Folia Pharmacologica Japonica最新文献_第7页

[A novel drug target VIPR2 to regulate migration and proliferation in breast cancer]. [一种新的药物靶向VIPR2调节乳腺癌的迁移和增殖]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.25006

Satoshi Asano, Kotaro Sakamoto, Yukio Ago

{"title":"[A novel drug target VIPR2 to regulate migration and proliferation in breast cancer].","authors":"Satoshi Asano, Kotaro Sakamoto, Yukio Ago","doi":"10.1254/fpj.25006","DOIUrl":"https://doi.org/10.1254/fpj.25006","url":null,"abstract":"Molecularly targeted drugs currently used in breast cancer target the epidermal growth factor receptors, and are less effective when used against breast cancer subtypes with low levels of these receptors. There is therefore an urgent need to identify a new target molecule for such breast cancer subtypes. Vasoactive intestinal peptide (VIP) receptor 2 (VIPR2) is a G-protein-coupled receptor that binds to Gαs, Gαi, and Gαq proteins to regulate their downstream signaling. VIPR2 is known to be highly expressed in the suprachiasmatic nucleus of the brain, but is also expressed in many peripheral organs. VIPR2 expression has also been reported in thyroid cancer, gastric cancer, lung cancer, pancreatic adenocarcinoma, sarcoma, and neuroendocrine tumors, and VIPR2 mRNA expression and VIPR2 gene copy number are particularly elevated in breast cancer. We therefore investigated the involvement of VIPR2 in the proliferation and migration of breast cancer cells. We showed that VIP-VIPR2 is a novel molecular mechanism that controls cell migration by activating phosphatidylinositol-3 kinaseγ (PI3Kγ), promoting the production of phosphatidylinositol 3,4,5-triphosphate, and then regulating the formation and extension of pseudopodia. VIP-VIPR2 also regulated cyclin D1 levels through the cAMP/PKA/extracellular signal-regulated kinase and PI3K/AKT/Akt-glycogen synthase kinase-3β signaling pathways, thereby controlling cell proliferation by regulating the G1/S transition in the cell cycle. Treatment with a selective VIPR2 antagonist peptide KS-133 suppressed VIP-induced cell proliferation and migration. These results suggest that VIPR2 is a novel target molecule associated with breast cancer and that KS-133 is a potential molecular targeted drug for breast cancer.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 3","pages":"163-166"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.25020

Kenzo Hirose

引用次数: 0

[Analysis for acquiring and overriding oral tolerance in food allergy to use murine models]. [用小鼠模型分析食物过敏获得和克服口服耐受的情况]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24104

Hirotaka Yamashita

{"title":"[Analysis for acquiring and overriding oral tolerance in food allergy to use murine models].","authors":"Hirotaka Yamashita","doi":"10.1254/fpj.24104","DOIUrl":"https://doi.org/10.1254/fpj.24104","url":null,"abstract":"Oral tolerance is an immune regulatory system for foods. Eating foods gives healthy people nutrition. However, foods are immune exclusion material in patients of food allergy. We thought possibilities for immune intolerance for foods, failing acquisition of oral tolerance and breaking acquired tolerance. Then, we made murine models for the possibilities. First, we made the food allergy model and oral tolerance model for ovalbumin (OVA). Experimental oral tolerance was induced by previously oral treatment with OVA solution before the sensitization by intraperitoneal injection of OVA. In the oral tolerance model, elevation of OVA-specific IgE was suppressed completely and anaphylaxis was not induced. Next, as the model of failing acquisition of oral tolerance, we used the food additives into the OVA solution for tolerance. As results, intake of the OVA solution with food additives prevented acquiring oral tolerance and induced anaphylaxis for OVA. Recently, \"dual-allergen exposure hypothesis\" was suggested. The hypothesis proposed allergic sensitization to food could occur through cutaneous sensitization and that consumption of food protein induced oral tolerance. We attempted to override oral tolerance for the food by sensitization via skin. We found that epicutaneous sensitization and sensitization by intradermal injection of OVA could override acquired oral tolerance. As two common denominators for immune intolerance for foods, we confirmed the change of migration of dendritic cells and prevention of inducing regulatory T cells.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 4","pages":"230-234"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Mechanism of pathogenesis by a gain-of-function variant of STAT6 causing severe allergic diseases and potential for development of molecularly targeted drugs]. 【STAT6的功能获得性变异引起严重过敏性疾病的发病机制及分子靶向药物的开发潜力】。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.25008

