Neoplasia最新文献

{"title":"Unveiling the role of AGT in lipid metabolism and regulated cell death in colon cancer","authors":"Mengdi Wu ,&nbsp;Yuyang Zhou ,&nbsp;Dongsheng Pei ,&nbsp;Shoucui Gao","doi":"10.1016/j.neo.2024.101009","DOIUrl":"https://doi.org/10.1016/j.neo.2024.101009","url":null,"abstract":"<div><h3>Background</h3><p>Lipid metabolism and regulated cell death (RCD) play a role in the remodeling of tumor immune microenvironment and regulation of cancer progression. Since the underlying immune mechanisms of colon cancer remain elusive, this study aims to identify potential therapeutic target genes.</p></div><div><h3>Methods</h3><p>Differential genes related to lipid metabolism and RCD in COAD patients were identified using R language and online tools. Based on the expression of genes, two groups were classified using consensus clustering. CIBERSORT and ssGSEA were used to detect immune infiltration in both groups. Prognostic signature genes for colon cancer were screened using machine learning algorithms. KEGG, GO and GSEA for gene pathway enrichment. In addition, interacting genes in the immune module were obtained using a weighted gene co-expression network (WGCNA). Finally, expression and mutation of key in colon cancer genes were detected using TIMER, HPR, cBioPortal website and qPCR.</p></div><div><h3>Results</h3><p>The consensus clustering analysis revealed that 231 relevant differential genes were highly associated with immune infiltration. A series of machine learning and website analyses identified AGT as a hub gene linked to lipid metabolism and regulated cell death, which is overexpressed in colon cancer.</p></div><div><h3>Conclusion</h3><p>AGT, as a signature gene of lipid metabolism and regulated cell death, plays a critical role in the development of COAD and is associated with tumor immune infiltration.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"54 ","pages":"Article 101009"},"PeriodicalIF":4.8,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000514/pdfft?md5=0cfe2c2e619f08323269842ddb6de29b&pid=1-s2.0-S1476558624000514-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141289470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial whole exome sequencing reveals the genetic features of highly-aggressive components in lung adenocarcinoma","authors":"Jianfu Li ,&nbsp;Shan Xiong ,&nbsp;Ping He ,&nbsp;Peng Liang ,&nbsp;Caichen Li ,&nbsp;Ran Zhong ,&nbsp;Xiuyu Cai ,&nbsp;Zhanhong Xie ,&nbsp;Jun Liu ,&nbsp;Bo Cheng ,&nbsp;Zhuxing Chen ,&nbsp;Hengrui Liang ,&nbsp;Shen Lao ,&nbsp;Zisheng Chen ,&nbsp;Jiang Shi ,&nbsp;Feng Li ,&nbsp;Yi Feng ,&nbsp;Zhenyu Huo ,&nbsp;Hongsheng Deng ,&nbsp;Ziwen Yu ,&nbsp;Wenhua Liang","doi":"10.1016/j.neo.2024.101013","DOIUrl":"https://doi.org/10.1016/j.neo.2024.101013","url":null,"abstract":"<div><p>In invasive lung adenocarcinoma (LUAD), patients with micropapillary (MIP) or solid (SOL) components had a significantly poorer prognosis than those with only lepidic (LEP), acinar (ACI) or papillary (PAP) components. It is interesting to explore the genetic features of different histologic subtypes, especially the highly aggressive components.</p><p>Based on a cohort of 5,933 patients, this study observed that in different tumor size groups, LUAD with MIP/SOL components showed a different prevalence, and patients with <em>ALK</em> alteration or <em>TP53</em> mutations had a higher probability of developing MIP/SOL components. To control individual differences, this research used spatial whole-exome sequencing (WES) via laser-capture microdissection of five patients harboring these five coexistent components and identified genetic features among different histologic components of the same tumor. In tracing the evolution of components, we found that <em>titin</em> (<em>TTN</em>) mutation might serve as a crucial intratumor potential driver for MIP/SOL components, which was validated by a cohort of 146 LUAD patients undergoing bulk WES. Functional analysis revealed that <em>TTN</em> mutations enriched the complement and coagulation cascades, which correlated with the pathway of cell adhesion, migration, and proliferation.