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1.
Clin Radiol ; 79(6): 446-452, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38580482

RESUMO

AIM: This study aimed to assess the imaging features of atypical lipomatous tumors (ALTs) and lipoma with fat necrosis. METHODS: This study included patients with histopathologically proven fat necrosis within adipocytic tumors who underwent preoperative imaging. Magnetic resonance imaging (MRI) and/or computer tomography (CT) findings of fat necrosis associated with lipomatous tumors were retrospectively reviewed, emphasizing the "fatty island sign (FIS)." FISs were defined as well-demarcated, focal fat-containing areas surrounded by more thickened septa compared with other intratumoral septa. Imaging findings of FIS were compared between ALT and lipoma. RESULTS: Fat necrosis was histopathologically confirmed in 17 patients (6 ALTs and 11 lipomas). Among them, 18 FISs were observed in 10 lesions (59%). Multiple FISs within a lesion were observed in 4 (40%) patients. The median maximum diameter of the FISs was 37 mm. Hypointense areas within FISs relative to the subcutaneous fat on T1- and T2-weighted images were observed in 8 (80%) and 9 (90%), respectively, whereas hyperintense areas within FISs on fat-suppressed T2-weighted images were observed in 2 (20%). Nonfatty solid components within FISs were observed in 2 (20%). On CT, increased fat attenuation and pure fat attenuation within FISs were observed in 6 (86%) and 1 (14%), respectively. The imaging findings of FIS were not significantly different between ALT and lipoma. CONCLUSION: FISs were observed in 59% of the histologically proven ALT and lipoma patients with fat necrosis. The hypointense areas relative to the subcutaneous fat on T1- and T2-weighted images and increased fat attenuation on CT were usually observed within FISs.


Assuntos
Necrose Gordurosa , Lipoma , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Humanos , Feminino , Masculino , Lipoma/diagnóstico por imagem , Lipoma/patologia , Pessoa de Meia-Idade , Necrose Gordurosa/diagnóstico por imagem , Necrose Gordurosa/patologia , Imageamento por Ressonância Magnética/métodos , Idoso , Adulto , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
2.
Clin Radiol ; 79(4): e554-e559, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38453389

RESUMO

AIM: To compare the radiation dose, image quality, and conspicuity of pancreatic ductal adenocarcinoma (PDAC) in pancreatic protocol dual-energy computed tomography (CT) between two X-ray tubes mounted in the same CT machine. MATERIAL AND METHODS: This retrospective study comprised 80 patients (median age, 73 years; 45 men) who underwent pancreatic protocol dual-energy CT from January 2019 to March 2022 using either old (Group A, n=41) or new (Group B, n=39) X-ray tubes mounted in the same CT machine. The imaging parameters were completely matched between the two groups, and CT data were reconstructed at 70 and 40 keV. The CT dose-index volume (CTDIvol); CT attenuation of the abdominal aorta, pancreas, and PDAC; background noise; and qualitative scores for the image noise, overall image quality, and PDAC conspicuity were compared between the two groups. RESULTS: The CTDIvol was lower in Group B than Group A (7.9 versus 9.2 mGy; p<0.001). The CT attenuation of all anatomical structures at 70 and 40 keV was comparable between the two groups (p=0.06-0.78). The background noise was lower in Group B than Group A (12 versus 14 HU at 70 keV, p=0.046; and 26 versus 30 HU at 40 keV, p<0.001). Qualitative scores for image noise and overall image quality at 70 and 40 keV and PDAC conspicuity at 40 keV were higher in Group B than Group A (p<0.001-0.045). CONCLUSION: The latest X-ray tube could reduce the radiation dose and improve image quality in pancreatic protocol dual-energy CT.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Imagem Radiográfica a Partir de Emissão de Duplo Fóton , Masculino , Humanos , Idoso , Intensificação de Imagem Radiográfica/métodos , Estudos Retrospectivos , Raios X , Tomografia Computadorizada por Raios X/métodos , Neoplasias Pancreáticas/diagnóstico por imagem , Pâncreas/diagnóstico por imagem , Carcinoma Ductal Pancreático/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Doses de Radiação , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos
3.
Clin Oncol (R Coll Radiol) ; 35(10): e601-e610, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37587000

