Carcinogenesis最新文献_第6页

CAFomics: convergence to translation for precision stroma approaches. CAFomics：精准基质方法的转化。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-11-22 DOI: 10.1093/carcin/bgae063

Ian C McCabe, Xianlu L Peng, Joseph F Kearney, Jen Jen Yeh

{"title":"CAFomics: convergence to translation for precision stroma approaches.","authors":"Ian C McCabe, Xianlu L Peng, Joseph F Kearney, Jen Jen Yeh","doi":"10.1093/carcin/bgae063","DOIUrl":"10.1093/carcin/bgae063","url":null,"abstract":"A noticeable characteristic of pancreatic ductal adenocarcinoma (PDAC) tumors is a dense tumor microenvironment with abundant and dense, desmoplastic stroma woven tightly with both cellular and matrix components. The high stromal density is associated with higher intratumor pressures which, until the last decade, was largely assumed to be tumor protective, confirmed by early studies demonstrating that altering the stroma was effective in genetically engineered models of PDAC. However, clinical trials using these approaches have been disappointing. There is increasing recognition that stroma heterogeneity is much greater than initially thought with an explosion of investigation into cancer-associated fibroblast (CAF) subpopulations led by experimental and single-cell transcriptomic studies. This review summarizes and attempts to harmonize the current transcriptomic data of CAF subpopulations. Understanding the heterogeneity of CAFs, the matrix, and other tumor microenvironment features will be critical to developing effective therapeutic approaches. Identifying model systems that best recapitulate the clinical behavior and treatment response of human PDAC will be important. Examining subpopulations as defined by clinical outcome will remain a critical step in defining clinically impactful CAF subtypes in larger clinical cohorts. The future of precision oncology in PDAC will depend on the integration of precision tumor epithelial and precision stroma approaches.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"817-822"},"PeriodicalIF":3.3,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602972","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

BRAF V600E-induced distinct DNA damage response defines the therapeutic potential of p53 activation for TP53 wild-type colorectal cancer. BRAF V600E 诱导的独特 DNA 损伤反应决定了 p53 激活对 TP53 野生型结直肠癌的治疗潜力。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-11-22 DOI: 10.1093/carcin/bgae040

Shinji Tokuyama, Hisakazu Kato, Hidekazu Takahashi, Kyoko Ueda, Asami Arita, Ryuta Ueda, Hiroto Seto, Yuki Sekido, Tsuyoshi Hata, Atsushi Hamabe, Takayuki Ogino, Norikatsu Miyoshi, Mamoru Uemura, Ken Matsuoka, Osamu Tsukamoto, Hirofumi Yamamoto, Yuichiro Doki, Hidetoshi Eguchi, Seiji Takashima

{"title":"BRAF V600E-induced distinct DNA damage response defines the therapeutic potential of p53 activation for TP53 wild-type colorectal cancer.","authors":"Shinji Tokuyama, Hisakazu Kato, Hidekazu Takahashi, Kyoko Ueda, Asami Arita, Ryuta Ueda, Hiroto Seto, Yuki Sekido, Tsuyoshi Hata, Atsushi Hamabe, Takayuki Ogino, Norikatsu Miyoshi, Mamoru Uemura, Ken Matsuoka, Osamu Tsukamoto, Hirofumi Yamamoto, Yuichiro Doki, Hidetoshi Eguchi, Seiji Takashima","doi":"10.1093/carcin/bgae040","DOIUrl":"10.1093/carcin/bgae040","url":null,"abstract":"BRAF V600E, one of the most frequent mutations in the MAPK pathway, confers poor prognosis to colorectal cancers (CRCs), partly because of chemotherapeutic resistance. Oncogene-induced DNA damage responses (DDRs) that primarily activate p53 are important mechanistic barriers to the malignant transformation of cells; however, the mechanism underlying this impairment in cancer remains unknown. Here, we evaluated the responses of BRAFV600E-induced DDRs in two CRC cell lines, SW48 and LIM1215, both of which harbor wild-type TP53, KRAS, and BRAF. BRAFV600E transduction exhibited distinct phenotypes in these cells: SW48 cell proliferation markedly decreased, whereas that of LIM1215 increased. BRAFV600E expression induced the activation of oncogene-induced DDR signaling in SW48 cells, but not in LIM1215 cells, whereas chemotherapeutic agents similarly activated DDRs in both cell lines. Knockdown experiments revealed that these responses in SW48 cells were mediated by p53-p21 pathway activation. Comet assay (both alkaline and neutral) revealed that BRAFV600E increased single-strand breaks to the same extent in both cell lines; however, in the case of LIM1215 cells, it only facilitated double-strand breaks. Furthermore, the proliferation of LIM1215 cells, wherein no oncogene-induced DDRs occurred, was synergistically inhibited upon MDM2 inhibitor-mediated p53 activation combined with MEK inhibition. Taken together, these distinct DDR signaling responses highlight the novel characteristics of BRAFV600E-mutated CRC cells and define the therapeutic potential of p53 activation combined with MAPK inhibition against TP53 wild-type CRC harboring a BRAFV600E mutation.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"857-867"},"PeriodicalIF":3.3,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310122","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

