Carcinogenesis最新文献_第4页

Germline alteration analysis reveals EPHB4R91H mutation as a key player in multiple primary lung tumors. 种系畸变分析揭示 EPHB4R91H 突变是多种原发性肺肿瘤的关键因素

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae074

Jing Li, Yanan Li, Xinjuan Wang, Zhigang Zhou, Xiangnan Li, Songwei Yue, Huaqi Wang, Ming Yang, Guojun Zhang

{"title":"Germline alteration analysis reveals EPHB4R91H mutation as a key player in multiple primary lung tumors.","authors":"Jing Li, Yanan Li, Xinjuan Wang, Zhigang Zhou, Xiangnan Li, Songwei Yue, Huaqi Wang, Ming Yang, Guojun Zhang","doi":"10.1093/carcin/bgae074","DOIUrl":"10.1093/carcin/bgae074","url":null,"abstract":"Multiple primary lung tumors are garnering attention from clinicians, with adenocarcinoma emerging as the predominant histological type. Because of the heterogeneity and diffuse distribution of lesions in the same patient, the treatment of multiple primary lung adenocarcinoma (MPLA) is a significant challenge. As a kind of variation unaffected by tumor heterogeneity, germline alterations may play a key role in the development of MPLA. Here, whole-exome sequencing of peripheral blood was employed to obtain germline alteration data. Intergroup comparative analyses on rare and deleterious alterations of MPLA, solitary lung adenocarcinoma, and healthy individuals in an MPLA family were performed to clarify the candidate alterations. Whole-exome sequencing and targeted Sanger sequencing were performed in 27 disseminated MPLA patients to detect the mutation site that had been screened. A rare and deleterious germline alteration, EPHB4R91H, was found in all of the patients of an MPLA family and a patient with disseminated MPLA. It was revealed that EPHB4R91H was able to enhance the proliferation, migration, and invasion ability of A549 cells through increased binding affinity to ephrinB2, which in turn activated the EPHB4/ERK/JNK/MAPK pathway. Our findings corroborate that germline alterations are involved in the development of MPLA. And it was found for the first time that the EPHB4R91H mutation promotes the development of MPLA by enhancing its affinity for ephrinB2 and thereby active EPHB4/ERK/JNK/MAPK pathway.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae080

Pu Yang, Qian Yu

{"title":"Immune-related genes for the prediction of response to imatinib therapy in chronic myeloid leukemia.","authors":"Pu Yang, Qian Yu","doi":"10.1093/carcin/bgae080","DOIUrl":"10.1093/carcin/bgae080","url":null,"abstract":"Chronic myeloid leukemia (CML) is a malignant hyperplastic tumor that originates from pluripotent hematopoietic stem cells in the bone marrow. The introduction of tyrosine kinase inhibitors has significantly improved the survival rates of CML patients. This study aimed to identify immune-related genes associated with the response to imatinib (IM) therapy in CML. Gene expression profiles from IM-treated CML patients were obtained from the Gene Expression Omnibus database and categorized into high- and low-score groups based on immune scores calculated using the ESTIMATE algorithm. Subsequent bioinformatics analysis identified 428 differentially expressed immune-related genes in the CML context. Functional enrichment analysis revealed that these genes were involved in immune-related pathways, including T-cell receptor signaling and cytokine-cytokine receptor interaction. Finally, based on five modules in weighted gene co-expression network analysis and the top-ranked degree, 10 hub genes were identified. Receiver operating characteristic analysis in two Gene Expression Omnibus datasets identified IL10RA, SCN9A, and SLC26A11 as potential biomarkers for predicting IM response. We further validated these biomarkers in an independent clinical cohort of 60 CML patients treated with IM. Results from quantitative real-time polymerase chain reaction (qRT-PCR) revealed high expression of IL10RA and SLC26A11 in responders, while SCN9A showed low expression. All three genes had an area under the curve greater than 0.75, confirming their potential as predictive biomarkers. These findings deepen our understanding of functional characteristics and immune-related molecular mechanisms underlying IM response and offer promising predictive biomarkers.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Testicular sex cord-stromal tumors in mice with constitutive activation of PI3K and loss of Pten. PI3K组成性激活和Pten缺失小鼠睾丸性索间质肿瘤。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae077

Marija Dinevska, Lachlan McAloney, Samuel S Widodo, Gulay Filiz, Jeremy Anderson, Sebastian Dworkin, Simon P Windley, Dagmar Wilhelm, Theo Mantamadiotis