RESUMO

AIMS: To evaluate computed tomography (CT) and 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) findings of invasive non-mucinous adenocarcinoma (INMA) of the lung as a predictor of histological tumour grade according to 2021 World Health Organization (WHO) classification. MATERIALS AND METHODS: This retrospective study included consecutive patients with surgically resected INMA who underwent both preoperative CT and 18F-FDG-PET/CT. A three-tiered tumour grade was performed based on the fifth edition of the WHO classification of lung tumours. CT imaging features and the maximum standardised uptake value (SUVmax) were compared among the three tumour grades. RESULTS: In total, 214 patients with INMA (median age 70 years; interquartile range 65-76 years; 123 men) were histologically categorised: 36 (17%) as grade 1, 102 (48%) as grade 2 and 76 (35%) as grade 3. Pure solid appearance was more frequent in grade 3 (83%) than in grades 1 (0%) and 2 (26%) (P < 0.001). The SUVmax of the entire tumour was higher in grade 3 than in grades 1 and 2 (P < 0.001). Multivariable analysis revealed that pure solid appearance (odds ratio = 94.0; P < 0.001), round/oval shape (odds ratio = 4.01; P = 0.001), spiculation (odds ratio = 2.13; P = 0.04), air bronchogram (odds ratio = 0.40; P = 0.03) and SUVmax (odds ratio = 1.45; P < 0.001) were significant predictors for grade 3 INMAs. CONCLUSION: Pure solid appearance, round/oval shape, spiculation, absence of air bronchogram and high SUVmax were associated with grade 3 INMAs. CT and 18F-FDG-PET/CT were potentially useful non-invasive imaging methods to predict the histological grade of INMAs.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Masculino , Humanos , Idoso , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/cirurgia , Tomografia Computadorizada por Raios X , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Biomarcadores , Organização Mundial da Saúde , Pulmão
4.
Clin Radiol ; 76(9): 710.e15-710.e24, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33879322

RESUMO

AIM: To evaluate the use of deep-learning-based image reconstruction (DLIR) algorithms in dynamic contrast-enhanced computed tomography (CT) of the abdomen, and to compare the image quality and lesion conspicuity among the reconstruction strength levels. MATERIALS AND METHODS: This prospective study included 59 patients with 373 hepatic lesions who underwent dynamic contrast-enhanced CT of the abdomen. All images were reconstructed using four reconstruction algorithms, including 40% adaptive statistical iterative reconstruction-Veo (ASiR-V) and DLIR at low, medium, and high-strength levels (DLIR-L, DLIR-M, and DLIR-H, respectively). The signal-to-noise ratio (SNR) of the abdominal aorta, portal vein, liver, pancreas, and spleen and the lesion-to-liver contrast-to-noise ratio (CNR) were calculated and compared among the four reconstruction algorithms. The diagnostic acceptability was qualitatively assessed and compared among the four reconstruction algorithms and the conspicuity of hepatic lesions was compared between <5 and ≥5 mm lesions. RESULTS: The SNR of each anatomical structure (p<0.0001) and CNR (p<0.0001) were significantly higher in DLIR-H than the other reconstruction algorithms. Diagnostic acceptability was significantly better in DLIR-M than the other reconstruction algorithms (p<0.0001). The conspicuity of hepatic lesions was highest when using 40% ASiR-V and tended to lessen as the reconstruction strength level was getting higher in DLIR, especially in <5 mm lesions; however, all hepatic lesions could be detected. CONCLUSIONS: DLIR improved the SNR, CNR, and image quality compared with 40% ASiR-V, while making it possible to decrease lesion conspicuity using higher reconstruction strength.


Assuntos
Neoplasias Abdominais/diagnóstico por imagem , Meios de Contraste , Aprendizado Profundo , Intensificação de Imagem Radiográfica/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia Abdominal/métodos
5.
Clin Radiol ; 75(4): 320.e17-320.e23, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31879024