Colorectal cancer cells with high metastatic potential drive metastasis by transmitting exosomal miR-20a-3p through modulating NF1/MAPK pathway. 具有高转移潜能的结直肠癌细胞通过调节 NF1/MAPK 通路传递外泌体 miR-20a-3p 推动转移。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-10-10 DOI: 10.1093/carcin/bgae036

Yahang Liang, Junyu Li, Tao Li, Mingming Li, Hualin Liao, Yang Liu, Yao Yao, Lingling Yang, Xiong Lei

{"title":"Colorectal cancer cells with high metastatic potential drive metastasis by transmitting exosomal miR-20a-3p through modulating NF1/MAPK pathway.","authors":"Yahang Liang, Junyu Li, Tao Li, Mingming Li, Hualin Liao, Yang Liu, Yao Yao, Lingling Yang, Xiong Lei","doi":"10.1093/carcin/bgae036","DOIUrl":"10.1093/carcin/bgae036","url":null,"abstract":"Cancer cells exhibit heterogeneous metastatic potential, and high metastatic (HM) subclones can enhance the metastatic potential of low metastatic subclones by transmitting some factors. Exosomal miRNAs play a pivotal role in the crosstalk of heterogeneous metastatic subclones. This study discovered that miR-20a-3p was upregulated in colorectal adenocarcinoma (CRA), correlated with metastasis, and potentially served as a prognostic indicator for CRA. miR-20a-3p could promote the proliferation, migration, and invasion of CRA cells. Interestingly, HM CRA cells could promote malignant phenotypes of low metastatic CRA cells by transmitting exosomal miR-20a-3p. Mechanically, miR-20a-3p could inhibit neurofibromin 1(NF1), thereby activate the rat sarcoma viral oncogene (RAS)-mediated mitogen-activated protein kinases (MAPK) signaling pathway to drive the metastasis of CRA. In summary, our study provided evidence that colorectal cancer cells with HM potential drive metastasis by transmitting exosomal miR-20a-3p through modulating the NF1/MAPK pathway.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"773-785"},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199183","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

Dehydroabietylamine exerts antitumor effects by affecting nucleotide metabolism in gastric cancer. 脱氢阿糖胞苷胺通过影响胃癌核苷酸代谢发挥抗肿瘤作用

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-10-10 DOI: 10.1093/carcin/bgae037

Jingsong Ma, Jiabao Zhao, Zhengxin Wu, Jinshui Tan, Meijuan Xu, Wenjie Ye, Mengya Zhong, Yubo Xiong, Guangchao Pan, Huiwen Zhou, Shengyi Zhou, Xuehui Hong

