Carcinogenesis最新文献_第6页

Inhibition of benzo[a]pyrene-induced DNA adduct in buccal cells of smokers by black raspberry lozenges. 黑覆盆子润喉糖抑制吸烟者口腔细胞中苯并[a]芘诱导的 DNA 加合物

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae067

Kun-Ming Chen, Nicolle M Krebs, Yuan-Wan Sun, Dongxiao Sun, Jiangang Liao, Lisa Reinhart, Jacek Krzeminski, Shantu Amin, Gary Stoner, Susan R Mallery, Karam El-Bayoumy

{"title":"Inhibition of benzo[a]pyrene-induced DNA adduct in buccal cells of smokers by black raspberry lozenges.","authors":"Kun-Ming Chen, Nicolle M Krebs, Yuan-Wan Sun, Dongxiao Sun, Jiangang Liao, Lisa Reinhart, Jacek Krzeminski, Shantu Amin, Gary Stoner, Susan R Mallery, Karam El-Bayoumy","doi":"10.1093/carcin/bgae067","DOIUrl":"10.1093/carcin/bgae067","url":null,"abstract":"Using LC-MS/MS analysis we previously showed for the first time (Carcinogenesis 43:746-753, 2022) that levels of DNA damage induced by benzo[a]pyrene (B[a]P), an oral carcinogen and tobacco smoke (TS) constituent, were significantly higher in buccal cells of smokers than those in nonsmokers; these results suggest the potential contribution of B[a]P in the development of oral squamous cell carcinoma (OSCC) in humans. Treating cancers, including OSCC, at late stages, even with improved targeted therapies, continues to be a major challenge. Thus interception/prevention remains a preferable approach for OSCC management and control. In previous preclinical studies, we and others demonstrated the protective effects of black raspberry (BRB) against carcinogen-induced DNA damage and OSCC. Thus, to translate preclinical findings, we tested the hypothesis in a Phase 0 clinical study that BRB administration reduces DNA damage induced by B[a]P in the buccal cells of smokers. After enrolling 27 smokers, baseline buccal cells were collected before the administration of BRB lozenges (5/day for 8 weeks, 1 gm BRB powder/lozenge) at baseline, at the middle and the end of BRB administration. The last samples were collected 4 weeks after BRB cessation (washout period). B[a]P-induced DNA damage (BPDE-N2-dG) was evaluated by LC-MS/MS. BRB administration resulted in a significant reduction in DNA damage: 26.3% at the midpoint (P = .01506) compared to baseline, 36.1% at the end of BRB administration (P = .00355), and 16.6% after BRB cessation (P = .007586). Our results suggest the potential benefits of BRB as a chemopreventive agent against the development of TS-initiated OSCC.","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/PMC11886790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379126","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

Inhibition of phospholipase D1 reduces pancreatic carcinogenesis in mice partly through a FAK-dependent mechanism. 抑制磷脂酶 D1 可部分通过 FAK 依赖性机制减少小鼠胰腺癌的发生。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae071

Hala A Addassi, Irena Krga, Fernando Villarreal, Joseph F LaComb, Michael A Frohman, Karen Matsukuma, Gerardo G Mackenzie

