Pub Date : 2025-08-14DOI: 10.1016/j.adcanc.2025.100149
Yanfei Cui , Minghua Zhang , Sijia Zhang , Yanli Cai , Yangang Qu , Lihua Luo
Background
Lung cancer often develops resistance to radiotherapy (RT), which undermines its therapeutic efficacy. Disulfiram (DSF), a drug commonly used in the treatment of alcohol use disorders, has shown potential in inducing anti-tumor effects. However, its impact on radioresistance in lung cancer and its effects on the tumor immune microenvironment have not been fully elucidated.
Methods
Clonogenic assays, Rad51 foci formation, and a nude mouse model were employed to assess the impact of DSF on lung cancer radiosensitivity. Immune profiling was conducted using flow cytometry, and downstream mechanisms were investigated using RT-qPCR and Western blotting. The therapeutic effects of the combination of DSF, RT, and anti-PD-L1 antibody were further validated in a C57BL/6 mouse tumor model.
Results
DSF increased radiosensitivity in lung cancer cells, enhanced CD8+ T cell infiltration, and upregulated PD-L1 expression through c-Myc. The combination of DSF, RT, and anti-PD-L1 antibody resulted in the most significant anti-tumor effects.
Conclusions
DSF effectively mitigates radioresistance in lung cancer and enhances the efficacy of radioimmunotherapy, offering a promising therapeutic strategy for improving treatment outcomes.
{"title":"Disulfiram alone regulates the radiosensitivity of lung cancer through NF-κB pathway and regulates the immune microenvironment after radiotherapy by targeting PD-L1 through c-Myc","authors":"Yanfei Cui , Minghua Zhang , Sijia Zhang , Yanli Cai , Yangang Qu , Lihua Luo","doi":"10.1016/j.adcanc.2025.100149","DOIUrl":"10.1016/j.adcanc.2025.100149","url":null,"abstract":"<div><h3>Background</h3><div>Lung cancer often develops resistance to radiotherapy (RT), which undermines its therapeutic efficacy. Disulfiram (DSF), a drug commonly used in the treatment of alcohol use disorders, has shown potential in inducing anti-tumor effects. However, its impact on radioresistance in lung cancer and its effects on the tumor immune microenvironment have not been fully elucidated.</div></div><div><h3>Methods</h3><div>Clonogenic assays, Rad51 foci formation, and a nude mouse model were employed to assess the impact of DSF on lung cancer radiosensitivity. Immune profiling was conducted using flow cytometry, and downstream mechanisms were investigated using RT-qPCR and Western blotting. The therapeutic effects of the combination of DSF, RT, and anti-PD-L1 antibody were further validated in a C57BL/6 mouse tumor model.</div></div><div><h3>Results</h3><div>DSF increased radiosensitivity in lung cancer cells, enhanced CD8<sup>+</sup> T cell infiltration, and upregulated PD-L1 expression through c-Myc. The combination of DSF, RT, and anti-PD-L1 antibody resulted in the most significant anti-tumor effects.</div></div><div><h3>Conclusions</h3><div>DSF effectively mitigates radioresistance in lung cancer and enhances the efficacy of radioimmunotherapy, offering a promising therapeutic strategy for improving treatment outcomes.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100149"},"PeriodicalIF":3.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-05DOI: 10.1016/j.adcanc.2025.100148
April Kirkendoll
The emergence of cancer is a multistep process, with passage through a so-called precancerous stage as part of the development. Biopsies of suspicious lesions often reveal cells that are altered or abnormal, and those anomalous cells, while often still benign, indicate local conditions conducive to carcinogenesis. Most of the altered cells never develop into cancers, and it is unknown what may trigger malignancy. This report reexamines existing data to provide insights into the conditions necessary to prime a relatively benign and latent cell with malignant potential to respond to a stimulus and transform into cancer. I propose that normal, well-established reactions to cellular insults over time induce conditions within the affected cell which predispose it to malignant transformation. Then, cumulative, age-related changes in the stromal milieu, from a burgeoning population of senescent cells, inadvertently facilitates the progression of mutant cells, contributing to the increase in late life cancers, via incremental seclusion from normal somatic tissues. Within an increasingly exclusive compartment, cells begin a cycle of crosstalk upon each other, incrementally modifying the isolated population of cells with multiple dynamic morphogen gradients that converge, amplify, and erase epigenetic memory within the innermost cells, reprogramming them to a stem cell-like state, and priming them to transform into a novel tissue.
