Pub Date : 2025-01-01Epub Date: 2024-11-08DOI: 10.3892/or.2024.8834
Mei Wang, Xu Chen, Guang Fu, Mingjian Ge
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the BrdU incorporation assay data shown in Fig. 7C were strikingly similar to data that had already appeared in another article written by different authors at different research institutes [Lu M, Qin X, Zhou Y, Li G, Liu Z, Geng X and Yue H: Long non‑coding RNA LINC00665 promotes gemcitabine resistance of Cholangiocarcinoma cells via regulating EMT and stemness properties through miR‑424‑5p/BCL9L axis. Cell Death Dis 12: 72, 2021]. 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 48: 207, 2022; DOI: 10.3892/or.2022.8422].
在这篇论文发表后,一位相关读者提请编辑注意,图 7C 中显示的某些 BrdU 结合实验数据与另一篇文章中的数据惊人地相似。图 7C 中显示的某些 BrdU 结合实验数据与不同研究机构不同作者撰写的另一篇文章中的数据惊人地相似[Lu M, Qin X, Zhou Y, Li G, Liu Z, Geng X and Yue H: Long non-coding RNA LINC00665 promotes gemcitabine resistance of Cholangiocarcinoma cells via regulating EMT and stemness properties through miR-424-5p/BCL9L axis.Cell Death Dis 12: 72, 2021]。由于上述文章中有争议的数据在提交给《肿瘤学报告》之前已经发表,因此编辑决定从杂志上撤下这篇论文。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 48: 207, 2022; DOI: 10.3892/or.2022.8422]。
{"title":"[Retracted] Glutathione peroxidase 2 overexpression promotes malignant progression and cisplatin resistance of KRAS‑mutated lung cancer cells.","authors":"Mei Wang, Xu Chen, Guang Fu, Mingjian Ge","doi":"10.3892/or.2024.8834","DOIUrl":"10.3892/or.2024.8834","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 BrdU incorporation assay data shown in Fig. 7C were strikingly similar to data that had already appeared in another article written by different authors at different research institutes [Lu M, Qin X, Zhou Y, Li G, Liu Z, Geng X and Yue H: Long non‑coding RNA LINC00665 promotes gemcitabine resistance of Cholangiocarcinoma cells via regulating EMT and stemness properties through miR‑424‑5p/BCL9L axis. Cell Death Dis 12: 72, 2021]. 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 48: 207, 2022; DOI: 10.3892/or.2022.8422].</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":"53 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605770","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 : 2025-01-01Epub Date: 2024-11-08DOI: 10.3892/or.2024.8836
Guiyu Zhang, Xinxin Hou, Shuhong Gao
Following the publication of this paper, after having performed an independent analysis of the data shown in the various of the figures in the Editorial Office, it was identified that, in Fig. 5A and B on p. 1232 showing the results of Transwell invasion and migration experiments, the majority of the data panels exhibited overlapping sections of data, such that the affected panels, which were intended to show the results of differently performed experiments, had all apparently been derived from the same original sources. Owing to the large number of duplications of data that have been identified in this paper, the Editor of Oncology Reports has decided that it should be retracted from the Journal on account of a lack of confidence in the presented data. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 33: 1227‑1234, 2015; DOI: 10.3892/or.2015.3729].
{"title":"[Retracted] Stimulation of peroxisome proliferator‑activated receptor γ inhibits estrogen receptor α transcriptional activity in endometrial carcinoma cells.","authors":"Guiyu Zhang, Xinxin Hou, Shuhong Gao","doi":"10.3892/or.2024.8836","DOIUrl":"10.3892/or.2024.8836","url":null,"abstract":"<p><p>Following the publication of this paper, after having performed an independent analysis of the data shown in the various of the figures in the Editorial Office, it was identified that, in Fig. 5A and B on p. 1232 showing the results of Transwell invasion and migration experiments, the majority of the data panels exhibited overlapping sections of data, such that the affected panels, which were intended to show the results of differently performed experiments, had all apparently been derived from the same original sources. Owing to the large number of duplications of data that have been identified in this paper, the Editor of <i>Oncology Reports</i> has decided that it should be retracted from the Journal on account of a lack of confidence in the presented data. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 33: 1227‑1234, 2015; DOI: 10.3892/or.2015.3729].</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":"53 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605775","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 : 2025-01-01Epub Date: 2024-11-08DOI: 10.3892/mmr.2024.13384
Jun Fan, Haoran Lin, Jinhua Luo, Liang Chen
Lung cancer is responsible for the highest number of tumor‑related deaths worldwide. A flavonoid extracted from the heartwood of Dalbergia sissoo Roxb., 4‑methoxydalbergione (4‑MD), exhibits potent anticancer activity in multiple malignancies; however, the potential anticancer activity of 4‑MD in lung cancer has not yet been elucidated. In the present study, A549 cells were treated with increasing concentrations of 4‑MD, and cell viability was assessed using a Cell Counting Kit‑8 assay. In addition, colony formation, 5‑ethynyl‑2'‑deoxyuridine, wound healing and Transwell assays were conducted to evaluate cell proliferation, migration and invasion, respectively. Cell morphology was observed using transmission electron microscopy, and ferroptosis was determined using thiobarbituric acid reactive substance, lipid reactive oxygen species (ROS) and iron assays. Moreover, molecular docking was used to verify the potential interaction between 4‑MD and DNA methyltransferase 1 (DNMT1). Tumor‑bearing mice were established and treated with 10 or 30 mg/kg 4‑MD, and tumor volume and weight were recorded. Immunohistochemistry and Prussian blue staining were conducted to examine Ki‑67 expression and iron deposition in tumor tissues, and protein expression was further explored using western blot analysis. The results of the present study revealed that 4‑MD significantly inhibited cell proliferation, migration, invasion and epithelial‑mesenchymal transition in a concentration‑dependent manner. Notably, 4‑MD induced ferroptosis via increased lipid peroxidation, lipid ROS and Fe2+ levels. In addition, it was revealed that 4‑MD can directly bind to DNMT1 to inhibit expression, and inhibit solute carrier family 7 member 11 (SLC7A11; also known as cystine‑glutamate antiporter) and glutathione peroxidase 4 expression. Following DNMT1 overexpression, the observed antitumor activity and ferroptosis‑promoting effects of 4‑MD were partially reversed. Furthermore, 4‑MD significantly inhibited tumor growth in vivo, and reduced tumor volume and weight. In addition, Ki‑67 expression was reduced while iron deposition was increased in the tumor tissues of mice following treatment with 4‑MD. In conclusion, 4‑MD may exhibit anticancer activity through the promotion of DNMT1‑mediated cell ferroptosis. Thus, 4‑MD may have potential as a novel therapeutic agent in the treatment of lung cancer.
