Translational Oncology最新文献

Berberine inhibits metastasis of ovarian cancer by blocking lipid metabolism, alleviating aging of adipose tissue and increasing tumor infiltrating immune cells

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-04-19 DOI: 10.1016/j.tranon.2025.102380

Xiaojie Zhang , Bing Xiong , Yujie Cheng , Jimei Huang , Jiaying Xue , Xiao Li , Wei Lu , Jihui Zhu , Lian Wang , Weihong Yang , Zhongping Cheng

Extensive peritoneal metastasis and malignant ascites continue to pose substantial challenges in achieving favorable treatment outcomes for ovarian cancer. Berberine (BBR), an active component of numerous traditional Chinese herbs, has demonstrated potent anti - tumor effects across various malignancies, including ovarian cancer. In this study, we comprehensively evaluated the impact of BBR on the growth and metastasis of ovarian cancer both in vitro and in vivo. RNA - sequencing was employed to elucidate the underlying mechanisms. Specifically, we investigated lipid metabolism and mitochondrial function in ovarian cancer cells and mice, comparing BBR - treated and untreated groups. Additionally, CIBERSORT analysis and immunohistochemical (IHC) staining were utilized to confirm BBR's ability to enhance the infiltration of tumor-infiltrating immune cells into adipose tissue and improve the inflammatory tumor microenvironment. Our findings indicate that BBR significantly inhibits the growth and metastasis of ovarian cancer in vitro and in vivo. The effects can be attributed to two key processes. Firstly, BBR suppresses the lipid metabolism by downregulating lipid uptake related receptor CD36, lipid metabolic enzyme and mitochondrial function. Secondly, BBR alleviates the aging of adipose tissue and adipose derived stem cells (ADSCs), thereby decreasing the secretion of senescence-associated secretory phenotype (SASP). These ultimately lead to the increasing the improvement of tumor infiltrating immune cells, such as CD4⁺ helper T cells (CD3⁺CD4⁺) and cytotoxic T lymphocytes (CD3⁺CD8⁺), and inflammation in ovarian cancer tissue. Collectively, these findings suggested a potential therapeutic effect of BBR in the treatment of advanced ovarian cancer, particularly cases complicated by peritoneal metastasis and malignant ascites.

{"title":"Berberine inhibits metastasis of ovarian cancer by blocking lipid metabolism, alleviating aging of adipose tissue and increasing tumor infiltrating immune cells","authors":"Xiaojie Zhang , Bing Xiong , Yujie Cheng , Jimei Huang , Jiaying Xue , Xiao Li , Wei Lu , Jihui Zhu , Lian Wang , Weihong Yang , Zhongping Cheng","doi":"10.1016/j.tranon.2025.102380","DOIUrl":"10.1016/j.tranon.2025.102380","url":null,"abstract":"<div><div>Extensive peritoneal metastasis and malignant ascites continue to pose substantial challenges in achieving favorable treatment outcomes for ovarian cancer. Berberine (BBR), an active component of numerous traditional Chinese herbs, has demonstrated potent anti - tumor effects across various malignancies, including ovarian cancer. In this study, we comprehensively evaluated the impact of BBR on the growth and metastasis of ovarian cancer both <em>in vitro</em> and <em>in vivo</em>. RNA - sequencing was employed to elucidate the underlying mechanisms. Specifically, we investigated lipid metabolism and mitochondrial function in ovarian cancer cells and mice, comparing BBR - treated and untreated groups. Additionally, CIBERSORT analysis and immunohistochemical (IHC) staining were utilized to confirm BBR's ability to enhance the infiltration of tumor-infiltrating immune cells into adipose tissue and improve the inflammatory tumor microenvironment. Our findings indicate that BBR significantly inhibits the growth and metastasis of ovarian cancer <em>in vitro</em> and <em>in vivo</em>. The effects can be attributed to two key processes. Firstly, BBR suppresses the lipid metabolism by downregulating lipid uptake related receptor CD36, lipid metabolic enzyme and mitochondrial function. Secondly, BBR alleviates the aging of adipose tissue and adipose derived stem cells (ADSCs), thereby decreasing the secretion of senescence-associated secretory phenotype (SASP). These ultimately lead to the increasing the improvement of tumor infiltrating immune cells, such as CD4⁺ helper T cells (CD3⁺CD4⁺) and cytotoxic T lymphocytes (CD3⁺CD8⁺), and inflammation in ovarian cancer tissue. Collectively, these findings suggested a potential therapeutic effect of BBR in the treatment of advanced ovarian cancer, particularly cases complicated by peritoneal metastasis and malignant ascites.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102380"},"PeriodicalIF":5.0,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

TRIM25 facilitates ferroptosis in ovarian cancer through promoting PIEZO1 K63-linked ubiquitination and degradation

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-04-18 DOI: 10.1016/j.tranon.2025.102386

Ya Li, Fei Zhou, Zhengmei Xu

Background

Ovarian cancer represents a significant threat to women's health. and ferroptosis is recognized as a potential natural inhibitor in cancer therapy, the regulatory mechanism of TRIM25 in ovarian cancer and its potential for regulating ferroptosis as a treatment remain unclear.