{"title":"Dehydroabietylamine exerts antitumor effects by affecting nucleotide metabolism in gastric cancer.","authors":"Jingsong Ma, Jiabao Zhao, Zhengxin Wu, Jinshui Tan, Meijuan Xu, Wenjie Ye, Mengya Zhong, Yubo Xiong, Guangchao Pan, Huiwen Zhou, Shengyi Zhou, Xuehui Hong","doi":"10.1093/carcin/bgae037","DOIUrl":"10.1093/carcin/bgae037","url":null,"abstract":"Nucleotide metabolism is the ultimate and most critical link in the self-replication process of tumors, including gastric cancer (GC). However, in clinical treatment, classic antitumor drugs such as 5-fluorouracil (5-FU) are mostly metabolic analogs of purines or pyrimidines, which lack specificity for tumor cells and therefore have significant side effects. It is unclear whether there are other drugs that can target nucleotide metabolism, except for nucleic acid analogs. Here, we found that a natural compound, dehydroabietylamine (DHAA), significantly reduced the viability and proliferation of GC cells and organoids. DHAA disrupts the purine and pyrimidine metabolism of GC cells, causing DNA damage and further inducing apoptosis. DHAA treatment decreased transcription and protein levels of key enzymes involved in the nucleotide metabolism pathway, with significant reductions in the expression of pyrimidine metabolism key enzymes CAD, DHODH, and purine metabolism key enzymes PAICS. We also found that DHAA directly binds to and reduces the expression of Forkhead box K2 (FOXK2), a common transcription factor for these metabolic enzymes. Ultimately, DHAA was shown to delay tumorigenesis in K19-Wnt1/C2mE transgenic mice model and reduce levels of CAD, DHODH, and PAICS in vivo. We demonstrate that DHAA exerts an anticancer effect on GC by targeting transcription factor FOXK2, reducing transcription of key genes for nucleotide metabolism and impairing nucleotide biosynthesis, thus DHAA is a promising candidate for GC therapy.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"759-772"},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310123","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

Allura Red AC is a xenobiotic. Is it also a carcinogen? Allura Red AC 是一种异生物。它也是一种致癌物质吗？

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-10-10 DOI: 10.1093/carcin/bgae057

Lorne J Hofseth, James R Hebert, Elizabeth Angela Murphy, Erica Trauner, Athul Vikas, Quinn Harris, Alexander A Chumanevich

{"title":"Allura Red AC is a xenobiotic. Is it also a carcinogen?","authors":"Lorne J Hofseth, James R Hebert, Elizabeth Angela Murphy, Erica Trauner, Athul Vikas, Quinn Harris, Alexander A Chumanevich","doi":"10.1093/carcin/bgae057","DOIUrl":"10.1093/carcin/bgae057","url":null,"abstract":"Merriam-Webster and Oxford define a xenobiotic as any substance foreign to living systems. Allura Red AC (a.k.a., E129; FD&C Red No. 40), a synthetic food dye extensively used in manufacturing ultra-processed foods and therefore highly prevalent in our food supply, falls under this category. The surge in synthetic food dye consumption during the 70s and 80s was followed by an epidemic of metabolic diseases and the emergence of early-onset colorectal cancer in the 1990s. This temporal association raises significant concerns, particularly given the widespread inclusion of synthetic food dyes in ultra-processed products, notably those marketed toward children. Given its interactions with key contributors to colorectal carcinogenesis such as inflammatory mediators, the microbiome, and DNA damage, there is growing interest in understanding Allura Red AC's potential impact on colon health as a putative carcinogen. This review discusses the history of Allura Red AC, current research on its effects on the colon and rectum, potential mechanisms underlying its impact on colon health, and provides future considerations. Indeed, although no governing agencies classify Allura Red AC as a carcinogen, its interaction with key guardians of carcinogenesis makes it suspect and worthy of further molecular investigation. The goal of this review is to inspire research into the impact of synthetic food dyes on colon health.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"711-720"},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916164","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

CDK12 is a promising therapeutic target for the transcription cycle and DNA damage response in metastatic osteosarcoma. CDK12 是转移性骨肉瘤转录周期和 DNA 损伤反应的一个很有前景的治疗靶点。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-10-10 DOI: 10.1093/carcin/bgae051

Zihao Li, Xiaoyang Li, Nicole A Seebacher, Xu Liu, Wence Wu, Shengji Yu, Francis J Hornicek, Changzhi Huang, Zhenfeng Duan