{"title":"Latency, microenvironment, and the priming of a precancerous senescent cell for malignant transformation","authors":"April Kirkendoll","doi":"10.1016/j.adcanc.2025.100148","DOIUrl":"10.1016/j.adcanc.2025.100148","url":null,"abstract":"<div><div>The emergence of cancer is a multistep process, with passage through a so-called precancerous stage as part of the development. Biopsies of suspicious lesions often reveal cells that are altered or abnormal, and those anomalous cells, while often still benign, indicate local conditions conducive to carcinogenesis. Most of the altered cells never develop into cancers, and it is unknown what may trigger malignancy. This report reexamines existing data to provide insights into the conditions necessary to prime a relatively benign and latent cell with malignant potential to respond to a stimulus and transform into cancer. I propose that normal, well-established reactions to cellular insults over time induce conditions within the affected cell which predispose it to malignant transformation. Then, cumulative, age-related changes in the stromal milieu, from a burgeoning population of senescent cells, inadvertently facilitates the progression of mutant cells, contributing to the increase in late life cancers, via incremental seclusion from normal somatic tissues. Within an increasingly exclusive compartment, cells begin a cycle of crosstalk upon each other, incrementally modifying the isolated population of cells with multiple dynamic morphogen gradients that converge, amplify, and erase epigenetic memory within the innermost cells, reprogramming them to a stem cell-like state, and priming them to transform into a novel tissue.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100148"},"PeriodicalIF":3.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144779774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-02DOI: 10.1016/j.adcanc.2025.100147
Ligang Ma , Ruixin Li , Junjie Su , Qiong Cao , Haojie Wang , Zhihao Wei , Chengliang Wang , Chengdong Zhang , Guanyu Li , Wang Qin , Zheng Zhang , Chu Wang , Yingao Zhu , Jingjing Zhao , Shiyong Xin , Jun Ma
Background
With increasing evidence indicating that immune cells significantly contribute to tumor progression, elucidating their role in tumor prognosis and therapy has become imperative. This study aims to thoroughly characterize tumor-infiltrating immune cells in bladder cancer (BLCA) and identify key immune cells and gene models associated with prognosis and therapeutic outcomes in BLCA.
Methods
Initially, we assessed the relationship between the abundance of infiltrating immune cells and prognosis, CD8+T cell was selected to establish the risk model, which was constructed based on five key genes. Then ROC curve was drawn to demonstrate the risk model had high prognosis predictive value in BLCA.
Results
Our correlation analysis revealed that riskscore was negatively associated with several steps of the tumor immune cycle. Additionally, the risk score exhibited a negative correlation with the expression levels of CD8,CD274,IFNG, Merck18, and several common immune checkpoints. Furthermore, the tumor exclusion score and Tumor Immune Dysfunction and Exclusion (TIDE) score were significantly higher in the high-score group compared to the low-score group. Notably, the risk score demonstrated a negative correlation with the enrichment score of immunotherapy-related pathways, indicating that the therapeutic benefit was greater in the low-score group than in the high-score group. Then, a total of 171 chemotherapy and targeted drugs were identified. Subsequently, immunohistochemistry, EDU and Western blot were used to verify our result.
Conclusions
Our results confirmed that the tumor infiltration CD8+ T cells in tumors plays a critical role in the prognosis and treatment of bladder cancer (BLCA). This insight may offer new directions and inspiration for prognostic prediction and therapeutic strategies for bladder cancer in the future.
