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1.
Hepatol Res ; 51(10): 1013-1025, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34533266

RESUMO

Nonalcoholic fatty liver disease (NAFLD) has become a serious public health issue not only in Western countries but also in Japan. Within the wide spectrum of NAFLD, nonalcoholic steatohepatitis (NASH) is a progressive form of disease that often develops into liver cirrhosis and increases the risk of hepatocellular carcinoma (HCC). While a definite diagnosis of NASH requires liver biopsy to confirm the presence of hepatocyte ballooning, hepatic fibrosis is the most important prognostic factor in NAFLD. With so many NAFLD patients, it is essential to have an effective screening method for NAFLD with hepatic fibrosis. As HCC with non-viral liver disease has increased markedly in Japan, effective screening and surveillance of HCC are also urgently needed. The most common death etiology in NAFLD patients is cardiovascular disease event. Gastroenterologists must, therefore, pay close attention to CVD when examining NAFLD patients. In the updated guidelines, we propose screening and follow-up methods for hepatic fibrosis, HCC, and CVD in NAFLD patients. Several drug trials are ongoing for NAFLD/NASH therapy, however, there is currently no specific drug therapy for NAFLD/NASH. In addition to vitamin E and thiazolidinedione derivatives, recent trials have focused on sodium glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) analogues, and effective therapies are expected to be developed. These practical guidelines for NAFLD/NASH were established by the Japanese Society of Gastroenterology in conjunction with the Japan Society of Hepatology. Clinical evidence reported internationally between 1983 and October 2018 was collected, and each clinical and background question was evaluated using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. This English summary pro- vides the core essentials of these clinical practice guidelines, which include the definition and concept, screening systems for hepatic fibrosis, HCC and CVD, and current therapies for NAFLD/NASH in Japan.

2.
J Gastroenterol ; 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34533632

RESUMO

Nonalcoholic fatty liver disease (NAFLD) has become a serious public health issue not only in Western countries but also in Japan. Within the wide spectrum of NAFLD, nonalcoholic steatohepatitis (NASH) is a progressive form of disease that often develops into liver cirrhosis and increases the risk of hepatocellular carcinoma (HCC). While a definite diagnosis of NASH requires liver biopsy to confirm the presence of hepatocyte ballooning, hepatic fibrosis is the most important prognostic factor in NAFLD. With so many NAFLD patients, it is essential to have an effective screening method for NAFLD with hepatic fibrosis. As HCC with non-viral liver disease has increased markedly in Japan, effective screening and surveillance of HCC are also urgently needed. The most common death etiology in NAFLD patients is cardiovascular disease (CVD) event. Gastroenterologists must, therefore, pay close attention to CVD when examining NAFLD patients. In the updated guidelines, we propose screening and follow-up methods for hepatic fibrosis, HCC, and CVD in NAFLD patients. Several drug trials are ongoing for NAFLD/NASH therapy, however, there is currently no specific drug therapy for NAFLD/NASH. In addition to vitamin E and thiazolidinedione derivatives, recent trials have focused on sodium glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) analogues, and effective therapies are expected to be developed. These practical guidelines for NAFLD/NASH were established by the Japanese Society of Gastroenterology in conjunction with the Japan Society of Hepatology. Clinical evidence reported internationally between 1983 and October 2018 was collected, and each clinical and background question was evaluated using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. This English summary provides the core essentials of these clinical practice guidelines, which include the definition and concept, screening systems for hepatic fibrosis, HCC and CVD, and current therapies for NAFLD/NASH in Japan.