RESUMO

AIM: To evaluate the value of virtual monochromatic images (VMIs) at lower energy levels in fast-voltage-switching dual-energy computed tomography (DECT) for assessing pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: The institutional review board approved this prospective study. Written informed consent was obtained from all patients. Seventy-four consecutive patients with PDAC underwent dynamic contrast-enhanced DECT. Two radiologists reviewed eight energy levels (40, 45, 50, 55, 60, 65, 70, and 75 keV) of the pancreatic parenchymal phase VMIs. CT attenuation of the PDAC and pancreatic parenchyma, background noise, signal-to-noise ratio (SNR) of the pancreas, tumour-to-pancreas contrast-to-noise ratio (CNR), major and minor axes of PDAC, and qualitative tumour conspicuity were compared among the VMIs at eight energy levels. RESULTS: CT attenuation of PDAC and pancreatic parenchyma, background noise, SNR, and CNR peaked on VMIs at 40 keV with statistically significant difference (p<0.0001) and gradually decreased with increasing energy levels. The reproducibility in measuring tumour size was better on VMIs at 40 keV (28.8 and 29.2 mm of major axis in readers 1 and 2, respectively) and tended to be overestimated at higher energy levels (29.8 and 30.9 mm of major axis at 75 keV in readers 1 and 2, respectively). Qualitative tumour conspicuity was also significantly superior on VMIs at 40 keV than at all other energy levels (p<0.0001). CONCLUSION: VMIs at 40 keV demonstrated significantly increased SNR of the pancreas, CNR, and tumour conspicuity and high reproducibility in measuring tumour size for assessing PDAC.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Carcinoma Ductal Pancreático/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Razão Sinal-Ruído
6.
Clin Radiol ; 74(12): 976.e19-976.e25, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31551148

RESUMO

AIM: To evaluate how computed tomography (CT) and magnetic resonance imaging (MRI) characteristics can be used to differentiate immunohistochemically confirmed mediastinal Müllerian cysts (MMCs) from bronchogenic cysts (BCs). MATERIALS AND METHODS: Sixteen patients with histopathologically and immunohistochemically confirmed mediastinal cysts (four with MMCs and 12 with BCs) were included in this study. CT and MRI images were reviewed retrospectively and the location, size, CT attenuation, and MRI signal intensity of the two pathologies were compared. RESULTS: On review of CT images, cysts could be located to the anterior mediastinum in four BCs, middle mediastinum in three MMCs and seven BCs, and posterior mediastinum in one MMC and one BC. Contact with a vertebral body was observed in 4/4 MMCs (100%) and 6/12 BCs (50%). The ratios of minimum-to-maximum diameter (0.57±0.09 versus 0.74±0.11, p<0.01), CT attenuation (7.8±6 versus 44.3±12 HU, p<0.01), and cyst-to-spinal cord signal intensity ratios (SIRs) on T1-weighted images (0.56±0.2 versus 1.31±0.4, p<0.01) were significantly lower for MMCs than BCs. No significant differences in maximum diameter, minimum diameter, and SIRs on T2-weighted images were found between MMCs and BCs. CONCLUSION: In characterising mediastinal cysts in a middle-aged female patient, contact with a vertebral body, flattened configuration, hypodensity on CT, and hypointensity compared to spinal cord on T1-weighted images are features that are specific to MMCs.


Assuntos
Cisto Broncogênico/diagnóstico por imagem , Cisto Mediastínico/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Cisto Broncogênico/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Cisto Mediastínico/diagnóstico , Mediastino/diagnóstico por imagem , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Adulto Jovem
7.
Clin Radiol ; 74(6): 490.e1-490.e6, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30914207

RESUMO

AIM: To evaluate the potential value of magnetic resonance imaging (MRI) for predicting postoperative pancreatic fistula (POPF) in patients with pancreatic cancer (PC) and non-pancreatic cancer (non-PC). MATERIAL AND METHODS: This retrospective study was approved by the institutional review board and written informed consent was waived. Forty patients underwent pancreatoduodenectomy due to PC (n=31) and non-PC (n=9). The pancreas-to-muscle signal intensity ratio (SIR) on three-dimensional (3D)- fast field echo (FFE) T1-, in- and opposed-phase T1-, and T2-weighted images, as well as the apparent diffusion coefficient (ADC) value of the pancreas were measured. The frequency of POPF and MRI measurements were compared between patients with PC and non-PC. The MRI measurements were also compared with the grade of pancreatic fibrosis on pathological findings, fat deposition, and interstitial oedema. RESULTS: The frequency of POPF was significantly higher in patients with non-PC than in those with PC (p=0.0067), with an odds ratio of 10.4. The SIR on 3D-FFE T1-weighted images was significantly higher in patients with non-PC (p=0.0001) and those with POPF (p=0.017) than in those with PC and those without POPF, respectively. Multiple regression analysis demonstrated that the SIR on 3D-FFE T1-weighted image was independently associated with the grade of pancreatic fibrosis (p<0.0001). CONCLUSION: The frequency of POPF was significantly higher in patients with non-PC than in those with PC was inversely related to the grade of pancreatic fibrosis. The SIR on 3D-FFE T1-weighted image might be a potential imaging biomarker for predicting POPF.


