Pub Date : 2024-11-01Epub Date: 2024-09-20DOI: 10.3892/or.2024.8810
Qi Zhong, Duo Li, Xiao-Ping Yang
Phenformin, a biguanide compound, has attracted increased attention due to its prominent antitumor activity. As a multi‑target agent, the antitumor effects of phenformin involve a wide range of factors, including inhibition of mitochondrial complex I, activation of AMP‑activated protein kinase, impact on the tumor microenvironment, suppression of cancer stem cells and others. In addition, phenformin has been shown to markedly augment the effectiveness of various clinical treatment methods, including radiotherapy, chemotherapy, targeted therapy and immunotherapy. It is noteworthy that breakthrough progress has been made in the treatment of cancer with phenformin with application in clinical trials for the treatment of melanoma. Phenformin not only reduces the lesion area of patients, but also enhances the efficacy of dalafinib/trimetinib. In the present review, the novel breakthroughs in the antitumor effects and mechanisms of phenformin were discussed. In addition, the current review focuses on the clinical development value of phenformin, striving to provide new insights into the future research direction of phenformin in the field of tumor treatment.
{"title":"Progress in antitumor mechanisms and applications of phenformin (Review).","authors":"Qi Zhong, Duo Li, Xiao-Ping Yang","doi":"10.3892/or.2024.8810","DOIUrl":"10.3892/or.2024.8810","url":null,"abstract":"<p><p>Phenformin, a biguanide compound, has attracted increased attention due to its prominent antitumor activity. As a multi‑target agent, the antitumor effects of phenformin involve a wide range of factors, including inhibition of mitochondrial complex I, activation of AMP‑activated protein kinase, impact on the tumor microenvironment, suppression of cancer stem cells and others. In addition, phenformin has been shown to markedly augment the effectiveness of various clinical treatment methods, including radiotherapy, chemotherapy, targeted therapy and immunotherapy. It is noteworthy that breakthrough progress has been made in the treatment of cancer with phenformin with application in clinical trials for the treatment of melanoma. Phenformin not only reduces the lesion area of patients, but also enhances the efficacy of dalafinib/trimetinib. In the present review, the novel breakthroughs in the antitumor effects and mechanisms of phenformin were discussed. In addition, the current review focuses on the clinical development value of phenformin, striving to provide new insights into the future research direction of phenformin in the field of tumor treatment.</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292694","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}
Pub Date : 2024-11-01Epub Date: 2024-09-02DOI: 10.3892/or.2024.8804
Zongquan Xu, Yu Chen, Guohui Xu, Cheng Peng, Enyu Liu, Yunguang Li, Jun Niu, Changhai Li
Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that the control western blots shown for Fig. 1A and B on p. 908 and Fig. 8A and C on p. 911 were apparently the same, where different experiments were intended to have been portrayed. After having re‑examined their original data files, the authors realized that these figures had been published with the control western blots shown incorrectly for Fig. 1A and 8C. The corrected versions of this pair of figures are shown on the next page. Note that the corrections made to these figures do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 33: 905‑912, 2015; DOI: 10.3892/or.2014.3656].
