware of this disease.

10.
J Dermatol ; 51(2): 294-300, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37804063

RESUMO

Deep dermatophytosis is an invasive and sometimes life-threatening fungal infection mainly reported in immunocompromised patients. However, a caspase recruitment domain-containing protein 9 (CARD9) deficiency has recently been reported to cause deep dermatophytosis. Herein, we report the first Japanese case of deep dermatophytosis associated with CARD9 deficiency. An 80-year-old Japanese man with tinea corporis presented with subcutaneous nodules on his left sole. Histopathological findings revealed marked epithelioid cell granulomas with filamentous fungal structures in the deep dermis and subcutis, and the patient was diagnosed with deep dermatophytosis. Despite antifungal therapy, the subcutaneous nodule on his left sole gradually enlarged, his left calcaneal bone was invaded, and the patient finally underwent amputation of his left leg. Genetic analysis revealed a homozygous CARD9 c.586 A > G (p. Lys196Glu) variant, suggesting a CARD9 deficiency. Here, we discuss the clinical features of CARD9 deficiency-associated deep dermatophytosis with a case report and review of the literature.


Assuntos
Arthrodermataceae , Candidíase Mucocutânea Crônica , Tinha , Masculino , Humanos , Idoso , Idoso de 80 Anos ou mais , Candidíase Mucocutânea Crônica/genética , Candidíase Mucocutânea Crônica/patologia , Candidíase Mucocutânea Crônica/terapia , Tinha/microbiologia , Trichophyton/genética , Proteínas Adaptadoras de Sinalização CARD
11.
Cancer Sci ; 104(9): 1178-88, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23718223

RESUMO

This study investigated the pathway underlying the antitumor activity of telomelysin, a telomerase-dependent, replication-selective oncolytic adenovirus, in soft tissue sarcoma cells. Treatment with telomelysin alone resulted in simultaneous induction of apoptosis and autophagy, whereas cotreatment with telomelysin and 3-methyladenine significantly reduced cell viability and increased apoptosis and the cellular ATP level compared to treatment with telomelysin alone, indicating that telomelysin-mediated autophagy is a death-protective but not death-promoting process. Cotreatment with Z-Val-Ala-Asp-CH2F significantly increased cellular ATP depletion compared to telomelysin-alone treatment while inhibiting telomelysin-induced apoptosis and having no significant effect on cell viability, indicating that it promotes transition from apoptotic to necrotic cell death.


Assuntos
Adenoviridae/metabolismo , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/fisiologia , Sarcoma/terapia , Sarcoma/virologia , Adenina/análogos & derivados , Adenina/farmacologia , Trifosfato de Adenosina/metabolismo , Infecções por Adenoviridae/metabolismo , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células HEK293 , Células HeLa , Humanos , Sarcoma/tratamento farmacológico , Sarcoma/metabolismo , Telomerase/metabolismo
12.
Transl Oncol ; 25: 101521, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35998437

RESUMO

BACKGROUND: T-cell receptor-engineered T-cell therapies have achieved promising response rates against synovial sarcoma in clinical trials, but their applicability is limited owing to the HLA matching requirement. Chimeric antigen receptor (CAR) can redirect primary T cells to tumor-associated antigens without requiring HLA matching. However, various obstacles, including the paucity of targetable antigens, must be addressed for synovial sarcoma. Ligands for natural killer (NK) cell-activating receptors are highly expressed by tumor cells. METHODS: The surface expression of ligands for NK cell-activating receptors in synovial sarcoma cell lines was analyzed. We analyzed RNA sequencing data deposited in a public database to evaluate NKp44-ligand expression. Primary T cells retrovirally transduced with CAR targeting NKp44 ligands were evaluated for their functions in synovial sarcoma cells. Alterations induced by various stimuli, including a histone deacetylase inhibitor, a hypomethylating agent, inflammatory cytokines, and ionizing radiation, in the expression levels of NKp44 ligands were investigated. RESULTS: Ligands for NKp44 and NKp30 were expressed in all cell lines. NKG2D ligands were barely expressed in a single cell line. None of the cell lines expressed NKp46 ligand. Primary synovial sarcoma cells expressed the mRNA of the truncated isoform of MLL5, a known cellular ligand for NKp44. NKp44-based CAR T cells specifically recognize synovial sarcoma cells, secrete interferon-γ, and exert suppressive effects on tumor cell growth. No stimulus altered the expression of NKp44 ligands. CONCLUSION: NKp44-based CAR T cells can redirect primary human T cells to synovial sarcoma cells. CAR-based cell therapies may be an option for treating synovial sarcomas.

