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1.
Nihon Shokakibyo Gakkai Zasshi ; 107(4): 639-48, 2010 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-20379099

RESUMO

A 28-year-old man complained of tarry stool. A series of examinations showed a submucosal tumor with bleeding at the papilla of Vater and a swollen # 17b lymph node, both of which indicated a hypervascular tumor. The pathological findings of the enucleated tumor specimens revealed gangliocytic paraganglioma with metastasis to the # 17b lymph node. Additional pancreaticoduodenectomy revealed another # 17b lymph node metastasis 7-mm in diameter. Although the majority of gangliocytic paragangliomas are benign, 7% of reported cases have lymph node metastases, as shown in the present case. These findings are important in treating patients with gangliocytic paraganglioma.


Assuntos
Metástase Linfática , Paraganglioma/patologia , Adulto , Humanos , Masculino
2.
J Gastroenterol Hepatol ; 23(5): 736-40, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18070008

RESUMO

BACKGROUND AND AIM: We investigated the usefulness of magnetic resonance cholangiopancreatography (MRCP) and the need for endoscopic retrograde cholangiopancreatography (ERCP) in patients with clinically suspicious spontaneous passage of bile duct stones. METHODS: The study population consisted of 113 patients suspected of having common duct bile stones. Of them, 50 patients were clinically suspected of spontaneous passage of bile duct stones based on the presence of gallbladder stones on ultrasound examination or a history of common bile duct stones after cholecystectomy, clinical symptoms including abdominal pain and fever associated with inflammatory reaction and marked rise of hepatobiliary enzymes which resolved or normalized after conservative treatment without evidence of stones in the common bile duct on MRCP. These 50 patients were prospectively followed up for a median of 10.2 months. RESULTS: All patients except for one had had no symptoms related to cholangitis. Only one patient received ERCP due to recurrence of symptoms after 6 months. CONCLUSION: When clinical symptoms improve, hematological parameters normalize, and MRCP indicates that there are no stones in the common bile duct, it can be considered that the stones have passed naturally.


Assuntos
Colangiopancreatografia por Ressonância Magnética , Cálculos Biliares/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Colangiopancreatografia Retrógrada Endoscópica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
3.
J Gastroenterol Hepatol ; 23(10): 1528-34, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17944882

RESUMO

BACKGROUND AND AIM: Although hypervascular appearance is characteristic in hepatocellular carcinoma (HCC), hepatic nodules without hypervascular appearance are sometimes found in patients with chronic liver disease (CLD). The aim of the present study was to clarify the efficacy of contrast-enhanced ultrasound (CEUS) with Levovist to characterize small, non-hypervascular hepatic nodules on contrast-enhanced computed tomography (CECT) in patients with CLD. METHODS: The subject was 41 hepatic nodules (<30 mm, 18.5 +/- 5.6 mm) which showed non-hypervascular appearance on CECT in 35 patients with CLD; their histological results were 31 HCC (15 well, 14 moderate, and two poor) and 10 regenerative nodules (RN). CEUS with Levovist was performed under intermittent scanning (1-s interval) using APLIO at the early phase and the liver-specific phase, and the contrast enhancement of the nodule was assessed in comparison to that of the surrounding liver parenchyma. The contrast-enhanced findings with the time-intensity analysis were compared with the histological results. RESULTS: Twelve nodules with weak enhancement in the liver-specific phase were HCC, regardless of their early-phase appearances. The other 29 nodules with equivalent or weak enhancement in the early phase and equivalent enhancement in the liver-specific phase were 19 HCC and 10 RN. Among them, the maximum-intensity ratio of tumor to non-tumor in the early phase was significantly higher in HCC than in RN (P < 0.01, n = 16), and the receiver-operating characteristic analysis showed a sensitivity of 1.0 and a specificity of 0.83 for their characterization. CONCLUSION: CEUS with Levovist may be an alternative to biopsy to characterize small, non-hypervascular hepatic nodules on CECT in patients with CLD.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Meios de Contraste , Hepatopatias/diagnóstico , Neoplasias Hepáticas/diagnóstico , Microbolhas , Polissacarídeos , Tomografia Computadorizada por Raios X , Biópsia por Agulha , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/diagnóstico por imagem , Doença Crônica , Estudos de Viabilidade , Humanos , Hepatopatias/diagnóstico por imagem , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Valor Preditivo dos Testes , Fatores de Tempo , Ultrassonografia
4.
Hepatogastroenterology ; 55(85): 1222-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18795661