</p><p>Collectively, the histologic subtypes of invasive LUAD were genetically different, and certain trunk genotypes might synergize with branching <em>TTN</em> mutation to develop highly aggressive components.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"54 ","pages":"Article 101013"},"PeriodicalIF":4.8,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000551/pdfft?md5=5aac495b31b38eff0134e6452cba3364&pid=1-s2.0-S1476558624000551-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141290352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PBI-05204, a supercritical CO2 extract of Nerium oleander, suppresses glioblastoma stem cells by inhibiting GRP78 and inducing programmed necroptotic cell death","authors":"Sharmistha Chakraborty ,&nbsp;Daoyan Wei ,&nbsp;Megan Tran ,&nbsp;Frederick F Lang ,&nbsp;Robert A Newman ,&nbsp;Peiying Yang","doi":"10.1016/j.neo.2024.101008","DOIUrl":"10.1016/j.neo.2024.101008","url":null,"abstract":"<div><p>Successful treatment of glioblastoma multiforme (GBM), an aggressive form of primary brain neoplasm, mandates the need to develop new therapeutic strategies. In this study, we investigated the potential of PBI-05204 in targeting GBM stem cells (GSCs) and the underlying mechanisms. Treatment with PBI-05204 significantly reduced both the number and size of tumor spheres derived from patient-derived GSCs (GBM9, GSC28 and TS543), and suppressed the tumorigenesis of GBM9 xenografts. Moreover, PBI-05204 treatment led to a significant decrease in the expression of CD44 and NANOG, crucial markers of progenitor stem cells, in GBM9 and GSC28 GSCs. This treatment also down-regulated GRP78 expression in both GSC types. Knocking down GRP78 expression through GRP78 siRNA transfection in GBM9 and GSC28 GSCs also resulted in reduced spheroid size and CD44 expression. Combining PBI-05204 with GRP78 siRNA further decreased spheroid numbers compared to GRP78 siRNA treatment alone. PBI-05204 treatment led to increased expression of pRIP1K and pRIP3K, along with enhanced binding of RIPK1/RIPK3 in GBM9 and GSC28 cells, resembling the effects observed in GRP78-silenced GSCs, suggesting that PBI-05204 induced necroptosis in these cells. Furthermore, oleandrin, a principle active cardiac glycoside component of PBI-05204, showed the ability to inhibit the self-renewal capacity in GSCs. These findings highlight the potential of PBI-05204 as a promising candidate for the development of novel therapies that target GBM stem cells.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"54 ","pages":"Article 101008"},"PeriodicalIF":4.8,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000502/pdfft?md5=51c01119074ff3c055b1edcfa6c6e613&pid=1-s2.0-S1476558624000502-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141187176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B7-H4 reduces the infiltration of CD8+T cells and induces their anti-tumor dysfunction in gliomas","authors":"Ying Qi ,&nbsp;Lang Hu ,&nbsp;Chunxia Ji ,&nbsp;Xinyu Yang ,&nbsp;Jiakai Yao ,&nbsp;Di Chen ,&nbsp;Yu Yao","doi":"10.1016/j.neo.2024.101007","DOIUrl":"https://doi.org/10.1016/j.neo.2024.101007","url":null,"abstract":"<div><p>B7-H4 is a promising immune checkpoint molecule in tumor immunotherapy. Our previous study showed that high B7-H4 expression was strongly correlated with deficiency in tumor infiltrated lymphocytes (TILs) in glioma