Journal of cellular signaling最新文献

{"title":"Targeting the Complex Protein Network of MYCN-amplified Anaplastic Ependymoma: A Case Report","authors":"MD Michael P. Castro","doi":"10.33696/signaling.3.082","DOIUrl":"https://doi.org/10.33696/signaling.3.082","url":null,"abstract":"The MYCN oncoprotein has been notoriously undruggable and is infamous for causing aggressive cancer with poor outcomes in children and adults. Following surgery, radiation, and chemotherapy, patients who develop progressive disease have few treatment options. An analysis of the dysregulated protein network caused by MYCN amplification suggested co-targeting PLK1, AURKA, CKS1, AKT, MTOR, and USP7 would be useful to take advantage of synthetic lethal vulnerabilities while overcoming redundancies and resistance mechanisms that stabilize N-Myc by preventing its proteasome degradation. Naturopathic compounds, (genistein, tanshinone, resveratrol, betulinic acid) and fluoxetine were re-purposed to target the complex protein network in a patient with MYCN -amplified and PTEN -deficient multifocal, relapsed anaplastic ependymoma following standard therapy. The patient achieved a clinically meaningful and durable response for 6 months prior to developing disease progression characterized by chromosome 11q ( YAP1, BIRC2/3 ) amplification. The experience suggests molecularly-informed integration of naturopathic compounds can have utility for disease control and survival. The success, although anecdotal, suggests that the previous failure of single agent strategies could be overcome with a network targeting approach that simultaneously precipitates cell cycle arrest, rescues FBXW7 ubiquitination, and enhances oxidative stress. As such, MYCN may no longer be strictly unactionable but appears amenable to co-targeting key nodes in its self-sustaining disease network.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"201 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74888730","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}

{"title":"New Insights into the Proteolytic Regulation of the Structural Protein Junctophilin-2 by Calpain","authors":"G. Weninger, S. Lehnart","doi":"10.33696/signaling.3.081","DOIUrl":"https://doi.org/10.33696/signaling.3.081","url":null,"abstract":"Citation","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75352320","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}

{"title":"Can Mono- or Combination Therapy of Metformin with Cimetidine and Ibuprofen be a Promising Potential Therapy for Breast Cancer?","authors":"S. Mostafavi, Hamidreza Zalpoor, Zuhair Mohammad Hassan","doi":"10.33696/signaling.3.080","DOIUrl":"https://doi.org/10.33696/signaling.3.080","url":null,"abstract":"and Ibuprofen be a Promising Potential Therapy for","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78318520","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}

{"title":"New Aspects in the Mechanism of Action of ALDH1A1 and 1A3 Isoforms in Carcinogenesis","authors":"","doi":"10.33696/signaling.3.078","DOIUrl":"https://doi.org/10.33696/signaling.3.078","url":null,"abstract":"","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75955435","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}

{"title":"MAGIs: Junctional Scaffolds Linking Inter-Cellular Junction Architecture, Actin Cytoskeleton Dynamics, and Signaling Pathways","authors":"","doi":"10.33696/signaling.3.076","DOIUrl":"https://doi.org/10.33696/signaling.3.076","url":null,"abstract":"","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"83 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83978236","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}

{"title":"Phosphoinositide-Specific Phospholipases C in Psychiatric Diseases and Suicide","authors":"","doi":"10.33696/signaling.3.075","DOIUrl":"https://doi.org/10.33696/signaling.3.075","url":null,"abstract":"","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87623589","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}

{"title":"Repurposed Anti-IL-6 Therapeutics, Another Way to Quell the Cytokine Storm in Tuberculosis","authors":"","doi":"10.33696/signaling.3.077","DOIUrl":"https://doi.org/10.33696/signaling.3.077","url":null,"abstract":"","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"55 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74867439","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}