{"title":"Identification of a risk model for prognostic and therapeutic prediction in bladder urothelial carcinoma based on infiltrating CD8+ T cells","authors":"Ligang Ma , Ruixin Li , Junjie Su , Qiong Cao , Haojie Wang , Zhihao Wei , Chengliang Wang , Chengdong Zhang , Guanyu Li , Wang Qin , Zheng Zhang , Chu Wang , Yingao Zhu , Jingjing Zhao , Shiyong Xin , Jun Ma","doi":"10.1016/j.adcanc.2025.100147","DOIUrl":"10.1016/j.adcanc.2025.100147","url":null,"abstract":"<div><h3>Background</h3><div>With increasing evidence indicating that immune cells significantly contribute to tumor progression, elucidating their role in tumor prognosis and therapy has become imperative. This study aims to thoroughly characterize tumor-infiltrating immune cells in bladder cancer (BLCA) and identify key immune cells and gene models associated with prognosis and therapeutic outcomes in BLCA.</div></div><div><h3>Methods</h3><div>Initially, we assessed the relationship between the abundance of infiltrating immune cells and prognosis, CD8<sup>+</sup>T cell was selected to establish the risk model, which was constructed based on five key genes. Then ROC curve was drawn to demonstrate the risk model had high prognosis predictive value in BLCA.</div></div><div><h3>Results</h3><div>Our correlation analysis revealed that riskscore was negatively associated with several steps of the tumor immune cycle. Additionally, the risk score exhibited a negative correlation with the expression levels of CD8,CD274,IFNG, Merck18, and several common immune checkpoints. Furthermore, the tumor exclusion score and Tumor Immune Dysfunction and Exclusion (TIDE) score were significantly higher in the high-score group compared to the low-score group. Notably, the risk score demonstrated a negative correlation with the enrichment score of immunotherapy-related pathways, indicating that the therapeutic benefit was greater in the low-score group than in the high-score group. Then, a total of 171 chemotherapy and targeted drugs were identified. Subsequently, immunohistochemistry, EDU and Western blot were used to verify our result.</div></div><div><h3>Conclusions</h3><div>Our results confirmed that the tumor infiltration CD8<sup>+</sup> T cells in tumors plays a critical role in the prognosis and treatment of bladder cancer (BLCA). This insight may offer new directions and inspiration for prognostic prediction and therapeutic strategies for bladder cancer in the future.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100147"},"PeriodicalIF":3.0,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-10DOI: 10.1016/j.adcanc.2025.100144
Marwa Zahra , Hassan Mohamed El-Said Azzazy
Mechanisms of aneuploidy set the stage for cancer. Aneuploidy, an aberration in chromosome number in a cell, occurs naturally during cellular development in certain tissues. However, aneuploidy is omnipresent in cancer as cancer cells express complex karyotypes with chromosome numbers that deviate from the norm. Aneuploidy is a hallmark in Hepatocellular Carcinoma (HCC), as it is linked to poor prognosis due to genetic and epigenetic aberrations. Mechanisms contributing to aneuploidy in HCC include chromosomal instability, telomere shortening, which promotes genomic instability in early tumor development, and telomere stabilization, which enhances tumor cell survival by preventing excessive telomere attrition in later stages. Multiple chromosomal alterations are linked to the progression of invasive tumors in HCC. Therefore, understanding the association between aneuploidy and HCC is critical because it could unravel the role of genetic and molecular alterations in HCC. This review sheds light on the risk factors associated with aneuploidy in HCC to aid the development of future therapeutic and diagnostic approaches for management of HCC.
{"title":"Aneuploidy in Hepatocellular Carcinoma: Risk factors, mechanisms, and clinical relevance","authors":"Marwa Zahra , Hassan Mohamed El-Said Azzazy","doi":"10.1016/j.adcanc.2025.100144","DOIUrl":"10.1016/j.adcanc.2025.100144","url":null,"abstract":"<div><div>Mechanisms of aneuploidy set the stage for cancer. Aneuploidy, an aberration in chromosome number in a cell, occurs naturally during cellular development in certain tissues. However, aneuploidy is omnipresent in cancer as cancer cells express complex karyotypes with chromosome numbers that deviate from the norm. Aneuploidy is a hallmark in Hepatocellular Carcinoma (HCC), as it is linked to poor prognosis due to genetic and epigenetic aberrations. Mechanisms contributing to aneuploidy in HCC include chromosomal instability, telomere shortening, which promotes genomic instability in early tumor development, and telomere stabilization, which enhances tumor cell survival by preventing excessive telomere attrition in later stages. Multiple chromosomal alterations are linked to the progression of invasive tumors in HCC. Therefore, understanding the association between aneuploidy and HCC is critical because it could unravel the role of genetic and molecular alterations in HCC. This review sheds light on the risk factors associated with aneuploidy in HCC to aid the development of future therapeutic and diagnostic approaches for management of HCC.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100144"},"PeriodicalIF":2.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-02DOI: 10.1016/j.adcanc.2025.100142
Zahra Tajik, Soudeh Ghafouri-Fard
As a chemotherapeutic agent, gemcitabine makes the backbone of several chemotherapeutic regimens, particularly those used for advanced cancers. However, drug resistance confines the long-term therapeutic impact of gemcitabine in cancer treatment and makes the patients' prognosis poor. Several mechanisms such as alteration of membrane transporters, abnormal regulation of activating and inactivating enzymes, and alterations in signaling pathway have been proposed for induction of resistance to gemcitabine. However, none of them could individually explain the varied spectrum of patients' responses to this agent. Recent recognition of the role of circular RNAs (circRNAs) in the pathoetiology of cancer has opened a new venue for identification of molecular events leading to chemoresistance. The current review provides insights into the role of specific circRNAs in determination of response to gemcitabine.