patients. On this basis, we investigated the impact of B7-H4 on CD8+TILs in gliomas and the associated molecular mechanism here. B7-H4-positive tumor samples (n=129) from our glioma cohort were used to assess B7-H4 expression and CD8+TIL quantification by immunohistochemistry. CD8+TILs from five glioma patients cultured with B7-H4 protein were used to evaluate anti-tumor dysfunction by flow cytometry and ELISpot. An orthotopic murine glioma model was used to investigate the role of B7-H4 in glioma CD8+TILs by immunohisto- chemistry and flow cytometry. CD8+TILs from glioma patients cultured with B7-H4 protein were used to explore the potential molecular mechanism by RNA sequencing and western blot. Our results showed that glioma CD8+TIL density was negatively correlated with B7-H4 expression both in glioma patient cohort (P &lt; 0.05) and orthotopic glioma murine model (P &lt; 0.01). B7-H4 also lowered the expression of CD137 and CD103 (P &lt; 0.05 for both) in glioma CD8+TILs and reduced their secretion of the anti-tumor cytokines IFN-γ and TNF-α (P &lt; 0.01 for both) in a dose-dependent manner. Furthermore, B7-H4 was found to induce early dysfunction of glioma CD8+TILs by downregulating the phosphorylation of AKT and eNOS (P &lt; 0.05 for both). In conclusion, B7-H4 reduced the infiltration of glioma CD8+TILs and induced an anti-tumor dysfunction phenotype. B7-H4 may also impair the anti-tumor function of glioma CD8+TILs via the AKT-eNOS pathway. These results indicated that B7-H4 may serve as a potential target in future glioma immunotherapy.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"54 ","pages":"Article 101007"},"PeriodicalIF":4.8,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000496/pdfft?md5=9fe7c57a98d733227c6bad4b9fb51af6&pid=1-s2.0-S1476558624000496-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced ApcMin/+ adenoma formation after epithelial CUL4B deletion by recruitment of myeloid-derived suppressor cells","authors":"Beibei Guo ,&nbsp;Yawen Zheng ,&nbsp;Yujia Fan ,&nbsp;Yang Yang ,&nbsp;Yuxing Wang ,&nbsp;Liping Qin ,&nbsp;Yachun An ,&nbsp;Xiaoran Xu ,&nbsp;Xiyu Zhang ,&nbsp;Gongping Sun ,&nbsp;Hao Dou ,&nbsp;Changshun Shao ,&nbsp;Yaoqin Gong ,&nbsp;Baichun Jiang ,&nbsp;Huili Hu","doi":"10.1016/j.neo.2024.101005","DOIUrl":"10.1016/j.neo.2024.101005","url":null,"abstract":"<div><p>Colorectal cancer (CRC) stands as a prevalent malignancy globally. A pivotal event in CRC pathogenesis involves the loss-of-function mutation in the <em>APC</em> gene, leading to the formation of benign polyps. Despite the well-established role of <em>APC</em>, the contribution of CUL4B to CRC initiation in the pre-tumorous stage remains poorly understood. In this investigation, we generated a murine model by crossing <em>Apc^Min/+</em> mice with <em>Cul4b^ΔIEC</em> mice to achieve specific deletion of <em>Cul4b</em> in the gut epithelium against an <em>Apc^Min/+</em> background. By employing histological methods, RNA-sequencing (RNA-seq), and flow cytometry, we assessed alterations and characterized the immune microenvironment. Our results unveiled that CUL4B deficiency in gut epithelium expedited <em>Apc^Min/+</em> adenoma formation. Notably, CUL4B in adenomas restrained the accumulation of tumor-infiltrating myeloid-derived suppressor cells (MDSCs). <em>In vivo</em> inhibition of MDSCs significantly delayed the growth of CUL4B deleted <em>Apc^Min/+</em> adenomas. Furthermore, the addition of MDSCs to <em>in vitro</em> cultured <em>Apc^Min/+; Cul4b^ΔIEC</em> adenoma organoids mitigated their alterations. Mechanistically, CUL4B directly interacted with the promoter of <em>Csf3</em>, the gene encoding granulocyte-colony stimulating factor (G-CSF) by coordinating with PRC2. Inhibiting CUL4B epigenetically activated the expression of G-CSF, promoting the recruitment of MDSCs. These findings offer novel insights into the tumor suppressor-like roles of CUL4B in regulating <em>Apc^Min/+</em> adenomas, suggesting a potential therapeutic strategy for CRC initiation and progression in the context of activated Wnt signaling.