{"title":"Testicular sex cord-stromal tumors in mice with constitutive activation of PI3K and loss of Pten.","authors":"Marija Dinevska, Lachlan McAloney, Samuel S Widodo, Gulay Filiz, Jeremy Anderson, Sebastian Dworkin, Simon P Windley, Dagmar Wilhelm, Theo Mantamadiotis","doi":"10.1093/carcin/bgae077","DOIUrl":"10.1093/carcin/bgae077","url":null,"abstract":"Testicular tumors are the most common malignancy of young men, and tumors affecting the testis are caused by somatic mutations in germ or germ-like cells. The PI3K pathway is constitutively activated in about one-third of testicular cancers. To investigate the role of the PI3K pathway in transforming stem-like cells in the testis, we investigated tumors derived from mice with post-natal, constitutive activation of PI3K signaling and homozygous deletion of tumor suppressor Pten, targeted to Nestin-expressing cells. Mice developed aggressive tumors, exhibiting heterogeneous histopathology and hemorrhaging. The tumors resemble the rare testis tumor type, testicular sex cord-stromal Leydig cell tumors. Single-cell resolution spatial tissue analysis demonstrated that T-cells are the dominant tumor-infiltrating immune cell type, with very few infiltrating macrophages observed in the tumor tissue, with CD8+ T-cells predominating. Further analysis showed that immune cells preferentially localize to, or accumulate within stromal regions.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The ‌BCL2-associated athanogene-3-Interferon-induced transmembrane protein 2 axis enhances pancreatic ductal adenocarcinoma growth via the Mitogen-activated protein kinase signaling pathway. BAG3-IFITM2 轴通过 MAPK 信号通路促进胰腺导管腺癌生长

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-12-30 DOI: 10.1093/carcin/bgae053

Peipei Wang, Congliang Chen, Kexin Lin, Yu Zhang, Junmei Hu, Tongbo Zhu, Xia Wang

{"title":"The ‌BCL2-associated athanogene-3-Interferon-induced transmembrane protein 2 axis enhances pancreatic ductal adenocarcinoma growth via the Mitogen-activated protein kinase signaling pathway.","authors":"Peipei Wang, Congliang Chen, Kexin Lin, Yu Zhang, Junmei Hu, Tongbo Zhu, Xia Wang","doi":"10.1093/carcin/bgae053","DOIUrl":"10.1093/carcin/bgae053","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy, exhibits escalating incidence and mortality rates, underscoring the urgent need for the identification of novel therapeutic targets and strategies. The BCL2-associated athanogene-3 (BAG3) protein, a multifunctional regulator involved in various cellular processes, notably plays a crucial role in promoting tumor progression and acts as a potential \"bridge\" between tumors and the tumor microenvironment. In this study, we demonstrate that PDAC cells secrete BAG3 (sBAG3), which engages the interferon-induced transmembrane protein 2 (IFITM2) receptor to activate the mitogen-activated protein kinase signaling pathway, specifically enhancing phospho-extracellular regulated protein (pERK) activity, thereby propelling PDAC growth. Furthermore, our preliminary investigation into the effects of sBAG3 on co-cultured natural killer cells intriguingly discovered that sBAG3 diminishes natural killer cell cytotoxicity and active molecule expression. In conclusion, our findings confirm the pivotal role of the sBAG3-IFITM2 axis in fostering PDAC progression, highlighting the potential significance of sBAG3 as a dual therapeutic target for both tumor and immune cells.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"928-939"},"PeriodicalIF":3.3,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Population dynamics is a cancer driver. 人口动态是癌症的驱动因素。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-12-30 DOI: 10.1093/carcin/bgae038

Mariana Dos Santos Oliveira, Marcelo de C Griebeler, Bernardo Henz, Filipe Ferreira Dos Santos, Gabriela D A Guardia, Helena B Conceição, Pedro A F Galante, Darlan C Minussi, Manuel M Oliveira, Guido Lenz