{"title":"CircRNAs modulate response of cancer cells to gemcitabine","authors":"Zahra Tajik, Soudeh Ghafouri-Fard","doi":"10.1016/j.adcanc.2025.100142","DOIUrl":"10.1016/j.adcanc.2025.100142","url":null,"abstract":"<div><div>As a chemotherapeutic agent, gemcitabine makes the backbone of several chemotherapeutic regimens, particularly those used for advanced cancers. However, drug resistance confines the long-term therapeutic impact of gemcitabine in cancer treatment and makes the patients' prognosis poor. Several mechanisms such as alteration of membrane transporters, abnormal regulation of activating and inactivating enzymes, and alterations in signaling pathway have been proposed for induction of resistance to gemcitabine. However, none of them could individually explain the varied spectrum of patients' responses to this agent. Recent recognition of the role of circular RNAs (circRNAs) in the pathoetiology of cancer has opened a new venue for identification of molecular events leading to chemoresistance. The current review provides insights into the role of specific circRNAs in determination of response to gemcitabine.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100142"},"PeriodicalIF":2.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-02DOI: 10.1016/j.adcanc.2025.100143
XianYi Zhou , JiuLin Li , XiuYong Liao , ChengYu Ding , SaiJiao Na , JiangRong Du , QingHui Meng , Peng Zheng , Fan Sun
DSF is a well-known alcohol withdrawal agent that has shown considerable anticancer effects in preclinical studies. In the present study, we aimed to elucidate the mechanism by which DSF and CTSB modulate of the migration and invasion of GCs. Our results illustrate that DSF plays a pivotal role in suppressing tumor migration, invasion, and EMT in GC by modulating CTSB expression. Furthermore, DSF was found to aggravate the reduction in β-catenin expression via GSK-3β, consequently inhibiting CTSB expression, which has a pronounced effect on invading gastric cancer cells as a metastasis-promoting gene. Notably, β-catenin was found to increase CTSB transcriptional activity by binding to the promoter of CTSB, leading to an increase in CTSB protein levels. Collectively, our findings elucidate the molecular mechanism by which DSF suppresses EMT, migration, and invasion in GC through the GSK-3β/β-catenin/CTSB pathway, underscoring the potential of CTSB as a therapeutic target for GC.
{"title":"Disulfiram inhibits migration, invasion and epithelial-mesenchymal transition of gastric cancer cells via β-catenin/CTSB pathway","authors":"XianYi Zhou , JiuLin Li , XiuYong Liao , ChengYu Ding , SaiJiao Na , JiangRong Du , QingHui Meng , Peng Zheng , Fan Sun","doi":"10.1016/j.adcanc.2025.100143","DOIUrl":"10.1016/j.adcanc.2025.100143","url":null,"abstract":"<div><div>DSF is a well-known alcohol withdrawal agent that has shown considerable anticancer effects in preclinical studies. In the present study, we aimed to elucidate the mechanism by which DSF and CTSB modulate of the migration and invasion of GCs. Our results illustrate that DSF plays a pivotal role in suppressing tumor migration, invasion, and EMT in GC by modulating CTSB expression. Furthermore, DSF was found to aggravate the reduction in β-catenin expression via GSK-3β, consequently inhibiting CTSB expression, which has a pronounced effect on invading gastric cancer cells as a metastasis-promoting gene. Notably, β-catenin was found to increase CTSB transcriptional activity by binding to the promoter of CTSB, leading to an increase in CTSB protein levels. Collectively, our findings elucidate the molecular mechanism by which DSF suppresses EMT, migration, and invasion in GC through the GSK-3β/β-catenin/CTSB pathway, underscoring the potential of CTSB as a therapeutic target for GC.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100143"},"PeriodicalIF":2.