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"53 ","pages":"Article 101005"},"PeriodicalIF":4.8,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000472/pdfft?md5=981809cde7ca598cce88c2020127eb0f&pid=1-s2.0-S1476558624000472-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor marker-based RecistTM is superior to RECIST as criteria to predict the long-term benefits of targeted therapy in advanced non-small-cell lung cancer with driver gene mutations","authors":"Kai Xiong ,&nbsp;Yi Yang ,&nbsp;Yanan Yang ,&nbsp;Zhengbo Wang ,&nbsp;Yun Liu ,&nbsp;Hong Duo ,&nbsp;Xinya Yuan ,&nbsp;Yao Xiao ,&nbsp;He Xiao ,&nbsp;Xueqin Yang","doi":"10.1016/j.neo.2024.101006","DOIUrl":"https://doi.org/10.1016/j.neo.2024.101006","url":null,"abstract":"<div><h3>Background</h3><p>Tyrosine kinase inhibitors (TKIs) are standard first-line treatments for advanced non-small-cell lung cancer (NSCLC) with driver gene mutations. The Response Evaluation Criteria in Solid Tumors (RECIST) are limited in predicting long-term patient benefits. A tumour marker-based evaluation criteria, RecistTM, was used to investigate the potential for assessing targeted-therapy efficacy in lung cancer treatment.</p></div><div><h3>Methods</h3><p>We retrospectively analysed patients with stage IIIA–IV NSCLC and driver gene mutations, whose baseline tumour marker levels exceeded the pre-treatment cut-off value three-fold and who received TKI-targeted therapy as a first-line treatment. We compared efficacy, progression-free survival (PFS), and overall survival (OS) between RecistTM and RECIST.</p></div><div><h3>Findings</h3><p>The median PFS and OS differed significantly among treatment-response subgroups based on RecistTM but not RECIST. The predicted 1-, 2-, and 3-year disease-progression risk, according to area under the receiver operating characteristic curve, as well as the 1-, 3-, and 5-year mortality risk, differed significantly between RecistTM and RECIST. The median PFS and OS of tmCR according to RecistTM, was significantly longer than (CR+PR) according to RECIST. Imaging analysis revealed that the ΔPFS was 11.27 and 6.17 months in the intervention and non-intervention groups, respectively, suggesting that earlier intervention could extend patients' PFS.</p></div><div><h3>Interpretation</h3><p>RecistTM can assess targeted-therapy efficacy in patients with advanced NSCLC and driver gene mutations, along with tumour marker abnormalities. RecistTM surpasses RECIST in predicting short- and long-term patient benefits, and allows the early identification of patients resistant to targeted drugs, enabling prompt intervention and extending the imaging-demonstrated time to progression.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"53 ","pages":"Article 101006"},"PeriodicalIF":4.8,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000484/pdfft?md5=0c68bd6818a934476316da96840c6452&pid=1-s2.0-S1476558624000484-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140951725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular signals induce dynamic ER remodeling through αTAT1-dependent microtubule acetylation","authors":"Hannah R. Ortiz ,&nbsp;Paola Cruz Flores ,&nbsp;Julia Podgorski ,&nbsp;Aaron Ramonett ,&nbsp;Tasmia Ahmed ,&nbsp;Nadine Hempel ,&nbsp;Pascale G. Charest ,&nbsp;Nathan A. Ellis ,&nbsp;Paul R. Langlais ,&nbsp;William R. Montfort ,&nbsp;Karthikeyan Mythreye ,&nbsp;Sanjay Kumar ,&nbsp;Nam