{"title":"CDK12 is a promising therapeutic target for the transcription cycle and DNA damage response in metastatic osteosarcoma.","authors":"Zihao Li, Xiaoyang Li, Nicole A Seebacher, Xu Liu, Wence Wu, Shengji Yu, Francis J Hornicek, Changzhi Huang, Zhenfeng Duan","doi":"10.1093/carcin/bgae051","DOIUrl":"10.1093/carcin/bgae051","url":null,"abstract":"Osteosarcoma (OS) is a bone malignant tumor affecting children, adolescents, and young adults. Currently, osteosarcoma is treated with chemotherapy regimens established over 40 years ago. The investigation of novel therapeutic strategies for the treatment of osteosarcoma remains an important clinical need. Cyclin-dependent kinases (CDKs) have been considered promising molecular targets in cancer therapy. Among these, CDK12 has been shown to play a crucial role in the pathogenesis of malignancies, but its clinical significance and biological mechanisms in osteosarcoma remain unclear. In the present study, we aim to determine the expression and function of CDK12 and evaluate its prognostic and therapeutic value in metastatic osteosarcoma. We found that overexpression of CDK12 was associated with high tumor grade, tumor progression and reduced patient survival. The underlying mechanism revealed that knockdown of CDK12 expression with small interfering RNA or functional inhibition with the CDK12-targeting agent THZ531 effectively exhibited time- and dose-dependent cytotoxicity. Downregulation of CDK12 paused transcription by reducing RNAP II phosphorylation, interfered with DNA damage repair with increased γH2AX, and decreased cell proliferation through the PI3K-AKT pathway. This was accompanied by the promotion of apoptosis, as evidenced by enhanced Bax expression and reduced Bcl-xL expression. Furthermore, the CDK12 selective inhibitor THZ531 also hindered ex vivo 3D spheroid formation, growth of in vitro 2D cell colony, and prevented cell mobility. Our findings highlight the clinical importance of CDK12 as a potentially valuable prognostic biomarker and therapeutic target in metastatic osteosarcoma.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"786-798"},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854933","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

Intratumoral vitamin D signaling and lethal prostate cancer. 肿瘤内维生素 D 信号传导与致命性前列腺癌

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-10-10 DOI: 10.1093/carcin/bgae055

Jane B Vaselkiv, Irene M Shui, Sydney T Grob, Caroline I Ericsson, Isabel Giovannucci, Cheng Peng, Stephen P Finn, Lorelei A Mucci, Kathryn L Penney, Konrad H Stopsack

{"title":"Intratumoral vitamin D signaling and lethal prostate cancer.","authors":"Jane B Vaselkiv, Irene M Shui, Sydney T Grob, Caroline I Ericsson, Isabel Giovannucci, Cheng Peng, Stephen P Finn, Lorelei A Mucci, Kathryn L Penney, Konrad H Stopsack","doi":"10.1093/carcin/bgae055","DOIUrl":"10.1093/carcin/bgae055","url":null,"abstract":"High circulating vitamin D levels and supplementation may lower prostate cancer mortality. To probe for direct effects of vitamin D signaling in the primary tumor, we assessed how activation of intratumoral vitamin D signaling in prostate cancer is associated with lethal prostate cancer during long-term follow-up. Among 404 participants with primary prostate cancer in the Health Professionals Follow-up Study and the Physicians' Health Study, we defined a gene score of expected activated intratumoral vitamin D signaling consisting of transcriptionally upregulated (CYP27A1, CYP2R1, RXRA, RXRB, and VDR) and downregulated genes (CYP24A1 and DHCR7). We contrasted vitamin D signaling in tumors that progressed to lethal disease (metastases/prostate cancer-specific death, n = 119) over up to three decades of follow-up with indolent tumors that remained nonmetastatic for >8 years post-diagnosis (n = 285). The gene score was downregulated in tumor tissue compared with tumor-adjacent histologically normal tissue of the same men. Higher vitamin D gene scores were inversely associated with lethal prostate cancer (odds ratio for highest versus lowest quartile: 0.46, 95% confidence interval: 0.21-0.99) in a dose-response fashion and after adjusting for clinical and pathologic factors. This association appeared strongest among men with high predicted plasma 25-hydroxyvitamin D3 and men with body mass index ≥25 kg/m2. Findings were replicated with broader gene sets. These data support the hypothesis that active intratumoral vitamin D signaling is associated with better prostate cancer outcomes and provide further rationale for testing how vitamin D-related interventions after diagnosis could improve prostate cancer survival through effects on the tumor.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"735-744"},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906007","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

