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1.
Cytotherapy ; 17(5): 680-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25804800

RESUMO

BACKGROUND: Patients with ulcerative colitis (UC) have elevated/activated myeloid lineage leucocytes and may respond favorably to adsorptive granulocyte/monocyte apheresis (GMA). However, there are patients who respond well to GMA, and patients who do not benefit. Therefore, predictive factors of GMA efficacy need to be defined. METHODS: In a prospective multicenter setting, 200 UC patients at 32 institutes received one GMA session per week over 10 weeks. Patients who achieved remission were followed for 12 months. The Clinical Activity Index (CAI) ≤3 meant remission, and response meant CAI decreased by ≥3. Quality of life was evaluated by the Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS: After final GMA, remission, response and no response rates were 67.0%, 15.0% and 18%, respectively. The remission group had a significant decrease in myeloid leucocytes and platelets. Corticosteroid dose decreased (P < 0.001); 49 of 97 patients on corticosteroids became steroid-free. Baseline CAI was lower in the remission group versus non-remission (P < 0.01), whereas IBDQ was higher in the remission group versus non-remission (P < 0.05). After 12 months, 52 of 134 patients had maintained remission. Disease duration was longer in the relapsed group versus maintained remission group (P = 0.041). Male gender, first UC episode and corticosteroid responder were significant factors for maintaining remission, whereas corticosteroid dependent UC was associating with relapse. DISCUSSION: Selective myeloid leucocyte depletion was effective for remission induction and improving patients' quality of life. Baseline demographics such as disease activity level, duration and corticosteroid dependency appear to predict response to GMA. Additionally, patients with a first UC episode who were drug naive responded well to GMA and achieved a favorable long-term disease course by avoiding pharmacologics from an early stage of their inflammatory bowel disease. These findings should help to end unnecessary use of medical resources by targeting GMA to patients who may respond well.


Assuntos
Linhagem da Célula , Colite Ulcerativa/terapia , Granulócitos/citologia , Leucócitos/citologia , Células Mieloides/citologia , Adsorção , Adulto , Remoção de Componentes Sanguíneos , Colite Ulcerativa/sangue , Feminino , Humanos , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Masculino , Monócitos/citologia , Prognóstico , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
2.
Gan To Kagaku Ryoho ; 42(12): 2018-20, 2015 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-26805250

RESUMO

A 79-year-old woman with symptomatic pyloric stenosis was diagnosed with advanced gastric cancer. CT revealed that the tumor had invaded into the pancreatic head.Since no contraindications were found at laparotomy, we performed pancreatoduodenectomy. The histopathologic diagnosis was pT4b (panc), pN3a (11/35), P0, CY0, H0, M0, pStage ⅢC, R0. The patient received adjuvant chemotherapy with S-1 for 1 year. The patient has survived without recurrence for more than 2 years. The efficacy of pancreatoduodenectomy for advanced gastric cancer is still controversial. Pancreatoduodenetomy may be indicated for selected cases of advanced gastric cancer, if an R0 resection can be achieved.


Assuntos
Pâncreas/cirurgia , Neoplasias Gástricas/cirurgia , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Combinação de Medicamentos , Feminino , Gastrectomia , Humanos , Invasividade Neoplásica , Ácido Oxônico/uso terapêutico , Pâncreas/patologia , Pancreaticoduodenectomia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Tegafur/uso terapêutico , Fatores de Tempo
3.
Gan To Kagaku Ryoho ; 39(12): 2413-5, 2012 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-23268095

RESUMO

The current treatment plan for squamous cell anal canal carcinoma using chemoradiotherapy (CRT) is becoming more standardized. We use CRT rather than surgery to select the appropriate treatment. We experienced 4 patients treated with abdominoperineal resection(APR), of which 1 underwent adjuvant CRT. We also experienced 3 patients treated with radiotherapy(RT) and 2 treated with CRT. A patient treated with RT underwent APR because of radiation colitis. RT and CRT are advantageous for quality of life and are expected to be effective for controlling the disease. We hope that the standard treatment plan for anal cancer in Japan will be determined on the basis of histological features.