RESUMO

BACKGROUNDS/AIMS: To elucidate the diagnostic confidence of contrast-enhanced ultrasound (CEUS) with Levovist for hepatic hemangioma. METHODOLOGY: The subjects were 34 patients with 38 hemangiomas and 12 patients with 15 hypervascular hepatocellular carcinomas. The early-phase (15-60 second) and liver-specific phase (after 5 min) were observed by the first injection. The 2nd injection was done for solo-phase method to observe liver-specific phase images without taking early-phase sonograms. The 3rd injection was done for changing posture method to observe liver-specific sonograms under left lateral ducubitus position. RESULTS: In the early-phase of hemangioma, nodular enhancement (NE) was found transiently in 13 lesions (34%) and continuously in 25 lesions (66%), while hepatocellular carcinoma (HCC, n = 15) did not show this pattern. Intratumoral arterioportal shunt was closely related to the short duration of NE. Two enhancement patterns were observed in the liver-specific phase of hemangioma, diffuse in 12 lesions (31%) and partial in 26 lesions (69%), which were dependent on the early-phase enhancement. Liver-specific findings were also affected by taking early-phase sonograms or changing the posture of the patient. This method provided sensitivity of 79% and specificity of 100% for the diagnosis of hemangioma. CONCLUSIONS: CEUS with Levovist may be promising method for the diagnosis of hepatic hemangioma.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Hemangioma Cavernoso/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Polissacarídeos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/irrigação sanguínea , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Hemangioma Cavernoso/irrigação sanguínea , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Sensibilidade e Especificidade , Fatores de Tempo , Ultrassonografia
5.
Hepatogastroenterology ; 55(86-87): 1801-5, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19102397

RESUMO

BACKGROUND/AIMS: The aim of this study was to investigate whether exogenous dehydrocholic acid (DHCA) was useful to enhance the delineation of hepatolithiasis. METHODOLOGY: Our study population comprised 9 patients. Magnetic resonance cholangiopancreatography (MRCP) was acquired before and after the administration of DHCA. Two different MRCP snap-shot techniques were applied: thick-slab two-dimensional (2D) (coronal) single shot turbo spin echo T2-weighted sequences and multisection thin-slab, 2D (coronal) single shot turbo spin echo T2-weighted sequences with three-dimensional (3D) maximum intensity projection (MIP) post processing. RESULTS: DHCA provided a better visualization of hepatolithiasis in 8 of 9 cases (88.9%). CONCLUSIONS: It was suggested that administration of DHCA could enhance the delineation of the hepatolithiasis on MRCP images.


Assuntos
Colagogos e Coleréticos , Colangiopancreatografia por Ressonância Magnética/métodos , Ácido Desidrocólico , Litíase/diagnóstico , Hepatopatias/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
Hepatogastroenterology ; 55(81): 17-20, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18507070