ETS1 deficiency in macrophages suppresses colorectal cancer progression by reducing the F4/80+TIM4+ macrophage population. 巨噬细胞中 ETS1 的缺失通过减少 F4/80+TIM4+ 巨噬细胞群抑制结直肠癌的进展

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-10-10 DOI: 10.1093/carcin/bgae058

Yuanyuan Cao, Anning Guo, Muxin Li, Xinghua Ma, Xiaofeng Bian, YiRong Chen, Caixia Zhang, Shijia Huang, Wei Zhao, Shuli Zhao

{"title":"ETS1 deficiency in macrophages suppresses colorectal cancer progression by reducing the F4/80+TIM4+ macrophage population.","authors":"Yuanyuan Cao, Anning Guo, Muxin Li, Xinghua Ma, Xiaofeng Bian, YiRong Chen, Caixia Zhang, Shijia Huang, Wei Zhao, Shuli Zhao","doi":"10.1093/carcin/bgae058","DOIUrl":"10.1093/carcin/bgae058","url":null,"abstract":"Tumor-associated macrophages (TAMs) take on pivotal and complex roles in the tumor microenvironment (TME); however, their heterogeneity in the TME remains incompletely understood. ETS proto-oncogene 1 (ETS1) is a transcription factor that is mainly expressed in lymphocytes. However, its expression and immunoregulatory role in colorectal cancer (CRC)-associated macrophages remain unclear. In the study, the expression levels of ETS1 in CD68+ macrophages in the CRC microenvironment were significantly higher than those in matched paracarcinoma tissues. Importantly, ETS1 increased the levels of chemokines C-C motif chemokine ligand 2 (CCL2) and C-X-C motif chemokine ligand 10 (CXCL10) in lipopolysaccharide-stimulated THP-1 cells. It also boosted the migration and invasion of CRC cells during the in vitro co-culture. In the ETS1 conditional knockout mouse model, ETS1 deficiency in macrophages ameliorated the histological changes in DSS-induced ulcerative colitis mouse models and prolonged the survival in an azomethane/dextran sodium sulfate (AOM/DSS)-induced CRC model. ETS1 deficiency in macrophages substantially inhibited tumor formation, reduced F4/80+TIM4+ macrophages in the mesenteric lymph nodes, and decreased CCL2 and CXCL10 protein levels in tumor tissues. Moreover, ETS1 deficiency in macrophages effectively prevented liver metastasis of CRC and reduced the infiltration of TAMs into the metastasis sites. Subsequent studies have indicated that ETS1 upregulated the expression of T-cell immunoglobulin mucin receptor 4 in macrophages through the signal transducer and activator of the transcription 1 signaling pathway activated by the autocrine action of CCL2/CXCL10. Collectively, ETS1 deficiency in macrophages potentiates antitumor immune responses by repressing CCL2 and CXCL10 expression, shedding light on potential therapeutic strategies for CRC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"745-758"},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003688","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

Machine learning based on biological context facilitates the identification of microvascular invasion in intrahepatic cholangiocarcinoma. 基于生物背景的机器学习有助于识别肝内胆管癌的微血管侵犯。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-10-10 DOI: 10.1093/carcin/bgae052

Shuaishuai Xu, Mingyu Wan, Chanqi Ye, Ruyin Chen, Qiong Li, Xiaochen Zhang, Jian Ruan