Methods

The role of TRIM25 in ovarian cancer was examined through functional gain- and loss-of-function assays both in vitro and in vivo, while its target genes were identified. The stability and ubiquitination sites of PIEZO1 were analyzed using protein docking and ubiquitination experiments.

Results

TRIM25 is highly expressed in ovarian cancer and promotes the growth and metastasis of ovarian cancer cells both in vivo and in vitro. Mechanistically, it facilitates PIEZO1 degradation through ubiquitination-dependent proteasome activity, inhibits ferroptosis, and stimulates ovarian cancer cell growth.

Conclusion

Our study clearly shows that TRIM25 stimulates ovarian cancer by inducing K63-linked ubiquitination of PIEZO1, which suppresses ferroptosis and promotes excessive proliferation of ovarian cancer cells. Further research identified the ubiquitination modification site on PIEZO1, providing insights for ovarian cancer treatment.

{"title":"TRIM25 facilitates ferroptosis in ovarian cancer through promoting PIEZO1 K63-linked ubiquitination and degradation","authors":"Ya Li, Fei Zhou, Zhengmei Xu","doi":"10.1016/j.tranon.2025.102386","DOIUrl":"10.1016/j.tranon.2025.102386","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian cancer represents a significant threat to women's health. and ferroptosis is recognized as a potential natural inhibitor in cancer therapy, the regulatory mechanism of TRIM25 in ovarian cancer and its potential for regulating ferroptosis as a treatment remain unclear.</div></div><div><h3>Methods</h3><div>The role of TRIM25 in ovarian cancer was examined through functional gain- and loss-of-function assays both in vitro and in vivo, while its target genes were identified. The stability and ubiquitination sites of PIEZO1 were analyzed using protein docking and ubiquitination experiments.</div></div><div><h3>Results</h3><div>TRIM25 is highly expressed in ovarian cancer and promotes the growth and metastasis of ovarian cancer cells both in vivo and in vitro. Mechanistically, it facilitates PIEZO1 degradation through ubiquitination-dependent proteasome activity, inhibits ferroptosis, and stimulates ovarian cancer cell growth.</div></div><div><h3>Conclusion</h3><div>Our study clearly shows that TRIM25 stimulates ovarian cancer by inducing K63-linked ubiquitination of PIEZO1, which suppresses ferroptosis and promotes excessive proliferation of ovarian cancer cells. Further research identified the ubiquitination modification site on PIEZO1, providing insights for ovarian cancer treatment.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102386"},"PeriodicalIF":5.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Dynamic predictive power of TP53 signatures in breast cancer prognosis: Pre- and post-neoadjuvant chemotherapy insights

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-04-16 DOI: 10.1016/j.tranon.2025.102398

Keiju Sasaki , Shin Takahashi , Kota Ouchi , Hidekazu Shirota , Nobuaki Sato , Kouji Kaneko , Norikazu Masuda , Fumiyoshi Fujishima , Satoko Sato , Chikashi Ishioka

Background

The TP53 signature determined using a biopsy specimen before neoadjuvant chemotherapy (pre-NAC biopsy specimens) predicts NAC response and prognosis in breast cancer. We aimed to compare the clinical utility of the TP53 signature determined using pre-NAC biopsy specimens and surgical specimens after NAC (post-NAC surgical specimens).

Methods

This observational cohort study included patients with paired pre-NAC biopsy and post-NAC surgical specimens, analyzing the association between the TP53 signature from each specimen and prognosis (UMIN000042055).

Results

Pre-NAC biopsy specimens classified 71 patients into those having a TP53 mutant signature (pre-mt, n = 47) and wild-type signature (pre-wt, n = 24), with the same for post-NAC surgical specimens (post-mt, n = 16 and post-wt, n = 55). Among the 47 pre-mt patients, 31 became post-wt (pre-mt/post-wt), whereas 16 remained post-mt (pre-mt/post-mt). All pre-wt patients remained post-wt (pre-wt/post-wt). Recurrence-free survival (RFS) was significantly shorter in the pre-mt group than in the pre-wt group, although no significant difference was observed between the post-mt and post-wt groups. Change in the TP53 signature following NAC did not affect predictive ability of the TP53 signature determined using pre-NAC biopsy specimens.