Assuntos
Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade
4.
Bioorg Med Chem Lett ; 22(10): 3408-11, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-22525313

RESUMO

Starting from a naphthol-based lead series with low oral bioavailability, we have identified potent TRPV1 antagonists with oral bioavailability in rats. These compounds emerged from SAR studies aimed at replacing the lead's phenol structure whilst maintaining potency. Compound rac-6a is an orally available TRPV1 antagonist with single-digit nanomolar activity. The enantiomers show a low eudismic ratio at the receptor level.


Assuntos
Naftóis/farmacologia , Canais de Cátion TRPV/antagonistas & inibidores , Administração Oral , Animais , Disponibilidade Biológica , Naftóis/administração & dosagem , Naftóis/farmacocinética , Ratos , Ratos Sprague-Dawley
5.
No Shinkei Geka ; 39(10): 975-80, 2011 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-21972187

RESUMO

A case of intraosseous lipoma in the frontal bone was reported. A 62-year-old woman had a hard tumor affecting the right frontal bone. The slowly growing tumor was first noticed when she was in her late teens. The completely excised right frontal lesion was composed of mature adipose tissue with abundant fibrous stroma. Intraosseous lipoma affecting the skull is extremely rare, with only 17 cases having been reported previously. Presurgical diagnosis of intraosseous lipoma of the skull is difficult because of its non-specific radiological features. Pathological study is indispensable for a correct diagnosis.


Assuntos
Osso Frontal , Lipoma/patologia , Neoplasias Cranianas/patologia , Feminino , Humanos , Lipoma/diagnóstico por imagem , Lipoma/cirurgia , Pessoa de Meia-Idade , Radiografia , Neoplasias Cranianas/diagnóstico por imagem , Neoplasias Cranianas/cirurgia
6.
J Agric Food Chem ; 59(18): 9770-5, 2011 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-21879707

RESUMO

A method for the determination of 4(5)-methylimidazole (4MeI) in naturally brewed soy sauce was developed for the first time using solid-phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). SPE on silica-based reversed-phase cartridges with heptafluorobutyric acid as an ion-pairing reagent was used for the efficient cleanup of 4MeI. A multimode ODS column was employed for the chromatographic separation. To subtract the matrix effect during LC-MS/MS analysis, a standard addition method was used. The levels of 4MeI found in naturally brewed soy sauce were extremely low (ranging from <0.002 to 0.023 µg/g), whereas those in soy sauces containing caramel color were generally high (ranging from 0.43 to 4.8 µg/g). The method proved to be useful for the analysis of 4MeI in other foods such as caramel colors, drinks, and Worcestershire sauce.


Assuntos
Cromatografia Líquida , Análise de Alimentos/métodos , Imidazóis/análise , Extração em Fase Sólida , Alimentos de Soja/análise , Espectrometria de Massas em Tandem , Carcinógenos/análise , Reprodutibilidade dos Testes
7.
Bioorg Med Chem Lett ; 21(11): 3354-7, 2011 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-21531136

RESUMO

We have identified naphthol derivatives as inhibitors of the vanilloid receptor TRPV1 by high throughput screening. The initial lead showed high clearance in rats and has been optimized by enhancing the acidity of the phenol group. Compound 6b has reduced clearance, improved potency and is active in rat cystometry models of urinary incontinence after intravenous administration.


Assuntos
Naftóis/química , Canais de Cátion TRPV/antagonistas & inibidores , Incontinência Urinária/tratamento farmacológico , Animais , Modelos Animais de Doenças , Feminino , Concentração Inibidora 50 , Estrutura Molecular , Naftóis/síntese química , Naftóis/uso terapêutico , Nutrição Parenteral , Ratos , Relação Estrutura-Atividade
8.
Gan To Kagaku Ryoho ; 37(12): 2340-2, 2010 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-21224566

RESUMO

A man in his early seventies underwent low anterior resection and partial resection of the liver for the rectal cancer and liver metastasis. However, 4 months after the surgery, he was found to have a liver tumor at S5 and S7 by abdominal CT scan. Then, he underwent chemotherapy (mFOLFOX6), but the metastatic tumor was progressive. We selected FOLFIRI + cetuximab regimen for second-line therapy to resect the metastatic tumor. As the metastatic lesion was become smaller after 4-course of the regimen including cetuximab, we decided to perform a radical resection. We conducted a right lobectomy of the liver, and the tumor was completely resected.