{"title":"Machine learning based on biological context facilitates the identification of microvascular invasion in intrahepatic cholangiocarcinoma.","authors":"Shuaishuai Xu, Mingyu Wan, Chanqi Ye, Ruyin Chen, Qiong Li, Xiaochen Zhang, Jian Ruan","doi":"10.1093/carcin/bgae052","DOIUrl":"10.1093/carcin/bgae052","url":null,"abstract":"Intrahepatic cholangiocarcinoma is a rare disease associated with a poor prognosis, primarily due to early recurrence and metastasis. An important feature of this condition is microvascular invasion (MVI). However, current predictive models based on imaging have limited efficacy in this regard. This study employed a random forest model to construct a predictive model for MVI identification and uncover its biological basis. Single-cell transcriptome sequencing, whole exome sequencing, and proteome sequencing were performed. The area under the curve of the prediction model in the validation set was 0.93. Further analysis indicated that MVI-associated tumor cells exhibited functional changes related to epithelial-mesenchymal transition and lipid metabolism due to alterations in the nuclear factor-kappa B and mitogen-activated protein kinase signaling pathways. Tumor cells were also differentially enriched for the interleukin-17 signaling pathway. There was less infiltration of SLC30A1+ CD8+ T cells expressing cytotoxic genes in MVI-associated intrahepatic cholangiocarcinoma, whereas there was more infiltration of myeloid cells with attenuated expression of the major histocompatibility complex II pathway. Additionally, MVI-associated intercellular communication was closely related to the SPP1-CD44 and ANXA1-FPR1 pathways. These findings resulted in a brilliant predictive model and fresh insights into MVI.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"721-734"},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859124","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

Absence of lung tumor promotion with reduced tumor size in mice after inhalation of copper welding fumes. 小鼠吸入铜焊烟雾后，肺部肿瘤不再增大，肿瘤体积缩小。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-09-11 DOI: 10.1093/carcin/bgae048

Patti C Zeidler-Erdely, Vamsi Kodali, Lauryn M Falcone, Robert Mercer, Stephen S Leonard, Aleksandr B Stefaniak, Lindsay Grose, Rebecca Salmen, Taylor Trainor-DeArmitt, Lori A Battelli, Walter McKinney, Samuel Stone, Terence G Meighan, Ella Betler, Sherri Friend, Kristen R Hobbie, Samantha Service, Michael Kashon, James M Antonini, Aaron Erdely

{"title":"Absence of lung tumor promotion with reduced tumor size in mice after inhalation of copper welding fumes.","authors":"Patti C Zeidler-Erdely, Vamsi Kodali, Lauryn M Falcone, Robert Mercer, Stephen S Leonard, Aleksandr B Stefaniak, Lindsay Grose, Rebecca Salmen, Taylor Trainor-DeArmitt, Lori A Battelli, Walter McKinney, Samuel Stone, Terence G Meighan, Ella Betler, Sherri Friend, Kristen R Hobbie, Samantha Service, Michael Kashon, James M Antonini, Aaron Erdely","doi":"10.1093/carcin/bgae048","DOIUrl":"10.1093/carcin/bgae048","url":null,"abstract":"Welding fumes are a Group 1 (carcinogenic to humans) carcinogen as classified by the International Agency for Research on Cancer. The process of welding creates inhalable fumes rich in iron (Fe) that may also contain known carcinogenic metals such as chromium (Cr) and nickel (Ni). Epidemiological evidence has shown that both mild steel (Fe-rich) and stainless steel (Fe-rich + Cr + Ni) welding fume exposure increases lung cancer risk, and experimental animal data support these findings. Copper-nickel (CuNi) welding processes have not been investigated in the context of lung cancer. Cu is intriguing, however, given the role of Cu in carcinogenesis and cancer therapeutics. This study examines the potential for a CuNi fume to induce mechanistic key characteristics of carcinogenesis in vitro and to promote lung tumorigenesis, using a two-stage mouse bioassay, in vivo. Male A/J mice, initiated with 3-methylcholanthrene (MCA; 10 µg/g), were exposed to CuNi fumes or air by whole-body inhalation for 9 weeks (low deposition-LD and high deposition-HD) and then sacrificed at 30 weeks. In BEAS-2B cells, the CuNi fume-induced micronuclei and caused DNA damage as measured by γ-H2AX. The fume exhibited high reactivity and a dose-response in cytotoxicity and oxidative stress. In vivo, MCA/CuNi HD and LD significantly decreased lung tumor size and adenomas. MCA/CuNi HD exposure significantly decreased gross-evaluated tumor number. In summary, the CuNi fume in vitro exhibited characteristics of a carcinogen, but in vivo, the exposure resulted in smaller tumors, fewer adenomas, less hyperplasia severity, and with HD exposure, less overall lung lesions/tumors.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"630-641"},"PeriodicalIF":3.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757312","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