Conclusions

The TP53 signature status should be determined using pre-NAC biopsy specimens.

{"title":"Dynamic predictive power of TP53 signatures in breast cancer prognosis: Pre- and post-neoadjuvant chemotherapy insights","authors":"Keiju Sasaki , Shin Takahashi , Kota Ouchi , Hidekazu Shirota , Nobuaki Sato , Kouji Kaneko , Norikazu Masuda , Fumiyoshi Fujishima , Satoko Sato , Chikashi Ishioka","doi":"10.1016/j.tranon.2025.102398","DOIUrl":"10.1016/j.tranon.2025.102398","url":null,"abstract":"<div><h3>Background</h3><div>The <em>TP53</em> signature determined using a biopsy specimen before neoadjuvant chemotherapy (pre-NAC biopsy specimens) predicts NAC response and prognosis in breast cancer. We aimed to compare the clinical utility of the <em>TP53</em> signature determined using pre-NAC biopsy specimens and surgical specimens after NAC (post-NAC surgical specimens).</div></div><div><h3>Methods</h3><div>This observational cohort study included patients with paired pre-NAC biopsy and post-NAC surgical specimens, analyzing the association between the <em>TP53</em> signature from each specimen and prognosis (UMIN000042055).</div></div><div><h3>Results</h3><div>Pre-NAC biopsy specimens classified 71 patients into those having a <em>TP53</em> mutant signature (pre-mt, <em>n</em> = 47) and wild-type signature (pre-wt, <em>n</em> = 24), with the same for post-NAC surgical specimens (post-mt, <em>n</em> = 16 and post-wt, <em>n</em> = 55). Among the 47 pre-mt patients, 31 became post-wt (pre-mt/post-wt), whereas 16 remained post-mt (pre-mt/post-mt). All pre-wt patients remained post-wt (pre-wt/post-wt). Recurrence-free survival (RFS) was significantly shorter in the pre-mt group than in the pre-wt group, although no significant difference was observed between the post-mt and post-wt groups. Change in the <em>TP53</em> signature following NAC did not affect predictive ability of the <em>TP53</em> signature determined using pre-NAC biopsy specimens.</div></div><div><h3>Conclusions</h3><div>The <em>TP53</em> signature status should be determined using pre-NAC biopsy specimens.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102398"},"PeriodicalIF":5.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Knockdown TNF family prognosis index crucial gene PDE4B promoted PANoptosis of ovarian carcinoma cell:Based in vitro and in vivo experiments

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-04-16 DOI: 10.1016/j.tranon.2025.102333

Qianqian Yu , Yunxiao Wang , Ting Fu , Dongyu Han , Linlin Wang , Lin Zhao , Yongle Xu

Ovarian cancer represents a malignancy characterized by high incidence and mortality rates, necessitating further elucidation of its underlying mechanisms. We conducted an analysis using bulk transcriptomic data of ovarian cancer and normal ovarian tissues, as well as single-cell sequencing data according to publicly available databases. Through calculation of Gene Set Variation Analysis (GSVA) scores for TNF family genes, weighted gene co-expression network analysis (WGCNA) for hub genes identification, and subsequent Gene Ontology (GO) enrichment analysis, we delineated pathways crucial in ovarian cancer pathogenesis. Furthermore, differential expression gene analysis facilitated the identification of genes with pronounced expression levels in tumor tissues and their intersection with hub genes, followed by GO analyses across molecular functions (MF), cellular components (CC), and biological processes (BP). Utilizing multivariable Cox regression and LASSO analyses, we constructed a prognostic model comprising 14 genes (GFPT2, PDE4B, PODNL1, TGFBI, CSF1R, PTGIS, SFRP2, COL5A2, TRAC, SLAMF7, VCAN, GBP1P1, C2, TRBV28). Both training and validation sets demonstrated robust diagnostic and prognostic capabilities. Clinical information and immune cell infiltration analyses were further conducted based on the model. In the single-cell sequencing analysis, reducing dimensional complexity and classifying cell types were performed, followed by exploration of gene expression patterns within each subtype and investigation of temporal expression variations across cell subtypes. Biological functional exploration and drug sensitivity analyses were also conducted. Our study contributes novel insights and theoretical foundations for prognosis, treatment, and development of drugs in patients.