Assuntos
Imageamento por Ressonância Magnética/métodos , Pancreatopatias/diagnóstico por imagem , Pancreatopatias/patologia , Fístula Pancreática/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Pâncreas/cirurgia , Pancreatopatias/cirurgia , Fístula Pancreática/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Complicações Pós-Operatórias/patologia
8.
Clin Radiol ; 73(10): 907.e9-907.e14, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29895387

RESUMO

AIM: To perform radiology-pathology correlation of the inchworm sign on diffusion-weighted imaging (DWI) in patients with endometrial cancer. MATERIALS AND METHODS: Consecutive patients (345) with histopathologically proven endometrial cancer who underwent preoperative magnetic resonance imaging (MRI), including DWI images, and hysterectomy were included in the present study. The inchworm sign was defined as a hypointense stalk between hyperintense endometrial cancer and hypointense myometrium on DWI images. A genitourinary pathologist reviewed the resected specimen at the site of the inchworm sign. RESULTS: The inchworm sign on DWI images was observed in 32 (9.3%) patients. On T2-weighted images, areas of hypointense stalk on DWI images showed hypointensity in 31 (97%) patients and hyperintensity in one (3%). Among them, the depth of myometrial invasion at histopathology was superficial (<50% myometrial invasion) in 28 (87.5%) patients and deep (≥50% myometrial invasion) in four (12.5%). As a result of histopathological investigation, the hypointense stalk of the inchworm sign was mainly composed of various degrees of stromal proliferation, including smooth muscle cells and metaplastic fibromuscular stroma, with or without intervening endometrial cancer. CONCLUSION: The inchworm sign of endometrial cancer on DWI images usually indicated superficial myometrial invasion and was caused by a stalk composed of stromal proliferation with or without intervening endometrial cancer.


Assuntos
Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Retrospectivos
9.
Oncogene ; 34(9): 1141-9, 2015 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-24662825

RESUMO

Dlg5 has been reported to participate in cancer progression; however, its role in prostate cancer still remains poorly understood. In this study, we demonstrate that Dlg5 is frequently downregulated in prostate cancer. We show here that Dlg5 is involved in the regulation of cell migration and cancer cell invasion. Knockdown of endogenous Dlg5 markedly increased prostate cancer cell migration and invasion. Our studies, for the first time, demonstrate the interaction between Dlg5 and Girdin, an actin-binding Akt substrate. Importantly, we found that levels of Akt-mediated Girdin phosphorylation (p-Girdin-Ser1416) are increased in Dlg5-depleted cells. Small interfering RNA directed against Girdin and wortmannin treatment, which was found to reduce Girdin phosphorylation, impaired the effect of Dlg5 depletion on cell migration. Taken together, our findings demonstrate that Dlg5 interacts with and inhibits the activity of Girdin, thereby suppressing the migration of prostate cancer cells.


Assuntos
Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/metabolismo , Neoplasias da Próstata/patologia , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Androstadienos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Masculino , Proteínas dos Microfilamentos/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Fosforilação/efeitos dos fármacos , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Transdução de Sinais , Proteínas de Transporte Vesicular/genética , Wortmanina
10.
Eye (Lond) ; 24(6): 1024-7, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19893590

RESUMO

PURPOSE: In this study, the effects of maternal smoking along with other clinical risk factors in developing severe retinopathy of prematurity (ROP) were evaluated. DESIGN: A case-control study. METHODS: Records of newborn infants with an estimated postmenstrual age of 32 weeks or less (n=86) were reviewed. ROP grading was evaluated in accordance with the International Classification of Retinopathy of Prematurity. Severe ROP was diagnosed when it progressed to stage 3 with plus disease. The factors were first evaluated using a univariate logistic regression analysis between the groups of severe and non-severe ROP, followed by a multivariate logistic regression analysis using STATA version 10 and R version 2.71. RESULTS: A low birth weight, a long duration of artificial ventilation and oxygen supplementation, presence of chronic lung disease, and absence of maternal smoking were found to be significantly associated with severe ROP in the univariate logistic regression analysis. In the multivariate logistic regression analysis, maternal smoking was revealed as a significant factor independently associated with the incidence of severe ROP. CONCLUSIONS: An inhibitory effect of maternal smoking against developing severe ROP is suggested. The mechanism by which smoking may reduce the incidence of severe ROP needs to be further investigated.