RESUMO

BACKGROUND/AIMS: The aim of this study was to investigate whether exogenous dehydrocholic acid (DHCA) was useful to enhance the delineation of anastomotic site. METHODOLOGY: DHCA is a cholagogue which produces an immediate effect by acting directly on liver cells. Its choleretic effect is strong, appearing 1 to 3 minutes after intravenous injection, reaching the maximum level in 20 to 30 minutes. Our study population comprised 9 patients. Magnetic resonance cholangiopancreatography (MRCP) was acquired before and after the administration of DHCA. Two different MRCP snap-shot techniques were applied: thick-slab two-dimensional (2D) (coronal) single-shot turbo spin echo T2-weighted sequences and multisection thin-slab, 2D (coronal) single shot turbo spin echo T2-weighted sequences with three-dimensional (3D) maximum intensity projection (MIP) post processing. RESULTS: DHCA provided a better visualization of the anastomotic site in 7 patients (77.8%). The two patients without improvement in visualization of anastomotic site included 1 patient with liver cirrhosis secondary to portoenterostomy for congenital biliary dilatation and 1 patient, who was not eligible for the evaluation because of motion artifact caused by the difficulty of breath holding motion artifact. CONCLUSIONS: It was suggested that administration of DHCA could enhance the delineation of the anastomotic site on MRCP images.


Assuntos
Colagogos e Coleréticos , Colangiopancreatografia por Ressonância Magnética/métodos , Ácido Desidrocólico , Aumento da Imagem/métodos , Adulto , Anastomose Cirúrgica , Coledocostomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
7.
Hepatogastroenterology ; 55(82-83): 323-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18613358

RESUMO

BACKGROUND/AIMS: The aim of this study was to investigate whether exogenous dehydrocholic acid (DHCA) was useful to enhance the delineation of the biliary tree. METHODOLOGY: Our study population comprised 14 patients. Magnetic resonance cholangiopancreatography was acquired before and after the administration of DHCA. Two different MRCP snap shot techniques were applied: thick-slab two-dimensional (2D) (coronal) single shot turbo spin echo T2-weighted sequences and multisection thin-slab, 2D (coronal) single shot turbo spin echo T2-weighted sequences with three-dimensional (3D) maximum intensity projection (MIP) post processing. Volume rendering was prepared based on the source images, and the pixel size was visually adjusted to the biliary area of MRCP to measure the biliary tree volume. RESULTS: DHCA increased the bile duct volume in 13 of the 14 patients. It provided a better visualization of the biliary tree in 11 patients. The three patients without improvement in visualization included 1 patient with liver cirrhosis secondary to portoenterostomy for congenital biliary dilatation and 2 patients with cholecystectomy who had the bile ducts filled with bile by the time of the administration. CONCLUSIONS: It was suggested that administration of DHCA could enhance the delineation of the biliary tree on MRCP images.


Assuntos
Doenças dos Ductos Biliares/diagnóstico , Colagogos e Coleréticos , Colangiopancreatografia por Ressonância Magnética , Ácido Desidrocólico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
Eur J Radiol ; 61(2): 279-89, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17070663

RESUMO

The aim of this study was to evaluate multidetector helical computed tomography (MDCT), superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging, and CT arterial portography (CTAP) and CT during hepatic arteriography (CTHA) for the detection and diagnosis of hepatocellular carcinomas (HCC). This included visual correlations of MDCT and SPIO-MR imaging in the detection of HCC using receiver operating characteristic (ROC) analysis. Twenty-five patients with 57 nodular HCCs were retrospectively analyzed. A total of 200 segments, including 49 segments with 57 HCCs, were reviewed independently by three observers. Each observer read four sets of images (set 1, MDCT; set 2, unenhanced and SPIO-enhanced MR images; set 3, combined MDCT and SPIO-enhanced MR images; set 4, combined CTAP and CTHA). The mean Az values representing the diagnostic accuracy for HCCs of sets 1, 2, 3, and 4 were 0.777, 0.814, 0.849, and 0.911, respectively, and there was no significant difference between sets 3 and 4. The sensitivity of set 4 was significantly higher than those of set 3 for all the lesions and for lesions 10 mm or smaller (p<0.05); however, for lesions larger than 10mm, the sensitivities of the two sets were similar. No significant difference in positive predictive value and specificity was observed between set 3 and set 4. Combined MDCT and SPIO-enhanced MR imaging may obviate the need for more invasive CTAP and CTHA for the pre-therapeutic evaluation of patients with HCC more than 10mm.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Cirrose Hepática/patologia , Neoplasias Hepáticas/diagnóstico , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Meios de Contraste , Dextranos , Óxido Ferroso-Férrico , Humanos , Ferro , Cirrose Hepática/diagnóstico por imagem , Nanopartículas de Magnetita , Variações Dependentes do Observador , Óxidos , Portografia/métodos , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos
9.
Hepatogastroenterology ; 54(80): 2212-5, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18265635