Y. Lee","doi":"10.1016/j.neo.2024.101003","DOIUrl":"https://doi.org/10.1016/j.neo.2024.101003","url":null,"abstract":"<div><p>Dynamic changes in the endoplasmic reticulum (ER) morphology are central to maintaining cellular homeostasis. Microtubules (MT) facilitate the continuous remodeling of the ER network into sheets and tubules by coordinating with many ER-shaping protein complexes, although how this process is controlled by extracellular signals remains unknown. Here we report that TAK1, a kinase responsive to various growth factors and cytokines including TGF-β and TNF-α, triggers ER tubulation by activating αTAT1, an MT-acetylating enzyme that enhances ER-sliding. We show that this TAK1/αTAT1-dependent ER remodeling promotes cell survival by actively downregulating BOK, an ER membrane-associated proapoptotic effector. While BOK is normally protected from degradation when complexed with IP3R, it is rapidly degraded upon their dissociation during the ER sheets-to-tubules conversion. These findings demonstrate a distinct mechanism of ligand-induced ER remodeling and suggest that the TAK1/αTAT1 pathway may be a key target in ER stress and dysfunction.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"53 ","pages":"Article 101003"},"PeriodicalIF":4.8,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000459/pdfft?md5=63bc207646b08e71bf25740cb60cc165&pid=1-s2.0-S1476558624000459-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140951041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of gemcitabine metabolizing enzymes and stromal components reveal complexities of preclinical pancreatic cancer models for therapeutic testing","authors":"Lisa Knoll ,&nbsp;Jacob Hamm ,&nbsp;Philipp Stroebel ,&nbsp;Todorovic Jovan ,&nbsp;Robert Goetze ,&nbsp;Shiv Singh ,&nbsp;Elisabeth Hessmann ,&nbsp;Volker Ellenrieder ,&nbsp;Christoph Ammer-Herrmenau ,&nbsp;Albrecht Neesse","doi":"10.1016/j.neo.2024.101002","DOIUrl":"https://doi.org/10.1016/j.neo.2024.101002","url":null,"abstract":"<div><h3>Background</h3><p>Pancreatic ductal adenocarcinoma (PDAC) poorly responds to antineoplastic agents. Discrepancies between preclinical success and clinical failure of compounds has been a continuous challenge and major obstacle in PDAC research.</p></div><div><h3>Aim</h3><p>To investigate the association of the tumor microenvironment (TME) composition and gemcitabine metabolizing enzyme (GME) expression <em>in vitro</em> and several i<em>n vivo</em> models.</p></div><div><h3>Methods</h3><p>mRNA expression and protein levels of GME (cytosolic 5′-nucleotidase 1 A; NT5C1A, cytidine deaminase; CDA, deoxycytidine kinase; DCK), gemcitabine transporters (ENT1, ENT2, RRM1, RRM2) and stromal components (hyaluroninc acid, podoplanin, masson trichrome, picrosirius) were assessed by qRT-PCR and immunohistochemistry in murine LSL-Kras^G12D/+;LSL-Trp53^{R172 H/+}; Pdx-1-Cre (KPC), orthotopically transplanted mice (OTM), human primary resected PDAC tissue (hPRT), corresponding patient-derived xenograft (PDX) mice, and KPC-SPARC^−/- mice. mRNA expression of GME was analyzed in PDAC cell lines (Panc-1, MIA PaCa, BXPC3 and L3.6) upon incubation on collagen or pancreatic stellate cell (PSC) conditioned media by qRT-PCR.</p></div><div><h3>Results</h3><p>Endogenous KPC tumors exhibited significantly higher levels of GME compared to OTM. However, GME levels did not differ between hPRT and corresponding PDX mice. Using Kendalls Tau correlation coefficient we did not show a significant correlation of GME and components of the TME except for NT5C1A and hyaluronic acid in PDX mice (p=0.029). GME were not significantly altered upon SPARC depletion <em>in vivo</em>, and upon treatment with PSC-conditioned media or incubation on collagen plated dishes <em>in vitro</em>.