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Epithelial-mesenchymal transition (EMT) is a key biological process that enables cancer cells to acquire invasive, migratory, and therapy-resistant properties, driving metastasis and poor clinical outcomes. Traditional tissue biopsies, while informative, provide only static and localized snapshots of tumors, limiting their ability to capture dynamic changes like EMT. Liquid biopsy has emerged as a powerful, minimally invasive tool to monitor tumor evolution in real time by analyzing circulating tumor cells (CTCs), cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), and extracellular vesicles (EVs) from body fluids. This review highlights the molecular mechanisms that govern EMT, including transcriptional, signaling, and epigenetic regulation, and discusses how EMT-associated alterations can be detected through liquid biopsy. We explore the clinical applications of EMT monitoring via liquid biopsy for early detection of metastasis, prognostic assessment, therapy selection, and monitoring minimal residual disease (MRD). Despite current challenges such as the biological complexity of EMT, detection sensitivity, and the need for standardization, technological advances and emerging computational tools are paving the way for the integration of liquid biopsy into precision oncology. Understanding and decoding EMT through liquid biopsy represents a promising frontier for improving cancer diagnosis, prognosis, and therapeutic strategies, offering hope for more personalized and effective cancer management in the future.
{"title":"Decoding EMT through liquid biopsy: A path to early detection and targeted therapy","authors":"Revathi Boyina , Prasanna Kumar Desu , Sreya Kosanam , Anusha Rapuri , Ramesh Alluri , Jadala Shankaraswamy , Sri Chandana Mavulati , Vanitha Kondi","doi":"10.1016/j.adcanc.2025.100141","DOIUrl":"10.1016/j.adcanc.2025.100141","url":null,"abstract":"<div><div>Epithelial-mesenchymal transition (EMT) is a key biological process that enables cancer cells to acquire invasive, migratory, and therapy-resistant properties, driving metastasis and poor clinical outcomes. Traditional tissue biopsies, while informative, provide only static and localized snapshots of tumors, limiting their ability to capture dynamic changes like EMT. Liquid biopsy has emerged as a powerful, minimally invasive tool to monitor tumor evolution in real time by analyzing circulating tumor cells (CTCs), cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), and extracellular vesicles (EVs) from body fluids. This review highlights the molecular mechanisms that govern EMT, including transcriptional, signaling, and epigenetic regulation, and discusses how EMT-associated alterations can be detected through liquid biopsy. We explore the clinical applications of EMT monitoring via liquid biopsy for early detection of metastasis, prognostic assessment, therapy selection, and monitoring minimal residual disease (MRD). Despite current challenges such as the biological complexity of EMT, detection sensitivity, and the need for standardization, technological advances and emerging computational tools are paving the way for the integration of liquid biopsy into precision oncology. Understanding and decoding EMT through liquid biopsy represents a promising frontier for improving cancer diagnosis, prognosis, and therapeutic strategies, offering hope for more personalized and effective cancer management in the future.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"15 ","pages":"Article 100141"},"PeriodicalIF":2.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-30DOI: 10.1016/j.adcanc.2025.100140
Farahanaz Kavian Manesh , Ali Jebali , Flora Forouzesh
To decrease the ETV4 gene, which is important in metastasis, the nanoliposome containing ETV4 antisense oligonucleotide conjugated with Arginylglycylaspartic acid (RGD) ligand was used in the study. The nanoliposome containing ETV4 antisense oligonucleotide conjugated with RGD ligand was synthesized and characterized by AFM, DLS, and FTIR. Then, MDA-MB-231, MCF-7, and MCF-10A cell lines were treated with different concentrations of nanoliposomes containing antisense ETV4 oligonucleotide conjugated with RGD, nanoliposomes without antisense ETV4 oligonucleotide, and antisense ETV4 oligonucleotide for 24 h. Finally, an MTT assay was used to evaluate cell viability, Real-time PCR was employed to assess the ETV4 mRNA expression, and western blotting was applied to evaluate the expression of ETV4 protein. Here, the characterization data revealed that the nanoliposome containing antisense ETV4 oligonucleotide conjugated with RGD had a spherical shape with a size range of 50–120 nm and zeta potential of −18mV to +7 mV. This study showed that although nanoliposomes containing antisense ETV4 oligonucleotide conjugated with RGD could effectively decrease the cell viability of MDA-MB-231 and MCF-7 cells, they could not dcrease cell viability of MCF-10A, indicating the effect of RGD ligand. Also, this novel carrier could decrease both mRNA and protein of the ETV4 gene in a dose dependent manner.
