Carcinogenesis最新文献

{"title":"Transgelin: a tumor suppressor candidate in neuroblastoma.","authors":"Yoko Hiyama, Akifumi Kanda, Takahiro Fukazawa, Keiji Tanimoto, Masato Kojima, Nagisa Morihara, Hiroaki Matsuo, Eiso Hiyama, Yusuke Sotomaru","doi":"10.1093/carcin/bgag016","DOIUrl":"10.1093/carcin/bgag016","url":null,"abstract":"<p><p>Neuroblastoma (NB), a common childhood solid tumor, is the leading cause of childhood cancer deaths. Transgelin (TAGLN) is an actin-binding protein of the calponin family, and it is involved in cell motility and migration. The TAGLN gene expression was induced in NB cell lines, such as GOTO, SK-N-SH, and TGW, by gene overexpression using a retroviral Tet-On inducible expression system, and was repressed by RNA interference (RNAi) treatment. TAGLN overexpression repressed cell growth and migration and induced cell arrest and differentiation. On the other hand, RNAi-mediated TAGLN repression activated cell growth. Cells overexpressing TAGLN showed decreased levels of undifferentiated cell markers, such as SOX2, OCT4, KLF4, and ID2. Single-cell analysis after TAGLN overexpression revealed a distinguishable cluster characterized by expression of POSTM, APOE, PDGFRA, IGFBP3, SMAD5, and IGFBP7. In TH-MYCN mice, which have a high frequency of NB development, Tagln overexpression by induction of the murine Tagln gene significantly reduced tumor formation and prolonged survival. In conclusion, these in vitro and in vivo analyses suggest that TAGLN is a candidate tumor suppressor gene in NB.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":"47 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509798","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}

{"title":"Tumor-associated astrocytes inhibit tumor cell apoptosis through TNF-α-TNF receptor 2-NF-κB pathway in lung cancer brain metastasis.","authors":"Shuo Zhang, Jinjin Cai, Yingying Feng, Man Yang, Yuhang Li, Yanghui Qu, Li Zhang, Chaonan Zheng, Yuan Wang","doi":"10.1093/carcin/bgaf090","DOIUrl":"10.1093/carcin/bgaf090","url":null,"abstract":"<p><p>Lung cancer represents the leading cause of cancer-related mortality worldwide, with up to 50% of cases developing brain metastasis during disease progression. Current therapeutic options for brain metastasis remain limited, resulting in poor clinical outcomes. Previous studies have demonstrated that tumor cell invasion into the brain involves localized activation of astrocytes, with these tumor-associated astrocytes (TAAs) exhibiting either pro-tumor or anti-tumor effects. However, the role of astrocytes during postcolonization stages remains unclear. In this study, employing both a murine model of lung cancer brain metastasis and an in vitro coculture system, we identified the presence of astrocytes within the tumor microenvironment of both clinical specimens and experimental models. Our in vitro experiments revealed that astrocytes significantly enhanced tumor cell survival without affecting proliferation, primarily through inhibition of apoptosis. Mechanistic investigations demonstrated that astrocyte-derived TNF-α mediates this anti-apoptotic effect via activation of the NF-κB signaling pathway in tumor cells. Genetic knockdown of TNF receptor 2 (TNFR2) in tumor cells or pharmacological inhibition of the NF-κB pathway effectively abolished this protective effect. Importantly, TNFR2 knockdown increased intracranial tumor cell apoptosis and prolonged survival in the brain metastasis mouse model. These findings collectively demonstrate that TAAs in lung cancer brain metastasis promote tumor cell survival through a TNFR2-NF-κB-dependent mechanism mediated by TNF-α secretion.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740802","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}

