Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 11 de 11
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Cancers (Basel) ; 12(3)2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32138169

RESUMO

Soft tissue sarcoma (STS) are rare and aggressive tumours. Their classification includes numerous histological subtypes of frequent poor prognosis. Liposarcomas (LPS) are the most frequent type among them, and the aggressiveness and deep localization of dedifferentiated LPS are linked to high levels of recurrence. Current treatments available today lead to five-year overall survival has remained stuck around 60%-70% for the past three decades. Here, we highlight a correlation between Aurora kinasa A (AURKA) and AURKB mRNA overexpression and a low metastasis - free survival. AURKA and AURKB expression analysis at genomic and protein level on a 9-STS cell lines panel highlighted STS heterogeneity, especially in LPS subtype. AURKA and AURKB inhibition by RNAi and drug targeting with AMG 900, a pan Aurora Kinase inhibitor, in four LPS cell lines reduces cell survival and clonogenic proliferation, inducing apoptosis and polyploidy. When combined with doxorubicin, the standard treatment in STS, aurora kinases inhibitor can be considered as an enhancer of standard treatment or as an independent drug. Kinome analysis suggested its effect was linked to the inhibition of the MAP-kinase pathway, with differential drug resistance profiles depending on molecular characteristics of the tumor. Aurora Kinase inhibition by AMG 900 could be a promising therapy in STS.

2.
J Biomed Opt ; 19(1): 16019, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24474505

RESUMO

Whole-body imaging of experimental tumor growth is more feasible within the near-infrared (NIR) optical window because of the highest transparency of mammalian tissues within this wavelength spectrum, mainly due to improved tissue penetration and lower autofluorescence. We took advantage from the recently cloned infrared fluorescent protein (iRFP) together with a human immunodeficiency virus (HIV)-based lentiviral vector to produce virally transduced tumor cells that permanently express this protein. We then noninvasively explored metastatic spread as well as primary tumor growth in deep organs and behind bone barriers. Intrabone tumor growth was investigated through intracranial and intratibial injections of glioblastoma and osteosarcoma cells, respectively, and metastasis was assessed by tail vein injection of melanoma cells. We found that the emitted fluorescence is captured as sharp images regardless of the organ or tissue considered. Furthermore, by overlaying fluorescence spots with the white light, it was possible to afford whole-body images yet never observed before. This approach allowed us to continuously monitor the growth and dissemination of tumor cells with a small number of animals, minimal animal handling, and without the need for any additive. This iRFP-based system provides high-resolution readouts of tumorigenesis that should greatly facilitate preclinical trials with anticancer therapeutic molecules.


Assuntos
Metástase Neoplásica , Neoplasias/patologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Animais , Linhagem Celular Tumoral , Progressão da Doença , Vetores Genéticos , Glioblastoma/patologia , Células HEK293 , Humanos , Processamento de Imagem Assistida por Computador , Lentivirus/genética , Proteínas Luminescentes/química , Masculino , Melanoma/patologia , Camundongos , Camundongos Nus , Transplante de Neoplasias , Óptica e Fotônica , Osteossarcoma/patologia , Imagem Corporal Total , Proteína Vermelha Fluorescente
3.
PLoS One ; 8(5): e64497, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23734203

RESUMO

BACKGROUND: Solitary fibrous tumors (SFTs) are rare spindle-cell tumors. Their cell-of-origin and molecular basis are poorly known. They raise several clinical problems. Differential diagnosis may be difficult, prognosis is poorly apprehended by histoclinical features, and no effective therapy exists for advanced stages. METHODS: We profiled 16 SFT samples using whole-genome DNA microarrays and analyzed their expression profiles with publicly available profiles of 36 additional SFTs and 212 soft tissue sarcomas (STSs). Immunohistochemistry was applied to validate the expression of some discriminating genes. RESULTS: SFTs displayed whole-genome expression profiles more homogeneous and different from STSs, but closer to genetically-simple than genetically-complex STSs. The SFTs/STSs comparison identified a high percentage (∼30%) of genes as differentially expressed, most of them without any DNA copy number alteration. One of the genes most overexpressed in SFTs encoded the ALDH1 stem cell marker. Several upregulated genes and associated ontologies were also related to progenitor/stem cells. SFTs also overexpressed genes encoding therapeutic targets such as kinases (EGFR, ERBB2, FGFR1, JAK2), histone deacetylases, or retinoic acid receptors. Their overexpression was found in all SFTs, regardless the anatomical location. Finally, we identified a 31-gene signature associated with the mitotic count, containing many genes related to cell cycle/mitosis, including AURKA. CONCLUSION: We established a robust repertoire of genes differentially expressed in SFTs. Certain overexpressed genes could provide new diagnostic (ALDH1A1), prognostic (AURKA) and/or therapeutic targets.