13.
Dev Growth Differ ; 53(1): 37-47, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21261609

RESUMO

This study investigated the development of Ca²(+) signaling mechanisms and their role in initiating morphogenetic cell movement in the presumptive ectoderm of Japanese newt (Cynops pyrrhogaster) during gastrulation. Histochemical staining using fluorescently labeled ryanodine and dihydropyridine probes revealed that dihydropyridine receptor (L-type Ca²(+) channels) appeared in stage 12b embryos, while ryanodine receptors were expressed in both stage 11 and 12b embryos. Transmission electron microscopy of stage 12b embryos showed abundant peripheral couplings, which are couplings of the endoplasmic reticulum and cell membrane with an approximate 12 nm gap. Caffeine increased the intracellular free Ca²(+) concentration ([Ca²(+)](i)) in presumptive ectodermal cells isolated from both stage 11 and 12b embryos, while (±)-Bay K 8644 ((±)-BayK) increased [Ca²(+)](i) in cells isolated from stage 12b embryos, but not in cells isolated from stage 11 embryos. Dantrolene and nifedipine completely inhibited increases in [Ca²(+)](i) after treatment with caffeine and (±)-BayK, respectively. Caffeine activated the motility of cells isolated from both stage 11 and 12b embryos, but (±)-BayK only activated the motility of cells isolated from stage 12b embryos. These findings suggested that formation of the Ca²(+) -induced Ca²(+) release system in presumptive ectodermal cells during gastrulation plays an important role in the initiation and execution of epibolic extension.


Assuntos
Sinalização do Cálcio/fisiologia , Movimento Celular/fisiologia , Gastrulação/fisiologia , Salamandridae/embriologia , Salamandridae/metabolismo , Animais , Canais de Cálcio Tipo L/metabolismo , Ectoderma/embriologia , Ectoderma/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo
14.
Pathol Int ; 61(8): 461-8, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21790860

RESUMO

We established a dedifferentiated liposarcoma cell line (NDDLS-1) that produces interleukin-6 (IL-6) and granulocyte-colony stimulating factor (G-CSF). The parental tumor showed high leukemoid reactions. The NDDLS-1 cell line was established from a pleural effusion associated with a lung metastasis. Pleomorphic tumor cells arranged in a haphazard growth pattern were seen in xenograft tumors. Numerous inflammatory cells including neutrophils or eosinophils were present throughout the tumor cells. This finding resembled the dedifferentiated area of the parental tumor. The mice bearing NDDLS-1 showed marked leukocytosis. In addition, the NDDLS-1 cells expressed IL-6 and G-CSF at both the mRNA and protein levels, while the NDDLS-1 cells produced near normal levels of tumor necrosis factor alpha (TNF-α). In the cytogenetic analysis, both the parental tumor and the NDDLS-1 cells showed a ring or giant marker chromosomes. The NDDLS-1 cell line demonstrated the amplification and expression of both MDM2 and CDK4 by fluorescence in situ hybridization and immunohistochemical analysis. The NDDLS-1 cell line is consistent with the parental dedifferentiated liposarcoma, and it should therefore be useful for further investigations of human dedifferentiated liposarcomas.


Assuntos
Técnicas de Cultura de Células , Linhagem Celular Tumoral/patologia , Lipossarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral/metabolismo , Linhagem Celular Tumoral/transplante , Aberrações Cromossômicas , Quinase 4 Dependente de Ciclina/genética , Quinase 4 Dependente de Ciclina/metabolismo , Fator Estimulador de Colônias de Granulócitos/metabolismo , Humanos , Hibridização in Situ Fluorescente , Interleucina-6/metabolismo , Leucocitose/patologia , Lipossarcoma/genética , Lipossarcoma/metabolismo , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Camundongos SCID , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , RNA Neoplásico/análise , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/metabolismo , Cariotipagem Espectral , Transplante Heterólogo
15.
Transl Oncol ; 14(12): 101227, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34555727

RESUMO

BACKGROUND: Synovial sarcoma is a rare malignant soft-tissue tumor that is prevalent in adolescents and young adults, and poor prognosis has been reported in patients with metastatic lesions. Chimeric antigen receptor (CAR) T-cell therapy is an emerging novel therapy for solid tumors; however, its application in synovial sarcoma has not yet been explored. METHODS: A novel human epidermal growth factor receptor 2 (HER2)-targeted CAR containing scFv-FRP5, CD8α hinge and transmembrane domains as well as 4-1BB costimulatory and CD3ζ signaling domains was developed. Three synovial sarcoma cell lines that expressed the fusion transcript SS18-SSX1/2/4 were used in the study. Cytokine secretion assay, cytotoxicity assay, and real-time cell analysis experiments were conducted to confirm the function of T cells transduced with the CAR gene. RESULTS: High cell-surface expression of HER2 was observed in all the cell lines. HER2-targeted/4-1BB-costimulated CAR T cells specifically recognized the synovial sarcoma cells, secreted interferon gamma and tumor necrosis factor alpha, and exerted cytotoxic effects in these cells. CONCLUSION: To the best of our knowledge, this is the first study to indicate that HER2-targeted CAR T cells are directly effective against molecularly defined synovial sarcoma cells. Furthermore, our findings might set the basis for developing improved CAR T cell-based therapies for chemo-refractory or relapsed synovial sarcoma.