{"title":"Genomic and transcriptomic characterization of gamma ray- and heavy-ion-induced precursor B-cell lymphomas in B6C3F1 mice: radiation-type-dependent interstitial chromosomal deletions at tumor-suppressor gene loci.","authors":"Kenta Amano, Hirotaka Tachibana, Chizuru Tsuruoka, Kazuhiro Daino, Takamitsu Morioka, Yi Shang, Atsuko Ishikawa, Tatsuhiko Imaoka, Akira Matsuura, Shizuko Kakinuma","doi":"10.1093/carcin/bgag002","DOIUrl":"10.1093/carcin/bgag002","url":null,"abstract":"<p><p>Epidemiological studies have revealed that ionizing radiation is a risk factor for acute lymphoblastic leukemia. Humans can be exposed to radiation via clinical radiotherapies or spaceflight, yet our knowledge of the potential carcinogenic effects of various types of radiation remains incomplete. To address this shortcoming, we analyzed the development of precursor B-cell lymphoma (pBL) in B6C3F1 mice after irradiation with gamma rays or heavy ions (carbon, silicon, argon, or iron ions) followed by array comparative genomic hybridization, whole-exome sequencing, and RNA-sequencing analyses. Heavy-ion irradiation predominantly induced late-onset pBLs. In addition, chromosomal deletions in late-onset pBLs depended on radiation type: gamma-ray-induced pBLs had interstitial deletions of chromosome 8 (del8) affecting the tumor-suppressor gene Cyld, whereas silicon-ion-induced pBLs had interstitial deletions of chromosome 19 (del19) affecting the tumor-suppressor genes Cd274, Pten, and Fas; notably, carbon ions induced both types of pBL and no pBLs harbored these deletions in the argon- or iron-ion-irradiated mice. Late-onset pBLs were classified into two clusters with differential mutation patterns based on their gene-expression profiles, and pBLs with del8 and del19 were classified into different gene-expression clusters. Furthermore, the mutational and transcriptomic profiles of the late-onset del8 pBLs were reminiscent of human activated B-cell-like diffuse large B-cell lymphoma (DLBCL), whereas those of the del19 pBLs resembled germinal center B-cell-like DLBCL. These results establish the molecular signatures in radiation-induced pBLs that depend on radiation type, which will help improve both targeted molecular therapies for patients and risk assessment after exposure.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988029","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}

{"title":"Role of colorectal cancer-derived exosomes in modulating macrophage phenotype during tumor development.","authors":"Khandu Wadhonkar, Dhruv Das, Rajani Kant Chittela, Alexander G Obukhov, Mirza S Baig","doi":"10.1093/carcin/bgag003","DOIUrl":"10.1093/carcin/bgag003","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is one of the deadliest malignancies and is characterized by a complex tumor microenvironment (TME) comprising cancer and immune cells engaged in extensive signaling crosstalk. The composition of the TME changes with disease stage and contributes to tumor aggressiveness and resistance to therapy. Although tumor associated immune cells are known to promote cancer progression, the mechanisms underlying these effects are not fully understood. In this study, we show that communication between CRC cells and immune cells, particularly tumor associated macrophages (TAMs), is mediated by soluble factors and extracellular vesicles, including exosomes. We find that the phenotypic transition of CRC associated TAMs is initially driven by activation of the nuclear factor kappa B transcription factor. With time, exosomal cargo promotes anti-inflammatory signaling, leading to the development of a tumor supportive microenvironment that favors tumor growth. Together, these findings highlight exosome mediated modulation of TAM function as an important mechanism in CRC progression and suggest that targeting this pathway to delay the shift of TAMs from pro-inflammatory to tumor supportive states may attenuate CRC aggressiveness.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003266","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}

{"title":"Smoking, alcohol, and colon cancer survival are modified by immune biomarkers: a population-representative study.","authors":"Yasemin Adali, Maurice B Loughrey, Stephanie Craig, Ronan T Gray, Jacqueline A James, Manuel Salto-Tellez, Philip D Dunne, Helen G Coleman","doi":"10.1093/carcin/bgag006","DOIUrl":"10.1093/carcin/bgag006","url":null,"abstract":"<p><p>Lifestyle factors such as smoking and alcohol may influence colon cancer (CC) survival, but it is unclear whether their effects vary by tumour-infiltrating immune biomarkers. This study examined CC-specific survival by smoking and alcohol status, stratified by immune cell density, in a large population-based cohort. The study included 661 individuals who underwent surgery for stage II or III CC between 2004 and 2008 within two Health and Social Care (HSC) Trusts in Northern Ireland. Representative formalin-fixed, paraffin-embedded (FFPE) tumour blocks were retrieved, and immunohistochemistry (IHC) was performed on tissue microarrays constructed from both the central tumour and the invasive margin. Cox proportional hazards models were used to assess CC-specific survival, adjusting for key clinical and demographic confounders. Ever smoking, compared to never smoking, was associated with poorer CC-specific survival among individuals with lower densities of CD3+, CD4 +, and FOXP3 + tumour-infiltrating immune cells. Among those with higher CD8 + cell density in the central tumour, ever smoking was linked to worse outcomes. Similar patterns were seen in the invasive margin, although these were not all statistically significant. No significant associations were observed between alcohol use and survival across any immune biomarker subgroups. Smoking was associated with poorer survival among patients with CC, and this association appears to be modified by the density of tumour-infiltrating immune cells.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13017039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112557","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}