3.
J Clin Med ; 10(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34362152

RESUMO

PURPOSE: The surgical strategy for esophagogastric junction (EGJ) cancer depends on the tumor location as measured relative to the EGJ line. The purpose of this study was to clarify the accuracy of diagnostic endoscopy in different clinicopathological backgrounds. METHODS: Subjects were 74 consecutive patients with abdominal esophagus to upper gastric cancer who underwent surgical resection. Image-enhanced endoscopy with narrow-band imaging (NBI) was used to determine the EGJ line, prioritizing the presence of palisade vessels, followed by the upper end of gastric folds, as a landmark. The relative positional relationship between the tumor epicenter and the EGJ line was classified into six categories, and the agreement between endoscopic and pathologic diagnoses was examined to evaluate prediction accuracy. RESULTS: The concordance rate of 69 eligible cases was 87% with a kappa coefficient (K) of 0.81. The palisade vessels were observed in 62/69 patients (89.9%). Of the 37 pathological EGJ cancers centered within 2 cm above and below the EGJ line, Barrett's esophagus was found to be a significant risk factor for discordance (risk ratio, 4.40; p = 0.042); the concordance rate of 60% (K = 0.50) in the Barrett's esophagus group was lower than the rate of 91% (K = 0.84) in the non-Barrett's esophagus group. In five of six discordant cases, the EGJ line was estimated to be proximal to the actual line. CONCLUSION: Diagnostic endoscopy is beneficial for estimating the location of EGJ cancer, with a risk of underestimating esophageal invasion length in patients with Barrett's esophagus.

4.
Am J Gastroenterol ; 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404084

RESUMO

INTRODUCTION: Placebo response rates are relatively higher in clinical trials of disorders of brain-gut interaction. However, placebo response in functional dyspepsia (FD) has not been well described. Minimizing placebo response is important in drug development. We therefore conducted a meta-analysis to determine placebo response in trials for FD and to identify factors affecting placebo response rates. METHODS: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched to identify double-blinded randomized controlled trials (RCTs) comparing medication with placebo in patients with FD. Both symptom improvement and complete relief were considered as separate primary endpoints in the analysis. Proportions of placebo patients experiencing any symptom improvement or complete relief were calculated. Dropouts after randomization for any reason were assumed to represent treatment failure for data extraction and analysis. Placebo response was pooled by a random-effects model, and effects of trial characteristics on the magnitude of placebo response were evaluated. RESULTS: In 58 eligible placebo-controlled RCTs of FD from 52 selected citations, 6,732 of 17,890 participants in all trials received placebo. Pooled placebo response rates for symptom improvement and complete relief were 44.3% and 15.6%, respectively. The placebo response rate was lower when improvements were assessed for ≥8 weeks. Trials assessing complete symptom relief showed lower placebo response rates even in trials for <8 weeks. DISCUSSION: Our systematic review and meta-analysis showed that pooled placebo response rates in double-blinded RCTs of FD depended on efficacy criteria. Trials assessing complete symptom relief showed stable low placebo response rates in short-term trials.

5.
BMJ Open ; 11(8): e046310, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373296

RESUMO

INTRODUCTION: Regardless of having effective vaccines against COVID-19, containment measures such as enhanced physical distancing and good practice of personal hygiene remain the mainstay of controlling the COVID-19 pandemic. Countries across Asia have imposed these containment measures to varying extents. However, residents in different countries would have a differing degree of compliance to these containment measures potentially due to differences in the level of awareness and motivation in the early phase of pandemic. OBJECTIVES: In our study, we aimed to describe and correlate the level of knowledge and attitude with the level of compliance with personal hygiene and physical distancing practices among Asian countries in the early phase of pandemic. METHODS: A multinational cross-sectional study was carried out using electronic surveys between May and June 2020 across 14 geographical areas. Subjects aged 21 years and above were invited to participate through social media, word of mouth and electronic mail. RESULTS: Among the 2574 responses obtained, 762 (29.6%) participants were from East Asia and 1812 (70.4%) were from Southeast Asia (SEA). A greater proportion of participants from SEA will practise physical distancing as long as it takes (72.8% vs 60.6%). Having safe distancing practices such as standing more than 1 or 2 m apart (AdjOR 5.09 95% CI (1.08 to 24.01)) or more than 3 or 4 m apart (AdjOR 7.05 95% CI (1.32 to 37.67)), wearing a mask when they had influenza-like symptoms before the COVID-19 pandemic, preferring online news channels such as online news websites/applications (AdjOR 1.73 95% CI (1.21 to 2.49)) and social media (AdjOR 1.68 95% CI (1.13 to 2.50) as sources of obtaining information about COVID-19 and high psychological well-being (AdjOR 1.39 95% CI (1.04 to 1.87)) were independent factors associated with high compliance. CONCLUSIONS: We found factors associated with high compliance behaviour against COVID-19 in the early phase of pandemic and it will be useful to consider them in risk assessment, communication and pandemic preparedness.