16.
Dev Growth Differ ; 52(7): 665-75, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20887567

RESUMO

Claudin proteins are the major components of tight junctions connecting adjacent cells, where they regulate a variety of cellular activities. In the present paper we identified two Xenopus claudin5 genes (cldn5a and 5b), which are expressed early in the developing cardiac region. Precocious cldn5 expression was observed in explants of non-heart-forming mesoderm under inhibition of the canonical Wnt pathway. Cardiogenesis was severely perturbed by antisense oligonucleotides against cldn5 or by Cldn5 proteins lacking the cytoplasmic domain. Results of light- and electron-microscopic observations suggested that cldn5a and 5b are required for Xenopus heart tube formation through epithelialization of the precardiac mesoderm.


Assuntos
Coração/embriologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Junções Íntimas/metabolismo , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Xenopus/genética , Xenopus/metabolismo , Animais , Claudina-5 , Regulação da Expressão Gênica no Desenvolvimento/genética , Proteínas de Membrana/química , Xenopus/embriologia , Proteínas de Xenopus/química
17.
Pathol Int ; 60(3): 193-202, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20403045

RESUMO

Podoplanin is known as a lymphatic marker because its expression is detected in lymphatic but not vascular endothelium. Podoplanin is also expressed in several normal tissues including osteocytes or osteoblasts. A systematic examination of the podoplanin expression was conducted in normal skeletal tissues and some bone tumor cell lines, and the diagnostic value determined in primary bone tumors. Podoplanin mRNA was expressed at a high level in bone marrow tissue and cartilage, and was upregulated with differentiation to osteoblasts in bone marrow cells. Strong podoplanin expression was seen in osteocytes, chondrocytes, and osteoblasts on immunohistochemistry. Podoplanin mRNA was expressed at a high level in several osteosarcoma and chondrosarcoma cell lines, whereas podoplanin was expressed at a low level in a Ewing's/primitive neuroectodermal tumor cell line. In the clinical samples, osteosarcomas (22/26) expressed podoplanin at various levels. In small cell osteosarcomas (2/2), podoplanin was expressed strongly, although the tissue samples included few diagnostic osteoids. Chondrosarcomas (10/10) expressed podoplanin strongly, and chondroblastomas (5/5) expressed podoplanin moderately, while podoplanin was absent or expressed at low levels in Ewing's sarcomas (0/5), chordomas (0/6) and giant cell tumors of bone (1/7). Therefore, podoplanin may be a sensitive immunohistochemical marker of osteogenic and chondrogenic bone tumors.


Assuntos
Neoplasias Ósseas/metabolismo , Osso e Ossos/metabolismo , Condrossarcoma/metabolismo , Glicoproteínas de Membrana/metabolismo , Osteossarcoma/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/genética , Osso e Ossos/citologia , Diferenciação Celular , Linhagem Celular Tumoral , Células Cultivadas , Condroblastoma/genética , Condroblastoma/metabolismo , Condrossarcoma/genética , Tumores de Células Gigantes/genética , Tumores de Células Gigantes/metabolismo , Humanos , Imuno-Histoquímica , Glicoproteínas de Membrana/genética , Osteossarcoma/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sarcoma de Ewing/genética , Sarcoma de Ewing/metabolismo , Sarcoma de Células Pequenas/genética , Sarcoma de Células Pequenas/metabolismo
18.
Nagoya J Med Sci ; 82(1): 85-92, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32273636

RESUMO

Stanniocalcin-1 (STC1) is a glycoprotein that was originally identified as a calcium-regulating hormone in bony fish, and that has been shown to also critically mediate cell growth, proliferation and differentiation, etc. in humans. Increased STC1 expression levels have been previously detected in different human cancer samples, such as those isolated from lung, breast, ovary, colon, pancreas, and liver tumors; thus, the present study evaluated STC1 expression in various soft-tissue tumors. STC1 mRNA isolated from 16 cell lines and 186 clinical soft-tissue tumor specimens were analyzed via quantitative real-time PCR, and the calculated expression levels were normalized to those exhibited by STC1-expressing MDA-MB-231 cells. The results of these analyses did not reveal any specific histological tumor types that displayed significantly increased STC1 expression; however, they did not indicate that STC1 expression was significantly higher in malignant compared to benign soft-tissue tumors. Furthermore, in adipocytic tumors, STC1 expression in dedifferentiated liposarcomas was found to be highest and lowest in lipoma tissues, respectively, suggesting that adipocytic tumors may express increasely high levels of STC1 mRNA as they become histologically more advanced. STC1 expression correlates with the malignancy grade in soft-tissue tumors.


