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1.
Jpn J Clin Oncol ; 53(3): 275-279, 2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36546711

RESUMO

Juvenile polyposis syndrome (JPS) is an autosomal dominant, inherited disorder caused by pathogenic germline variants of mainly SMAD4 or BMPR1A genes. Some patients with JPS, especially with SMAD4 variants, also develop hereditary, hemorrhagic telangiectasia (HHT). HHT is also an autosomal dominant inherited disorder. Herein, we identified a novel germline pathogenic variant of the SMAD4 in a Japanese family with JPS and HHT. A six-base pair deletion in the SMAD4 gene (NM_005359.6:c.1495_1500delTGCATA) was identified in the patients. Two amino acids are deleted from SMAD4 protein (p.Cys499_Ile500del), which are located in MSH2 domain essential for the binding with SMAD3. This is a novel variant that has not been registered in any database surveyed. Amino acid structural analysis predicted significant changes in the secondary and three-dimensional structures in the vicinity of the two amino acids' deletion. The variant is classified as 'Likely Pathogenic' according to the American College of Medical Genetics and Genomics guidelines.


Assuntos
Polipose Intestinal , Síndromes Neoplásicas Hereditárias , Telangiectasia Hemorrágica Hereditária , Humanos , Telangiectasia Hemorrágica Hereditária/genética , Telangiectasia Hemorrágica Hereditária/complicações , Proteína Smad4/genética , População do Leste Asiático , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/complicações , Polipose Intestinal/genética , Polipose Intestinal/complicações , Células Germinativas
2.
Biochem Biophys Res Commun ; 602: 41-48, 2022 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-35248948

RESUMO

Knockout mice of diacylglycerol kinase (DGK) η, which has been repeatedly suggested to be associated with bipolar disorder (BPD) by genome-wide association studies, exhibited abnormal behaviors similar to the manic phase of BPD. Chronic stress is also linked to changes in mood symptoms, including BPD. In the present study, we analyzed the effects of the glucocorticoid stress hormones, triamcinolone acetonide (TAA) and dexamethasone (DEX), on DGKη protein levels in neuroblastoma cell lines, Neuro-2a and SH-SY5Y. The protein levels of DGKη were significantly increased in the undifferentiated Neuro-2a and SH-SY5Y cells by TAA and DEX, but not in the differentiated neuroblastoma cells. To assess the functions of DGKη in undifferentiated neuroblastoma cells, we established DGKη-deficient SH-SY5Y cells using the clustered regularly interspaced palindromic repeat/caspase 9 system. Notably, proliferation of DGKη-deficient SH-SY5Y cells was markedly attenuated, concomitant with the decrease in levels of phosphorylated extracellular signal-regulated kinase. Taken together, these results suggest that DGKη levels are increased in undifferentiated neuroblastoma cells by glucocorticoid stress hormones and regulate cell proliferation.


Assuntos
Diacilglicerol Quinase , Neuroblastoma , Animais , Linhagem Celular Tumoral , Proliferação de Células , Diacilglicerol Quinase/metabolismo , Estudo de Associação Genômica Ampla , Glucocorticoides/farmacologia , Camundongos , Camundongos Knockout
3.
Anticancer Res ; 42(3): 1599-1605, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35220257

RESUMO

BACKGROUND/AIM: The impact of clinical response to taxanes plus ramucirumab (RAM) on overall survival (OS) has not been clarified for advanced gastric cancer (AGC), although this type of therapy is already in use as second-line chemotherapy (CTx). This study aimed to investigate the prognostic impact of the clinical response to taxanes plus ramucirumab (RAM) for AGC patients. PATIENTS AND METHODS: This study included AGC patients treated with paclitaxel (PTX) or nab-paclitaxel (nab-PTX) and RAM. A retrospective analysis of response and survival rates in consecutive medical records of patients was performed. RESULTS: Forty-two patients were enrolled. Median progression-free survival and OS were 5.4 months [95% confidence interval (CI)=4.440-6.361] and 11.8 months (95% CI=8.648-15.019), respectively. In Cox-hazard multivariate analysis, peritoneal metastasis [hazard ratio (HR)=2.830; 95% CI=1.320-6.067; p=0.008], and disease control rate (HR=0.310; 95% CI=0.129-0.741; p=0.008) were independent factors. CONCLUSION: The response to taxanes plus RAM CTx had an impact on the survival of patients with AGC.