{"title":"Inhibition of phospholipase D1 reduces pancreatic carcinogenesis in mice partly through a FAK-dependent mechanism.","authors":"Hala A Addassi, Irena Krga, Fernando Villarreal, Joseph F LaComb, Michael A Frohman, Karen Matsukuma, Gerardo G Mackenzie","doi":"10.1093/carcin/bgae071","DOIUrl":"10.1093/carcin/bgae071","url":null,"abstract":"Phospholipase D (PLD) plays a critical role in cancer progression. However, its role in pancreatic cancer remains unclear. Thus, we evaluated the role of PLD1, one of two classical isoforms of PLD, in pancreatic carcinogenesis in vivo. The role of PLD1 in tumor growth was evaluated by subcutaneously transplanting human MIA PaCa-2 cells expressing endogenous PLD1 levels (Ctr KD cells) or cells in which PLD1 was knocked down (Pld1 KD cells) into immunodeficient mice. Twenty days post-implantation, tumors that arose from Pld1-KD cells were significantly smaller, compared to controls (Ctr KD). Then, we assessed the role of PLD1 in the tumor microenvironment, by subcutaneously implanting mouse LSL-KrasG12D/+;Trp53R172H/+;Pdx-1-Cre (KPC) cells into wild-type or PLD1 knockout (Pld1-/-) mice. Compared to wild type, tumor growth was attenuated in Pld1-/- mice by 39%, whereas treatment of Pld1-/- mice with gemcitabine reduced tumor growth by 79%. When PLD1 was ablated in LSL-KrasG12D;Ptf1Cre/+ (KC) mice, no reduction in acinar cell loss was observed, compared to KC mice. Finally, treatment of KC mice with a small molecule inhibitor of PLD1 and PLD2 (FIPI) significantly reduced acinar cell loss and cell proliferation, compared to vehicle-treated mice. Mechanistically, the effect of PLD on tumor growth is mediated, partly, by the focal adhesion kinase pathway. In conclusion, while PLD1 is a critical regulator of pancreatic xenograft and allograft growth, playing an important role at the tumor and at the microenvironment levels, the inhibition of PLD1 and PLD2 is necessary to reduce pancreatic carcinogenesis in KC mice and might represent a novel therapeutic target.","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":"142564080","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

Ubiquitin-specific peptidase 49 promotes adenocarcinoma of the esophagogastric junction malignant progression via activating SHCBP1-β-catenin-GPX4 axis. USP49 通过激活 SHCBP1-β-catenin-GPX4 轴促进食管胃交界处腺癌的恶性发展。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae060

Yun Ding, Zhen Liu, Xiaofeng Dai, Ruiwen Ruan, Hongguang Zhong, Zhipeng Wu, Yangyang Yao, Jun Chen, Jun Deng, Jianping Xiong

{"title":"Ubiquitin-specific peptidase 49 promotes adenocarcinoma of the esophagogastric junction malignant progression via activating SHCBP1-β-catenin-GPX4 axis.","authors":"Yun Ding, Zhen Liu, Xiaofeng Dai, Ruiwen Ruan, Hongguang Zhong, Zhipeng Wu, Yangyang Yao, Jun Chen, Jun Deng, Jianping Xiong","doi":"10.1093/carcin/bgae060","DOIUrl":"10.1093/carcin/bgae060","url":null,"abstract":"Adenocarcinoma of the esophagogastric junction (AEG) has received widespread attention because of its increasing incidence. However, the molecular mechanism underlying tumor progression remains unclear. Here, we report that the downregulation of ubiquitin-specific peptidase 49 (USP49) promotes ferroptosis in OE33 and OE19 cells, thereby inhibiting cell proliferation in vitro and in vivo, whereas the overexpression of USP49 had the opposite effect. In addition, USP49 downregulation promoted AEG cell radiotherapy sensitivity. Moreover, overexpression of Glutathione PeroXidase 4 reversed the ferroptosis and proliferation inhibition induced by USP49 knockdown. Mechanistically, USP49 deubiquitinates and stabilizes Shc SH2-domain-binding protein 1, subsequently facilitating the entry of β-catenin into the nucleus to enhance Glutathione PeroXidase 4 transcriptional expression. Finally, high USP49 expression was correlated with shorter overall survival in patients with AEG. In summary, our findings identify USP49 as a novel regulator of ferroptosis in AEG cells, indicating that USP49 may be a potential therapeutic target in AEG.","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":"142131937","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

SMARCA4/BRG1 deficiency induces a targetable dependence on oxidative phosphorylation in clear cell renal cell carcinoma. 在透明细胞肾细胞癌中，SMARCA4/BRG1缺陷诱导氧化磷酸化的可靶向依赖性。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgaf002

Ru Fang, Xiaotong Wang, Ruina Wu, Rui Pan, Miaomiao Tian, Rusong Zhang, Xue Wei, Xuan Wang, Shengbing Ye, Feng Li, Qiuyuan Xia, Yang Cheng, Qiu Rao