{"title":"Knockdown TNF family prognosis index crucial gene PDE4B promoted PANoptosis of ovarian carcinoma cell:Based in vitro and in vivo experiments","authors":"Qianqian Yu , Yunxiao Wang , Ting Fu , Dongyu Han , Linlin Wang , Lin Zhao , Yongle Xu","doi":"10.1016/j.tranon.2025.102333","DOIUrl":"10.1016/j.tranon.2025.102333","url":null,"abstract":"<div><div>Ovarian cancer represents a malignancy characterized by high incidence and mortality rates, necessitating further elucidation of its underlying mechanisms. We conducted an analysis using bulk transcriptomic data of ovarian cancer and normal ovarian tissues, as well as single-cell sequencing data according to publicly available databases. Through calculation of Gene Set Variation Analysis (GSVA) scores for TNF family genes, weighted gene co-expression network analysis (WGCNA) for hub genes identification, and subsequent Gene Ontology (GO) enrichment analysis, we delineated pathways crucial in ovarian cancer pathogenesis. Furthermore, differential expression gene analysis facilitated the identification of genes with pronounced expression levels in tumor tissues and their intersection with hub genes, followed by GO analyses across molecular functions (MF), cellular components (CC), and biological processes (BP). Utilizing multivariable Cox regression and LASSO analyses, we constructed a prognostic model comprising 14 genes (GFPT2, PDE4B, PODNL1, TGFBI, CSF1R, PTGIS, SFRP2, COL5A2, TRAC, SLAMF7, VCAN, GBP1P1, C2, TRBV28). Both training and validation sets demonstrated robust diagnostic and prognostic capabilities. Clinical information and immune cell infiltration analyses were further conducted based on the model. In the single-cell sequencing analysis, reducing dimensional complexity and classifying cell types were performed, followed by exploration of gene expression patterns within each subtype and investigation of temporal expression variations across cell subtypes. Biological functional exploration and drug sensitivity analyses were also conducted. Our study contributes novel insights and theoretical foundations for prognosis, treatment, and development of drugs in patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102333"},"PeriodicalIF":5.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

LUNAR: Full Moon or Eclipse? An exploration into tumor treating fields in lung cancer

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-04-16 DOI: 10.1016/j.tranon.2025.102397

Timothée Olivier , Vinay Prasad

The LUNAR trial investigated the addition of Tumor Treating Fields (TTFs) to “standard therapy” in patients with metastatic lung cancer after at least one line of platinum-based chemotherapy. The “standard therapy” was either an anti-PD(L)1 therapy (immunotherapy) or docetaxel. The addition of TTFs provided a 3.3 months median survival gain. We raised concerns about LUNAR results internal and external validity.

First, patient selection and the control arm do not mirror current practice. Two-thirds of patients did not receive prior immunotherapy, which is standard in first-line treatment. Also, the “choice” of the “standard therapy” was restricted by drug availability, resulting in 41 % of patients not receiving immunotherapy during the trial – those allocated to receive docetaxel – had no prior exposure to immunotherapy. Some patients may have harbored actionable mutations, and did not receive targeted therapy.

Second, we raised statistical questions. The sample size was shrunk after an unplanned analysis, with unshared and unclear justifications. The decision may have been influenced by a chance deviation in data favoring the intervention. Also, as significantly more patients were censored after withdrawals in the TTFs group, informative censoring could have amplified the survival gain.

Third and last, without a sham-control design (the equivalent of placebo for devices), it's hard to isolate the impact of TTFs from the extra-attention associated with its administration (continuous 24/7 support, frequent home-based interactions).

Overall, LUNAR do not apply to clinical settings where immunotherapy and molecular testing is offered, and many factors may have artificially boosted the reported survival gain. A sham-controlled trial is needed to answer whether TTFs are beneficial.