上述论文发表后,一位感兴趣的读者提请作者注意,第 908 页的图 1A 和 B 以及第 911 页的图 8A 和 C 所显示的对照 Western 印迹显然是相同的,而这两张图本应描述不同的实验。在重新检查了原始数据文件后,作者意识到在发表这些图时,图 1A 和图 8C 的对照 Western 印迹显示有误。这对图的更正版本见下页。请注意,对这些图的更正并不影响论文中报告的总体结论。作者感谢《肿瘤学报告》编辑允许他们有机会发表本更正,并对给读者带来的不便表示歉意。[肿瘤学报告 33: 905-912, 2015; DOI: 10.3892/or.2014.3656]。
{"title":"[Corrigendum] Omi/HtrA2 pro-apoptotic marker differs in various hepatocellular carcinoma cell lines owing to ped/pea-15 expression level.","authors":"Zongquan Xu, Yu Chen, Guohui Xu, Cheng Peng, Enyu Liu, Yunguang Li, Jun Niu, Changhai Li","doi":"10.3892/or.2024.8804","DOIUrl":"10.3892/or.2024.8804","url":null,"abstract":"<p><p>Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that the control western blots shown for Fig. 1A and B on p. 908 and Fig. 8A and C on p. 911 were apparently the same, where different experiments were intended to have been portrayed. After having re‑examined their original data files, the authors realized that these figures had been published with the control western blots shown incorrectly for Fig. 1A and 8C. The corrected versions of this pair of figures are shown on the next page. Note that the corrections made to these figures do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of <i>Oncology Reports</i> for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 33: 905‑912, 2015; DOI: 10.3892/or.2014.3656].</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110420","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}
Pub Date : 2024-11-01Epub Date: 2024-09-20DOI: 10.3892/or.2024.8811
Yi Zhou, Zhigang Ji, Weigang Yan, Zhien Zhou, Hanzhong Li, Yu Xiao
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell invasion assay data shown in Fig. 3B on p. 839 were strikingly similar to data that had already appeared in another article written by different authors at different research institutes [Mao Y, Zhang L, Yuan L, Yan M and He Y: MiR‑218 suppresses cell progression by targeting APC in cervical cancer. Int J Clin Exp Pathol: 10, 2259‑2269, 2017]. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 38: 837‑842, 2017; DOI: 10.3892/or.2017.5768].
在这篇论文发表后,有相关读者提请编辑注意,第839页图3B所示的某些Transwell侵袭实验数据与不同研究机构不同作者撰写的另一篇文章[Mao Y, Zhang L, Yuan L, Yan M and He Y: MiR-218 suppresses cell progression by targeting APC in cervical cancer.Int J Clin Exp Pathol: 10, 2259-2269, 2017]。由于上述文章中存在争议的数据在投稿至《肿瘤学报告》之前已经发表,编辑决定将该论文从杂志上撤下。作者被要求解释这些问题,但编辑部没有收到回复。对于给读者带来的不便,编辑深表歉意。[肿瘤学报告 38: 837-842, 2017; DOI: 10.3892/or.2017.5768]。
{"title":"[Retracted] Tetramethylpyrazine inhibits prostate cancer progression by downregulation of forkhead box M1.","authors":"Yi Zhou, Zhigang Ji, Weigang Yan, Zhien Zhou, Hanzhong Li, Yu Xiao","doi":"10.3892/or.2024.8811","DOIUrl":"10.3892/or.2024.8811","url":null,"abstract":"<p><p>Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell invasion assay data shown in Fig. 3B on p. 839 were strikingly similar to data that had already appeared in another article written by different authors at different research institutes [Mao Y, Zhang L, Yuan L, Yan M and He Y: MiR‑218 suppresses cell progression by targeting APC in cervical cancer. Int J Clin Exp Pathol: 10, 2259‑2269, 2017]. Owing to the fact that the contentious data in the above article had already been published prior to its submission to <i>Oncology Reports</i>, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 38: 837‑842, 2017; DOI: 10.3892/or.2017.5768].</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292693","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}
Pub Date : 2024-11-01Epub Date: 2024-09-27DOI: 10.3892/or.2024.8813
Yuqing Yang, Fang Wang, Yuqin Li, Ruxi Chen, Xiangyu Wang, Jiahong Chen, Xi Lin, Haipeng Zhang, Youwei Huang, Rui Wang
Lack of effective tumor‑specific delivery systems remains an unmet clinical challenge for the employment of chemotherapy using cytotoxic drugs. Extracellular vesicles (EVs) have recently been investigated for their potential as an efficient drug‑delivery platform, due to their good biodistribution, biocompatibility and low immunogenicity. In the present study, the formulation of GE11 peptide‑modified EVs (GE11‑EVs) loaded with doxorubicin (Dox‑GE11‑EVs), was developed to target epidermal growth factor receptor (EGFR)‑positive tumor cells. The results obtained demonstrated that GE11‑EVs exhibited highly efficient targeting and drug delivery to EGFR‑positive tumor cells compared with non‑modified EVs. Furthermore, treatment with Dox‑GE11‑EVs led to a significantly inhibition of cell proliferation and increased apoptosis of EGFR‑positive tumor cells compared with Dox‑EVs and free Dox treatments. In addition, it was observed that treatment with either free Dox or Dox‑EVs exhibited a high level of cytotoxicity to normal cells, whereas treatment with Dox‑GE11‑EVs had only a limited effect on cell viability of normal cells. Taken together, the findings of the present study demonstrated that the engineered Dox‑GE11‑EVs can treat EGFR‑positive tumors more accurately and have higher safety than traditional tumor therapies.