Assuntos
Retinopatia da Prematuridade/prevenção & controle , Fumar , Peso ao Nascer , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Recém-Nascido , Recém-Nascido Prematuro , Modelos Logísticos , Pneumopatias/epidemiologia , Masculino , Oxigenoterapia , Respiração Artificial , Retinopatia da Prematuridade/epidemiologia , Retinopatia da Prematuridade/etiologia , Fatores de Risco , Fumar/efeitos adversos
11.
Clin Neuropathol ; 28(6): 445-52, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19919819

RESUMO

OBJECTIVE: 5-lipoxygenase (5-LO) is a key enzyme in the synthesis of leukotrienes (LTs), that might promote carcinogenesis. We investigated 5-LO expression and examined whether the 5-LO pathway is associated with the proliferation of human brain tumors. METHODS: We immunohistochemically evaluated the profile of 5-LO expression in various types of brain tumors obtained from 42 patients, and examined the proliferative effects of the 5-LO pathway in human glioma cell lines using a proliferation assay. RESULTS: Immunohistochemistry of glioblastomas, astrocytomas, meningiomas, medulloblastomas, craniopharyngiomas, ependymomas, neurinomas, oligodendrogliomas, malignant lymphomas, dysembryoplastic neuroepithelial and metastatic brain tumors revealed 5-LO expression in the cytoplasm and nuclei or nuclear envelopes of tumor cells. The 5-LO inhibitor A861 and the LTA4 hydrolase inhibitor Bestatin dose-dependently suppressed the proliferation of A172 cells, a glioma cell line. CONCLUSIONS: We confirmed the expression of 5-LO in various human brain tumors and demonstrated the partial suppression of tumor growth by inhibitors of the 5-LO-LTA4 hydrolase pathway in human glioma cell lines. The 5-LO-LTA4 pathway might play roles in the proliferation of human glioma cells.


Assuntos
Araquidonato 5-Lipoxigenase/fisiologia , Neoplasias Encefálicas/patologia , Proliferação de Células , Glioma/patologia , Transdução de Sinais/fisiologia , Adolescente , Adulto , Idoso , Astrocitoma/patologia , Astrocitoma/fisiopatologia , Neoplasias Encefálicas/fisiopatologia , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Glioblastoma/patologia , Glioblastoma/fisiopatologia , Glioma/fisiopatologia , Humanos , Leucina/análogos & derivados , Leucina/farmacologia , Leucotrieno A4/antagonistas & inibidores , Leucotrieno A4/fisiologia , Inibidores de Lipoxigenase , Masculino , Meningioma/patologia , Meningioma/fisiopatologia , Pessoa de Meia-Idade , Inibidores de Proteases/farmacologia , Células Tumorais Cultivadas , Adulto Jovem
12.
Oncogene ; 28(36): 3197-208, 2009 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-19561643

RESUMO

The receptor tyrosine kinase Ror2 regulates cell migration by acting as a receptor or co-receptor for Wnt5a. Although Wnt5a has been implicated in the invasiveness of several types of tumors, the role of Ror2 in tumor invasion remains elusive. Here we show that osteosarcoma cell lines SaOS-2 and U2OS show invasive properties in vitro by activating Wnt5a/Ror2 signaling in a cell-autonomous manner. The suppressed expression of either Wnt5a or Ror2 in osteosarcoma cells inhibits cell invasiveness accompanying decreased invadopodia formation. Gene-expression profiling identified matrix metalloproteinase 13 (MMP-13) as one of the genes whose expression is downregulated in SaOS-2 cells following suppression of Ror2 expression. Reduced expression or activity of MMP-13 suppresses invasiveness of SaOS-2 cells. Moreover, expression of MMP-13 and cell invasiveness by Wnt5a/Ror2 signaling can be abrogated by an inhibitor of the Src-family protein tyrosine kinases (SFKs), suggesting the role of the SFKs in MMP-13 expression through Wnt5a/Ror2 signaling. We further show that activation of an SFK is inhibited by the suppressed expression of Ror2. Collectively, these results indicate that Wnt5a/Ror2 signaling involves the activation of a SFK, leading to MMP-13 expression, and that constitutively active Wnt5a/Ror2 signaling confers invasive properties on osteosarcoma cells in a cell-autonomous manner.