{"title":"LUNAR: Full Moon or Eclipse? An exploration into tumor treating fields in lung cancer","authors":"Timothée Olivier , Vinay Prasad","doi":"10.1016/j.tranon.2025.102397","DOIUrl":"10.1016/j.tranon.2025.102397","url":null,"abstract":"<div><div>The LUNAR trial investigated the addition of Tumor Treating Fields (TTFs) to “standard therapy” in patients with metastatic lung cancer after at least one line of platinum-based chemotherapy. The “standard therapy” was either an anti-PD(L)1 therapy (immunotherapy) or docetaxel. The addition of TTFs provided a 3.3 months median survival gain. We raised concerns about LUNAR results internal and external validity.</div><div>First, patient selection and the control arm do not mirror current practice. Two-thirds of patients did not receive prior immunotherapy, which is standard in first-line treatment. Also, the “choice” of the “standard therapy” was restricted by drug availability, resulting in 41 % of patients not receiving immunotherapy during the trial – those allocated to receive docetaxel – had no prior exposure to immunotherapy. Some patients may have harbored actionable mutations, and did not receive targeted therapy.</div><div>Second, we raised statistical questions. The sample size was shrunk after an unplanned analysis, with unshared and unclear justifications. The decision may have been influenced by a chance deviation in data favoring the intervention. Also, as significantly more patients were censored after withdrawals in the TTFs group, informative censoring could have amplified the survival gain.</div><div>Third and last, without a sham-control design (the equivalent of placebo for devices), it's hard to isolate the impact of TTFs from the extra-attention associated with its administration (continuous 24/7 support, frequent home-based interactions).</div><div>Overall, LUNAR do not apply to clinical settings where immunotherapy and molecular testing is offered, and many factors may have artificially boosted the reported survival gain. A sham-controlled trial is needed to answer whether TTFs are beneficial.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102397"},"PeriodicalIF":5.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Bidirectional roles of neutrophil extracellular traps in oral microbiota carcinogenesis: A systematic review

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-04-15 DOI: 10.1016/j.tranon.2025.102361

Jie Shen , Haitao Lin , Kangnan Mo , Zhong Liang , Yan Zhang , Huatao Quan , Xing Wang , Chenping Zhang , Chao Chen

Background

Neutrophil extracellular traps (NETs) are network structures composed of DNA, histones, and antimicrobial proteins,released by activated neutrophils to trap and eliminate extracellular pathogens. Recent research has demonstrated a strong correlation between NETs and various diseases, including immune dysregulation, thrombosis, and malignancies. This review synthesizes current research on NETs, focusing on its biological role in oral squamous cell carcinoma (OSCC) and explores its potential in treating.

Methods

A literature review in the PubMed database was conducted to examine the impact of NETs on the homeostasis of oral microbiota and the involvement in the development of oral microbiota-related carcinogenesis.

Results

Various microorganisms, including Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus spp., along with Candida albicans, as well as certain viruses such as Human papillomavirus (HPV), Human herpes virus 8 (HHV-8), and Herpes simplex virus-1 (HSV-1)are regulated by NETs during oral colonization and proliferation and have been identified as contributors to the pathogenesis of oral squamous cell carcinoma. NETs have been shown to play a dual role in the carcinogenic process of oral microbiota in humans. At the initial stage of tumor formation, NETs inhibit tumorigenesis by eliminating tumorigenic bacteria that infiltrated the tumor; however, following tumor establishment, various cytokines and chemokines that promote tumor progression are released by neutrophils during the NETs formation.

Conclusion

This article reviews the oncogenic mechanisms of NETs in the oral microbiota, with potential implications for early tumor detection and the development of microbe-targeted therapies.

{"title":"Bidirectional roles of neutrophil extracellular traps in oral microbiota carcinogenesis: A systematic review","authors":"Jie Shen , Haitao Lin , Kangnan Mo , Zhong Liang , Yan Zhang , Huatao Quan , Xing Wang , Chenping Zhang , Chao Chen","doi":"10.1016/j.tranon.2025.102361","DOIUrl":"10.1016/j.tranon.2025.102361","url":null,"abstract":"<div><h3>Background</h3><div>Neutrophil extracellular traps (NETs) are network structures composed of DNA, histones, and antimicrobial proteins,released by activated neutrophils to trap and eliminate extracellular pathogens. Recent research has demonstrated a strong correlation between NETs and various diseases, including immune dysregulation, thrombosis, and malignancies. This review synthesizes current research on NETs, focusing on its biological role in oral squamous cell carcinoma (OSCC) and explores its potential in treating.</div></div><div><h3>Methods</h3><div>A literature review in the PubMed database was conducted to examine the impact of NETs on the homeostasis of oral microbiota and the involvement in the development of oral microbiota-related carcinogenesis.</div></div><div><h3>Results</h3><div>Various microorganisms, including <em>Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus</em> spp., along with <em>Candida albicans</em>, as well as certain viruses such as Human papillomavirus (HPV), Human herpes virus 8 (HHV-8), and Herpes simplex virus-1 (HSV-1)are regulated by NETs during oral colonization and proliferation and have been identified as contributors to the pathogenesis of oral squamous cell carcinoma. NETs have been shown to play a dual role in the carcinogenic process of oral microbiota in humans. At the initial stage of tumor formation, NETs inhibit tumorigenesis by eliminating tumorigenic bacteria that infiltrated the tumor; however, following tumor establishment, various cytokines and chemokines that promote tumor progression are released by neutrophils during the NETs formation.</div></div><div><h3>Conclusion</h3><div>This article reviews the oncogenic mechanisms of NETs in the oral microbiota, with potential implications for early tumor detection and the development of microbe-targeted therapies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102361"},"PeriodicalIF":5.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Targeting FASN enhances cisplatin sensitivity via SLC7A11-mediated ferroptosis in cervical cancer 靶向 FASN 可通过 SLC7A11 介导的宫颈癌铁变态反应增强顺铂敏感性