RESUMO

BACKGROUND/AIMS: To assess the diagnostic value of magnetic resonance cholangiopancreatography (MRCP) and examine the indications for endoscopic retrograde cholangiopancreatography (ERCP). METHODOLOGY: MRCP was performed in 185 patients with hepatobiliary disease in whom abdominal ultrasonography (US) had not been of diagnostic value. These patients were selected for MRCP in view of their abdominal symptoms, high levels of hepatobiliary enzymes, and pancreatic/bile duct dilatation found by abdominal US. Based on MRCP findings, 75 patients were selected for ERCP. RESULTS: ERCP provided new findings in 14 (18.%) patients. In 110 patients subjected to only MRCP and follow-up as well as in 75 patients with MRCP followed by ERCP, MRCP-based diagnosis corresponded with the final diagnosis. In our study, patients who would have conventionally required ERCP, such as those with natural passed choledocholithiasis and postoperative bile duct dilatation, could be followed up without ERCP. These results the importance of considering indications for ERCP. CONCLUSIONS: MRCP can be an alternative to ERCP at least for diagnosis.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Colangiopancreatografia por Ressonância Magnética , Doenças do Sistema Digestório/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ductos Biliares/patologia , Neoplasias do Sistema Biliar/diagnóstico , Colecistolitíase/diagnóstico , Coledocolitíase/patologia , Colestase Intra-Hepática/diagnóstico , Dilatação Patológica , Endoscopia Gastrointestinal , Endossonografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ductos Pancreáticos/patologia , Neoplasias Pancreáticas/diagnóstico , Pancreatite Crônica/diagnóstico
10.
Brain Res ; 1104(1): 18-26, 2006 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-16814752

RESUMO

We have identified the murine Clast1/LR8 gene by subtraction of cDNA derived from CD40 ligand-activated and naive B cells. The Clast1 gene is ubiquitously expressed in various organs of adult mice. However, its physiological function was largely unknown. To study a role of Clast1, we established Clast1-deficient (Clast1-KO) mice. Here, we reveal that approximately 65% of Clast1-KO mice showed severe ataxia. The Clast1-KO cerebellum with ataxia is small in size and revealed a severely aberrant lobulation, loss of the internal granule cell layer, and the disorganized Purkinje cells. Clast1 mRNA is expressed in the cerebellar granule cells of normal adult mice. Developmentally, Clast1 mRNA is also detected in the external germinal layer of the embryonic cerebellum, indicating its expression in granule cell precursors. Histopathological analysis of the developing Clast1-KO cerebellum demonstrated the reduced number of cells in the external germinal layer. Thus, Clast1 is required for development of cerebellar granule cells.


Assuntos
Cerebelo/citologia , Cerebelo/crescimento & desenvolvimento , Lipoproteínas/fisiologia , Camundongos Knockout/genética , Neurônios/fisiologia , Animais , Animais Recém-Nascidos , Ataxia/genética , Northern Blotting/métodos , Southern Blotting/métodos , Células Cultivadas , Clonagem Molecular , Embrião de Mamíferos , Expressão Gênica/fisiologia , Imuno-Histoquímica/métodos , Hibridização In Situ/métodos , Lipoproteínas/deficiência , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
11.
World J Gastroenterol ; 12(6): 868-73, 2006 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-16521213