Assuntos
Movimento Celular/fisiologia , Proteínas Proto-Oncogênicas/metabolismo , Receptores de Superfície Celular/metabolismo , Transdução de Sinais/fisiologia , Proteínas Wnt/metabolismo , Proteína Tirosina Quinase CSK , Linhagem Celular Tumoral , Movimento Celular/genética , Ativação Enzimática/efeitos dos fármacos , Matriz Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Immunoblotting , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Microscopia de Fluorescência , Invasividade Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos , Osteossarcoma/genética , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas/genética , Pirimidinas/farmacologia , RNA Interferente Pequeno/genética , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase , Receptores de Superfície Celular/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genética , Transfecção , Proteínas Wnt/genética , Proteína Wnt-5a , Quinases da Família src
13.
Int J Oral Maxillofac Surg ; 37(3): 275-81, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18262760

RESUMO

The aim of this study was to evaluate the effects of combining a porous poly(L-lactide-co-epsilon-caprolactone)/beta-tricalcium phosphate membrane and gelatin sponge incorporating basic fibroblastic growth factor (bFGF) on bone regeneration in mandibular ridges. Four full-thickness saddle-type defects (10 mm long x 5 mm deep) were symmetrically created in both edentulous mandibular alveolar ridges of 6 beagles. The dome-shaped membrane was secured to each defect site, and a gelatin sponge containing 200 microg bFGF was implanted on the left side of each defect (experimental group). Only the membranes (control group) were secured to the defect sites on the right. Three and 6 months later, 3 animals were killed. Bone regeneration was analyzed by soft X-ray photographs, micro-computed tomography (CT) images, and peripheral quantitative CT (pQCT), and then examined histologically. Soft X-ray examination revealed an increase in new bone volume in the experimental group 6 months postoperatively. pQCT showed that immature bone density was higher in the experimental group. Micro-CT images revealed well formed new bone along the original contour of the dome-shaped membrane in the experimental group. Histologically, inflammatory infiltration of tissue surrounding the membranes was slight. These results suggest that combining the poly(L-lactide-co-epsilon-caprolactone)/beta-tricalcium phosphate membrane and bFGF-gelatin sponge is promising for alveolar ridge reconstruction.


Assuntos
Perda do Osso Alveolar/cirurgia , Materiais Biocompatíveis , Regeneração Óssea/fisiologia , Fosfatos de Cálcio , Fator 2 de Crescimento de Fibroblastos/uso terapêutico , Esponja de Gelatina Absorvível/uso terapêutico , Hemostáticos/uso terapêutico , Doenças Mandibulares/cirurgia , Membranas Artificiais , Poliésteres , Perda do Osso Alveolar/patologia , Perda do Osso Alveolar/fisiopatologia , Processo Alveolar/patologia , Processo Alveolar/fisiopatologia , Animais , Materiais Biocompatíveis/química , Densidade Óssea/fisiologia , Fosfatos de Cálcio/química , Cães , Regeneração Tecidual Guiada/métodos , Arcada Edêntula/fisiopatologia , Arcada Edêntula/cirurgia , Mandíbula/patologia , Mandíbula/fisiopatologia , Doenças Mandibulares/patologia , Doenças Mandibulares/fisiopatologia , Osteogênese/fisiologia , Poliésteres/química , Telas Cirúrgicas , Tomografia Computadorizada por Raios X/métodos
14.
Ann Hum Genet ; 72(Pt 2): 288-91, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18269687

RESUMO

Recently, the axonal-SMN (a-SMN) protein, which is generated by the gene responsible for spinal muscular atrophy (SMA), SMN, has been reported. Surprisingly, the a-SMN transcript includes the entire sequence of SMN intron 3. We had expected a high frequency of insertion/deletion mutations at a polyadenine tract in this intron, since simple repetitive sequence motifs are prone to mutations. Such mutations could change the C-terminal structure of the a-SMN protein. However, our study showed that almost all individuals, including healthy individuals, SMA patients and SMA-like patients, carried only alleles with a normal polyadenine tract. Hypomutability of the polyadenine tract in SMN intron 3 suggests the existence of transcriptional mechanisms preventing alterations to the open reading frame of axonal SMN and not allowing variability in the protein structure of a-SMN.