{"title":"Population dynamics is a cancer driver.","authors":"Mariana Dos Santos Oliveira, Marcelo de C Griebeler, Bernardo Henz, Filipe Ferreira Dos Santos, Gabriela D A Guardia, Helena B Conceição, Pedro A F Galante, Darlan C Minussi, Manuel M Oliveira, Guido Lenz","doi":"10.1093/carcin/bgae038","DOIUrl":"10.1093/carcin/bgae038","url":null,"abstract":"Most tissues are continuously renovated through the division of stem cells and the death of old or damaged cells, which is known as the cell turnover rate (CTOR). Despite being in a steady state, tissues have different population dynamics thus producing diverse clonality levels. Here, we propose and test that cell population dynamics can be a cancer driver. We employed the evolutionary software esiCancer to show that CTOR, within a range comparable to what is observed in human tissues, can amplify the risk of a mutation due to ancestral selection (ANSEL). In a high CTOR tissue, a mutated ancestral cell is likely to be selected and persist over generations, which leads to a scenario of elevated ANSEL profile, characterized by few niches of large clones, which does not occur in low CTOR. We found that CTOR is significantly associated with the risk of developing cancer, even when correcting for mutation load, indicating that population dynamics per se is a cancer driver. This concept is central to understanding cancer risk and for the design of new therapeutic interventions that minimizes the contribution of ANSEL in cancer growth.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"893-902"},"PeriodicalIF":3.3,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antitumor activity of niclosamide-mediated oxidative stress against acute lymphoblastic leukemia. 烟酰胺介导的氧化应激对急性淋巴细胞白血病的抗肿瘤活性。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-12-30 DOI: 10.1093/carcin/bgae035

Jing Yang, Yong Liu, Zefan Du, Qin Zhou, Luo Yang, Qianyun Ye, Jingxuan Pan, Waiyi Zou, Chun Chen, Bei Jin

引用次数: 0

Editor-in-Chief's Note-Thank you to Reviewers. 总编辑注：感谢审稿人。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-12-30 DOI: 10.1093/carcin/bgae076

引用次数: 0

Correction to: Characterization of microRNA-29 family expression and investigation of their mechanistic roles in gastric cancer. 更正为microRNA-29家族的表达特征及其在胃癌中的作用机制研究。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-12-30 DOI: 10.1093/carcin/bgae070

引用次数: 0

Effect of vitamin E δ-tocotrienol and aspirin on Wnt signaling in human colon cancer stem cells and in adenoma development in APCmin/+ mice. 维生素 E δ-生育三烯酚和阿司匹林对人类结肠癌干细胞 Wnt 信号转导和 APCmin/+ 小鼠腺瘤发育的影响

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-12-30 DOI: 10.1093/carcin/bgae041

Kazim Husain, Domenico Coppola, Chung S Yang, Mokenge P Malafa

{"title":"Effect of vitamin E δ-tocotrienol and aspirin on Wnt signaling in human colon cancer stem cells and in adenoma development in APCmin/+ mice.","authors":"Kazim Husain, Domenico Coppola, Chung S Yang, Mokenge P Malafa","doi":"10.1093/carcin/bgae041","DOIUrl":"10.1093/carcin/bgae041","url":null,"abstract":"In this study, we evaluated the effects of vitamin E δ-tocotrienol (DT3) and aspirin on Wnt signaling in human colon cancer stem cells (CCSCs) and in the prevention of adenoma formation in APCmin/+ mice. We found that knockdown of the adenomatous polyposis coli (APC) gene led to subsequent activation of Wnt signaling in colon epithelial cells (NCM460-APCsiRNA) and induction of β-catenin and its downstream target proteins c-MYC, cyclin D1, and survivin. When aspirin and DT3 were combined, cell growth and survival were inhibited and apoptosis was induced in colon epithelial cells and CCSCs. However, DT3 and/or aspirin had little or no effect on the control of normal colon epithelial cells (NCM460-NCsiRNA). The induction of apoptosis was directly related to the activation of caspase 8 and cleavage of BH3-interacting-domain (BID) to truncated BID. In addition, DT3- and/or aspirin-induced apoptosis was associated with cleaved Poly (ADP-ribose) polymerase (PARP), elevated levels of cytosolic cytochrome c and BAX, and depletion of antiapoptotic protein BCl-2 in CCSCs. The combination of aspirin and DT3 inhibited the self-renewal capacity, Wnt/β-catenin receptor activity, and expression of β-catenin and its downstream targets c-MYC, cyclin D1, and survivin in CCSCs. We also found that treatment with DT3 alone or combined with aspirin significantly inhibited intestinal adenoma formation and Wnt/β-catenin signaling and induced apoptosis, compared with vehicle, in APCmin/+ mice. Our study demonstrated a rationale for further investigation of the combination of DT3 and aspirin for colorectal cancer prevention and therapy.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"881-892"},"PeriodicalIF":3.3,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The ubiquitin ligase STUB1 suppresses tumorigenesis of renal cell carcinomas through regulating YTHDF1 stability. 泛素连接酶STUB1通过调节YTHDF1的稳定性抑制肾细胞癌的肿瘤发生。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-12-30 DOI: 10.1093/carcin/bgae033

Siquan Ma, Yi Sun, Guoyao Gao, Jin Zeng, Ke Chen, Zhenyu Zhao

引用次数: 0