{"title":"SMARCA4/BRG1 deficiency induces a targetable dependence on oxidative phosphorylation in clear cell renal cell carcinoma.","authors":"Ru Fang, Xiaotong Wang, Ruina Wu, Rui Pan, Miaomiao Tian, Rusong Zhang, Xue Wei, Xuan Wang, Shengbing Ye, Feng Li, Qiuyuan Xia, Yang Cheng, Qiu Rao","doi":"10.1093/carcin/bgaf002","DOIUrl":"10.1093/carcin/bgaf002","url":null,"abstract":"The tumor suppressor gene SMARCA4, a critical component of the SWI/SNF chromatin remodeling complex, is frequently inactivated in various cancers, including clear cell renal cell carcinoma (ccRCC). Despite its significance, the role of SMARCA4 in ccRCC development and its potential therapeutic vulnerabilities have not been fully explored. Our research found that SMARCA4 deficiency was associated with poor prognosis and was observed in a subset of high-grade ccRCCs. Through functional assays, we determined that the suppression of SMARCA4 led to an increase in RCC cell proliferation. Further gene expression analysis unveiled that SMARCA4-deficient cells exhibit an upregulation of the oxidative phosphorylation (OXPHOS) pathway. Delving deeper, we combined RNA sequencing (RNA-Seq) and Assay for transposase-accessible chromatin with sequencing (ATAC-Seq) data to uncover that SMARCA4 plays a crucial role in modulating chromatin accessibility and the expression of genes essential for the respiratory electron transport chain. A significant finding from our study is that RCC cells and xenograft tumors lacking SMARCA4 demonstrated an increased sensitivity to the inhibition of the OXPHOS pathway by the novel small molecule IACS-010759. This sensitivity is attributed to the heightened energy demands and susceptibility to energy stress observed in SMARCA4-deficient cells, driven by their amplified biosynthetic requirements. The efficacy of IACS-010759 stems from its ability to induce energy deprivation, pinpointing OXPHOS inhibition as a promising therapeutic approach for targeting SMARCA4-mutant tumors. This strategy offers a novel avenue to address a currently unmet therapeutic need, highlighting the potential of OXPHOS inhibition in the treatment of cancers harboring SMARCA4 mutations.","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":"143032311","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

Advanced glycation end products promote the progression of endometrial cancer via activating the RAGE/CHKA/PI3K/AKT signaling pathway. 高级糖化终末产物通过激活 RAGE/CHKA/PI3K/AKT 信号通路促进子宫内膜癌的进展。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae059

Wan Shu, Teng Hua, Xiaoyan Xin, Jun Zhang, Jing Lin, Rui Shi, Rong Zhao, Wei Zhang, Ke-Jun Dong, Hongbo Wang, Xing Zhou

{"title":"Advanced glycation end products promote the progression of endometrial cancer via activating the RAGE/CHKA/PI3K/AKT signaling pathway.","authors":"Wan Shu, Teng Hua, Xiaoyan Xin, Jun Zhang, Jing Lin, Rui Shi, Rong Zhao, Wei Zhang, Ke-Jun Dong, Hongbo Wang, Xing Zhou","doi":"10.1093/carcin/bgae059","DOIUrl":"10.1093/carcin/bgae059","url":null,"abstract":"Endometrial cancer (EC) is a common malignant tumor that is closely associated with metabolic disorders such as diabetes and obesity. Advanced glycation end products (AGEs) are complex polymers formed by the reaction of reducing sugars with the amino groups of biomacromolecules, mediating the occurrence and development of many chronic metabolic diseases. Recent research has demonstrated that the accumulation of AGEs can affect the tumor microenvironment, metabolism, and signaling pathways, thereby affecting the malignant progression of tumors. However, the mechanism by which AGEs affect EC is unclear. Our research aimed to investigate how AGEs promote the development of EC through metabolic pathways and to explore their potential underlying mechanisms. Our experimental results demonstrated that AGEs upregulated the choline metabolism mediated by choline kinase alpha (CHKA) through the receptor for advanced glycation end products, activating the PI3K/AKT pathway and enhancing the malignant biological behavior of EC cells. Virtual screening and molecular dynamics simulation revealed that timosaponin A3 could target CHKA to inhibit AGE-induced progression of EC and that a newly discovered CHKA inhibitor could be a novel targeted inhibitor for the treatment of EC. This study provides new therapeutic strategies and contributes to the treatment of EC.","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":"142046408","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

