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1.
Org Biomol Chem ; 21(29): 5990-5996, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37435658

RESUMO

(-)-Epigallocatechin gallate (EGCG), a key component of green tea, exerts therapeutic anticancer and antiallergic properties through its binding to the 67 kDa laminin receptor. The functionalization of EGCG is a promising strategy for creating new drug candidates and chemical probes. In our study, we developed a method for effectively modifying the A ring of EGCG through an electrophilic aromatic substitution with amidomethyl 2-alkynylbenzoates initiated with a gold complex. The 2-alkynylbenzoates treated with (Ph3P)AuOTf under neutral conditions yielded N-acylimines. A further electrophilic aromatic substitution resulted in a mixture of EGCG substituted with acylaminomethyl groups at the 6 and 8 positions with a significant amount noted at the 6 position. We then explored the synthesis of 18F-labeled EGCG with a neopentyl labeling group, an effective labeling group for radiohalogens of not only fluorine-18 but also of astatine-211. To achieve this, we prepared precursors that possessed acid-sensitive protecting groups and base-unstable leaving groups using our established method. Substitution of EGCG with a neopentyl labeling group at either the C6 or C8 position did not affect its anticancer efficacy in U266 cells. Finally, we investigated the preparation of 18F-labeled EGCG. The 18F-fluorination of a mixture of 6- and 8-substituted precursors yielded the corresponding 18F-labeled compounds in 4.5% and 3.0% radiochemical yields (RCYs), respectively. Under acidic conditions, the 18F-labeled 8-substituted compound produced 18F-labeled EGCG in 37% RCY, which heralds the potential of our functionalization approach.


Assuntos
Catequina , Polifenóis , Polifenóis/farmacologia , Radioisótopos de Flúor , Catequina/farmacologia , Catequina/metabolismo , Chá/química , Halogenação
2.
Scand J Gastroenterol ; 47(8-9): 1108-14, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22783937

RESUMO

OBJECTIVE: Delayed bleeding is a major complication of endoscopic submucosal dissection (ESD) of gastric neoplasms. We aimed to clarify risk factors for delayed bleeding from ESD. MATERIAL AND METHODS: This study included 447 patients in whom 544 gastric neoplasms were resected by ESD between April 2006 and March 2011 in Yamaguchi University Hospital. We analyzed risk factors for delayed bleeding from ESD in relation to various clinical and pathological factors. RESULTS: En bloc resection rate was 95.4% (519/544), and curative resection rate was 87.8% (477/544). Delayed bleeding occurred in 7.0% (38/544) and perforation occurred in 1.8% (10/544) of patients. Univariate analysis revealed platelet count (Plt) <15 × 104/µl (p = 0.013), prothrombin time (PT) <70% (p = 0.044), resected size ≥ 50 mm (p = 0.038), and positive/indeterminate lateral margin (p = 0.012) to be risk factors for delayed bleeding. Multivariate analysis showed that Plt <15 × 104/µl (odds ratio [OR], 2.62; 95% confidence interval [CI]: 1.17-5.53, p = 0.020) and positive/indeterminate lateral margin (OR, 5.45; 95% CI: 1.39-17.95, p = 0.018) were independent risk factors for delayed bleeding. CONCLUSIONS: Low Plt, low PT, large resected size, and positive/indeterminate lateral margin were significant risk factors for delayed bleeding from ESD. Patients with these risk factors must be carefully observed for signs of delayed bleeding.


Assuntos
Dissecação/efeitos adversos , Mucosa Gástrica/cirurgia , Hemorragia Gastrointestinal/etiologia , Hemorragia Pós-Operatória/etiologia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalos de Confiança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Contagem de Plaquetas , Tempo de Protrombina , Estudos Retrospectivos , Fatores de Risco , Gastropatias/etiologia , Neoplasias Gástricas/patologia
3.
J Gastroenterol Hepatol ; 25(10): 1636-41, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20880172

RESUMO

BACKGROUND AND AIM: Magnifying endoscopy with narrow-band imaging (ME-NBI) enhances images of the irregular mucosal structures and microvessels of gastric carcinoma, and could be useful for determining the margin between cancerous and non-cancerous mucosa. We evaluated the usefulness of ME-NBI for determining the tumor margin compared with indigocarmine chromoendoscopy (ICC). METHODS: The subjects were 110 patients (with 118 lesions) who underwent endoscopic submucosal dissection for gastric tumors. They were randomized into ME-NBI and ICC groups. Marking was carried out by electrocautery with the tip of a high-frequency snare at the tumor margins determined by each observation. The distance from the marking dots to the tumor margin was measured histopathologically in the resected specimens. Marking was diagnosed as accurate if the distance was less than 1 mm. RESULTS: Of the 118 gastric lesions, 55 were allocated to the ME-NBI group, and 63 to the ICC group. Seventeen lesions in the ME-NBI group and 18 lesions in the ICC group were excluded because the distance from the marking dots to the tumor margin was immeasurable histopathologically. Thirty-eight lesions in the ME-NBI group and 45 lesions in the ICC group were evaluated. The rate of accurate marking of the ME-NBI group was significantly higher than that of the ICC group (97.4% vs 77.8%, respectively; P-value = 0.009). CONCLUSION: Magnifying endoscopy with narrow-band imaging can identify gastric tumor margins more clearly than ICC.


