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The β-catenin/YAP signaling axis is a key regulator of melanoma-associated fibroblasts

Signal Transduction and Targeted Therapy 2019年第1期4卷 34-48页

作者： Tianyi Liu Linli Zhou Kun Yang kentaro iwasawa Ana Luisa Kadekaro Takanori Takebe Thomas Andl Yuhang Zhang Division of Pharmaceutical Sciences College of PharmacyUniversity of CincinnatiCincinnatiOH45267USA Division of Gastroenterology Hepatology&NutritionCincinnati Children’s Hospital Medical Center3333 Burnet AvenueCincinnatiOH45229-3039USA Division of Developmental Biology Cincinnati Children’s Hospital Medical Center3333 Burnet AvenueCincinnatiOH45229-3039USA Department of Dermatology College of MedicineUniversity of CincinnatiCincinnatiOH45267USA Center for Stem Cell and Organoid Medicine(CuSTOM) Cincinnati Children’s Hospital Medical Center3333 Burnet AvenueCincinnatiOH45229-3039USA Department of Pediatrics University of Cincinnati College of Medicine3333 Burnet AvenueCincinnatiOH45229-3039USA Institute of Research Tokyo Medical and Dental University 1-5-45 YushimaBunkyo-kuTokyo113-8510Japan Burnett School of Biological Sciences University of Central FloridaOrlandoFL32816USA

β-catenin is a multifunctional protein that plays crucial roles in embryonic development,physiological homeostasis,and a wide variety of human ***,we showed that in vivo targeted ablation ofβ-catenin in melanoma-associated fibroblasts after melanoma formation significantly suppressed tumor ***,when the expression ofβ-catenin was ablated in melanoma-associated fibroblasts before tumor initiation,melanoma development was surprisingly *** stromalβ-catenin deficiency leads to opposite biological effects in melanoma progression is not completely ***,we report thatβ-catenin is indispensable for the activation of primary human stromal fibroblasts and the mediation of fibroblast-melanoma cell *** coimmunoprecipitation and proximity ligation assays,we identified Yes-associated protein(YAP)as an importantβ-catenin-interacting partner in stromal *** is highly expressed in the nuclei of cancer-associated fibroblasts(CAFs)in both human and murine *** investigation revealed that YAP nuclear translocation is significantly modulated by Wnt/β-catenin activity in *** Wnt/β-catenin signaling in stromal fibroblasts inhibited YAP nuclear *** the absence of YAP,the ability of stromal fibroblasts to remodel the extracellular matrix(ECM)was inhibited,which is consistent with the phenotype observed in cells withβ-catenin *** studies showed that the expression of ECM proteins and enzymes required for remodeling the ECM was suppressed in stromal fibroblasts after YAP ***,our data provide a new paradigm in which theβ-catenin-YAP signaling axis regulates the activation and tumor-promoting function of stromal fibroblasts.

关键词： melanoma inhibited homeostasis

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Childhood-onset inflammatory bowel diseases associated with mutation of Wiskott-Aldrich syndrome protein gene

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World Journal of Gastroenterology 2017年第48期23卷 8544-8552页

作者： Takashi Ohya Masakatsu Yanagimachi kentaro iwasawa Shuichiro Umetsu Tsuyoshi Sogo Ayano Inui Tomoo Fujisawa Shuichi Ito Department of Pediatrics Yokohama City University Department of Pediatric Hepatology and Gastroenterology Saiseikai Yokohama-shi Tobu Hostopital Department of Pediatrics Tokyo Medical and Dental University

AIM To screen primary immunodeficiency,Wiskott-Aldrich syndrome(WAS),and chronic granulomatous disease(CGD) among children with inflammatory bowel disease(IBD).METHODS This was a single-center retrospective study. Eighteen children with IBD were investigated. We analyzed their expression of Wiskott-Aldrich syndrome protein(WASP) in lymphocytes and superoxide generation in phagocytes using flow cytometry. When the expression of WASP or superoxide generation was low or absent,we performed genetic analysis to determine the cause of this. RESULTS Eighteen patients were classified as having ulcerative colitis(n = 10),Crohn's disease(n = 5),or IBDunclassified(n = 3). In total,three patients revealed low expression of WASP associated with a WAS gene c.1378 C>T ***460 Ser mutation,which has previously been reported as a pathogenic mutation in WAS and X-linked thrombocytopenia. However,with respect to the major symptoms of WAS,none of these three patients showed either thrombocytopenia or increased susceptibility to infection,but one patient showed generalized eczema. No CGD patients were discovered in this *** Despite the lack of typical clinical manifestations of WAS,low expression of WASP could be associated with the pathogenesis of a subtype of IBD patients.

关键词： Inflammatory bowel disease WiskottAldrich syndrome Primary immunodeficiency Children Screening

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Intestinal ascariasis at pediatric emergency room in a developed country

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World Journal of Gastroenterology 2014年第38期20卷 14058-14062页

作者： Shuichiro Umetsu Tsuyoshi Sogo kentaro iwasawa Takeo Kondo Tomoyuki Tsunoda Manari Oikawa-Kawamoto Haruki Komatsu Ayano Inui Tomoo Fujisawa Department of Pediatric Hepatology and Gastroenterology Saiseikai Yokohama City Tobu Hospital Department of Pediatrics Toho University Medical CenterSakura Hospital

Ascaris lumbricoides infection is rare among children in developed *** large numbers of adult Ascaris in the small intestine can cause various abdominal symptoms,this infection remains asymptomatic until the number of worms in the intestine considerably increases in most *** causing bilious vomiting suggesting ileus is rare,especially in developed countries.A 6-year-old boy who lived in Japan,presented with abdominal colic,bilious vomiting at the pediatric emergency *** appeared pale,and had no abdominal distention,tenderness,palpable abdominal mass,or findings of *** experienced bilious vomiting again during a physical *** tests showed mild elevation of white blood cells and C-reactive protein *** of adenovirus,rotavirus,and norovirus were not detected from his stool,and stool culture showed normal *** showed multiple,round-shaped structures within the small intestine,and a tubular structure in a longitudinal scan of the small *** endoscopy showed a moving worm of Ascaris in the *** ascariasis should be considered as a cause of bilious vomiting in children,even at the emergency room in industrial *** examination and capsule endoscopy are useful for diagnosis of pediatric intestinal ascariasis.

关键词： Ascaris lumbricoides Paralytic ileus Capsule endoscopy Ultrasound Bilious vomiting

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