RESUMO

AIM: To investigate the relationship between the chemotherapeutic drug efficacy and the expression of P-glycoprotein (PGP) and p53 protein in advanced hepatocellular carcinoma (HCC). METHODS: The study was conducted on 41 patients with advanced HCC who were treated by repeated arterial infusion chemotherapy. Biopsy specimens from the tumor were collected before the start of treatment in all the patients, and the specimens were stored frozen until immunohistochemical staining, which was performed after the start of treatment, to detect PGP and p53 protein expressions. Twenty of the forty-one patients were treated with an anthracycline drug (epirubicin hydrochloride; anthracycline group), and the remaining 21 were treated with a non-anthracycline drug (mitoxantrone hydrochloride in 11 patients and carboplatin in 10 patients; non-anthracycline group). The relationship between the chemotherapeutic efficacy and the results of immunostaining were compared between the two groups. RESULTS: Before the start of the treatment, PGP-positive rate was 90.2% (strongly-positive, 36.6%) and p53 protein-positive rate was 34.1% (strongly-positive, 19.5%). In the anthracycline group, the response rate was 40.0%. The number of patients showing poor response to the treatment was significantly larger in the patients with strongly positive PGP expression (P=0.005), and their prognoses were poor (P=0.001). In the non-anthracycline group, the response rate was 42.9%, and there was no significant relationship between the chemotherapeutic drug efficacy and the PGP or p53 protein expression. When only the data from the 11 patients treated with anthraquinone drug, mitoxantrone, were analyzed, however, the number of patients who showed poor response to treatment was significantly higher among the p53-positive patients (P=0.012), irrespective of the survival outcome. CONCLUSION: The chemotherapeutic efficacy with an anthracycline drug for advanced HCC can be predicted by immunohistochemical analysis of PGP expression. Similarly, immunostaining to evaluate p53 protein may be useful to predict the response in patients treated with an anthraquinone drug.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Carboplatina/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Epirubicina/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes p53/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Mitoxantrona/uso terapêutico , Carboplatina/administração & dosagem , Carcinoma Hepatocelular/genética , Epirubicina/administração & dosagem , Humanos , Imuno-Histoquímica , Infusões Intra-Arteriais , Neoplasias Hepáticas/genética , Mitoxantrona/administração & dosagem , Estudos Retrospectivos
12.
Ultrasound Med Biol ; 32(12): 1809-15, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17169692

RESUMO

Contrast enhancement in the portal vein was repeatedly observed at 1 min intervals with wide-band Doppler ultrasonography in 152 consecutive patients (132 with liver cirrhosis and HCC, 20 controls), 5 min after the injection of Levovist. The duration time of contrast enhancement in the portal vein (microbubble disappearance-time; MD-T) was measured in all patients and contrast-enhanced appearances were compared between the 5 min phase and MD-T phase in 68 HCC nodules. MD-T in patients with liver cirrhosis (572.4 +/- 117.9 s) was significantly longer than in controls (481.6 +/- 89.3 s, p < 0.05). MD-T was prolonged in patients with Child B and C compared with Child A (p < 0.05). The contrast-enhanced appearances between the two phases were different in 30 of 68 HCC nodules (44.1%), showing positive enhancement in the 5 min phase and negative enhancement in the MD-T phase. The proposed MD-T may become an essential factor for the evaluation of liver-specific sonograms.


Assuntos
Meios de Contraste/administração & dosagem , Hepatopatias/diagnóstico por imagem , Fígado/diagnóstico por imagem , Microbolhas , Polissacarídeos/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico por imagem , Feminino , Humanos , Aumento da Imagem , Injeções Intravenosas , Cirrose Hepática/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Veia Porta/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Tempo , Ultrassonografia Doppler/métodos
13.
Hepatol Int ; 9(2): 330-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25788204

