Martin Tobi, Harvinder Talwar, Noreen F Rossi, Warren Lockette, Benita McVicker
{"title":"A Practical Format to Organize Cancer Constellations Using Innate Immune System Biomarkers: Implications for Early Diagnosis and Prognostication.","authors":"Martin Tobi, Harvinder Talwar, Noreen F Rossi, Warren Lockette, Benita McVicker","doi":"10.3390/ijtm4040050","DOIUrl":"10.3390/ijtm4040050","url":null,"abstract":"<p><p>Cancer discovery is directed at the identification of a specific cancer type which allows for specific therapeutic interventions.</p><p><strong>Background/objectives: </strong>Recently, similar immune checkpoint therapeutics have been applied with success across several cancer types, opening the field for other immune disruptive interventions that have practical applications.</p><p><strong>Methods: </strong>We have discovered an innate immune system (InImS) biomarker that allows for the characterization of allied cancer subtypes and outliers that might aid with diagnosis, treatment, and prognostication.</p><p><strong>Results: </strong>These InImS biomarkers are related to PD-L1 treatment outcomes and can be potentially manipulated by dietary means.</p><p><strong>Conclusions: </strong>The FERAD (ferritin-fecal p87) and absolute neutrophil/lymphocyte (aNLR) ratios are two such InImS biomarkers and we show herein, that they allow for the discovery of diagnosis and prognostication patterns, as demonstrated by this study.</p>","PeriodicalId":520354,"journal":{"name":"International journal of translational medicine (Basel, Switzerland)","volume":"4 4","pages":"726-739"},"PeriodicalIF":0.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adam P Burch, M Kristen Hall, Debra Wease, Ruth A Schwalbe
{"title":"Reduction of N-Acetylglucosaminyltransferase-I Activity Promotes Neuroblastoma Invasiveness and EGF-Stimulated Proliferation In Vitro.","authors":"Adam P Burch, M Kristen Hall, Debra Wease, Ruth A Schwalbe","doi":"10.3390/ijtm4030035","DOIUrl":"10.3390/ijtm4030035","url":null,"abstract":"<p><p>Aberrant N-glycosylation has been associated with progression of the pediatric cancer neuroblastoma (NB) but remains understudied. Here we investigated oligomannose N-glycans in NB by genetic editing of <i>MGAT1</i> in a human NB cell line, BE(2)-C, called BE(2)-C(MGAT1<sup>-/-</sup>). Lectin binding studies confirmed that BE(2)-C(MGAT1<sup>-/-</sup>) had decreased complex and increased oligomannose N-glycans. The relevance of 2D and 3D cell cultures was demonstrated for cell morphology, cell proliferation, and cell invasion, thereby highlighting the necessity for 3D cell culture in investigating cancerous properties. Western blotting revealed that oligomannosylated EGFR had increased autophosphorylation. Proliferation was decreased in BE(2)-C(MGAT1<sup>-/-</sup>) using 2D and 3D cultures, but both cell lines had similar proliferation rates using 3D cultures without serum. Upon EGF treatment, BE(2)-C(MGAT1<sup>-/-</sup>), but not BE(2)-C, showed increased proliferation, and furthermore, the mutant proliferated much faster than BE(2)-C under 3D conditions. Cell spheroid invasiveness was greatly increased in BE(2)-C(MGAT1<sup>-/-</sup>) compared with BE(2)-C. Moreover, invasiveness was reduced in both cell lines with either EGF or RhoA activator treatment, regardless of the N-glycan population. Thus, this study further extends our earlier findings that oligomannose N-glycans enhance NB cell invasiveness, and that EGF stimulation of oligomannosylated EGFR greatly enhances cell proliferation rates, underlining the role of oligomannose N-glycans in the promotion of NB.</p>","PeriodicalId":520354,"journal":{"name":"International journal of translational medicine (Basel, Switzerland)","volume":"4 3","pages":"519-538"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}