{"title":"The tumour microenvironment in paediatric rhabdomyosarcomas: a systematic review.","authors":"Megan Richards, Christina Putnam, Timothy J Underwood, Zoë S Walters","doi":"10.1093/carcin/bgag011","DOIUrl":"10.1093/carcin/bgag011","url":null,"abstract":"<p><p>Rhabdomyosarcoma (RMS) is a predominantly paediatric cancer that is classified by the presence or absence of a PAX-FOXO1 fusion gene, which is associated with a worse prognosis. Previous classification was based on histology, alveolar RMS (ARMS) or embryonal RMS (ERMS). In other paediatric cancers, fusion gene status has been shown to associate with differences in the tumour microenvironment (TME). However, comprehensive understanding of the TME in RMS and how it may differ between subtypes is lacking. This systematic review aimed to identify differences in the TME between fusion-positive RMS and fusion-negative RMS, to better understand how the fusion gene drives malignancy. The Web of Science, MEDLINE (Ovid), and EMBASE (Ovid) were searched to identify relevant studies investigating the TME in RMS. A total of 17 studies met the inclusion criteria and were included in the review, but only three studies specified fusion status in their sample data. Nine studies investigated the extracellular matrix and stroma, and another nine investigated the immune microenvironment. Significant differences in CD163+ macrophages, matrix metalloproteinases and stromal platelet-derived growth factor receptors-α/β were observed between ARMS and ERMS. Regarding fusion status, there were differences in the prevalence of T cell dysfunction, NECTIN-3 expression, and genes related to PD-1 signalling and interferon (IFN) response. This review highlights a need for further research of the TME in each fusion subtype. This will improve our understanding of how the fusion gene drives malignancy and ultimately aids in the development of novel treatment strategies.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13017844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257608","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}

{"title":"The carcinogenicity of e-cigarettes: a qualitative risk assessment.","authors":"Bernard W Stewart, Henry Marshall, Billie Bonevski, Hayley J Griffin, Ashley M Hopkins, Malinda Itchins, Cassandra J Mazza, Natansh D Modi, Marissa Ryan, Megan Varlow, Freddy Sitas","doi":"10.1093/carcin/bgag015","DOIUrl":"10.1093/carcin/bgag015","url":null,"abstract":"<p><p>This review involves a qualitative carcinogenic risk assessment of nicotine-based e-cigarettes. Though direct epidemiological evidence of cancer causation takes time to accumulate, carcinogenicity of e-cigarettes is evident from different types of investigation including, with respect to studies in humans, some case reports but mainly involving monitoring of biomarkers of exposure and biomarkers of harm implicating tumorigenesis. Complementary laboratory investigations of e-cigarette aerosols and constituent chemicals include rodent bioassays and a range of approaches to elucidate mechanism(s). In respect of e-cigarettes, each of these types of investigation have been subject to successive reviews, sometimes more than once per year. Consequently, this over-arching review is restricted to publications since 2017 to avoid possible selection bias. Physiological evidence of exposure using biomarkers reveals DNA damage correlated with vape-derived metabolites attributable to carcinogens including nicotine-derived nitrosamines, volatile organic compounds, flavour-derived agents, and certain metals. Biomarkers also indicate vaping-attributable oxidative stress, epigenetic change and inflammation in oral and respiratory tissue often specified in comparison with smoking. Rodent bioassays include inhalation exposure of mice to e-cigarette aerosol described as causing lung adenocarcinomas. Mechanistic data are presented using the key characteristics of carcinogens and taken together implicate a complex mixture mediating carcinogenicity via genotoxic and other processes. From 2017 to 2025, the conclusions in e-cigarette reviews addressing different avenues of investigation moved from describing a need for more evidence to notifying concern about e-cigarette carcinogenicity. Nicotine-based e-cigarettes are likely to be carcinogenic to humans who use them causing an indeterminate burden of oral cancer and lung cancer.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":"47 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572755","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}