{"title":"Engineered extracellular vesicles with polypeptide for targeted delivery of doxorubicin against EGFR‑positive tumors.","authors":"Yuqing Yang, Fang Wang, Yuqin Li, Ruxi Chen, Xiangyu Wang, Jiahong Chen, Xi Lin, Haipeng Zhang, Youwei Huang, Rui Wang","doi":"10.3892/or.2024.8813","DOIUrl":"10.3892/or.2024.8813","url":null,"abstract":"<p><p>Lack of effective tumor‑specific delivery systems remains an unmet clinical challenge for the employment of chemotherapy using cytotoxic drugs. Extracellular vesicles (EVs) have recently been investigated for their potential as an efficient drug‑delivery platform, due to their good biodistribution, biocompatibility and low immunogenicity. In the present study, the formulation of GE11 peptide‑modified EVs (GE11‑EVs) loaded with doxorubicin (Dox‑GE11‑EVs), was developed to target epidermal growth factor receptor (EGFR)‑positive tumor cells. The results obtained demonstrated that GE11‑EVs exhibited highly efficient targeting and drug delivery to EGFR‑positive tumor cells compared with non‑modified EVs. Furthermore, treatment with Dox‑GE11‑EVs led to a significantly inhibition of cell proliferation and increased apoptosis of EGFR‑positive tumor cells compared with Dox‑EVs and free Dox treatments. In addition, it was observed that treatment with either free Dox or Dox‑EVs exhibited a high level of cytotoxicity to normal cells, whereas treatment with Dox‑GE11‑EVs had only a limited effect on cell viability of normal cells. Taken together, the findings of the present study demonstrated that the engineered Dox‑GE11‑EVs can treat EGFR‑positive tumors more accurately and have higher safety than traditional tumor therapies.</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351305","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}
Pub Date : 2024-11-01Epub Date: 2024-09-02DOI: 10.3892/or.2024.8803
Wanli Liu, Xianze Wang, Wenming Wu
Interleukin‑17 (IL‑17), an inflammatory cytokine primarily secreted by T helper 17 cells, serves a crucial role in numerous inflammatory diseases and malignancies via its receptor, IL‑17R. In addition to stimulating inflammatory responses, IL‑17 exhibits dual functions in tumors, exerting both pro‑ and antitumor effects. Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic malignancy and accounts for >90% of pancreatic cancer cases. PDAC is characterized by a prominent stromal microenvironment with significant heterogeneity, which contributes to treatment resistance. IL‑17/IL‑17R signaling has a notable effect on tumorigenesis, the tumor microenvironment and treatment efficacy in various cancer types, including PDAC. However, the specific mechanisms of IL‑17/IL‑17R signaling in pancreatic cancer remain uncertain. This review presents a brief overview of the current knowledge and recent advances in the role and functional mechanisms of IL‑17/IL‑17R signaling in pancreatic cancer. Furthermore, the potential of IL‑17‑targeted therapeutic strategies for PDAC treatment is also discussed.