Assuntos
COVID-19 , Pandemias , Vacinas contra COVID-19 , Estudos Transversais , Humanos , Pandemias/prevenção & controle , SARS-CoV-2 , Inquéritos e Questionários
6.
Biomedicines ; 9(6)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34204993

RESUMO

Although probiotics may be useful for the treatment of irritable bowel syndrome (IBS), it is unclear how probiotics play a role in colonic mucosal integrity and immunity. Here, we aimed to investigate the effect of Bifidobacterium bifidum G9-1 (BBG9-1) on colonic mucosal integrity and macrophage behavior in rats subjected to maternal separation (MS) as a model of IBS. MS pups were individually separated from their mother rats, and a proportion of the MS rats were orally administered BBG9-1. The colonic mucosal permeability was evaluated by Ussing chamber assay. The expression of tight junction proteins and cytokines and the population of CD80-positive cells was examined in the colonic tissues by real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Caco2 cells were stimulated with cytokines and the transepithelial electric resistance (TEER) was measured. MS rats showed significantly higher colonic permeability and lower claudin 4 expression in the colonic epithelium relative to controls. The number of CD80-positive macrophages was significantly increased in the colonic mucosa of MS rats, accompanied by the increase of IL-6 and IFN-γ expression. BBG9-1 treatment ameliorated the increase of M1 macrophage and IL-6/IFN-γ expression in the colonic tissue of MS rats. Simultaneously, BBG9-1 treatment improved the enhanced mucosal permeability and the decreased claudin 4 expression in the colon of MS rats. IL-6 and IFN-γ, whose expression is enhanced in the colon of MS rats, significantly decreased TEER in Caco2 cells in vitro. Probiotic BBG9-1 has a preventive effect on the acceleration of colonic permeability and M1 macrophage population in maternally separated rats.

7.
Int J Mol Sci ; 22(13)2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34281249

RESUMO

Regenerating gene (REG) family proteins serve as multifunctional secretory molecules with trophic, antiapoptotic, anti-inflammatory, antimicrobial and probably immuno-regulatory effects. Since their discovery, accumulating evidence has clarified the potential roles of the REG family in the occurrence, progression and development of a wide range of inflammatory and inflammation-associated diseases of the gastrointestinal (GI) tract. However, significant gaps still exist due to the undefined nature of certain receptors, regulatory signaling pathways and possible interactions among distinct Reg members. In this narrative review, we first describe the structural features, distribution pattern and purported regulatory mechanisms of REG family proteins. Furthermore, we summarize the established and proposed roles of REG proteins in the pathogenesis of various inflammation-associated pathologies of the GI tract and the body as a whole, focusing particularly on carcinogenesis in the ulcerative colitis-colitic cancer sequence and gastric cancer. Finally, the clinical relevance of REG products in the context of diagnosis, treatment and prognostication are also discussed in detail. The current evidence suggests a need to better understanding the versatile roles of Reg family proteins in the pathogenesis of inflammatory-associated diseases, and their broadened future usage as therapeutic targets and prognostic biomarkers is anticipated.