RESUMO

BACKGROUND AND AIMS: Some follow-up studies of large regenerative nodules (LRNs) and dysplastic nodules (DNs) were reported previously. However, the pre-malignant potentiality of LRNs has remained controversial up to now. No LRNs showed malignant transformation in our previous study. We aimed to evaluate the pre-malignant potentiality of LRNs and DNs with a greater number of cases and longer follow-up periods. METHODS: From 1982 to 2005, 1,500 consecutive nodular lesions up to 2 cm in diameter were subjected to US guided thin-needle biopsy in cirrhotic patients at Chiba University Hospital. Of these lesions, 68 LRNs in 60 cases and 20 DNs in 22 cases were followed up for more than 6 months without any anti-cancer therapy. The last US examination was in 2010. The total study period was 28 years. We analyzed the histological findings and the clinical data of all cases retrospectively. The outcome of the lesions was examined. RESULTS: The mean follow-up period was 38.9 (16-119) months in LRNs and 31.9 (6-101 months) in DNs. Rate of nodule enlargement was higher in DNs (8/24 nodules, 33%) than LRNs (11/68 nodules, 16 %), (p = 0.0743, not significant). Rate of malignant transformation was also higher in DNs (10/24 nodules, 42%) than LRNs (9/68 nodules, 13%), (p = 0.0040, significant). The rate of disappearance in images was similar between LRNs and DNs. CONCLUSIONS: We should recognize LRN as low risk pre-malignant lesions whereas DNs as high risk lesions.


Assuntos
Carcinoma Hepatocelular/patologia , Transformação Celular Neoplásica/patologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Regeneração Hepática , Fígado/patologia , Lesões Pré-Cancerosas/patologia , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Biópsia Guiada por Imagem , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Tempo , Ultrassonografia , Adulto Jovem
14.
Int J Oncol ; 21(3): 553-9, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12168099

RESUMO

c-Jun has a variety of functions including proliferation, differentiation and death. c-Jun is specifically phosphorylated by c-Jun N-terminal kinase (JNK) which is regulated by Ras-MEKK1-MKK4/7 pathway. Previous studies showed that c-Jun protein plays a positive role in cell proliferation of normal hepatocytes and was detected in hepatocellular carcinoma (HCC) tissues. However, the function of c-Jun in HCC cells has not been examined. The aim of this study was to investigate whether the MEKK1-JNK signaling pathway and c-Jun may be involved in the survival and proliferation of HCC. Surprisingly, an active not dominant negative form of MEKK1 (CA-MEKK1) remarkably inhibited the colony formation of HCC cells. Gel retardation assays indicated that CA-MEKK1 induces c-Jun DNA binding, and luciferase assays exhibited that CA-MEKK1 enhances the transactivating activity of c-Jun in HCC cells. These results suggested that the inhibitory effect of CA-MEKK1 on colony formation is likely to be mediated by c-Jun. As expected, when wild-type c-Jun was transfected, the colony formation was significantly reduced. Especially in HuH7 cells, c-Jun transfected cells failed to make any colonies. Our data suggested that c-Jun activation can induce negative effect on survival and proliferation of HCC cells.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , MAP Quinase Quinase Quinase 1 , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Proteínas Serina-Treonina Quinases/fisiologia , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/genética , Divisão Celular/fisiologia , Sobrevivência Celular/fisiologia , DNA de Neoplasias/metabolismo , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/metabolismo , Ativação Enzimática , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/genética , Sistema de Sinalização das MAP Quinases/fisiologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Fator de Transcrição AP-1/biossíntese , Fator de Transcrição AP-1/metabolismo , Ativação Transcricional , Transfecção , Células Tumorais Cultivadas , Ensaio Tumoral de Célula-Tronco
15.
J Gastroenterol ; 39(12): 1196-201, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15622485