{"title":"Role and functional mechanisms of IL‑17/IL‑17R signaling in pancreatic cancer (Review).","authors":"Wanli Liu, Xianze Wang, Wenming Wu","doi":"10.3892/or.2024.8803","DOIUrl":"10.3892/or.2024.8803","url":null,"abstract":"<p><p>Interleukin‑17 (IL‑17), an inflammatory cytokine primarily secreted by T helper 17 cells, serves a crucial role in numerous inflammatory diseases and malignancies via its receptor, IL‑17R. In addition to stimulating inflammatory responses, IL‑17 exhibits dual functions in tumors, exerting both pro‑ and antitumor effects. Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic malignancy and accounts for >90% of pancreatic cancer cases. PDAC is characterized by a prominent stromal microenvironment with significant heterogeneity, which contributes to treatment resistance. IL‑17/IL‑17R signaling has a notable effect on tumorigenesis, the tumor microenvironment and treatment efficacy in various cancer types, including PDAC. However, the specific mechanisms of IL‑17/IL‑17R signaling in pancreatic cancer remain uncertain. This review presents a brief overview of the current knowledge and recent advances in the role and functional mechanisms of IL‑17/IL‑17R signaling in pancreatic cancer. Furthermore, the potential of IL‑17‑targeted therapeutic strategies for PDAC treatment is also discussed.</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110423","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}
Pub Date : 2024-11-01Epub Date: 2024-09-06DOI: 10.3892/or.2024.8807
Shan Xu, Ning Zhao, Lian Hui, Min Song, Zi-Wei Miao, Xue-Jun Jiang
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the cell apoptotic data in Fig. 4 on p. 1389 and the migration and invasion assay data shown in Figs. 6 and 7 on p. 1391 were strikingly similar to data that were submitted for publication at around the same time in different articles written by different authors at different research institutes (several of which have subsequently been retracted). In addition, there appeared to be instances of duplication of the same data within Figs. 7 and 8, where data that were intending to have shown the results from differently performed experiments had apparently been derived from the same original sources. Owing to the fact that the contentious data in the above article had already been submitted for publication elsewhere prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 35: 1385-1394, 2016; DOI: 10.3892/or.2015.4524].
{"title":"[Retracted] MicroRNA-124-3p inhibits the growth and metastasis of nasopharyngeal carcinoma cells by targeting STAT3.","authors":"Shan Xu, Ning Zhao, Lian Hui, Min Song, Zi-Wei Miao, Xue-Jun Jiang","doi":"10.3892/or.2024.8807","DOIUrl":"10.3892/or.2024.8807","url":null,"abstract":"<p><p>Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the cell apoptotic data in Fig. 4 on p. 1389 and the migration and invasion assay data shown in Figs. 6 and 7 on p. 1391 were strikingly similar to data that were submitted for publication at around the same time in different articles written by different authors at different research institutes (several of which have subsequently been retracted). In addition, there appeared to be instances of duplication of the same data within Figs. 7 and 8, where data that were intending to have shown the results from differently performed experiments had apparently been derived from the same original sources. Owing to the fact that the contentious data in the above article had already been submitted for publication elsewhere prior to its submission to <i>Oncology Reports</i>, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 35: 1385-1394, 2016; DOI: 10.3892/or.2015.4524].</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11391259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140701","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}
Pub Date : 2024-11-01Epub Date: 2024-09-20DOI: 10.3892/or.2024.8809
Bo Tang, Yi Zhang, Rui Liang, Zhenming Gao, Deguang Sun, Liming Wang
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the control western blotting data featured in Fig. 2C on p. 1039 and the cell cycle distribution images shown in Fig. 6A on p. 1041 were strikingly similar to data that had appeared in a pair of other articles written by different authors at different research institutes, one of which had already been submitted for publication when this article was received at Oncology Reports, the other of which was received some time afterwards, but which has subsequently been retracted. Owing to the fact that the abovementioned data had already been submitted for publication prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 29: 1037‑1042, 2013; DOI: 10.3892/or.2013.2222].