Assuntos
Albuminas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Paclitaxel/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Idoso , Albuminas/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Masculino , Prontuários Médicos , Paclitaxel/efeitos adversos , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Fatores de Tempo , Ramucirumab
4.
J Nippon Med Sch ; 89(3): 246-254, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35082204

RESUMO

Colorectal cancer (CRC) is the third most common cancer worldwide, and surgical treatment remains the first-line treatment to provide a cure. In addition to the aging population, obesity, low physical activity, and smoking habits increase CRC risk. Despite advances in surgical techniques, chemotherapy, and radiotherapy, colorectal cancer remains the second leading cause of cancer-related deaths worldwide. For early-stage CRC, endoscopic treatment, including endoscopic mucosal resection and endoscopic submucosal dissection, has been performed. However, lymph node dissection is an integral part of surgical treatment for advanced-stage cancer because of the high incidence of lymph node metastasis. Conventional open surgery has evolved into laparoscopic and robotic surgery. Although prospective studies have confirmed the safety and feasibility of laparoscopic surgery for CRC, relevant treatment models of transverse colon cancer and rectal cancer still need to be further explored and validated. Furthermore, multidisciplinary treatment is needed to cure CRC completely. This review aimed to provide an update on recent advances in the surgical treatment of CRC.


Assuntos
Neoplasias Colorretais , Laparoscopia , Neoplasias Retais , Idoso , Neoplasias Colorretais/cirurgia , Humanos , Excisão de Linfonodo/métodos , Metástase Linfática , Estudos Prospectivos , Neoplasias Retais/cirurgia
5.
Clin J Gastroenterol ; 14(4): 1053-1059, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34100257

RESUMO

Histiocytic sarcoma is a relatively new disease category and the gastrointestinal origin is sporadic. We report a case of a 74-year-old woman who underwent chemotherapy and proximal gastrectomy for extremely rare, advanced gastric histiocytic sarcoma. The resected specimen was subjected to numerous immunostainings to meet the diagnostic criteria of histiocytic sarcoma and was positive for the histiocyte markers' cluster of differentiation 68 and lysozyme. The markers of Langerhans cells, follicular dendritic cells, and myelocyte were all negative. Six reports of surgical resection of histiocytic sarcoma originating in the stomach exist, including our case. We reviewed the clinical course and the histological and immunohistochemical diagnostic features of surgically resected gastric histiocytic sarcoma.


Assuntos
Sarcoma Histiocítico , Neoplasias Gástricas , Idoso , Feminino , Gastrectomia , Sarcoma Histiocítico/tratamento farmacológico , Sarcoma Histiocítico/cirurgia , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia
6.
Clin J Gastroenterol ; 14(2): 494-499, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33512639

RESUMO

Reports of gastric collision tumors, comprising adenocarcinoma and gastrointestinal stromal tumor, are extremely rare. Here, we report the case of a 68-year-old male who was diagnosed with a lower-body, moderately differentiated, tubular-type adenocarcinoma and submucosal tumor and underwent an elective D2 distal gastrectomy. The tumor cells of the gastrointestinal stromal tumor were positive for H-caldesmon and CD117, weakly positive for smooth muscle actin and DOG-1, and negative for desmin, S-100 protein, CD31, and AE1/AE3. The tumor had grown into a mixed form of adenocarcinoma and gastrointestinal stromal tumor. Thus, we report the first case of a preoperatively diagnosed collision tumor in the stomach consisting of adenocarcinoma and gastrointestinal stromal tumor.


Assuntos
Adenocarcinoma , Tumores do Estroma Gastrointestinal , Neoplasias Gástricas , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Masculino , Proteínas Proto-Oncogênicas c-kit , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirurgia
7.
J Nippon Med Sch ; 88(3): 242-247, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32863341

RESUMO

Chylous ascites associated with radical resection of gastric cancer is a serious clinical condition. Lymph node dissection is indispensable during gastrectomy for gastric cancer. However, postoperative chylous ascites prolongs the hospital stay and re-operation. There are few reports on this subject. Most cases of chylous ascites resolve without treatment, but the condition can result in substantial morbidity. The definition of chylous ascites is ambiguous and varies in the English literature. In this report, we discuss a case of chylous ascites in a 68-year-old man who underwent distal gastrectomy for early gastric cancer at our hospital. He was admitted 8 months after surgery with a main complaint of abdominal swelling. Abdominal puncture helped to diagnose chylous ascites with marked elevation of triglyceride level. The patient received a hypercaloric infusion through a central line, and octreotide acetate, but did not improve. After assessment of lymph outflow by lymph scintigraphy, surgical ligation of the lymph vessels was performed through laparotomy. The volume of milky-white ascites in the abdominal cavity was 3,000 mL. Macroscopically, the fluid was confirmed as flowing from behind the common hepatic artery. Thus, ligation was performed. Chylous ascites has not recurred at 12 months after the re-operation. In summary, a case of chylous ascites after radical gastrectomy for gastric cancer was successfully treated by surgery. We review and discuss the relevant literature.