Assuntos
Gastroenteropatias/metabolismo , Trato Gastrointestinal/metabolismo , Inflamação/imunologia , Animais , Apoptose/genética , Gastroenteropatias/imunologia , Trato Gastrointestinal/imunologia , Humanos , Inflamação/metabolismo , Doenças Inflamatórias Intestinais , Mucosa Intestinal/metabolismo , Lectinas Tipo C/metabolismo , Litostatina/genética , Litostatina/metabolismo , Proteínas Associadas a Pancreatite/genética , Proteínas Associadas a Pancreatite/metabolismo , Neoplasias Gástricas
8.
Glia ; 69(10): 2332-2348, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34309082

RESUMO

Microglia are the resident immune cells of the brain, and play essential roles in neuronal development, homeostatic function, and neurodegenerative disease. Human microglia are relatively different from mouse microglia. However, most research on human microglia is performed in vitro, which does not accurately represent microglia characteristics under in vivo conditions. To elucidate the in vivo characteristics of human microglia, methods have been developed to generate and transplant induced pluripotent or embryonic stem cell-derived human microglia into neonatal or adult mouse brains. However, its widespread use remains limited by the technical difficulties of generating human microglia, as well as the need to use immune-deficient mice and conduct invasive surgeries. To address these issues, we developed a simplified method to generate induced pluripotent stem cell-derived human microglia and transplant them into the brain via a transnasal route in immunocompetent mice, in combination with a colony stimulating factor 1 receptor antagonist. We found that human microglia were able to migrate through the cribriform plate to different regions of the brain, proliferate, and become the dominant microglia in a region-specific manner by occupying the vacant niche when exogenous human cytokine is administered, for at least 60 days.

9.
Hepatol Res ; 51(7): 725-749, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34228859

RESUMO

The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japanese Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.

10.
J Gastroenterol ; 56(7): 593-619, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34231046

RESUMO

The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japan Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.

14.
15.
PLoS One ; 16(6): e0252835, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34097719

RESUMO

IMPORTANCE: Knowledge and attitude influence compliance and individuals' practices. The risk and protective factors associated with high compliance to these preventive measures are critical to enhancing pandemic preparedness. OBJECTIVE: This survey aims to assess differences in mental health, knowledge, attitudes, and practices (KAP) of preventive measures for COVID-19 amongst healthcare professionals (HCP) and non-healthcare professionals. DESIGN: Multi-national cross-sectional study was carried out using electronic surveys between May-June 2020. SETTING: Multi-national survey was distributed across 36 countries through social media, word-of-mouth, and electronic mail. PARTICIPANTS: Participants ≥21 years working in healthcare and non-healthcare related professions. MAIN OUTCOME: Risk factors determining the difference in KAP towards personal hygiene and social distancing measures during COVID-19 amongst HCP and non-HCP. RESULTS: HCP were significantly more knowledgeable on personal hygiene (AdjOR 1.45, 95% CI -1.14 to 1.83) and social distancing (AdjOR 1.31, 95% CI -1.06 to 1.61) compared to non-HCP. They were more likely to have a positive attitude towards personal hygiene and 1.5 times more willing to participate in the contact tracing app. There was high compliance towards personal hygiene and social distancing measures amongst HCP. HCP with high compliance were 1.8 times more likely to flourish and more likely to have a high sense of emotional (AdjOR 1.94, 95% CI (1.44 to 2.61), social (AdjOR 2.07, 95% CI -1.55 to 2.78), and psychological (AdjOR 2.13, 95% CI (1.59-2.85) well-being. CONCLUSION AND RELEVANCE: While healthcare professionals were more knowledgeable, had more positive attitudes, their higher sense of total well-being was seen to be more critical to enhance compliance. Therefore, focusing on the well-being of the general population would help to enhance their compliance towards the preventive measures for COVID-19.


Assuntos
COVID-19/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/psicologia , Pandemias/prevenção & controle , Cooperação do Paciente , Adulto , Estudos Transversais , Feminino , Saúde Global , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários
16.
In Vivo ; 35(4): 2247-2251, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34182503