Kumiko Yanagi, Tadashi Kaname

{"title":"[Mechanism of pathogenesis by a gain-of-function variant of STAT6 causing severe allergic diseases and potential for development of molecularly targeted drugs].","authors":"Kumiko Yanagi, Tadashi Kaname","doi":"10.1254/fpj.25008","DOIUrl":"https://doi.org/10.1254/fpj.25008","url":null,"abstract":"Allergic diseases have been considered multifactorial diseases. However, comprehensive genome sequencing, such as whole exome analysis, is revealing a group of diseases in which single genes are deeply involved in their pathogenesis. We identified a de novo missense variant of STAT6 [NM_003153:c.1255G>A,p.(Asp419Asn)] in a severely allergic patient with atopic dermatitis, hyper IgE, eosinophilic gastroenteritis, and food allergy by whole exome sequencing analysis. STAT6 is known as a transcription factor induced by IL-4 stimulation. Stimulation with IL-4 induces STAT6 phosphorylation via the JAK-STAT pathway and dimer formation. The STAT6 dimer quickly translocates into the nucleus and ultimately activates the expression of genes specific for TH2-type immune responses. Our experiments in vitro showed that nuclear translocation of mutant STAT6 (p.Asp419Asn) is enhanced compared to wild-type STAT6. In addition, even in the absence of IL-4 stimulation, we observed the translocation of mutant STAT6 in its unphosphorylated state, which activated gene expression. Mutant STAT6 knock-in mice elicited an abnormal TH2-dominant immune response in vivo, with findings similar to those observed in patients. Our findings suggest that mutant STAT6 is a gain-of-function variant. Currently, anti-IL-4Rα monoclonal antibodies, JAK inhibitors that block the JAK-STAT pathway, and non-specific anti-inflammatory drugs such as steroids are shown to be effective in treating this disease. The pathogenesis of immune dysregulation caused by gain-of-function variants of the STAT6 gene is being elucidated. Further efforts are required to elucidate the detailed mechanisms of this disease and it will hopefully lead to the development of more essential agents that specifically regulate STAT6 activity.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 4","pages":"244-249"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Myofibroblast differentiation induced by mechanical stimulation]. 机械刺激诱导的肌成纤维细胞分化。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.25016

Hiroki Mieno, Michio Nakaya

引用次数: 0

[Analysis of the therapeutic efficacy of bacterial infections through medical big data]. 【利用医疗大数据分析细菌感染的治疗效果】。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24086

Mitsuhiro Goda, Takahiro Niimura, Keisuke Ishizawa

{"title":"[Analysis of the therapeutic efficacy of bacterial infections through medical big data].","authors":"Mitsuhiro Goda, Takahiro Niimura, Keisuke Ishizawa","doi":"10.1254/fpj.24086","DOIUrl":"https://doi.org/10.1254/fpj.24086","url":null,"abstract":"In recent years, many studies have been conducted on various diseases to evaluate clinical efficacy reflecting actual clinical conditions through comprehensive analysis using medical big data, which include various patient groups and factors in clinical practice. On the other hand, there are still very few research reports in the world related to the treatment of infectious diseases using medical big data. This is due to the fact that much medical big data lacks information on the causative organisms of infectious diseases and on determining the effectiveness of infectious disease treatment. In this paper, we introduce a research case study in which analysis on the effectiveness of infectious disease treatment was conducted using medical big data. In this study, we performed a retrospective analysis of two real databases with the aim of validating the usefulness of cefmetazole and flomoxef in urinary tract infections (UTI) in which broad-spectrum β-lactamase (ESBL)-producing bacteria are the primary initiating organisms. Third-generation cephalosporin-resistant E. coli and K. pneumoniae, including ESBL-producing strains, were similarly susceptible to flomoxef and cefmetazole. JMDC Claims data analysis showed that the median time of hospital stay duration was significantly shorter in the flomoxef group than in the cefmetazole group. Flomoxef exhibits effectiveness that is comparable to cefmetazole in treating UTI. When using currently available medical big data to conduct analyses related to infectious disease treatment, valuable analysis results may be obtained by understanding the characteristics of the database and collaborating with clinicians who are familiar with infectious disease treatment.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 3","pages":"191-194"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Preface]. [序言]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24099

Osamu Kaminuma, Keiko Yasumatsu

引用次数: 0

[Current status of MPS studies in domestic and overseas-introduction of cardiac MPS]. [国内外 MPS 研究现状--引进心脏 MPS]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24070

Daiju Yamazaki

{"title":"[Current status of MPS studies in domestic and overseas-introduction of cardiac MPS].","authors":"Daiju Yamazaki","doi":"10.1254/fpj.24070","DOIUrl":"10.1254/fpj.24070","url":null,"abstract":"MPS is already being utilized in various aspects of drug development. This paper introduces MPS from a different viewpoint in previous reviews. First, I will introduce how the term \"microphysiological systems\" came to be used based on the results of the PubMed search, and show the results of an abstract analysis at the MPS World Summit 2023 held in Berlin, which quantified the organs of interest in MPS and the needs of pharmaceutical companies. Next, the author's activities in the AMED-MPS2 (the identification and experimental validation of device or cell considerations as MPS evaluation systems) and MPS-RS (the development of CoUs suitable for guidelines) projects as MPS projects in Japan will be introduced. I am also engaged in the construction of an evaluation system using cardiac MPS. The features and results of several cardiac MPS devices that have been developed for the contraction evaluation will be introduced, including the author's own efforts. Evaluation systems using MPS are attracting attention not only in drug discovery but also in the food and chemical industries, and while social implementation is gradually advancing, discussion groups are being created around the world to discuss how MPS should truly be utilized in society and in regulations. Countries seem to be focusing on acquiring data using useful devices that have survived the race for survival. For Japan to lead the world, it will be necessary to quickly identify useful devices and acquire enough data to discuss them.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 2","pages":"87-91"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.25022

Koh Nakayama, Takashi Nakagawa

引用次数: 0

[Preface]. (前言)。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24100

Kazuo Takayama, Daiju Yamazaki

引用次数: 0