Assuntos
Ascite Quilosa/terapia , Adesivo Tecidual de Fibrina/uso terapêutico , Gastrectomia/efeitos adversos , Vasos Linfáticos/cirurgia , Neoplasias Gástricas/cirurgia , Idoso , Ascite , Ascite Quilosa/diagnóstico , Ascite Quilosa/etiologia , Humanos , Ligadura , Vasos Linfáticos/diagnóstico por imagem , Masculino , Recidiva Local de Neoplasia , Cintilografia , Resultado do Tratamento
8.
J Nippon Med Sch ; 86(3): 183-186, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31292331

RESUMO

The preoperative diagnosis of cecal volvulus (CV) is rare and difficult and emergent laparotomy is frequently performed. Here, we report a case of CV that was diagnosed by preoperative computed tomography in a patient with an intellectual disability. In addition, we demonstrate that elective laparoscopic cecopexy can be performed following conservative treatment, such as the use of an ileus tube per anus.


Assuntos
Doenças do Ceco/diagnóstico por imagem , Doenças do Ceco/cirurgia , Ceco/cirurgia , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/etiologia , Volvo Intestinal/diagnóstico por imagem , Volvo Intestinal/cirurgia , Adulto , Doenças do Ceco/complicações , Tratamento Conservador , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Deficiência Intelectual/complicações , Volvo Intestinal/complicações , Laparoscopia , Recidiva , Tomografia Computadorizada por Raios X , Resultado do Tratamento
9.
Xenobiotica ; 48(10): 1006-1020, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29092680

RESUMO

The human mass balance of [14 C]Z-215, a novel proton pump inhibitor, was characterised in six healthy male volunteers following single oral administration of [14 C]Z-215 (20 mg, 3.7 MBq) to determine the elimination pathway of Z-215 and the distribution of its metabolites in plasma, urine, and faeces (NCT02618629). [14 C]Z-215 was rapidly absorbed, with a Cmax of 434 ng/mL at 0.38 h for Z-215 and 732 ng eq./mL at 0.5 h for total radioactivity. Means of 59.61% and 31.36% of the administered radioactive dose were excreted in urine and faeces, respectively, within 168 h post-dose. The majority of the dose was recovered within 24 h in urine and 96 h in faeces. Unchanged Z-215 was excreted in urine at trace levels but was not detected in faeces. The main components in plasma were Z-215 and Z-215 sulphone, accounting for 29.8% and 13.3% of the total circulating radioactivity, respectively. Additionally, Z-215 was metabolised through oxidation, reduction and conjugation. Our in vitro Z-215 metabolism study showed that the major isozyme contributing to the oxidation of Z-215, including the formation of Z-215 sulphone, was CYP3A4. In conclusion, Z-215 is well absorbed in humans and primarily eliminated via metabolism, where CYP3A4 plays an important role.


Assuntos
Voluntários Saudáveis , Inibidores da Bomba de Prótons/metabolismo , Administração Oral , Cromatografia Líquida de Alta Pressão , Sistema Enzimático do Citocromo P-450/metabolismo , Fezes/química , Humanos , Isoenzimas/metabolismo , Masculino , Metaboloma , Metabolômica , Microssomos Hepáticos/metabolismo , Oxirredução , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/química , Inibidores da Bomba de Prótons/farmacocinética , Radioatividade , Padrões de Referência
10.
Asian J Endosc Surg ; 10(1): 59-62, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27554920

RESUMO

Limy bile syndrome extending to the common bile duct (CBD) is a rare condition that lacks a standardized treatment. Laparoscopic cholecystectomy with laparoscopic choledocholithotomy by CBD exploration is preferred because it preserves the function of the sphincter of the Vater's papilla and allows treatment of both lesions. A 37-year-old man who was receiving entecavir for chronic hepatitis B developed right upper quadrant pain. Abdominal ultrasonography revealed a calcified shadow in the gallbladder and CBD. Abdominal imaging revealed a liquid-like material identified by a calcified shadow in two phases separated by a fluid-fluid level. Abdominal and 3-D drip infusion cholangiography CT showed stones in the gallbladder and CBD with limy bile. The patient underwent laparoscopic cholecystectomy and choledocholithotomy. Intraoperatively, white-yellow-colored bile and stones were drained from the CBD. A C-tube was placed. Postoperatively, remnant stones and radiopaque materials were absent. The stones comprised of >95% calcium carbonate.