</p></div><div><h3>Conclusions</h3><p>Our findings suggest that the expression of GME is independent from the deposition of stromal components. KPC mice are most appropriate to study stromal composition whereas PDX mice maintain GME expression of the corresponding hPRT and could be best suited for pharmacokinetic studies.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"53 ","pages":"Article 101002"},"PeriodicalIF":4.8,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000447/pdfft?md5=d4784a933cf06c8cf7d72283c02da32f&pid=1-s2.0-S1476558624000447-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140918891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inducing ubiquitination and degradation of TrxR1 protein by LW-216 promotes apoptosis in non-small cell lung cancer via triggering ROS production","authors":"Runde Wang ,&nbsp;Liuyi Zhong ,&nbsp;Tiepeng Wang ,&nbsp;Tifan Sun ,&nbsp;Jinming Yang ,&nbsp;XinYe Liu ,&nbsp;Yifan Wu ,&nbsp;Qinglong Guo ,&nbsp;Yuan Gao ,&nbsp;Kai Zhao","doi":"10.1016/j.neo.2024.101004","DOIUrl":"10.1016/j.neo.2024.101004","url":null,"abstract":"<div><p>Thioredoxin reductases are frequently overexpressed in various solid tumors as a protective mechanism against heightened oxidative stress. Inhibitors of this system, such as Auranofin, are effective in eradicating cancer cells. However, the clinical significance of thioredoxin reductase 1 (TrxR1) in lung cancer, as well as the potential for its antagonist as a treatment option, necessitated further experimental validation. In this study, we observed significant upregulation of TrxR1 specifically in non-small cell lung cancer (NSCLC), rather than small cell lung cancer. Moreover, TrxR1 expression exhibited associations with survival rate, tumor volume, and histological classification. We developed a novel TrxR1 inhibitor named LW-216 and assessed its antitumor efficacy in NSCLC. Our results revealed that LW-216 is effectively bound with intracellular TrxR1 at sites R371 and G442, facilitating TrxR1 ubiquitination and suppressing TrxR1 expression, while not affecting TrxR2 expression. Treatment of LW-216-induced DNA damage and cell apoptosis in NSCLC cells through the generation of reactive oxygen species (ROS). Importantly, supplementation with N-acetylcysteine (NAC) or ectopic TrxR1 expression reversed LW-216-induced apoptosis. Furthermore, LW-216 displayed potent tumor growth inhibition in NSCLC cell-implanted mice, reducing TrxR1 expression in xenografts. Remarkably, LW-216 exhibited superior antitumor activity compared to Auranofin <em>in vivo.</em> Collectively, our research provides compelling evidence supporting the potential of targeting TrxR1 by LW-216 as a promising therapeutic strategy for NSCLC.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"53 ","pages":"Article 101004"},"PeriodicalIF":4.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000460/pdfft?md5=13178073486e00b7c403923045574cc3&pid=1-s2.0-S1476558624000460-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140909670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to Corrigendum to \"Activation of hepatic stellate cells during liver carcinogenesis requires fibrinogen/integrin αvβ5 in zebrafish\" Neoplasia 33(2022) 100831.","authors":"Chuan Yan ,&nbsp;Qiqi Yang ,&nbsp;Zhiyuan Gong","doi":"10.1016/j.neo.2024.101001","DOIUrl":"https://doi.org/10.1016/j.neo.2024.101001","url":null,"abstract":"","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"52 ","pages":"Article 101001"},"PeriodicalIF":4.8,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000435/pdfft?md5=d51270c7246a702a26d9fae72fa58e8a&pid=1-s2.0-S1476558624000435-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140822006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}