RESUMO

BACKGROUND: Multimodality treatment including immune check point inhibitors is required for stage IV oesophagogastric junction cancer (OGJC). CASE REPORT: A 69-year-old man, was diagnosed with advanced OGJC and para-aortic lymph node metastasis (T3N+M1, stage IV), which upon biopsy, was shown to be an adenocarcinoma. After eight courses of nivolumab as third-line chemotherapy, the primary tumour and enlarged regional and para-aortic lymph nodes shrunk markedly, while tumour markers decreased within normal ranges. We performed a minimally invasive Ivor-Lewis oesophagectomy with completion of an abdominal D2 and transhiatal lower mediastinal lymph node dissection. Pathological findings revealed a complete response for the primary tumour and a regional lymph node metastasis. A biopsy of the previous sample revealed microsatellite instability-negativity, Epstein-Barr virus-negativity, and programmed cell death-1-ligand combined positive score of 2. He was followed up for 3 months without recurrence. CONCLUSION: Nivolumab may induce pathological complete response for stage IV OGJC even in cases negative for microsatellite instability and Epstein-Barr virus, besides the programmed cell death-1-ligand combined positive score of <5.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Esofagectomia , Junção Esofagogástrica/cirurgia , Herpesvirus Humano 4 , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Recidiva Local de Neoplasia , Nivolumabe/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia
17.
J Gastroenterol ; 56(6): 489-526, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33885977

RESUMO

Inflammatory bowel disease (IBD) is a general term for chronic or remitting/relapsing inflammatory diseases of the intestinal tract and generally refers to ulcerative colitis (UC) and Crohn's disease (CD). Since 1950, the number of patients with IBD in Japan has been increasing. The etiology of IBD remains unclear; however, recent research data indicate that the pathophysiology of IBD involves abnormalities in disease susceptibility genes, environmental factors and intestinal bacteria. The elucidation of the mechanism of IBD has facilitated therapeutic development. UC and CD display heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management depends on the understanding and tailoring of evidence-based interventions by physicians. In 2020, seventeen IBD experts of the Japanese Society of Gastroenterology revised the previous guidelines for IBD management published in 2016. This English version was produced and modified based on the existing updated guidelines in Japanese. The Clinical Questions (CQs) of the previous guidelines were completely revised and categorized as follows: Background Questions (BQs), CQs, and Future Research Questions (FRQs). The guideline was composed of a total of 69 questions: 39 BQs, 15 CQs, and 15 FRQs. The overall quality of the evidence for each CQ was determined by assessing it with reference to the Grading of Recommendations Assessment, Development and Evaluation approach, and the strength of the recommendation was determined by the Delphi consensus process. Comprehensive up-to-date guidance for on-site physicians is provided regarding indications for proceeding with the diagnosis and treatment.

18.
Pathogens ; 10(4)2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33917384

RESUMO

Although sessile serrated adenoma/polyps (SSA/Ps) may arise through a pathway different from the traditional adenoma-carcinoma sequence, details of SSA/P tumorigenesis still remain unclear. Fusobacterium nucleatum (Fn) is frequently detected in colorectal cancer (CRC) tissues and may play a pivotal role in colorectal carcinogenesis. Here, we investigated the relationship between Fn and the ß-catenin/REG Iα axis in SSA/Ps and their involvement in the proliferation of these lesions. Fn was detected in SSA/Ps by fluorescence in situ hybridization using a Fn-targeted probe, and expression of ß-catenin, REG Iα and Ki67 was examined using immunohistochemistry. Sixteen of 30 SSA/P lesions (53.3%) were positive for Fn. Eighteen SSA/P lesions (60%) showed ß-catenin immunoreactivity in the tumor cell nuclei. A significant majority of Fn-positive lesions showed nuclear expression of ß-catenin (87.5%) and higher REG Iα scores and Ki67 labeling indices relative to Fn-negative lesions. The SSA/P lesions expressing ß-catenin in nuclei had significantly higher REG Iα scores and Ki67 labeling indices than those expressing ß-catenin on cytomembranes. The REG Iα score was positively correlated with the Ki67 labeling index in SSA/P lesions. The treatment with Wnt agonist SKL2001 promoted nuclear ß-catenin translocation and enhanced REG Ia expression in Caco2 cells. Fn may play a role in the proliferation of SSA/P lesions through promotion of ß-catenin nuclear translocation and REG Iα expression.