Assuntos
Bile , Colecistectomia Laparoscópica , Coledocolitíase/cirurgia , Ducto Colédoco/cirurgia , Cálculos Biliares/cirurgia , Adulto , Coledocolitíase/patologia , Cálculos Biliares/patologia , Humanos , Masculino , Síndrome
11.
PLoS One ; 9(6): e98737, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24892523

RESUMO

WRKY transcription factors and mitogen-activated protein kinase (MAPK) cascades have been shown to play pivotal roles in the regulation of plant defense responses. We previously reported that OsWRKY53-overexpressing rice plants showed enhanced resistance to the rice blast fungus. In this study, we identified OsWRKY53 as a substrate of OsMPK3/OsMPK6, components of a fungal PAMP-responsive MAPK cascade in rice, and analyzed the effect of OsWRKY53 phosphorylation on the regulation of basal defense responses to a virulence race of rice blast fungus Magnaporthe oryzae strain Ina86-137. An in vitro phosphorylation assay revealed that the OsMPK3/OsMPK6 activated by OsMKK4 phosphorylated OsWRKY53 recombinant protein at its multiple clustered serine-proline residues (SP cluster). When OsWRKY53 was coexpressed with a constitutively active mutant of OsMKK4 in a transient reporter gene assay, the enhanced transactivation activity of OsWRKY53 was found to be dependent on phosphorylation of the SP cluster. Transgenic rice plants overexpressing a phospho-mimic mutant of OsWRKY53 (OsWRKY53SD) showed further-enhanced disease resistance to the blast fungus compared to native OsWRKY53-overexpressing rice plants, and a substantial number of defense-related genes, including pathogenesis-related protein genes, were more upregulated in the OsWRKY53SD-overexpressing plants compared to the OsWRKY53-overexpressing plants. These results strongly suggest that the OsMKK4-OsMPK3/OsMPK6 cascade regulates transactivation activity of OsWRKY53, and overexpression of the phospho-mimic mutant of OsWRKY53 results in a major change to the rice transcriptome at steady state that leads to activation of a defense response against the blast fungus in rice plants.


Assuntos
Oryza/metabolismo , Oryza/microbiologia , Doenças das Plantas/microbiologia , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Plantas Geneticamente Modificadas/microbiologia , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica de Plantas , Oryza/genética , Doenças das Plantas/genética , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Fatores de Transcrição/genética
12.
Biosci Biotechnol Biochem ; 73(8): 1901-4, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19661718

RESUMO

OsWRKY53, a chitin oligosaccharide elicitor-responsive rice WRKY gene, has been found to be involved in defense responses in rice. We identified three tandem W-box elements, putative recognition sites for WRKY transcription factors, as cis elements that are essential to the elicitor-responsiveness of OsWRKY53 by deletion and mutation analysis of the promoter by dual luciferase assay.


Assuntos
Oryza/genética , Oryza/fisiologia , Proteínas de Plantas/genética , Regiões Promotoras Genéticas/genética , Fatores de Transcrição/genética , Sequência de Bases , Células Cultivadas , Quitina/metabolismo , Luciferases/genética , Proteínas de Plantas/metabolismo , Elementos de Resposta , Deleção de Sequência , Fatores de Transcrição/metabolismo
13.
Colloids Surf B Biointerfaces ; 38(3-4): 103-9, 2004 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-15542309

RESUMO

Gelation dynamics and gel structure of fibrinogen induced by serine protease, thrombin, was investigated by light scattering, real space observation using confocal laser scanning microscopy (CLSM), and turbidity. Effects of additives, such as (linear) saccharides, glucose to dextran, and cyclodextrin, were studied focusing on the interaction with fibrin(ogen) and thrombin. Light scattering measurement was ascertained to be able to characterize the gelation process and growth kinetics. Stepwise (two-step) gelation process, formation of fibrin monomers and protofibrils followed by the lateral aggregation to form fibrin fibers and gel network, was clearly ascertained. Gelation point could be characterized quantitatively. At the gelation point, dynamic light scattering exhibited a self-similar nature of the fibrin gel network, and the fractal dimension was evaluated in good accordance with the reconstructed 3D image of gel network by CLSM. The interaction between the additives and fibrin(ogen) and thrombin were studied by the inhibition test using synthesized substrate. Temporal variation of microstructure of fibrin gel network (lateral fiber growth) was investigated by turbidity in detail. Addition of saccharides affects significantly the network formation as revealed by turbidity. The interaction of dextran with fibrin fibers was examined by fluorescence microscopy, too, and the characteristic spatial distribution was observed.


Assuntos
Fibrinogênio/química , Géis , Microscopia Confocal , Estrutura Molecular
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