{"title":"The targeted delivery of anti-metastasis oligonucleotide in breast cancer cells by the nanoliposomes conjugated with RGD ligand","authors":"Farahanaz Kavian Manesh , Ali Jebali , Flora Forouzesh","doi":"10.1016/j.adcanc.2025.100140","DOIUrl":"10.1016/j.adcanc.2025.100140","url":null,"abstract":"<div><div>To decrease the <em>ETV4</em> gene, which is important in metastasis, the nanoliposome containing ETV4 antisense oligonucleotide conjugated with Arginylglycylaspartic acid (RGD) ligand was used in the study. The nanoliposome containing ETV4 antisense oligonucleotide conjugated with RGD ligand was synthesized and characterized by AFM, DLS, and FTIR. Then, MDA-MB-231, MCF-7, and MCF-10A cell lines were treated with different concentrations of nanoliposomes containing antisense ETV4 oligonucleotide conjugated with RGD, nanoliposomes without antisense ETV4 oligonucleotide, and antisense ETV4 oligonucleotide for 24 h. Finally, an MTT assay was used to evaluate cell viability, Real-time PCR was employed to assess the <em>ETV4</em> mRNA expression, and western blotting was applied to evaluate the expression of ETV4 protein. Here, the characterization data revealed that the nanoliposome containing antisense ETV4 oligonucleotide conjugated with RGD had a spherical shape with a size range of 50–120 nm and zeta potential of −18mV to +7 mV. This study showed that although nanoliposomes containing antisense ETV4 oligonucleotide conjugated with RGD could effectively decrease the cell viability of MDA-MB-231 and MCF-7 cells, they could not dcrease cell viability of MCF-10A, indicating the effect of RGD ligand. Also, this novel carrier could decrease both mRNA and protein of <em>the ETV4</em> gene in a dose dependent manner.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"14 ","pages":"Article 100140"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-03DOI: 10.1016/j.adcanc.2025.100139
Saeed Homaeii, Mahsa Kavousi, Elahe Ali Asgari
Breast cancer is the most common cancer in the world and the second leading cause of cancer-related deaths in women worldwide. Although great progress has been made in elucidating the molecular features and underlying pathogenesis of breast tumors and various therapeutic strategies have been applied for individualized treatment, some types of breast cancer patients with aggressive features have a poor prognosis in terms of treatment. Nanotechnology is increasingly used in biology and medicine, including as a tool for diagnosing, treating and targeting tumors. The aim of this study is therefore to develop a drug delivery system based on niosomes loaded with daphnetin, a phytochemical coumarin. To confirm the synthesis of the loaded nano niosome, their physical and chemical properties were examined using SEM, FTIR and DLS. In this study, the toxic effect of daphnetin-loaded nanoparticles on the MCF-7 cell line was measured using the MTT assay. The expression level of apoptotic genes Bax and Caspase 3; and metastatic genes MMP2 and ITGA5 were quantitatively evaluated using the Real-time PCR method, and the division and metastatic potential of cancer cells were qualitatively evaluated by performing the scratch (repair) method. Finally, the effect of the investigated compounds on the amount of apoptosis and necrosis and the induced cell cycle was evaluated using the flow cytometry method.
The results of the SEM study showed that the synthesized nanoparticles had a spherical morphology and a diameter of less than 200 nm. The zeta potential was determined to be 39.1 mV using a DLS device. The results of the FTIR study also showed successful interactions between niosome and daphnetin. According to the flow cytometry results, the frequency of early apoptosis and delayed apoptosis was significantly higher in the cells treated with the IC50 concentration of daphnetin-loaded nanoparticles than in the group treated with daphnetin and free niosome. The expression of apoptotic genes was also increased in the group treated with the IC50 concentration of the loaded nanoparticles and the expression of antimetastatic genes was decreased. The results of the cell migration assay (scratch test) also show that treatment with the IC50 concentration of the loaded nanoparticles can effectively control cell migration. Therefore, they can be considered as chemotherapeutic agents against breast cancer.