Assuntos
Endoscópios Gastrointestinais , Endoscopia Gastrointestinal/métodos , Gastrectomia/métodos , Aumento da Imagem/métodos , Neoplasias Gástricas/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Dissecação/métodos , Feminino , Seguimentos , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Neoplasias Gástricas/cirurgia
4.
J Gastroenterol Hepatol ; 25(9): 1514-7, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20796148

RESUMO

BACKGROUND AND AIM: Strip biopsy and endoscopic submucosal dissection (ESD) have been developed as a local treatment for early gastric cancer (EGC). However, the lesion criteria for the use of ESD, rather than strip biopsy, remain to be elucidated. METHODS: On the basis of reviews of literature and our observations concerning the outcome of strip biopsy, we set the criteria for selecting strip biopsy and ESD as follows. The indications for strip biopsy were lesions less than 10 mm in size and located in the anterior wall or greater curvature of the lower and middle stomach. ESD was indicated for all other lesions. The validity of the criteria was then analyzed prospectively in 156 patients. The rate of en bloc R0 resection and local recurrence were evaluated. RESULTS: Subsequently, 156 lesions were divided according to the criteria and were endoscopically resected by strip biopsy (n = 13) or ESD (n = 143). The en bloc R0 resection rates for the whole group and the strip biopsy and ESD groups was 93.5% (146/156), 92.3% (12/13), and 93.7% (134/143), respectively. None of the patients had suffered from local recurrence in either the strip biopsy or ESD groups. CONCLUSION: The validity of our criteria for selecting strip biopsy and ESD was verified. Our criteria exploit the advantages of both procedures and obtain better endoscopic therapy outcomes for EGC.


Assuntos
Carcinoma/cirurgia , Dissecação/métodos , Mucosa Gástrica/cirurgia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma/diagnóstico , Carcinoma/patologia , Distribuição de Qui-Quadrado , Feminino , Mucosa Gástrica/patologia , Gastroscopia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Prospectivos , Reprodutibilidade dos Testes , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Fatores de Tempo , Resultado do Tratamento
5.
Electrophoresis ; 29(15): 3192-200, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18604870

RESUMO

Gastric cancer is the most common cancer in Japan and infection with Epstein-Barr virus (EBV) is responsible for about 10% of gastric cancers worldwide. Although EBV infection may be involved at an early stage of gastric carcinogenesis, the mechanisms underlying its involvement remain unknown. To investigate the role of EBV in gastric carcinogenesis, we performed proteomic analyses of an EBV-infected gastric carcinoma cell line NU-GC-3 (EBV(+)) and its uninfected control (EBV(-)). 2-DE was combined with MS to identify differentially expressed proteins. We found that EBV infection upregulated one of the phosphorylated heat shock protein 27 kDa (HSP27). The phosphorylated HSP27 isoform which increased in EBV(+) cells can be induced by both heat shock and arsenite. The increase of phosphorylated HSP27 in EBV(+) cells was reduced by treatment with the phosphoinositide 3-kinase (PI3K) inhibitors (LY294002 and wortmannin). In addition, we found increased levels of phosphorylated Akt in EBV(+) cells. These findings suggest that EBV infection upregulates the phosphorylation of HSP27 via the PI3K/Akt pathway. Thus, activation of the PI3K/Akt pathway may contribute to the establishment of a malignant phenotype in EBV-infected gastric carcinomas.


Assuntos
Transformação Celular Viral/fisiologia , Regulação Viral da Expressão Gênica , Proteínas de Choque Térmico HSP27/biossíntese , Herpesvirus Humano 4/fisiologia , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Neoplasias Gástricas/virologia , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/virologia , Sequência de Aminoácidos , Androstadienos/farmacologia , Arsenitos/farmacologia , Linhagem Celular Tumoral , Cromonas/farmacologia , Eletroforese em Gel Bidimensional , Feminino , Proteínas de Choque Térmico HSP27/análise , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico , Temperatura Alta , Humanos , Masculino , Pessoa de Meia-Idade , Chaperonas Moleculares , Dados de Sequência Molecular , Morfolinas/farmacologia , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação/efeitos dos fármacos , Isoformas de Proteínas/análise , Isoformas de Proteínas/biossíntese , Isoformas de Proteínas/genética , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , RNA Viral/genética , RNA Viral/fisiologia , Transdução de Sinais/fisiologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Regulação para Cima , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/fisiologia , Wortmanina
7.
J Gastroenterol Hepatol ; 22(12): 2233-7, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17559384

RESUMO

BACKGROUND AND AIM: A beneficial effect of Helicobacter pylori (H. pylori) eradication in patients with H. pylori-positive idiopathic thrombocytopenic purpura (ITP) has been reported by several investigators; however, it was not clear whether the recovered platelet count after H. pylori eradication was maintained for a long period. METHOD: Thirty-eight ITP patients who were examined for H. pylori infection were assessed. H. pylori-positive patients received a standard antibiotic therapy for H. pylori eradication. We investigated the long-term effect of H. pylori eradication on platelet recovery in patients with H. pylori-positive ITP. RESULTS: Of the 38 ITP patients, 26 (68.4%) were positive for H. pylori. The response rate of platelet recovery was 56.5% (13/23 patients). Twelve patients showed complete response (CR) and one showed partial response (PR). The mean platelet counts 6 months after eradication significantly increased from 31 x 10(9)/L to 129 x 10(9)/L in 23 H. pylori-eradicated patients (P < 0.001). The median platelet counts of responders 1, 2, 3, and 4 years after eradication were 168 x 10(9)/L (n = 10), 193 x 10(9)/L (n = 9), 168 x 10(9)/L (n = 7), and 243 x 10(9)/L (n = 4) after a mean follow-up of 25.8 months. CONCLUSION: Eradication therapy for H. pylori-positive patients with ITP was effective and a favorable effect was maintained for long periods.


Assuntos
Infecções por Helicobacter/complicações , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/isolamento & purificação , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Fatores de Tempo , Resultado do Tratamento
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