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-04-15 DOI: 10.1016/j.tranon.2025.102396

Xiaojun Wang , Qiqiao Du , Qiuwen Mai , Qiaojian Zou , Shuyi Wang , Xiaoying Lin , Qianrun Chen , Mengxun Wei , Chudan Chi , Zhangqing Peng , Karima Abdugheni , Liu Du , Yili Chen , Shuzhong Yao , Junxiu Liu

Objective

The cisplatin resistance significantly hinders the prospects for curing patients with advanced, recurrent, and metastatic cervical cancer (CC). Our study aims to clarify the mechanisms underlying cisplatin resistance in CC and provide a novel treatment strategy to overcome the cisplatin resistance of CC patients.

Methods

Intracellular levels of reactive oxygen species, glutathione, malondialdehyde and Fe²⁺ were measured as indicators of ferroptosis. Biological information analyses, IC₅₀, immunofluorescence assays, qPCR and western blot analyses were conducted to elucidate the functions of FASN in CC. In vivo studies were conducted to examine the antitumor effects of the combination of TVB-2640 and cisplatin.

Results

Fatty acid synthase (FASN) was identified as a key driver of cisplatin resistance in CC through transcriptome sequencing and Gene Expression Omnibus (GEO) data analysis. The clinically safe FASN inhibitor TVB-2640 was found to restore cisplatin sensitivity, resulting in synergistic tumor growth attenuation in xenograft models. Mechanistically, FASN downregulation promoted ferroptosis and reduced solute carrier family 7 member 11 (SLC7A11) expression, both in vitro and in vivo models.

Conclusion

Targeting FASN enhances cisplatin sensitivity in CC by promoting SLC7A11-mediated ferroptosis. TVB-2640 combined with cisplatin had superior synergistic antitumor effects in cisplatin-resistant CC models.

{"title":"Targeting FASN enhances cisplatin sensitivity via SLC7A11-mediated ferroptosis in cervical cancer","authors":"Xiaojun Wang , Qiqiao Du , Qiuwen Mai , Qiaojian Zou , Shuyi Wang , Xiaoying Lin , Qianrun Chen , Mengxun Wei , Chudan Chi , Zhangqing Peng , Karima Abdugheni , Liu Du , Yili Chen , Shuzhong Yao , Junxiu Liu","doi":"10.1016/j.tranon.2025.102396","DOIUrl":"10.1016/j.tranon.2025.102396","url":null,"abstract":"<div><h3>Objective</h3><div>The cisplatin resistance significantly hinders the prospects for curing patients with advanced, recurrent, and metastatic cervical cancer (CC). Our study aims to clarify the mechanisms underlying cisplatin resistance in CC and provide a novel treatment strategy to overcome the cisplatin resistance of CC patients.</div></div><div><h3>Methods</h3><div>Intracellular levels of reactive oxygen species, glutathione, malondialdehyde and Fe<sup>2+</sup> were measured as indicators of ferroptosis. Biological information analyses, IC<sub>50</sub>, immunofluorescence assays, qPCR and western blot analyses were conducted to elucidate the functions of FASN in CC. In vivo studies were conducted to examine the antitumor effects of the combination of TVB-2640 and cisplatin.</div></div><div><h3>Results</h3><div>Fatty acid synthase (FASN) was identified as a key driver of cisplatin resistance in CC through transcriptome sequencing and Gene Expression Omnibus (GEO) data analysis. The clinically safe FASN inhibitor TVB-2640 was found to restore cisplatin sensitivity, resulting in synergistic tumor growth attenuation in xenograft models. Mechanistically, FASN downregulation promoted ferroptosis and reduced solute carrier family 7 member 11 (SLC7A11) expression, both in vitro and in vivo models.</div></div><div><h3>Conclusion</h3><div>Targeting FASN enhances cisplatin sensitivity in CC by promoting SLC7A11-mediated ferroptosis. TVB-2640 combined with cisplatin had superior synergistic antitumor effects in cisplatin-resistant CC models.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102396"},"PeriodicalIF":5.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Mesenteric benign lymph node enlargement in colorectal cancer: Friend or foe? 结直肠癌肠系膜良性淋巴结肿大：是敌是友？

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-04-14 DOI: 10.1016/j.tranon.2025.102368

Wang Junwei , Chen Xin , Guo Limei , Li Fei , Lu Siyi , Ma Yao , Hsinyi Lin , Shi Xiangchao , Fu Wei , Zhou Xin

Introduction

Benign lymph node enlargement (BLNE) is common in colorectal cancer; however, few studies have investigated its influence on prognosis, clinicopathological features, and pathogenesis.