{"title":"[Retracted] RNAi‑mediated EZH2 depletion decreases MDR1 expression and sensitizes multidrug‑resistant hepatocellular carcinoma cells to chemotherapy.","authors":"Bo Tang, Yi Zhang, Rui Liang, Zhenming Gao, Deguang Sun, Liming Wang","doi":"10.3892/or.2024.8809","DOIUrl":"https://doi.org/10.3892/or.2024.8809","url":null,"abstract":"<p><p>Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the control western blotting data featured in Fig. 2C on p. 1039 and the cell cycle distribution images shown in Fig. 6A on p. 1041 were strikingly similar to data that had appeared in a pair of other articles written by different authors at different research institutes, one of which had already been submitted for publication when this article was received at <i>Oncology Reports</i>, the other of which was received some time afterwards, but which has subsequently been retracted. Owing to the fact that the abovementioned data had already been submitted for publication prior to its submission to <i>Oncology Reports</i>, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 29: 1037‑1042, 2013; DOI: 10.3892/or.2013.2222].</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292692","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}
CellSearch, the only approved epithelial cell adhesion molecule (EpCAM)‑dependent capture system approved for clinical use, overlooks circulating tumor cells (CTCs) undergoing epithelial‑mesenchymal transition (EMT‑CTCs), which is considered a crucial subtype responsible for metastasis. To address this limitation, a novel polymeric microfluidic device 'CTC‑chip' designed for the easy introduction of any antibody was developed, enabling EpCAM‑independent capture. In this study, antibodies against EpCAM and cell surface vimentin (CSV), identified as cancer‑specific EMT markers, were conjugated onto the chip (EpCAM‑chip and CSV‑chip, respectively), and the capture efficiency was examined using lung cancer (PC9, H441 and A549) and colon cancer (DLD1) cell lines, classified into three types based on EMT markers: Epithelial (PC9), intermediate (H441 and DLD1) and mesenchymal (A549). PC9, H441 and DLD1 cells were effectively captured using the EpCAM‑chip (average capture efficiencies: 99.4, 88.8 and 90.8%, respectively) when spiked into blood. However, A549 cells were scarcely captured (13.4%), indicating that EpCAM‑dependent capture is not suitable for mesenchymal‑type cells. The expression of CSV tended to be higher in cells exhibiting mesenchymal properties and A549 cells were effectively captured with the CSV‑chip (72.4 and 88.4% at concentrations of 10 and 100 µg/ml, respectively) when spiked into PBS. When spiked into blood, the average capture efficiencies were 27.7 and 46.8% at concentrations of 10 and 100 µg/ml, respectively. These results suggest that the CSV‑chip is useful for detecting mesenchymal‑type cells and has potential applications in capturing EMT‑CTCs.
{"title":"Enhanced capture system for mesenchymal‑type circulating tumor cells using a polymeric microfluidic device 'CTC‑Chip' incorporating cell‑surface vimentin.","authors":"Masatoshi Kanayama, Kazue Yoneda, Taiji Kuwata, Masataka Mori, Takehiko Manabe, Rintaro Oyama, Hiroki Matsumiya, Masaru Takenaka, Koji Kuroda, Takashi Ohnaga, Fumihiro Tanaka","doi":"10.3892/or.2024.8815","DOIUrl":"https://doi.org/10.3892/or.2024.8815","url":null,"abstract":"<p><p>CellSearch, the only approved epithelial cell adhesion molecule (EpCAM)‑dependent capture system approved for clinical use, overlooks circulating tumor cells (CTCs) undergoing epithelial‑mesenchymal transition (EMT‑CTCs), which is considered a crucial subtype responsible for metastasis. To address this limitation, a novel polymeric microfluidic device 'CTC‑chip' designed for the easy introduction of any antibody was developed, enabling EpCAM‑independent capture. In this study, antibodies against EpCAM and cell surface vimentin (CSV), identified as cancer‑specific EMT markers, were conjugated onto the chip (EpCAM‑chip and CSV‑chip, respectively), and the capture efficiency was examined using lung cancer (PC9, H441 and A549) and colon cancer (DLD1) cell lines, classified into three types based on EMT markers: Epithelial (PC9), intermediate (H441 and DLD1) and mesenchymal (A549). PC9, H441 and DLD1 cells were effectively captured using the EpCAM‑chip (average capture efficiencies: 99.4, 88.8 and 90.8%, respectively) when spiked into blood. However, A549 cells were scarcely captured (13.4%), indicating that EpCAM‑dependent capture is not suitable for mesenchymal‑type cells. The expression of CSV tended to be higher in cells exhibiting mesenchymal properties and A549 cells were effectively captured with the CSV‑chip (72.4 and 88.4% at concentrations of 10 and 100 µg/ml, respectively) when spiked into PBS. When spiked into blood, the average capture efficiencies were 27.7 and 46.8% at concentrations of 10 and 100 µg/ml, respectively. These results suggest that the CSV‑chip is useful for detecting mesenchymal‑type cells and has potential applications in capturing EMT‑CTCs.</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372457","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}
The immune system is integral to the surveillance and eradication of tumor cells. Interactions between the natural killer group 2 member D (NKG2D) receptor and its ligands (NKG2DLs) are vital for activating NKG2D receptor‑positive immune cells, such as natural killer cells. This activation enables these cells to identify and destroy tumor cells presenting with NKG2DLs, which is an essential aspect of tumor immunity. However, tumor immune escape is facilitated by soluble NKG2DL (sNKG2DL) shed from the surface of tumor cells. The production of sNKG2DL is predominantly regulated by metalloproteinases [a disintegrin and metalloproteinases (ADAM) and matrix metalloproteinase (MMP) families] and exosomes. sNKG2DL not only diminish immune recognition on the tumor cell surface but also suppress the function of immune cells, such as NK cells, and reduce the expression of the NKG2D receptor. This process promotes immune evasion, progression, and metastasis of tumors. In this review, an in‑depth summary of the mechanisms and factors that influence sNKG2DL production and their contribution to immune suppression within the tumor microenvironment are provided. Furthermore, due to the significant link between sNKG2DLs and tumor progression and metastasis, they have great potential as novel biomarkers. Detectable via liquid biopsies, sNKG2DLs could assess tumor malignancy and prognosis, and act as pivotal targets for immunotherapy. This could lead to the discovery of new drugs or the enhancement of existing treatments. Thus, the application of sNKG2DLs in clinical oncology was explored, offering substantial theoretical support for the development of innovative immunotherapeutic strategies for sNKG2DLs.