Epigenetic mechanisms underlying endometrial cancer outcomes: race-specific patterns of DNA methylation associated with molecular subtypes and survival. 子宫内膜癌（EC）预后的表观遗传机制：与分子亚型和生存相关的DNA甲基化的种族特异性模式

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgaf004

Emery Hoos, Lauren E Koval, David L Corcoran, Lauren A Eaves, Kyle Roell, Julia E Rager, Xianming Tan, Sherette Godfrey, Temitope O Keku, Victoria Bae-Jump, Andrew F Olshan, Hazel B Nichols, Bernard E Weissman, Rebecca C Fry

{"title":"Epigenetic mechanisms underlying endometrial cancer outcomes: race-specific patterns of DNA methylation associated with molecular subtypes and survival.","authors":"Emery Hoos, Lauren E Koval, David L Corcoran, Lauren A Eaves, Kyle Roell, Julia E Rager, Xianming Tan, Sherette Godfrey, Temitope O Keku, Victoria Bae-Jump, Andrew F Olshan, Hazel B Nichols, Bernard E Weissman, Rebecca C Fry","doi":"10.1093/carcin/bgaf004","DOIUrl":"10.1093/carcin/bgaf004","url":null,"abstract":"Endometrial cancer (EC) is the fourth most common cancer in women in the USA. Stark racial disparities are present in EC outcomes in which Black women have significantly higher EC-related mortality than White women. The social and biologic factors that contribute to these disparities are complex and may include racial differences in epigenetic landscapes. To investigate race-specific epigenetic differences in EC tumor characteristics and outcomes, we utilized the most recent data within the Cancer Genome Atlas (TCGA). Genome-wide CpG methylation data for more than 850 000 CpG sites were analyzed across 245 tumor samples, including 52 from Black women and 181 from White women. Race-adjusted and race-stratified associations among CpG methylation in ECs and molecular subtypes and disease-free survival were examined. Race-specific analysis identified subtype-associated CpGs within 9572 genes in tumors from White women and only 10 genes in tumors that were from Black women. Race-specific analyses also identified survival-associated CpGs with 1119 unique genes identified in tumors from White women and none identified in tumors from Black women. Genes identified with differential methylation among subtypes included those involved in oxidative stress (HIF3A), and DNA repair (MLH1). Data from a replication cohort highlighted genes overlapping with those identified within the TCGA, such as G Protein Subunit Beta 1 (GNB1), involved in G-protein signaling, and Interleukin 37 (IL37), involved in cytokine signaling. Identification of these racial differences in EC tumor epigenetic landscapes and associated changes in gene expression may provide insight into strategies to improve outcomes and reduce disparities.","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/PMC11894373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051743","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

Elevated expression of Golgi Transport 1B promotes the progression of cervical cancer by activating the NF-kappaB signaling pathway via interaction with TANK-Binding Kinase 1. 高尔基体转运 1B 通过与 TBK1 相互作用激活 NF-κB 信号通路，从而促进宫颈癌的进展。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae054

Yixuan Sun, Qihua Peng, Ruiwen Wang, Yifan Yin, Musitaba Mutailifu, Lipeng Hu, Yincheng Teng, Yang Zhou

{"title":"Elevated expression of Golgi Transport 1B promotes the progression of cervical cancer by activating the NF-kappaB signaling pathway via interaction with TANK-Binding Kinase 1.","authors":"Yixuan Sun, Qihua Peng, Ruiwen Wang, Yifan Yin, Musitaba Mutailifu, Lipeng Hu, Yincheng Teng, Yang Zhou","doi":"10.1093/carcin/bgae054","DOIUrl":"10.1093/carcin/bgae054","url":null,"abstract":"As a preventable disease, cervical cancer (cervical squamous cell carcinoma and endocervical adenocarcinoma-CESC) remains a tumor with high morbidity and mortality worldwide, underscoring the pressing need for effective treatment strategies. This research identified Golgi transport 1B (GOLT1B) as a critical gene involved in the development of cervical cancer. Gene Expression Omnibus (GEO) datasets were investigated to determine the upregulation of GOLT1B in cervical cancer tissue compared with normal tissue. Besides, GOLT1B was found to predict poor prognosis in cervical cancer by utilizing Gene Expression Profiling Interactive Analysis (GEPIA). The functional assay indicated that GOLT1B promoted CESC viability and migration in vitro and in vivo. RNA sequencing results suggested that GOLT1B likely influenced the nuclear factor-kappaB (NF-κB) pathway. The subsequent western blot and dual luciferase reporter assay revealed the interaction between GOLT1B and TANK binding kinase 1 (TBK1), modulating the NF-κB pathway. More importantly, GOLT1B was also found to regulate immune cell infiltration, suggesting its potential role in the tumor microenvironment. In conclusion, GOLT1B promotes CESC progression via interaction with TBK1 and augmentation of NF-κB signaling-mediated cancer-associated inflammation, which provides us with a new approach to CESC target therapy.","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":"141901038","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