RESUMO

BACKGROUND: Metallothionein (MT), which is known to detoxify heavy metal ions, is considered to serve as a mechanism of resistance to platinum complex compounds. In the present study, MT expression in hepatocellular carcinoma (HCC) was immunohistologically investigated to clarify its relationship to clinical background factors and responsiveness to anticancer drugs. METHODS: Specimens from 117 patients with HCC were immunohistologically studied, using a monoclonal anti-MT antibody. the percentage of MT-positive HCC (MT ratio) cells was determined, to evaluate the extent of staining with anti-MT antibody. Staining with an MT ratio of more than 50% was categorized as diffusely positive; an MT ratio of 5% to less than 50% was focally positive; and an MT ratio of less than 5% was negative. Twenty-two patients received repeated arterial infusion chemotherapy with carboplatin (CBDCA), a platinum-containing compound, and the MT expression was analyzed in relation to their chemotherapeutic response. RESULTS: The ratio of MT-positive cells in HCC decreased with the degree of histological differentiation and also decreased with higher tumor stage. In patients treated with CBDCA, the ratio of MT-positive cells in responders was significantly lower than that in non-responders. CONCLUSIONS: MT expression decreases with the degree of histological differentiation and decreases with increasing tumor stage in HCC. In addition, MT expression may lower the antitumor effect of CBDCA.


Assuntos
Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Metalotioneína/biossíntese , Carcinoma Hepatocelular/patologia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade
16.
Oncol Rep ; 12(4): 821-5, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15375506

RESUMO

Poly[adenosine diphosphate (ADP)-ribose] polymerase (PARP), which is mainly located in the nucleus, catalyzes poly-ADP-ribosylation, and is associated with a variety of biological events such as DNA repair, cell proliferation and malignant transformation. The aim of this study was, using biopsy samples obtained under sonographic guidance, to assess whether PARP expression is altered in human hepatocellular carcinoma (HCC), and also to analyze the correlation between the expression of PARP and the patients' clinicopathologic features. Tumor and non-tumor specimens were obtained from a total of 27 HCC patients by percutaneous biopsy under sonographic guidance. Using homogenates of these samples, the expression of PARP in HCC was evaluated by Western blotting and compared with the patients' clinicopathologic features. Western blot analysis, using a total of 29 HCC and 27 non-tumor specimens, revealed that the expression of PARP was significantly increased in HCC compared with the non-tumor portions (p<0.01), and was greater in moderately differentiated HCC than in well differentiated HCC (p<0.05). The expression of PARP in HCC was increased in cirrhotic patients and tended to be greater in less differentiated tumors.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Idoso , Biópsia , Western Blotting , Diferenciação Celular , Feminino , Humanos , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Ultrassonografia , alfa-Fetoproteínas/metabolismo
17.
Int J Mol Med ; 9(6): 597-600, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12011976

RESUMO

CCAAT/enhancer binding protein alpha (C/EBPalpha), expressed at a high level in liver, plays an important role in proliferation and differentiation of hepatocytes. Previous studies showed that an expression level of the C/EBPalpha gene in hepatocytes was downregulated in response to proliferation signals and that forced expression of the C/EBPalpha gene in a number of cells caused cell cycle arrest. We compared the expression level of the C/EBPalpha gene in surgical specimens between hepatocellular carcinoma and non-tumorous regions of the same patients. In 9 out of 13 cases, the expression level in the tumors was decreased compared with that in corresponding non-tumorous regions. Transfection of the C/EBPalpha gene into C/EBPalpha-negative human hepatocellular carcinoma HLF cells, however, did not influence the rate of cell proliferation or cell cycle. Our present data suggest that the expression of the C/EBPalpha gene was downregulated in the majority of human hepatocellular carcinoma but the expression may not be directly associated with impaired proliferative activity of hepatocellular carcinoma cells.


Assuntos
Proteína alfa Estimuladora de Ligação a CCAAT/biossíntese , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Animais , Northern Blotting , Células COS , Divisão Celular , DNA Complementar/metabolismo , Regulação para Baixo , Citometria de Fluxo , Hepatócitos/patologia , Humanos , Fígado/metabolismo , Ligação Proteica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo
18.
Hepatol Res ; 23(2): 122-129, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12048066