Assuntos
Adenocarcinoma/terapia , Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Colo/patologia , Hepatectomia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Idoso , Anticorpos Monoclonais Humanizados , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cetuximab , Terapia Combinada , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino
9.
Gan To Kagaku Ryoho ; 37(12): 2346-8, 2010 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-21224568

RESUMO

A woman in her fifties underwent a right hemicolectomy (D3) for cancer of the ascending colon in October 2007, definitively and pathologically diagnosed as papillary adenocarcinoma invading to the subserosa, and no metastasis was detected to lymph node. But 13 months after the surgery, she was found to have a mass near the anastomosis by an abdominal CT scan. Colonoscopy showed an evaluating lesion with ulcer in the anal side of the anastomosis. We tried to resect the metastasis, but it was not resectable because of the invasion to the pancreas. The mFOLFOX regimen was effective. After the chemotherapy (6 courses), we decided to perform a radical resection. We conducted pancreatoduodenectomy in May 2009. She is still alive 12 months after surgery.


Assuntos
Adenocarcinoma Papilar/patologia , Adenocarcinoma Papilar/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/patologia , Neoplasias do Colo/terapia , Metástase Linfática/patologia , Neoplasias Pancreáticas/secundário , Neoplasias Pancreáticas/terapia , Duodeno/cirurgia , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Compostos Organoplatínicos/uso terapêutico , Pancreatectomia
10.
Bioorg Med Chem Lett ; 18(11): 3310-4, 2008 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-18440813

RESUMO

Benzimidazolone derivatives were discovered as novel CB2 selective agonists. Structure Activity Relationship (SAR) studies around them were examined to improve metabolic stability. Compound 39 exhibited excellent metabolic stability in human liver microsomes (HLM) and significant attenuation of the chronic colonic allodynia in the TNBS-treated rats by po administration.


Assuntos
Benzimidazóis/síntese química , Benzimidazóis/farmacologia , Receptor CB2 de Canabinoide/agonistas , Animais , Benzimidazóis/química , Técnicas de Química Combinatória , Desenho de Fármacos , Humanos , Estrutura Molecular , Ratos , Receptor CB1 de Canabinoide/agonistas , Relação Estrutura-Atividade
12.
Fungal Genet Biol ; 44(5): 330-8, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17178246

RESUMO

The asexual ascomycete Aspergillus oryzae has an steA homolog in its genome. The steA homolog of A. oryzae was transcribed in the wild-type strain but steA disruption did not affect the phenotype of the disruptant strain. On the other hand, the steA-overexpressing strain showed the restriction of vegetative hyphal growth and conidiation, and the formation of balloon-shaped structures. The restriction of vegetative hyphal growth and conidiation were partially rescued by high osmolarity. In addition, the hyphal growth of the steA-overexpressing strain was inhibited by Calcofluor white, and the strain was found to be sensitive to cell-wall-degrading reagents. Increase of secretory cell-wall-degrading enzymes of the steA-overexpressing strain was detected. These results indicate that SteA regulates cell-wall-degrading enzymes and that the phenotypes of A. oryzae steA-overexpressing strain may be due to cell wall abnormalities. steA may participate in cell wall metabolism.


Assuntos
Aspergillus oryzae/genética , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Aspergillus oryzae/metabolismo , Southern Blotting , Parede Celular/metabolismo , Proteínas Fúngicas/química , Proteínas Fúngicas/fisiologia , Galactosidases/metabolismo , Hifas/genética , Hifas/metabolismo , Microscopia de Fluorescência , Modelos Genéticos , Fenótipo , Polissacarídeo-Liases/metabolismo , Estrutura Terciária de Proteína , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição Gênica , Dedos de Zinco/genética
13.
Mol Genet Genomics ; 275(5): 460-70, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16470383

RESUMO

In the koji molds Aspergillus sojae and Aspergillus oryzae, exogenous DNA is integrated in the genome, in most cases irrespective of the sequence homology, suggesting that DNA integration occurs predominantly through a nonhomologous end joining pathway where two ku genes, namely, ku70 and ku80, play a key role. To determine the effect of ku gene disruption on the gene targeting frequency, we constructed ku70-, ku80-, and ku70-ku80-disrupted strains of A. sojae and A. oryzae. The gene targeting frequency of the tannase gene in ku70 and ku80 strains of both Aspergillus species was markedly enhanced as compared with that of the parental strains. The gene targeting frequency of the aflR and ku80 genes was also enhanced in an A. sojae ku70 background. Therefore, the koji mold strains with ku-disrupted genes will be excellent tools as hosts for efficient gene targeting.