Methods

A cohort study was conducted to analyze the clinicopathologic features and prognosis of colorectal cancer patients, categorized based on the presence or absence of BLNE. Given the correlation between lymph nodes and immune response, immunohistochemistry, transcriptome analysis, and exon sequencing were employed to further investigate the differences in the immune microenvironment of primary tumors.

Results

Overall, 630 AJCC stage I/II patients were included in the study, with 131 in the BLNE group and 499 in the Non-BLNE (NBLNE) group. Patients in the BLNE group were found to have a significantly better disease-free survival (DFS) (hazard ratio [HR] 0.44, P = 0.016) and overall survival (OS) (HR 0.46, P = 0.011) than those in the NBLNE group. Pathologically, compared with the NBLNE group, the BLNE group had more mature tertiary lymphoid structures (66.7 % vs. 36.5 %, P = 0.002) and higher immunoscores (18.8 % vs. 2.1 %, P = 0.004) in primary tumor tissue. Also, transcriptome analysis showed that, compared with NBLNE, the genes upregulated in BLNE were enriched in immune-related pathways, such as adaptive immune response and immuno-regulatory interactions. Whole-exon sequencing analysis revealed a higher tumor mutation burden (TMB) in the BLNE group [6.03 (5.59, 7.59) vs. 5.33 (4.62, 6.34), P = 0.025].

Conclusion

BLNE is positively associated with the prognosis of colorectal cancer, possibly because patients with BLNE have a stronger anti-tumor immune response.

{"title":"Mesenteric benign lymph node enlargement in colorectal cancer: Friend or foe?","authors":"Wang Junwei , Chen Xin , Guo Limei , Li Fei , Lu Siyi , Ma Yao , Hsinyi Lin , Shi Xiangchao , Fu Wei , Zhou Xin","doi":"10.1016/j.tranon.2025.102368","DOIUrl":"10.1016/j.tranon.2025.102368","url":null,"abstract":"<div><h3>Introduction</h3><div>Benign lymph node enlargement (BLNE) is common in colorectal cancer; however, few studies have investigated its influence on prognosis, clinicopathological features, and pathogenesis.</div></div><div><h3>Methods</h3><div>A cohort study was conducted to analyze the clinicopathologic features and prognosis of colorectal cancer patients, categorized based on the presence or absence of BLNE. Given the correlation between lymph nodes and immune response, immunohistochemistry, transcriptome analysis, and exon sequencing were employed to further investigate the differences in the immune microenvironment of primary tumors.</div></div><div><h3>Results</h3><div>Overall, 630 AJCC stage I/II patients were included in the study, with 131 in the BLNE group and 499 in the Non-BLNE (NBLNE) group. Patients in the BLNE group were found to have a significantly better disease-free survival (DFS) (hazard ratio [HR] 0.44, <em>P</em> = 0.016) and overall survival (OS) (HR 0.46, <em>P</em> = 0.011) than those in the NBLNE group. Pathologically, compared with the NBLNE group, the BLNE group had more mature tertiary lymphoid structures (66.7 % vs. 36.5 %, <em>P</em> = 0.002) and higher immunoscores (18.8 % vs. 2.1 %, <em>P</em> = 0.004) in primary tumor tissue. Also, transcriptome analysis showed that, compared with NBLNE, the genes upregulated in BLNE were enriched in immune-related pathways, such as adaptive immune response and immuno-regulatory interactions. Whole-exon sequencing analysis revealed a higher tumor mutation burden (TMB) in the BLNE group [6.03 (5.59, 7.59) vs. 5.33 (4.62, 6.34), <em>P</em> = 0.025].</div></div><div><h3>Conclusion</h3><div>BLNE is positively associated with the prognosis of colorectal cancer, possibly because patients with BLNE have a stronger anti-tumor immune response.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102368"},"PeriodicalIF":5.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Characterization of a novel cell line established from mice gastrointestinal stromal model by chemical induction

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-04-14 DOI: 10.1016/j.tranon.2025.102388

Zhan Zhao , Shenghui Qiu , Xiangwei Zhang , Shijin Liu , Lu Wang , Hanyang Guan , Jiashuai He , Yangzhi Hu , Xiaobo Li , Simin Luo , Zuyang Chen , Tianmu Mo , Yiran Zhang , Xiaoxu Zhao , Yunlong Pan , Hui Ding , Jie Cao , Jinghua Pan

Background

Gastrointestinal stromal tumors (GISTs) are a type of tumor that originates from gastrointestinal mesenchymal tissue. Although several somatic or germline mutation GIST mice were established, however, there is still a lack of an authentic mice GIST cell lines for further experimental study.