{"title":"A watercress drink increases detoxification of common environmental carcinogens such as acrolein and benzene: results of a randomized clinical trial.","authors":"Stephen S Hecht, Steven G Carmella, Saonli Basu, Menglan Chen, Milo Wittman, Mei Kuen Tang, Yingchun Zhao, Jessica Lu, Debbie Ng, Emily Heath, Naomi Fujioka, Andy Egbert, Lori Strayer, Ayaantuu Usman, Nicole M Thomson, Sharon E Murphy, Dorothy K Hatsukami","doi":"10.1093/carcin/bgag007","DOIUrl":"10.1093/carcin/bgag007","url":null,"abstract":"<p><p>Human exposure to toxicants and carcinogens occurs via polluted air, the diet, occupational settings, endogenous processes, and tobacco products. The glutathione-S-transferase detoxification pathway resulting in the excretion of mercapturic acids is one of the most important human systems for processing and excreting toxicants and carcinogens. Maximizing effectiveness of this pathway through dietary modifications can potentially decrease the impact of such exposures. We conducted a two-site clinical trial with a crossover, single blind (to participants) design, randomized to order of product receipt comparing levels of selected urinary mercapturic acids when participants consumed a drink made from freeze-dried watercress (3× daily, 2 weeks) naturally containing 2-phenethyl isothiocyanate (PEITC) vs. a placebo drink containing maltodextrin (3× daily, 2 weeks) with a 4-week washout between the treatment periods. Two hundred forty participants (157 F) were recruited and 188 (125 F, 152 non-smokers) were compliant and completed the study. Among compliant subjects, urinary mercapturic acid detoxification products of acrolein, acrylonitrile, benzene, crotonaldehyde, methacrolein, and methyl vinyl ketone increased significantly (P ≤ 0.002), with the largest increases being observed for the mercapturic acids of acrolein (65.6%) and benzene (37.3%), both P < 0.001. Consumption of a drink, three times daily, prepared from freeze-dried watercress containing PEITC (total of approximately 40 mg/day) significantly increased the detoxification of 6 of 7 environmental toxicants and carcinogens monitored. The results indicate that watercress consumption can ameliorate exposure to environmental toxicants and carcinogens. These results are particularly timely and relevant to exposures to atmospheric pyrolysis products resulting from wildfires. Clinical trial registration number: NCT03978117.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13221842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146206580","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}

{"title":"Retraction of: Leptin-mediated regulation of MT1-MMP localization is KIF1B dependent and enhances gastric cancer cell invasion.","authors":"","doi":"10.1093/carcin/bgag012","DOIUrl":"https://doi.org/10.1093/carcin/bgag012","url":null,"abstract":"","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":"47 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389376","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}

{"title":"Plasma proteomic profiling identified prognostic indicators with therapeutic potential for colorectal cancer.","authors":"Xuan Xie, Jiahao Zhou, Qingbin Wu, Jing Sun, Chi Shu, Jun Huang, Changtao Li, Xin Wang, Xia Shen, Xue Li, Zhipeng Luo, Chuan Xu, Ziqiang Wang, Yazhou He","doi":"10.1093/carcin/bgag001","DOIUrl":"10.1093/carcin/bgag001","url":null,"abstract":"<p><p>Plasma proteins have been reported as predictors and potential targets for reducing colorectal cancer (CRC) risk. However, their potential roles in CRC prognosis remain unexplored. We measured plasma levels of 367 neuro-related proteins in CRC patients from the West China Hospital (WCH) cohort (N = 150, median follow-up = 46.72 months) via proximity extension assay. The least absolute shrinkage and selection operator penalized Cox regression identified five overall survival (OS)-and eleven disease-free survival-associated proteins, and the multiprotein signature for OS prediction was then validated in the UK Biobank (UKB) cohort (N = 1133). To overcome possible effects from confounders, we then employed Mendelian randomization analysis leveraging protein quantitative trait loci to investigate associations between genetically determined protein concentration and OS and cancer-specific survival of CRC in the UKB. We found that multiprotein signature developed in the WCH cohort (c-index = 0.784, 95% CI = 0.713-0.855) showed significant discriminative ability in the external UKB cohort (c-index = 0.616, 95% CI = 0.559-0.673). A significant association between genetically determined PD-L1 and OS (P = 0.043, HR = 1.53, 95% CI = 1.01-2.29) was observed, although we did not find strong evidence for colocalization. Additionally, single-cell and spatial transcriptome analyses illustrated PD-L1 expression localized predominantly to epithelial cells and immune cells (especially myeloid cells) in CRC tissue. The potential interactions of identified proteins were evaluated in the STRING database. Druggability evaluation also supported PD-L1 as a potential therapeutic target for CRC. Taken together, this study established multiprotein signatures for CRC prognosis and identified plasma PD-L1 as a possible biomarker and therapeutic target.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984523","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}