{"title":"Insights from Natural Product PHGDH Inhibitor Studies","authors":"Zhaodan Wang, Xueqin Chen, Qingxiang Sun","doi":"10.33696/signaling.3.073","DOIUrl":"https://doi.org/10.33696/signaling.3.073","url":null,"abstract":"The synthetic activity of serine is significantly upregulated in several cancers [1]. Homo sapiens 3-phosphoglycerate dehydrogenase (PHGDH) catalyzes the rate-limiting step of serine synthesis, which converts 3-phosphoglycerate (3PG) and NAD+ to 3-phosphohydroxypyruvate and NADH [2,3]. PHGDH inhibitors were extensively pursued recently for their use in the treatment of affected cancers [4,5]. Among the inhibitors identified, three natural products including azacoccone E [6], ixocarpalactone A [7], withaferin A and oridonin [8] were shown to effectively inhibit PHGDH enzyme activity and cancer cell growth.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"92 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86535347","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}

{"title":"The Role of FCH Domain Only 1 (FCHO1) as an Oncogene in Lung Cancer","authors":"M. Cho, S. Park, Soon‐Kyung Hwang","doi":"10.33696/signaling.3.070","DOIUrl":"https://doi.org/10.33696/signaling.3.070","url":null,"abstract":"Akt, or protein kinase B, a serine/threonine protein kinase [4], is activated downstream from phosphatidylinositol 3-kinase (PI3K), by various growth factors, including insulin, insulin-like growth factor-I, and epidermal growth factor [5]. Activated Akt (phospho-Akt, p-Akt) is a strong promoter of cell survival because it antagonizes and inactivates various components of the apoptotic cascade such as proapoptotic Bad, caspase-9, and forkhead transcription factor family members [6,7]. The PI3K/Akt signaling pathway regulates the G1/S cell cycle transition by modulating the transcription of cell cycle proteins and suppressing cell cycle inhibitors [8]. A dysregulated cell cycle is often associated with increased tumorigenesis and accelerated tumor growth [9].","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86220186","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}

{"title":"The Effect of Diet Induced Obesity on Serotonin in Zebrafish","authors":"L. Uyttebroek, S. V. Remoortel, Laura Buyssens, Nastasia Popowycz, G. Hubens, Jean-Pierre, Timmermans, L. Nassauw","doi":"10.33696/signaling.3.074","DOIUrl":"https://doi.org/10.33696/signaling.3.074","url":null,"abstract":"Obesity is a worldwide epidemic and a major risk factor for numerous diseases. The regulation of feeding behavior and body weight depends on a wide range of neuronal pathways influencing satiety and hunger. Serotonin (5-HT) is one of those players identified to have a profound effect on energy homeostasis. The effect of obesity on 5-HT metabolism in the gastrointestinal (GI) tract and its underlying mechanisms still needs to be further elaborated. The aim of the present study was to investigate the effect of diet-induced obesity (DIO) on 5-HT in the enteric nervous system, the expression of different enzymes and receptors of the 5-HT pathway in the brain and GI tract, GI transit and behavior. Zebrafish were fed either a high caloric diet during 4 weeks or a normal diet (CNTL). The proportion of serotonergic neurons in the GI tract was analyzed using immunofluorescent double staining. Quantitative PCR (qPCR) was performed on brain and GI tissue to analyze the expression of 5-HT receptors, the 5-HT precursor, tryptophan hydroxylase (tph), 5-HT transporter (SERTa/b) and monoamine oxidase (MAO). GI transit was measured by gavaging glass beads or providing fluorescently labeled food and calculating the geometric centre (GC). Swim behavior was calculated as preferential swim area, swim speed and distance. Results showed an increase in body mass index after 4 weeks. Overfeeding increased the proportion of serotonergic neurons in the proximal GI tract. qPCR revealed significantly elevated levels for tph2, but not for tph1a/b, in the brain and the intestine of DIO fish. Furthermore, a significant increase in the expression of the 5-HT4 receptor and SERTa were observed in the brain, but not in the GI tract, while 5-HT2b receptor showed to be upregulated in the GI tract, but not the brain. GC was increased after feeding with fluorescently labeled food. Also, the intestinal length in DIO fish was significantly larger, indicating higher transit rates compared to CNTL fish. No differences in behavior were observed between the two groups. This study, revealed an increase in 5-HT expression in enteric neurons probably due to an increased tph2 expression in the intestine, resulting in increased GI transit. Furthermore, DIO exhibited increased expression of the 5-HT4 receptor and SERTa in the brain, and 5-HT2b receptor in the GI tract, respectively. The present data obtained from zebrafish are in line with earlier findings in mammalian models and further validate the zebrafish as a model for GI research.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85443927","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}