免疫系统是监视和消灭肿瘤细胞不可或缺的一部分。自然杀伤细胞 2 组 D (NKG2D) 受体与其配体(NKG2DLs)之间的相互作用对于激活 NKG2D 受体阳性的免疫细胞(如自然杀伤细胞)至关重要。这种激活使这些细胞能够识别并摧毁呈递 NKG2DLs 的肿瘤细胞,这是肿瘤免疫的一个重要方面。然而,肿瘤细胞表面脱落的可溶性 NKG2DL(sNKG2DL)会促进肿瘤免疫逃逸。sNKG2DL 的产生主要受金属蛋白酶(a disintegrin and metalloproteinases(ADAM)和基质金属蛋白酶(matrix metalloproteinase(MMP)家族)和外泌体的调控。sNKG2DL 不仅会降低肿瘤细胞表面的免疫识别能力,还会抑制 NK 细胞等免疫细胞的功能,并减少 NKG2D 受体的表达。这一过程促进了肿瘤的免疫逃避、进展和转移。本综述深入总结了影响 sNKG2DL 生成的机制和因素及其对肿瘤微环境中免疫抑制的贡献。此外,由于 sNKG2DLs 与肿瘤进展和转移之间的重要联系,它们作为新型生物标记物具有巨大的潜力。sNKG2DLs 可通过液体活检进行检测,可评估肿瘤的恶性程度和预后,并可作为免疫疗法的关键靶点。这将有助于发现新药或改进现有疗法。因此,我们探讨了 sNKG2DLs 在临床肿瘤学中的应用,为针对 sNKG2DLs 开发创新性免疫治疗策略提供了大量理论支持。
{"title":"A potential mechanism of tumor immune escape: Regulation and application of soluble natural killer group 2 member D ligands (Review).","authors":"Shuhao Huang, Zihao Qin, Feiyang Wang, Yiping Kang, Biqiong Ren","doi":"10.3892/or.2024.8796","DOIUrl":"10.3892/or.2024.8796","url":null,"abstract":"<p><p>The immune system is integral to the surveillance and eradication of tumor cells. Interactions between the natural killer group 2 member D (NKG2D) receptor and its ligands (NKG2DLs) are vital for activating NKG2D receptor‑positive immune cells, such as natural killer cells. This activation enables these cells to identify and destroy tumor cells presenting with NKG2DLs, which is an essential aspect of tumor immunity. However, tumor immune escape is facilitated by soluble NKG2DL (sNKG2DL) shed from the surface of tumor cells. The production of sNKG2DL is predominantly regulated by metalloproteinases [a disintegrin and metalloproteinases (ADAM) and matrix metalloproteinase (MMP) families] and exosomes. sNKG2DL not only diminish immune recognition on the tumor cell surface but also suppress the function of immune cells, such as NK cells, and reduce the expression of the NKG2D receptor. This process promotes immune evasion, progression, and metastasis of tumors. In this review, an in‑depth summary of the mechanisms and factors that influence sNKG2DL production and their contribution to immune suppression within the tumor microenvironment are provided. Furthermore, due to the significant link between sNKG2DLs and tumor progression and metastasis, they have great potential as novel biomarkers. Detectable via liquid biopsies, sNKG2DLs could assess tumor malignancy and prognosis, and act as pivotal targets for immunotherapy. This could lead to the discovery of new drugs or the enhancement of existing treatments. Thus, the application of sNKG2DLs in clinical oncology was explored, offering substantial theoretical support for the development of innovative immunotherapeutic strategies for sNKG2DLs.</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000447","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}