RESUMO

The portal-systemic venous shunt is uncommon in patients without portal hypertension. We present two cases of portal-systemic encephalopathy due to extrahepatic shunt without liver cirrhosis and portal hypertension. Two women in their seventies were admitted to our hospital because of recurrent episodes of altered sensorium, drowsiness, slurred speech, disorientation, asterexis and high blood ammonia levels. There was no history of abdominal surgery or abdominal trauma. Clinical examination revealed no signs of portal hypertension or stigmata of chronic liver diseases. Brain CT and MRI scanning were unremarkable except for a high intensity signal in the basal ganglia on T1 weighted MRI images. Laboratory tests were almost normal except for the hyperammonemia occurring on several occasions. There was no evidence of liver cirrhosis by imaging. However, color Doppler showed an extra-hepatic shunt in both patients and pulsed Doppler showed decreased velocity and volume of the portal venous flow. These sonographic findings were confirmed during percutaneous transhepatic portography (PTP). Portal pressures measured during PTP were 9 and 11 mmHg. Needle biopsy ruled out idiopathic portal hypertension and liver cirrhosis. The diagnosis was portal systemic encephalopathy due to extra-hepatic portosystemic venous shunting. Both patients were treated by embolization of the shunting vessel with metallic coils.

19.
J Biochem Mol Biol ; 35(5): 452-8, 2002 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-12359085

RESUMO

Exposure to ultraviolet light (UV) induces apoptosis in mammalian cells. The caspase group of proteases is required for the apoptosis. This pathway is initiated by a release of cytochrome c from the mitochondria into the cytosol. Several Bcl-2 family proteins can regulate the release of cytochrome c by stabilizing the mitochondrial membrane. Here we show that expression of the endogenous bcl-xL was strongly downregulated in NIH3T3 cells within 2 h after UV-C irradiation, and that of bax was upregulated from 8 h after irradiation. Apoptosis was induced in more than 50% of the NIH3T3 cells 48 h after irradiation. Constitutive overexpression of bcl-xL in NIH3T3 cells protected the UV-induced apoptosis by preventing the loss of mitochondrial membrane potential and the activation of caspase 9. These results suggest that downregulation of Bcl-xL is relevant to UV-induced apoptosis of fibroblasts.


Assuntos
Apoptose/efeitos da radiação , Regulação para Baixo/efeitos da radiação , Proteínas Proto-Oncogênicas c-bcl-2/genética , Raios Ultravioleta , Células 3T3 , Animais , Anexina A5/metabolismo , Caspase 9 , Caspases/metabolismo , Caspases/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Ativação Enzimática , Fibroblastos , Potenciais da Membrana/efeitos da radiação , Camundongos , Mitocôndrias/efeitos da radiação , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-2/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2/efeitos da radiação , Proteína X Associada a bcl-2 , Proteína bcl-X
20.
Eur J Radiol ; 41(1): 49-56, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11750152

RESUMO

OBJECTIVE: To elucidate the cause of the signal intensity of gallstones on magnetic resonance (MR) images and to determine whether MR imaging would enable the prediction of the composition of gallstones. MATERIALS AND METHODS: 50 gallstones removed by cholecystectomy from 50 patients were used for in vitro study. All 50 gallstones were examined by MR imaging using a body phantom. After imaging, all gallstones were cut into two pieces, and the MR appearances were compared with their cross-sections. Chemical analysis was subsequently performed on 32 gallstones. RESULTS: On T2-weighted (T2W) images, 24 of 50 gallstones showed high signal intensities only in their center. These central high intensities seen on T2W images corresponded to the clefts filled with fluid within gallstones. In 45 of 50 gallstones there were high signal intensity areas in central and/or peripheral regions on T1-weighted (T1W) images. On T1W images, not only the clefts within gallstones but also other regions were seen as high intensity, and these regions had a brown to black color, coarse structure, and contained much copper. CONCLUSION: MR imaging can visualize the structures and compositions of gallstones in detail.


Assuntos
Colelitíase/química , Imageamento por Ressonância Magnética , Carbonato de Cálcio/análise , Colesterol/análise , Cobre/análise , Humanos , Técnicas In Vitro , Ferro/análise , Modelos Estruturais , Imagens de Fantasmas , Processamento de Sinais Assistido por Computador
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