Assuntos
Antígenos Nucleares/genética , Aspergillus oryzae/genética , Proteínas de Ligação a DNA/genética , Frequência do Gene , Marcação de Genes , Genes Fúngicos , Reparo do DNA/fisiologia , Regulação para Baixo/fisiologia , Deleção de Genes , Autoantígeno Ku , Mutação Puntual
14.
Biosci Biotechnol Biochem ; 70(1): 135-43, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16428831

RESUMO

Ku genes play a key role in the non-homologous end-joining pathway. We have identified Ku70 and Ku80 homologs in the koji molds Aspergillus sojae and Aspergillus oryzae, and have constructed the disruption mutants of Ku70, Ku80, and Ku70-80 to characterize the phenotypic change in these mutants. Neither Ku70- nor Ku80-disrupted strains show hypersensitivity to the DNA damaging agents methylmethane sulfonate (MMS) and phleomycin. Moreover, undesirable phenotypes, such as poor growth or repressed conidiospore formation, were not observed in the Ku-disrupted A. sojae and A. oryzae.


Assuntos
Antígenos Nucleares/metabolismo , Aspergillus/metabolismo , Proteínas de Ligação a DNA/metabolismo , Sequência de Aminoácidos , Antígenos Nucleares/química , Antígenos Nucleares/genética , Aspergillus/química , Clonagem Molecular , Sequência Conservada , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Deleção de Genes , Vetores Genéticos/genética , Autoantígeno Ku , Modelos Biológicos , Dados de Sequência Molecular , Fenótipo , Filogenia , Plasmídeos/genética , Alinhamento de Sequência
15.
Bioorg Med Chem Lett ; 14(15): 4013-7, 2004 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-15225717

RESUMO

A series of 2-amino-3-cyano-4-alkyl-6-(2-hydroxyphenyl)pyridine derivatives was synthesized and evaluated as IkappaB kinase beta (IKK-beta) inhibitors. Substitution of an aminoalkyl group for the aromatic group at the 4-position on the core pyridine ring resulted in a marked increase in both kinase enzyme and cellular potencies, and provided potent IKK-beta inhibitors with IC(50) values of below 100 nM.


Assuntos
Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Inibidores Enzimáticos/química , Humanos , Quinase I-kappa B , Cinética , Modelos Moleculares , Conformação Molecular , Proteínas Recombinantes/antagonistas & inibidores , Relação Estrutura-Atividade
16.
Bioorg Med Chem Lett ; 14(15): 4019-22, 2004 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-15225718

RESUMO

A series of 2-amino-3-cyano-4-alkyl-6-(2-hydroxyphenyl)pyridine derivatives was synthesized and evaluated as I kappaB kinase beta (IKK-beta) inhibitors. Modification of a novel IKK-beta inhibitor 1 (IKK-beta IC(50)=1500 nM, Cell IC(50)=8000 nM) at the 4-phenyl ring and 6-phenol group on the pyridine core ring resulted in a marked increased in biological activities. An optimized compound, 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-piperidin-4-yl nicotinonitrile, exhibited excellent in vitro profiles (IKK-beta IC(50)=8.5 nM, Cell IC(50)=60 nM) and a strong oral efficacy in in vivo anti-inflammatory assays (significant effects at 1mg/kg, po in arachidonic acid-induced ear edema model in mice).


Assuntos
Anti-Inflamatórios/síntese química , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Piridinas/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças , Edema/prevenção & controle , Humanos , Quinase I-kappa B , Cinética , Camundongos , Modelos Moleculares , Estrutura Molecular , Piridinas/síntese química , Proteínas Recombinantes/antagonistas & inibidores , Relação Estrutura-Atividade
17.
Bioorg Med Chem Lett ; 13(5): 913-8, 2003 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-12617920

RESUMO

IkappaB kinase beta (IKK-beta) is a serine-threonine protein kinase critically involved in the activation of the transcription factor Nuclear Factor kappa B (NF-kappaB) in response to various inflammatory stimuli. We have identified a small molecule inhibitor of IKK-beta. Optimization of the lead compound resulted in improvements in both in vitro and in vivo potency, and provided IKK-beta inhibitors exhibiting potent activity in an acute cytokine release model (LPS-induced TNFalpha).


Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Animais , Linhagem Celular , Quimiocina CCL5/análise , Humanos , Quinase I-kappa B , Concentração Inibidora 50 , Camundongos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Recombinantes/antagonistas & inibidores , Proteínas Recombinantes/metabolismo , Relação Estrutura-Atividade
18.
Biosci Biotechnol Biochem ; 66(3): 693-6, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12005075

RESUMO

Aspergillus oryzae produces multinucleate conidia, which makes the obtaining of homokaryons labor-intensive. Analysis of conidia by flow cytometry clarified the relationship that conidia of lower nuclear number were smaller in size. Based on this, we have developed a simple way to enrich uninucleate conidia with a membrane filter. Our results also suggest that the method is useful for elimination of heterokaryons.


Assuntos
Aspergillus oryzae/crescimento & desenvolvimento , Aspergillus oryzae/ultraestrutura , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/ultraestrutura , Citometria de Fluxo , Microesferas , Espalhamento de Radiação , Ultrafiltração
19.
Chem Pharm Bull (Tokyo) ; 50(5): 615-22, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-12036015

RESUMO

(Ss)-3-(p-Tolylsufinyl)-2-furaldimine was synthesized, and condensation of the chiral furaldimine with lithium ester enolates has been examined. The product distribution of the reaction is dependent upon reaction conditions and on the kind of the substituent placed on the esters. Disubstituted ester enolate resulted in the exclusive formation of (4R)-beta-lactam, while unsubstituted, tert-butyl ester enolate preferentially gave (3R)-beta-amino ester. With the monosubstituted ester enolates, the condensation afforded (4R)-beta-lactams and/or (3R)-beta-amino esters as major products. This method has been applied to an efficient route to chiral furyl beta-lactams.


Assuntos
Furaldeído/análogos & derivados , Furaldeído/química , Cristalografia por Raios X , Iminas , Indicadores e Reagentes , Lactamas/química , Lítio , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estereoisomerismo
20.
Magn Reson Med Sci ; 1(1): 7-13, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-16037662

RESUMO

The lactate (LAC), creatine (CRN), taurine (TAU), anserine (ANS) and carnosine (CAR) content of the masseter muscles (MM), long extensor muscles of digits (EDL) and soleus muscles (SOL) of young rats were determined using in vitro 1H-NMR spectroscopy to assess the significance of CRN, TAU, ANS and CAR in these muscles. The muscles of Wistar rats at the ages of 6, 12 and 18 weeks were dissected after decapitation and used for the metabolite analyses. The LAC and CAR content of all muscle groups showed no age dependence. The CRN content was increased age-dependently in MM but not in EDL or SOL. The LAC and CRN content was higher in MM and EDL (fast-twitch) than in SOL (slow-twitch) (P<0.01-0.001 at 18 weeks). A significant positive correlation existed between the LAC and CRN content (P<0.00001, r=0.80), suggesting that the CRN content reflects the capacity of the anaerobic glycolysis of the individual muscles. The TAU content was higher in SOL and MM than in EDL (P<0.05) and showed an approximately 1.5-fold increase with age in all three muscle groups. The ANS content was higher in EDL than in SOL and MM (P<0.001), and showed an approximately threefold increase with age in all three muscle groups. The ANS content positively correlated with the LAC content (P<0.001, r=0.41), and the chemical shift of the imidazole proton in ANS showed a correlation with the LAC content (P<0.0001, r>0.76), indicating that ANS would buffer the pH change produced by LAC. These results suggest that 1H-NMR spectroscopy would provide an adjunct method of assessing the muscle types and their development.


Assuntos
Espectroscopia de Ressonância Magnética/métodos , Fibras Musculares de Contração Rápida/metabolismo , Fibras Musculares de Contração Lenta/metabolismo , Análise de Variância , Animais , Anserina/metabolismo , Carnosina/metabolismo , Creatina/metabolismo , Técnicas In Vitro , Ácido Láctico/metabolismo , Masculino , Ratos , Ratos Wistar , Taurina/metabolismo
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