Novel inhibitory effect of Omega-3 fatty acids regulating pancreatic cancer progression. Omega-3脂肪酸调节胰腺癌进展的新抑制作用。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae081

María I Garay, Tamara Mazo, Victoria Ferrero, Nelso N Barotto, Clarisa Lagares, María F Granton, María J Moreira-Espinoza, David C Cremonezzi, Andrea Comba, Mabel N Brunotto, Ezequiel J Tolosa, Martín E Fernandez-Zapico, María E Pasqualini

{"title":"Novel inhibitory effect of Omega-3 fatty acids regulating pancreatic cancer progression.","authors":"María I Garay, Tamara Mazo, Victoria Ferrero, Nelso N Barotto, Clarisa Lagares, María F Granton, María J Moreira-Espinoza, David C Cremonezzi, Andrea Comba, Mabel N Brunotto, Ezequiel J Tolosa, Martín E Fernandez-Zapico, María E Pasqualini","doi":"10.1093/carcin/bgae081","DOIUrl":"10.1093/carcin/bgae081","url":null,"abstract":"Pancreatic cancer is a devastating malignancy in great need of new and more effective treatment approaches. In recent years, studies have indicated that nutritional interventions, particularly nutraceuticals, may provide novel avenues to modulate cancer progression. Here, our study characterizes the impact of ω-3 polyunsaturated fatty acids, eicosapentaenoic acid, and docosahexaenoic acid, as a nutraceutical intervention in pancreatic cancer using a genetically engineered mouse model driven by KrasG12D and Trp53R172H. This model closely resembles human pancreatic carcinogenesis, offering a disease relevant platform for translational research. Our findings showed that ω-3 polyunsaturated fatty acids intervention (using a diet supplemented with 6% cod liver oil) significantly reduced tumor volume as well as lung and liver metastasis and a trend toward improved survival rate compared with control treated mice. This antitumoral effect was accompanied by distinct changes in tumor membrane fatty acid profile and eicosanoids release. Furthermore, the eicosapentaenoic acid and docosahexaenoic acid intervention also reduced malignant histological parameters and induced apoptosis without affecting cell proliferation. Of note is the significant reduction in tumor fibrosis that was associated with decreased levels of Sonic Hedgehog, a major ligand controlling this cellular compartment in pancreatic cancer. All together our results demonstrate the impact of eicosapentaenoic acid and docosahexaenoic acid as antitumor regulators in pancreatic cancer, suggesting potential for ω-3 polyunsaturated fatty acids as a possible antitumoral dietary intervention. This research opens new avenues for integrating nutraceutical strategies in pancreatic cancer management.","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/PMC12097994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913827","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

Prognostic value of circulating tumor DNA in different cancer types detected by ultra-low-pass whole-genome sequencing: a systematic review and patient-level survival data meta-analysis. 通过超低通量全基因组测序检测不同癌症类型中循环肿瘤DNA的预后价值。系统综述和患者生存数据荟萃分析。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae073

Miguel Sogbe, Daniel Aliseda, Paloma Sangro, Manuel de la Torre-Aláez, Bruno Sangro, Josepmaria Argemi