Assuntos
Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Tumores Fibrosos Solitários/genética , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Análise por Conglomerados , Feminino , Ontologia Genética , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Tumores Fibrosos Solitários/metabolismo , Análise Serial de Tecidos , Adulto Jovem
4.
Genes Chromosomes Cancer ; 52(2): 156-64, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23073997

RESUMO

Solitary fibrous tumors (SFTs) are rare spindle cell tumors with limited therapeutic options. Their molecular basis is poorly known. No consistent cytogenetic abnormality has been reported. We used high-resolution whole-genome array-based comparative genomic hybridization (Agilent 244K oligonucleotide chips) to profile 47 samples, meningeal in >75% of cases. Few copy number aberrations (CNAs) were observed. Sixty-eight percent of samples did not show any gene CNA after exclusion of probes located in regions with referenced copy number variation (CNV). Only low-level CNAs were observed. The genomic profiles were very homogeneous among samples. No molecular class was revealed by clustering of DNA copy numbers. All cases displayed a "simplex" profile. No recurrent CNA was identified. Imbalances occurring in >20%, such as the gain of 8p11.23-11.22 region, contained known CNVs. The 13q14.11-13q31.1 region (lost in 4% of cases) was the largest altered region and contained the lowest percentage of genes with referenced CNVs. A total of 425 genes without CNV showed copy number transition in at least one sample, but only but only 1 in at least 10% of samples. The genomic profiles of meningeal and extra-meningeal cases did not show any differences.


Assuntos
Hibridização Genômica Comparativa/métodos , Variações do Número de Cópias de DNA , Genoma Humano/genética , Tumores Fibrosos Solitários/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Aberrações Cromossômicas , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 8/genética , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Neoplasias Meníngeas/genética , Pessoa de Meia-Idade , Adulto Jovem
5.
Skeletal Radiol ; 37(12): 1141-5, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18685844

RESUMO

We report on the clinical, imaging-including ultrasound, computed tomography, and magnetic resonance imaging-and histological features of a fibroma of the tendon sheath with mineralized chondroid and osseous metaplasia, presenting as a semimembranosus bursitis. The anatomical characteristics of the semimembranosus bursa are demonstrated by dissection in a cadaveric specimen and correlated with the imaging findings in our patient.


Assuntos
Bursite/etiologia , Fibroma/diagnóstico , Articulação do Joelho , Neoplasias de Tecidos Moles/diagnóstico , Tendões/patologia , Adolescente , Bolsa Sinovial/patologia , Bolsa Sinovial/cirurgia , Bursite/diagnóstico , Calcinose/diagnóstico , Diagnóstico Diferencial , Fibroma/complicações , Fibroma/cirurgia , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Imageamento por Ressonância Magnética , Masculino , Neoplasias de Tecidos Moles/complicações , Neoplasias de Tecidos Moles/cirurgia , Tendões/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Ultrassonografia
6.
Joint Bone Spine ; 75(4): 479-81, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18439866

RESUMO

We report on the clinical, histologic, and radiologic features - including CT and MRI - of extraskeletal chondroma in a rare case of diffuse calcification of the chondroid matrix. T2-weighted MR imaging showed a well-demarcated mass of low signal intensity in the left flexor digitalis profundus, with a slight surrounding intramuscular edema. Histopathological examination revealed a heavily calcified soft-tissue chondroma generating macrophagic foreign body reaction. Knowledge of this unusual pattern of mineralization may help in the radiological diagnosis of extraskeletal chondroma.


Assuntos
Calcinose/diagnóstico , Condroma/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Adulto , Calcinose/diagnóstico por imagem , Condroma/diagnóstico por imagem , Antebraço , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias de Tecidos Moles/diagnóstico por imagem , Tomografia Computadorizada por Raios X
7.
Childs Nerv Syst ; 22(12): 1603-10, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16951965