Methods

We developed a chemically induced C57BL/6 J GIST model using 3- methylcholanthrene. Tumor characteristics were confirmed through histology and IHC. Primary cells were isolated to establish the mGSTc01 cell line, and molecular profiling was conducted. Additionally, we established GIST model in immunocompetent mice to evaluate their sensitivity to imatinib.

Results

Our study successfully developed a chemically induced murine GIST model, characterized by positive staining of c-kit and DOG-1. The mGSTc01 monoclonal cell line exhibited slender morphology and expressed the c-kit marker, Whole exome sequencing uncovered mutations of Lamb1, MMP9, and c-kit in GIST cells and provided a detailed picture of the entire genome's copy number variations. RNA sequencing indicated genes associated with cell adhesion and focal adhesion were enriched in mGSTc01 cells. The mGSTc01 cells demonstrated obvious malignant behaviors, notably elevated migration, adhesion, and proliferation. In immunocompetent mice, subcutaneous xenografts not only reserved the aggressive phenotype but also displayed a response to imatinib, underscoring the model's applicability for advancing therapeutic research.

Conclusion

We firstly established a mGSTc01 cell line derived from C57BL/6 J mice GIST tumor offers, which closely mimicking human disease characteristics. It is a potent platform for investigating tumor microenvironment of GIST in mice model, and provides a novel way for new therapeutic discoveries in GIST.

背景胃肠间质瘤（GIST）是一种起源于胃肠间质组织的肿瘤。尽管已经建立了几种体细胞或种系突变的 GIST 小鼠，但仍然缺乏真正的小鼠 GIST 细胞系用于进一步的实验研究。通过组织学和 IHC 确认了肿瘤特征。分离原代细胞，建立 mGSTc01 细胞系，并进行分子谱分析。此外，我们还在免疫功能正常的小鼠体内建立了 GIST 模型，以评估它们对伊马替尼的敏感性。结果我们的研究成功建立了化学诱导的小鼠 GIST 模型，其特征是 c-kit 和 DOG-1 染色阳性。mGSTc01单克隆细胞系表现出细长的形态，并表达c-kit标记。全外显子组测序发现了GIST细胞中Lamb1、MMP9和c-kit的突变，并提供了整个基因组拷贝数变异的详细情况。RNA 测序表明，mGSTc01 细胞中富含与细胞粘附和病灶粘附相关的基因。mGSTc01 细胞表现出明显的恶性行为，尤其是迁移、粘附和增殖能力增强。在免疫功能正常的小鼠体内，皮下异种移植不仅保留了侵袭性表型，而且对伊马替尼有反应，这突出表明该模型适用于推进治疗研究。它是在小鼠模型中研究 GIST 肿瘤微环境的有效平台，为 GIST 的新疗法发现提供了一条新途径。

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引用次数: 0

Research progress on estrogen receptor-positive/progesterone receptor-negative breast cancer 雌激素受体阳性/孕激素受体阴性乳腺癌的研究进展

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-04-14 DOI: 10.1016/j.tranon.2025.102387

Zhengjia Lu, Tingrui Wang, Lu Wang, Jia Ming

Breast cancer, which arises from the epithelial tissue of the breast, is one of the most common cancers affecting women worldwide. Its incidence and mortality rates have been increasing in both developed and developing countries. As a hormone-dependent cancer, breast cancer is classified into several molecular subtypes based on the expression of key markers: Estrogen Receptor (ER), Progesterone Receptor (PR), Human Epidermal Growth Factor Receptor 2 (HER-2), and Ki67. PR loss is associated with endocrine resistance and a poorer prognosis in breast cancer. Despite this, the underlying mechanisms of ER-positive/PR-negative (ER+PR-) breast cancer remain poorly understood. This study aims to review recent advancements in research on ER+PR- breast cancer, analyze its clinical characteristics and molecular mechanisms, and provide recommendations for more targeted therapeutic approaches.

引用次数: 0