19.
Medicine (Baltimore) ; 100(15): e25494, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33847661

RESUMO

ABSTRACT: Recent breakthrough results from immune checkpoint inhibitors (ICIs) have paved the way to a new era of cancer immunotherapy, and have thus led to a paradigm shift of cancer treatment. In particular, inhibition of the antiprogrammed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis with ICI, including nivolumab and pembrolizumab, has been emerging as a novel treatment strategy for advanced gastric cancers. An accurate noninvasive assessment of the response to ICI is important for the management of patients with advanced or metastatic gastric cancer.To examine whether the European Organization for Research and Treatment of Cancer (EORTC) and PET Response Criteria in Solid Tumors (PERCIST) are valuable for predicting progression-free survival (PFS) in patients with advanced or metastatic gastric cancers treated with nivolumab.Six patients with advanced or metastatic gastric cancers who underwent 18F-FDG-PET/computed tomography (CT) scans before, and from 2 to 6 months after initiation of nivolumab therapy between September 2017 and August 2019, were evaluated retrospectively. The correlation between tumor progression and EORTC or PERCIST was assessed with the Fisher's exact test. The PFS was assessed with the Kaplan-Meier method.Two patients were alive without progression, and the remaining 4 patients exhibited tumor progression. Two patients without progression were classified as partial metabolic response (PMR) patients based on EORTC or PERCIST, while the other 4 patients with progression were classified as progressive metabolic disease (PMD) patients based on EORTC (P = .067), or stable metabolic disease (SMD) patients, or PMD patients based on PERCIST (P = .067).The mean and median PFS of all patients was 12.7 months (95% confidence interval [CI], 4.9-20.4 months) and 5 months (95%CI, 4.0-11.0 months). Two EORTC or PERCIST PMR patients showed significantly longer median PFS compared with 4 non-PMR patients (not reached vs 4.0 months, P = .044). Three PERCIST PMR or SMD patients also showed significantly longer median PFS compared with 3 PMD patients (not reached vs 4.0 months, P = .022). These results suggest that EORTC or PERCIST has the potential to predict PFS of patients with advanced or metastatic gastric cancers treated by nivolumab and further studies are needed to determine its value in larger study populations.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Nivolumabe/uso terapêutico , Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Critérios de Avaliação de Resposta em Tumores Sólidos , Neoplasias Gástricas/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Tomografia por Emissão de Pósitrons/métodos , Valor Preditivo dos Testes , Intervalo Livre de Progressão , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade
20.
Biology (Basel) ; 10(3)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803334

RESUMO

Gastrointestinal (GI) disorders such as celiac disease and inflammatory bowel disease are attributed to intestinal barrier disruption. Imbalance of cytokines has been reported in the intestinal epithelium of patients with GI disorders. Short-chain fatty acids (SCFAs), derived from the fermentation of dietary fiber in the intestine, have been reported to benefit the intestinal barrier. Accordingly, we evaluated the effect of specific SCFAs on intestinal barrier function under cytokine-stimulated conditions. Caco-2 cells were cultured on insert membranes to generate monolayers, which then were used to investigate the effects of SCFAs. Tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), or interleukin-13 (IL-13) was added to the basolateral side of the membrane while SCFAs were added to the apical side. After a 24 h stimulation, transepithelial electrical resistance (TEER) was measured, and the protein levels of claudin-1, claudin-2, claudin-3, claudin-4, occludin, and zonula occludens-1 (ZO-1) were evaluated by Western blot. Butyrate, but not acetate, propionate, or succinate, ameliorated the TNF-α/IFN-γ-induced decrease in TEER. TNF-α/IFN-γ stimulation significantly increased the protein level of claudin-2 and decreased the level of claudin-3. Butyrate significantly attenuated the upregulation of claudin-2 induced by TNF-α/IFN-γ. Butyrate blocked the decrease in TEER and the upregulation of claudin-2 induced by IL-13 without changing the level of other tight junction proteins. Our results suggested that butyrate is the main component of SCFAs to alleviate barrier dysfunction and that claudin-2 is the major target of this SCFA.

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