Assuntos
Axônios/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Mutação/genética , Proteínas do Tecido Nervoso/genética , Conformação Proteica , Proteínas de Ligação a RNA/genética , Nucleotídeos de Adenina/genética , Sequência de Aminoácidos , Sequência de Bases , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Feminino , Frequência do Gene , Humanos , Íntrons/genética , Masculino , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas do Complexo SMN , Análise de Sequência de DNA
15.
SAR QSAR Environ Res ; 16(4): 323-37, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16234174

RESUMO

Binding of chemicals to the estrogen receptor (ER) is known to be a key mode of action of endocrine disruption effects. In this study, combined quantitative structure-activity relationship (QSAR) models from discriminant and multilinear regression (MLR) analyses, termed a two-step model, were developed. These were used to predict the binding potency to human ERalpha of four chemical groups, namely alkylphenols, phthalates, diphenylethanes and benzophenones. These groups are considered to be important chemical classes of ER-binders. The descriptors investigated were calculated following the simulation of docking between the receptor and ligand. Discriminant analysis in the first step of a two-step model was applied to distinguish binders from non-binders. It had a concordance, following leave-one-out (LOO), of greater than 87% for all chemical classes. Binders were defined as chemicals whose IC50 was reliably measured in a competitive binding assay. The MLR analysis in the second step was performed for the quantitative prediction of the binding affinity of chemicals that were previously discriminated as binders. The q2 values for alkylphenols and diphenylethanes were 0.75 and 0.74, respectively. However good MLR relationships were not obtained for phthalates and benzophenones as the observed binding affinities of chemicals in these categories were weak and in a too narrow range.


Assuntos
Receptor alfa de Estrogênio/metabolismo , Ligantes , Relação Quantitativa Estrutura-Atividade , Derivados de Benzeno/química , Derivados de Benzeno/metabolismo , Benzofenonas/química , Benzofenonas/metabolismo , Análise Discriminante , Modelos Lineares , Modelos Químicos , Fenóis/química , Fenóis/metabolismo , Ácidos Ftálicos/química , Ácidos Ftálicos/metabolismo
16.
Br J Radiol ; 78(930): 558-61, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15900064

RESUMO

We report a case of cystic adenomyosis, presenting as a huge exophytic cystic mass with florid glandular differentiation. MR findings of the mass mimicked ovarian carcinoma associated with endometriosis. The presence of signal voids bridging the uterus and tumour should suggest a mass of uterine origin. Hyperintense protuberance in a hypointense loculus on T(2) weighted images may suggest benign disease. However, surgical exploration and resection is still required to exclude an ovarian malignancy.


Assuntos
Endometriose/diagnóstico , Doenças Ovarianas/diagnóstico , Adulto , Diferenciação Celular , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Neoplasias Ovarianas/diagnóstico , Doenças Uterinas/diagnóstico
17.
Br J Cancer ; 92(9): 1690-5, 2005 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-15841081

RESUMO

We have reported that the selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib ('Iressa', ZD1839), suppressed intrahepatic metastasis of hepatocellular carcinoma CBO140C12 cells. In this study, we focused on the tumour necrosis factor-alpha (TNF-alpha) signalling pathways. Real-time reverse transcription-polymerase chain reaction showed that TNF-alpha mRNA was expressed in large quantities in the implanted tumour. Gefitinib inhibited EGF- but not hepatocyte growth factor (HGF)-induced activation of mitogen-activated protein kinase (MAPK) cascades, suggesting selectivity of the inhibitor. However, gefitinib inhibited the TNF-alpha-induced activation of MAPKs and Akt. In addition, TNF-alpha-induced metastatic properties including adhesion to fibronectin, mRNA expression of integrin alpha v, production of matrix metalloproteinase-9 and invasion were inhibited by gefitinib without affecting cell proliferation. Furthermore, the TNF-alpha-induced responses except for NF-kappaB activation were blocked by metalloprotease inhibitors, suggesting that gefitinib inhibited the transactivation of EGFR induced by TNF-alpha. These results suggest that the TNF-alpha signalling pathway is a possible target of gefitinib in suppressing the intrahepatic metastasis of hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/patologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Quinazolinas/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Fator de Crescimento Epidérmico/farmacologia , Feminino , Gefitinibe , Sistema de Sinalização das MAP Quinases , Camundongos , Metástase Neoplásica/prevenção & controle , Inibidores de Proteínas Quinases/farmacologia
18.
Clin Transplant ; 18 Suppl 11: 34-8, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15191371

RESUMO

We retrospectively studied the occurrence of vesicoureteral reflux (VUR)-associated pyelonephritis using renal biopsies obtained from the transplanted kidneys, and correlated the histological changes with clinical parameters. Out of a total of 131 renal biopsies performed between 1990 and 2001 on renal transplant patients at the department of Urology of Nagasaki University Graduate School of Biomedical Sciences, 12 patients showed pyuria more than twice in a single year. Seven of these 12 patients were available for determining VUR by voiding cystourethrography (VCUG). Cystoureterography demonstrated VUR in three of seven studied patients with pyuria. A histopathological examination revealed dilatation of both proximal and distal tubules in renal biopsies of transplant patients with VUR, compared to renal biopsies of transplant patients without VUR, or non-transplanted patients with thin membrane disease. One of the patients with VUR showed advanced features of chronic pyelonephritis in four consecutive biopsies at different time points, suggesting a late stage of reflux nephropathy in the transplanted kidney. We conclude from our study that the occurrence of VUR-related pyelonephritis may be one of the important long-term complications in the survival of renal allografts.