{"title":"Prognostic value of circulating tumor DNA in different cancer types detected by ultra-low-pass whole-genome sequencing: a systematic review and patient-level survival data meta-analysis.","authors":"Miguel Sogbe, Daniel Aliseda, Paloma Sangro, Manuel de la Torre-Aláez, Bruno Sangro, Josepmaria Argemi","doi":"10.1093/carcin/bgae073","DOIUrl":"10.1093/carcin/bgae073","url":null,"abstract":"Ultra-low-pass whole-genome sequencing (ULP-WGS) (≤0.5 × coverage) of plasma cell-free DNA (cfDNA) has emerged as a low-cost, promising tool to assess the circulating tumor DNA (ctDNA) fraction. This meta-analysis aims to summarize the current findings and comprehensively investigate the prognostic value of baseline ctDNA detected by ULP-WGS in solid tumors. A systematic review was carried out by searching PubMed/MEDLINE and Scopus databases to identify eligible studies conducted between January 2014 and January 2024. Inclusion criteria comprised studies with reported overall survival and progression-free survival outcomes across therapy-naïve patients with different solid tumors. All patients underwent baseline ULP-WGS of plasma cfDNA and were categorized as ctDNA positive (tumor fraction ≥10%) or negative (tumor fraction <10%). A one-stage meta-analysis was performed using patient-level survival data reconstructed from published articles. A Cox proportional hazards model with shared frailty was used to assess the difference in survival between arms. A total of six studies, comprising 620 patients (367 negative ctDNA and 253 positive ctDNA), were included in the overall survival analysis, while five studies, involving 349 patients (212 negative ctDNA and 137 positive ctDNA), were included in the progression-free survival analysis. The meta-analysis showed that patients with baseline positive ctDNA had a significantly higher risk of death (HR = 2.60, 95% CI: 2.01-3.36) and disease progression (HR = 2.28, 95% CI: 1.71-3.05) compared to those with negative ctDNA. The presence of a positive ctDNA at baseline is associated with increased risk of death and progression in patients with same-stage cancer.","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/PMC11886806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643499","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

Copper in colorectal cancer patients: a systematic review and meta-analysis. 铜在结直肠癌患者中的作用：一项系统综述和荟萃分析。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgaf001

Carlos Muñoz-Bravo, Inés Marín-Burdallo, Lucas González-Herrera, Carla González-Palacios Torres, Macarena Lozano-Lorca, José Juan Jiménez-Moleón, Rocío Olmedo-Requena

{"title":"Copper in colorectal cancer patients: a systematic review and meta-analysis.","authors":"Carlos Muñoz-Bravo, Inés Marín-Burdallo, Lucas González-Herrera, Carla González-Palacios Torres, Macarena Lozano-Lorca, José Juan Jiménez-Moleón, Rocío Olmedo-Requena","doi":"10.1093/carcin/bgaf001","DOIUrl":"10.1093/carcin/bgaf001","url":null,"abstract":"Several clinical studies have evaluated the relationship between copper on colorectal cancer (CRC), but the results are contradictory. This study aimed to conduct a systematic review and meta-analysis to investigate copper measured in two biological matrices (serum/plasma/blood and tissue) and dietary intake in CRC patients compared to healthy controls. We conducted a comprehensive and systematic search in PubMed, Scopus, Embase, and Web of Science. We included studies that reported copper levels in serum/plasma/blood, tissue, or from the diet, with an observational study design (cohort and case-control studies). Study quality was assessed with the Newcastle-Ottawa scale and potential causes of heterogeneity were evaluated. Standardized mean differences (SMD) with 95% confidence interval (CI) were pooled using random-effect models. Overall pooled odds ratio and 95% CI for the risk of CRC were calculated. Twenty-six studies (23 case-control and 3 cohort studies) with a total of 227 354 participants were included. Most of the studies presented low (50%) or moderate quality (42.3%). No differences in serum/plasma/blood copper levels (SMD = 0.23; 95% CI: -0.23, 0.70; I2 = 97.3%, 19 studies), tissue copper levels (SMD = -1.69; 95% CI: -3.41, 0.03; I2 = 85.6%, 2 studies), or copper/zinc ratio (SMD = 1.19; 95% CI: 0.54, 1.84; I2 = 95.3%, 6 studies) were found between CRC patients and healthy controls. Regarding dietary copper, CRC patients had a lower intake (SMD = -0.27; 95% CI: -0.51, -0.03; I2 = 0.0%, 2 studies). No differences were found in copper levels between CRC patients and healthy controls. However, evidence shows mostly low or moderate quality, and results were heterogeneous. More prospective studies with an adequate methodological approach are needed.","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/PMC11826919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027992","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}

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