RESUMO

OBJECT: Thalamic tumors represent only 1 to 5% of brain neoplasms but frequently affect children. However, pediatric series are rare and go back to several years in spite of recent advances in the neuroradiological, pathological, and molecular fields. METHODS: We report a series of 14 pediatric thalamic gliomas with clinical, neuroradiological, and pathological studies including p53 immunostaining in 11 cases and 1p19q status in three cases. RESULTS: Our series included five pilocytic astrocytomas, seven oligodendrogliomas, and two glioblastomas. Pilocytic astrocytomas were characterized by strong contrast enhancement, lack of p53 expression, and excellent prognosis. Oligodendrogliomas frequently demonstrated an aspect of unilateral thalamic enlargement lacking or with slight contrast enhancement. Some of them expressed p53 or demonstrated 1p loss. Anaplastic oligodendrogliomas and glioblastomas displayed a poor outcome, with a mean survival of 8 months after surgery. CONCLUSION: Our series of pediatric thalamic gliomas clearly distinguishes pilocytic astrocytomas from anaplastic oligodendrogliomas regarding neuroimaging, pathology, and prognosis.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Glioma/diagnóstico por imagem , Glioma/patologia , Tálamo/diagnóstico por imagem , Tálamo/patologia , Adolescente , Astrocitoma/diagnóstico por imagem , Astrocitoma/patologia , Astrocitoma/terapia , Neoplasias Encefálicas/terapia , Criança , Pré-Escolar , Feminino , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Glioblastoma/terapia , Glioma/terapia , Humanos , Masculino , Oligodendroglioma/diagnóstico por imagem , Oligodendroglioma/patologia , Oligodendroglioma/terapia , Prognóstico , Radiografia , Taxa de Sobrevida , Resultado do Tratamento
8.
Cancer ; 107(5): 1055-64, 2006 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-16878328

RESUMO

BACKGROUND: Clear cell sarcoma (CCS) is a rare tumor with a very poor prognosis that occurs predominantly in the distal extremities of young adults. Most patients bear the t(12;22) reciprocal translocation, which involves the EWS and ATF1 genes. The diagnosis of CCS usually is easy but may be challenging in unusual sites, and the detection of EWS-ATF1 fusion transcripts is helpful to rule out a metastatic melanoma. METHODS: Forty-four patients with CCS and 14 conventional melanomas were examined for the presence of EWS-ATF1 transcripts by using real-time polymerase chain reaction (PCR) analysis on paraffin embedded tissues, including frozen samples for 9 CCS samples and 9 melanoma samples. Prior to molecular analysis, the diagnosis of CCS was considered certain in 35 patients and as probable in 9 patients on the basis of location, histologic features, and immunohistochemical profile. Treatment modalities and follow-up were available for 41 patients with CCS. RESULTS: EWS-ATF1 fusion transcripts were detected in 38 paraffin embedded CCS tissues (86% of all samples; 93% of interpretable samples), 3 samples (7%) were negative, and 3 samples (7%) were considered uninterpretable. Fusion transcripts were detected in 7 of 9 samples for which the diagnosis of CCS was considered probable. EWS-ATF1 transcripts were not detected in the 14 samples of melanoma. Results from frozen tissues were concordant with those from all corresponding paraffin embedded samples. Twenty-eight of 41 patients (68%) experienced lymph node and/or distant metastasis, and the 5 year-survival rate was 44%. Mitotic index and histologic grade were predictive of survival and distant metastasis. CONCLUSIONS: The results of this study showed that the molecular detection of EWS-ATF1 fusion transcript by real-time PCR on paraffin embedded tissues is a sensitive and specific method for the diagnosis of CCS. It is an efficient tool for the diagnosis of unusual tumors, especially with regard to its distinction from melanoma. The current results also confirmed the poor prognosis for patients with this tumor type. Mitotic index and grade were predictive factors for survival and distant metastasis.


Assuntos
Proteínas de Fusão Oncogênica/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Sarcoma de Células Claras/diagnóstico , Fatores de Transcrição/genética , Adolescente , Adulto , Criança , Sistemas Computacionais , Feminino , França , Humanos , Imuno-Histoquímica , Masculino , Melanoma/diagnóstico , Proteínas de Fusão Oncogênica/análise , Inclusão em Parafina , Prognóstico , Sarcoma de Células Claras/genética , Análise de Sobrevida , Fatores de Transcrição/análise
9.
Neurosurgery ; 53(3): 544-53; discussion 554-5, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12943571

RESUMO

OBJECTIVE: Pilocytic astrocytomas (PA) are Grade I brain tumors characterized by an excellent prognosis. In some cases, however, the patient has a bad outcome. The aim of our study was to search for the clinicopathological factors underlying the prognosis for patients with this disease. METHODS: We reviewed the clinical, neuroradiological, and histopathological features of 80 PAs (33 cerebellar, 18 optochiasmatic, 16 brainstem, 7 spinal cord, 3 thalamic, 2 optic nerve, and 1 hemispheric) in pediatric patients. RESULTS: Pathological examination revealed 58 classic PAs and 20 pilomyxoid astrocytomas, which are a histological variant of PAs. Two cases remained unclassified. The mean overall follow-up period was 58 months, the 5-year progression-free survival rate was 75%, and the 5-year survival rates were 100 and 92% after total and partial removal. Univariate statistical analysis revealed that partial resection, optochiasmatic PA localization, and pilomyxoid variant were associated with a worse prognosis, but the latter two parameters were too closely related to the extent of resection to be independent prognostic factors in multivariate analysis. Among the patients who underwent partial surgical removal, only invasion of the surrounding structures was related to prognosis. CONCLUSION: PAs are benign tumors, but some clinicopathological factors, such as partial resection, optochiasmatic location, invasion of surrounding structures, and the pilomyxoid variant, have a worse prognosis.