Assuntos
Transplante de Rim/patologia , Complicações Pós-Operatórias/patologia , Pielonefrite/patologia , Refluxo Vesicoureteral/patologia , Adulto , Biópsia , Feminino , Humanos , Glomérulos Renais/patologia , Túbulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Pielonefrite/etiologia , Refluxo Vesicoureteral/complicações
19.
Med J Malaysia ; 59(4): 512-4, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15779584

RESUMO

In Malaysia, Spinal Muscular Atrophy (SMA) is diagnosed based on clinical observation with or without muscle biopsy. Molecular analyses of the SMA-related genes have not been available so far. In this preliminary study, we searched for homozygous deletion of Survival Motor Neuron (SMN1) and Neuronal Apoptosis Inhibitory Protein (NAIP) genes in Malay patients with SMA and found homozygous deletion of SMN1 exon 7 and 8 in all the patients while homozygous deletion of NAIP exon 5 was detected in only our type 1 patients but not in the type 3 patient. To the best of our knowledge, these are the first SMA cases diagnosed at the molecular level in Malaysia.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Atrofia Muscular Espinal/genética , Proteínas do Tecido Nervoso/genética , Proteínas de Ligação a RNA/genética , Humanos , Malásia , Proteína Inibidora de Apoptose Neuronal , Proteínas do Complexo SMN , Proteína 1 de Sobrevivência do Neurônio Motor
20.
Clin Radiol ; 58(10): 778-86, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14521887

RESUMO

AIM: To assess the frequency, cause, and significance of early-enhancing, non-neoplastic (EN) lesions on gadolinium-enhanced magnetic resonance imaging (MRI) of the liver performed for the detection of malignant hepatic tumours. MATERIALS AND METHODS: From September 1997 to September 2000, we reviewed the images of 125 patients, suspected of having hepatic tumours, in whom (1) gadolinium-enhanced triphasic dynamic gradient-recalled-echo (GRE) imaging in addition to unenhanced T1- and T2-weighted MRI was performed, (2) conventional angiography and combination computed tomography (CT) hepatic arteriography and CT during arterial portography were performed within 2 weeks of the MRI, and (3) definitive surgery within 2 weeks of the MRI or follow-up study by means of intravenously contrast-enhanced CT or MRI in 10 months or more was performed. Angiographic studies were correlated to determine the underlying causes of the EN lesions. RESULTS: We found 78 EN lesions in 36 patients (29%), ranging in size from 4 and 50 mm (mean, 12.2 mm). From the MR reports, our radiologists had prospectively diagnosed EN lesions as probable malignant tumours in eight (10%), possible malignant tumours in 36 (46%), and probable non-neoplastic lesion in 34 (44%). EN lesions were found in 27 of 81 (33%) cirrhotic patients and in nine of 44 (20%) non-cirrhotic patients. Fifty-one EN lesions (65%) were located along the liver edge. The shape was circular in 42 (54%), oval in 14 (18%), irregular in 12 (15%), wedge-shaped in seven (9%), and fan-shaped in three (4%). Twenty EN lesions (26%) appeared slightly hyperintense on T2-weighted images. The causes were non-neoplastic arterio-portal shunting in 48 (62%), cystic venous drainage in four (5%), rib compression in four (5%), aberrant right gastric venous drainage in two (3%), and unknown in 20 (26%). CONCLUSION: Over half the number of EN lesions were caused by non-neoplastic arterio-portal shunting, occasionally showing slight hyperintensity on T2-weighted images. On MR images the non-neoplastic nature of the EN lesion was often ascertained. Radiologists should not overcall EN lesions as malignant as the patients involved would be inappropriately considered inoperable. In problematic cases, further investigation with angiographic CT or follow-up imaging studies should be performed.


Assuntos
Meios de Contraste , Gadolínio DTPA , Hepatopatias/diagnóstico , Imageamento por Ressonância Magnética , Idoso , Idoso de 80 Anos ou mais , Humanos , Hepatopatias/etiologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
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