{"title":"Investigating the apoptotic and antimetastatic effect of daphnetin-containing nano niosomes on MCF-7 cells","authors":"Saeed Homaeii, Mahsa Kavousi, Elahe Ali Asgari","doi":"10.1016/j.adcanc.2025.100139","DOIUrl":"10.1016/j.adcanc.2025.100139","url":null,"abstract":"<div><div>Breast cancer is the most common cancer in the world and the second leading cause of cancer-related deaths in women worldwide. Although great progress has been made in elucidating the molecular features and underlying pathogenesis of breast tumors and various therapeutic strategies have been applied for individualized treatment, some types of breast cancer patients with aggressive features have a poor prognosis in terms of treatment. Nanotechnology is increasingly used in biology and medicine, including as a tool for diagnosing, treating and targeting tumors. The aim of this study is therefore to develop a drug delivery system based on niosomes loaded with daphnetin, a phytochemical coumarin. To confirm the synthesis of the loaded nano niosome, their physical and chemical properties were examined using SEM, FTIR and DLS. In this study, the toxic effect of daphnetin-loaded nanoparticles on the MCF-7 cell line was measured using the MTT assay. The expression level of apoptotic genes <em>Bax</em> and <em>Caspase 3</em>; and metastatic genes <em>MMP2</em> and <em>ITGA5</em> were quantitatively evaluated using the Real-time PCR method, and the division and metastatic potential of cancer cells were qualitatively evaluated by performing the scratch (repair) method. Finally, the effect of the investigated compounds on the amount of apoptosis and necrosis and the induced cell cycle was evaluated using the flow cytometry method.</div><div>The results of the SEM study showed that the synthesized nanoparticles had a spherical morphology and a diameter of less than 200 nm. The zeta potential was determined to be 39.1 mV using a DLS device. The results of the FTIR study also showed successful interactions between niosome and daphnetin. According to the flow cytometry results, the frequency of early apoptosis and delayed apoptosis was significantly higher in the cells treated with the IC<sub>50</sub> concentration of daphnetin-loaded nanoparticles than in the group treated with daphnetin and free niosome. The expression of apoptotic genes was also increased in the group treated with the IC<sub>50</sub> concentration of the loaded nanoparticles and the expression of antimetastatic genes was decreased. The results of the cell migration assay (scratch test) also show that treatment with the IC<sub>50</sub> concentration of the loaded nanoparticles can effectively control cell migration. Therefore, they can be considered as chemotherapeutic agents against breast cancer.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"14 ","pages":"Article 100139"},"PeriodicalIF":2.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.adcanc.2025.100137
Sonam Agarwal, Anita Chauhan, Pramod Kumar Gautam
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal).
This article has been retracted at the request of the Editor-in-Chief.
Concern was raised about validity and reliability of the data, experimental procedures, data analysis methods and consequently the result of the article.
The Editors requested the corresponding author to repeat the experiments at least three times and provide the raw data and standard deviations for the statistically evaluated results. However, the authors did not follow the Editors' recommendations and were unable to provide adequate response for comment. The overall validity of the results could not be confirmed. Therefore, the Editor-in-Chief decided to retract the article.
{"title":"Retraction notice to “Immunomodulatory effects of β-defensin 2 on tumor associated macrophages induced antitumor function in breast cancer” [Adv. Cancer Biol. – Metastasis 7 (2023) 100102]","authors":"Sonam Agarwal, Anita Chauhan, Pramod Kumar Gautam","doi":"10.1016/j.adcanc.2025.100137","DOIUrl":"10.1016/j.adcanc.2025.100137","url":null,"abstract":"<div><div>This article has been retracted: please see Elsevier Policy on Article Withdrawal (<span><span>https://www.elsevier.com/about/policies/article-withdrawal</span><svg><path></path></svg></span>).</div><div>This article has been retracted at the request of the Editor-in-Chief.</div><div>Concern was raised about validity and reliability of the data, experimental procedures, data analysis methods and consequently the result of the article.</div><div>The Editors requested the corresponding author to repeat the experiments at least three times and provide the raw data and standard deviations for the statistically evaluated results. However, the authors did not follow the Editors' recommendations and were unable to provide adequate response for comment. The overall validity of the results could not be confirmed. Therefore, the Editor-in-Chief decided to retract the article.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"13 ","pages":"Article 100137"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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