Assuntos
Astrocitoma/cirurgia , Neoplasias Encefálicas/cirurgia , Neoplasias do Nervo Óptico/cirurgia , Avaliação de Resultados em Cuidados de Saúde , Neoplasias da Medula Espinal/cirurgia , Adolescente , Fatores Etários , Astrocitoma/diagnóstico , Astrocitoma/mortalidade , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidade , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Neoplasias do Nervo Óptico/diagnóstico , Neoplasias do Nervo Óptico/mortalidade , Prognóstico , Estudos Retrospectivos , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/mortalidade , Taxa de Sobrevida , Tomografia Computadorizada por Raios X
10.
AJNR Am J Neuroradiol ; 24(5): 829-34, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12748079

RESUMO

BACKGROUND AND PURPOSE: Dysembryoplastic neuroepithelial tumors (DNTs) are benign lesions affecting children and are associated with epilepsy. The goal of our study was to better characterize the clinical-radiologic-pathologic spectrum of DNTs (complex and simple forms only) in a series of 14 children. METHODS: Clinical, neuroradiologic, and pathologic features of all cases were retrospectively studied. RESULTS: Eleven cases of complex and three cases of simple DNTs were identified. Mean follow-up was 87 months, and no recurrence was recorded except for one case of simple DNT. We found that some neuroradiologic features may be helpful to support the diagnosis of DNT: presence of "septations," triangular pattern of distribution, and absence of contrast enhancement. CONCLUSION: The evidence of the specific glioneuronal element is found by pathologic examination, but the typical neuroradiologic aspect of DNT suggests this diagnosis preoperatively. Radiologic examination may be helpful for the diagnosis of DNT when pathologic findings are inconclusive.


Assuntos
Neoplasias Encefálicas/diagnóstico , Imageamento por Ressonância Magnética , Neoplasias Neuroepiteliomatosas/diagnóstico , Adolescente , Encéfalo/patologia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Epilepsias Parciais/etiologia , Feminino , Humanos , Masculino , Neoplasias Neuroepiteliomatosas/complicações , Neoplasias Neuroepiteliomatosas/patologia , Neuroglia/patologia , Estudos Retrospectivos
11.
J Neurooncol ; 60(2): 127-34, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12635659

RESUMO

CD44, a family of cell surface glycoproteins involved in cell-cell and cell-extracellular matrix adhesion, is widely expressed in the white matter of the normal brain and in astrocytic gliomas under its standard form (CD44s also called CD44H). On the other hand, several variants have been found in brain metastases and rarely found in gliomas. We have investigated by immunohistochemistry CD44H and CD44v6 expression in 28 oligodendrogliomas. All tumors were CD44v6 negative whereas nearly all tumors were immunolabelled with anti-CD44H antibody. Immunostaining increased in parallel with grade and was particulary strong around vessels and in tumoral subpial nodules. Western blot analysis showed that oligodendrogliomas expressed the same 80-kDa CD44 isoform as normal brain. Since gliomas may arise from a dividing progenitor cell, we also studied CD44H expression during the oligodendrocyte lineage in vitro in parallel with specific markers of the O-2A cells. Precursor cells (PSA-NCAM positive), O-2A progenitor cells, as well as preoligodendrocytes (A2B5 positive cells) and immature oligodendrocytes (O4 positive cells), coexpressed CD44H. Our data showed that CD44H is expressed by cells of the oligodendrocyte lineage in vitro and by oligodendrogliomas in vivo especially in sites of dissemination such as subpial spaces. This suggests that CD44H could play a role in migration of tumor cells in oligodendrocytic tumors.


Assuntos
Neoplasias Encefálicas/metabolismo , Receptores de Hialuronatos/biossíntese , Oligodendroglia/metabolismo , Oligodendroglioma/metabolismo , Animais , Animais Recém-Nascidos , Encéfalo/citologia , Neoplasias Encefálicas/química , Neoplasias Encefálicas/patologia , Linhagem da Célula , Movimento Celular , Células Cultivadas , Humanos , Receptores de Hialuronatos/análise , Imuno-Histoquímica , Oligodendroglia/química , Oligodendroglia/citologia , Oligodendroglioma/química , Oligodendroglioma/patologia , Ratos , Células-Tronco/química , Células-Tronco/citologia , Células-Tronco/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...