Assuntos
Biomarcadores Tumorais/genética , Glicoproteínas/genética , RNA Mensageiro/genética , Neoplasias de Tecidos Moles/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Glicoproteínas/metabolismo , Humanos , Gradação de Tumores , RNA Mensageiro/metabolismo , Neoplasias de Tecidos Moles/metabolismo , Neoplasias de Tecidos Moles/patologia
19.
Knee ; 27(1): 257-262, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31813700

RESUMO

BACKGROUND: Patellar tendon autograft after intraoperative extracorporeal radiotherapy has been used for reconstruction of the extensor mechanism following limb-sparing wide tumor resection around the knee. The purpose of this study was to determine the clinical outcome of this reconstruction technique. METHODS: We retrospectively reviewed six consecutive patients with peripatellar tendon and proximal tibial sarcoma who underwent reconstruction of the knee extensor mechanism. The resection area was planned to be contained with the patellar tendon in order to obtain a wide margin. First, the patella was osteotomized at the midline, and the inferior half of patella, patellar tendon, and tibial tuberosity were excised en bloc. The resected segments were devitalized with intraoperative extracorporeal radiotherapy and reimplanted into the original site. A follow-up evaluation included an assessment of the range of motion, extensor lag, the International Society of Limb Salvage score, and complications. RESULTS: Six patients were followed up for 121-270 months. One patient underwent an additional reconstruction with total knee arthroplasty due to a collapse of the tibial subchondral bone. A supracondylar fracture of the femur occurred in two patients, and a delayed union of the osteosynthesis site of the tibial shaft was observed in one patient. At the latest follow up, extensor lag had a median of five degrees, and International Society of Limb Salvage scores had a median of 83%. No local recurrence or rupture of the patellar tendon was observed. CONCLUSIONS: Reconstruction of the knee extensor mechanism using a patellar tendon treated with intraoperative radiotherapy is a reliable and successful method.


Assuntos
Artroplastia/métodos , Neoplasias Ósseas/cirurgia , Articulação do Joelho/cirurgia , Ligamento Patelar/transplante , Sarcoma/cirurgia , Adolescente , Adulto , Neoplasias Ósseas/radioterapia , Criança , Feminino , Fêmur/cirurgia , Humanos , Salvamento de Membro , Masculino , Amplitude de Movimento Articular , Estudos Retrospectivos , Ruptura/cirurgia , Sarcoma/radioterapia , Tíbia/cirurgia , Transplante Autólogo , Resultado do Tratamento
20.
Anticancer Res ; 29(6): 2219-25, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19528484

RESUMO

BACKGROUND: A giant cell tumor (GCT) of bone is a locally aggressive tumor with a propensity for local recurrence. A characteristic pattern of peripheral bone formation has been described in GCT recurrence in soft tissue, and in some pulmonary metastases from benign GCT. Although the bone formation in GCT in supposedly due to bone morphogenetic proteins (BMPs), the expression pattern of BMPs in GCT has not been well investigated. MATERIALS AND METHODS: The expression of BMPs in GCT tissues, cultured stromal cells from GCT, and osteoclast-like giant cells harvested by laser microdissection (LM), as well as from control osteosarcoma (NOS-1) cells was analyzed using reverse transcriptional-semiquantitative PCR. RESULTS: BMP 2, 3, 4, 5 and 6 were expressed in the GCT tissue. The cultured GCT cells expressed BMP 2, 4, 5 and 6. The osteoclast-like giant cells expressed BMP 2, 3, 5 and 6 and BMP 5 was expressed at the highest level. CONCLUSION: Both stromal cells and osteoclast-like cells in GCT expressed several kinds of BMPs.


Assuntos
Proteínas Morfogenéticas Ósseas/genética , Neoplasias Ósseas/genética , Tumor de Células Gigantes do Osso/genética , Adulto , Proteínas Morfogenéticas Ósseas/metabolismo , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Feminino , Tumor de Células Gigantes do Osso/metabolismo , Tumor de Células Gigantes do Osso/patologia , Humanos , Lasers , Masculino , Microdissecção , Pessoa de Meia-Idade , Osteossarcoma/genética , Osteossarcoma/metabolismo , Osteossarcoma/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Estromais/metabolismo , Células Estromais/patologia , Células Tumorais Cultivadas , Adulto Jovem
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