Prostate cancer (PCa) is the leading cause of cancer‑related death among men worldwide. PCa often develops resistance to standard androgen deprivation therapy and androgen receptor (AR) pathway inhibitors, such as enzalutamide (ENZ). Therefore, there is an urgent need to develop novel therapeutic strategies for this disease. The efficacy of ADA‑308 was evaluated through in vitro assessments of AR activity and cell proliferation, alongside in vivo studies. ADA‑308 has emerged as a promising candidate, demonstrating potent inhibition of AR‑sensitive adenocarcinoma as well as ENZ‑resistant PCa cell lines. The results of the study revealed that ADA‑308 effectively blocked AR activity, including its nuclear localization, and inhibited cell proliferation in vitro. Furthermore, ADA‑308 demonstrated notable efficacy in vivo, with a robust antitumor response in ENZ‑resistant models. These findings establish the role of ADA‑308 as a potent AR inhibitor that overcomes resistance to AR‑targeted therapies and highlights its potential as a novel therapeutic approach in advanced PCa management.
前列腺癌(PCa)是全球男性因癌症死亡的主要原因。PCa通常会对标准的雄激素剥夺疗法和雄激素受体(AR)通路抑制剂(如恩扎鲁胺(ENZ))产生耐药性。因此,迫切需要针对这种疾病开发新的治疗策略。ADA-308 的疗效通过 AR 活性和细胞增殖的体外评估以及体内研究进行了评估。ADA-308 对 AR 敏感的腺癌细胞系和 ENZ 抗性 PCa 细胞系都有很强的抑制作用,是一种很有前途的候选药物。研究结果表明,ADA-308 能有效阻断 AR 活性,包括其核定位,并抑制体外细胞增殖。此外,ADA-308 在体内也表现出了显著的疗效,在 ENZ 抗性模型中产生了强大的抗肿瘤反应。这些发现确立了ADA-308作为一种强效AR抑制剂的作用,它能克服AR靶向疗法的耐药性,并突显了它作为一种新型治疗方法在晚期PCa治疗中的潜力。
{"title":"Targeting adenocarcinoma and enzalutamide‑resistant prostate cancer using the novel anti‑androgen inhibitor ADA‑308.","authors":"Shaghayegh Nouruzi, Fraser Johnson, Sahil Kumar, Olena Sivak, Nakisa Tabrizian, Milla Koistinaho, Anu Muona, Amina Zoubeidi","doi":"10.3892/or.2024.8791","DOIUrl":"10.3892/or.2024.8791","url":null,"abstract":"<p><p>Prostate cancer (PCa) is the leading cause of cancer‑related death among men worldwide. PCa often develops resistance to standard androgen deprivation therapy and androgen receptor (AR) pathway inhibitors, such as enzalutamide (ENZ). Therefore, there is an urgent need to develop novel therapeutic strategies for this disease. The efficacy of ADA‑308 was evaluated through <i>in vitro</i> assessments of AR activity and cell proliferation, alongside <i>in vivo</i> studies. ADA‑308 has emerged as a promising candidate, demonstrating potent inhibition of AR‑sensitive adenocarcinoma as well as ENZ‑resistant PCa cell lines. The results of the study revealed that ADA‑308 effectively blocked AR activity, including its nuclear localization, and inhibited cell proliferation <i>in vitro</i>. Furthermore, ADA‑308 demonstrated notable efficacy <i>in vivo</i>, with a robust antitumor response in ENZ‑resistant models. These findings establish the role of ADA‑308 as a potent AR inhibitor that overcomes resistance to AR‑targeted therapies and highlights its potential as a novel therapeutic approach in advanced PCa management.</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917275","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}