{"title":"4‑Methoxydalbergione inhibits the tumorigenesis and metastasis of lung cancer through promoting ferroptosis via the DNMT1/system Xc‑/GPX4 pathway.","authors":"Jun Fan, Haoran Lin, Jinhua Luo, Liang Chen","doi":"10.3892/mmr.2024.13384","DOIUrl":"10.3892/mmr.2024.13384","url":null,"abstract":"<p><p>Lung cancer is responsible for the highest number of tumor‑related deaths worldwide. A flavonoid extracted from the heartwood of <i>Dalbergia sissoo</i> Roxb., 4‑methoxydalbergione (4‑MD), exhibits potent anticancer activity in multiple malignancies; however, the potential anticancer activity of 4‑MD in lung cancer has not yet been elucidated. In the present study, A549 cells were treated with increasing concentrations of 4‑MD, and cell viability was assessed using a Cell Counting Kit‑8 assay. In addition, colony formation, 5‑ethynyl‑2'‑deoxyuridine, wound healing and Transwell assays were conducted to evaluate cell proliferation, migration and invasion, respectively. Cell morphology was observed using transmission electron microscopy, and ferroptosis was determined using thiobarbituric acid reactive substance, lipid reactive oxygen species (ROS) and iron assays. Moreover, molecular docking was used to verify the potential interaction between 4‑MD and DNA methyltransferase 1 (DNMT1). Tumor‑bearing mice were established and treated with 10 or 30 mg/kg 4‑MD, and tumor volume and weight were recorded. Immunohistochemistry and Prussian blue staining were conducted to examine Ki‑67 expression and iron deposition in tumor tissues, and protein expression was further explored using western blot analysis. The results of the present study revealed that 4‑MD significantly inhibited cell proliferation, migration, invasion and epithelial‑mesenchymal transition in a concentration‑dependent manner. Notably, 4‑MD induced ferroptosis via increased lipid peroxidation, lipid ROS and Fe2+ levels. In addition, it was revealed that 4‑MD can directly bind to DNMT1 to inhibit expression, and inhibit solute carrier family 7 member 11 (SLC7A11; also known as cystine‑glutamate antiporter) and glutathione peroxidase 4 expression. Following DNMT1 overexpression, the observed antitumor activity and ferroptosis‑promoting effects of 4‑MD were partially reversed. Furthermore, 4‑MD significantly inhibited tumor growth <i>in vivo</i>, and reduced tumor volume and weight. In addition, Ki‑67 expression was reduced while iron deposition was increased in the tumor tissues of mice following treatment with 4‑MD. In conclusion, 4‑MD may exhibit anticancer activity through the promotion of DNMT1‑mediated cell ferroptosis. Thus, 4‑MD may have potential as a novel therapeutic agent in the treatment of lung cancer.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"31 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603302","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 : 2024-12-31Epub Date: 2024-11-08DOI: 10.1080/15384047.2024.2421584
Jennifer M Finan, Roberto Di Niro, Soon Young Park, Kang Jin Jeong, Madeline D Hedberg, Alexander Smith, Grace A McCarthy, Alex O Haber, John Muschler, Rosalie C Sears, Gordon B Mills, William H Gmeiner, Jonathan R Brody
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease soon to become the second leading cause of cancer deaths in the US. Beside surgery, current therapies have narrow clinical benefits with systemic toxicities. FOLFIRINOX is the current standard of care, one component of which is 5- Fluorouracil (5-FU), which causes serious gastrointestinal and hematopoietic toxicities and is vulnerable to resistance mechanisms. Recently, we have developed polymeric fluoropyrimidines (F10, CF10) which unlike 5-FU, are, in principle, completely converted to the thymidylate synthase inhibitory metabolite FdUMP, without generating appreciable levels of ribonucleotides that cause systemic toxicities while displaying much stronger anti-cancer activity. Here, we confirm the potency of CF10 and investigate enhancement of its efficacy through combination with inhibitors in vitro targeting replication stress, a hallmark of PDAC cells. CF10 is 308-times more potent as a single agent than 5-FU and was effective in the nM range in primary patient derived models. Further, we find that activity of CF10, but not 5-FU, is enhanced through combination with inhibitors of ATR and Wee1 that regulate the S and G2 DNA damage checkpoints and can be reversed by addition of dNTPs indicative of CF10 acting, at least in part, through inducing replication stress. Our results indicate CF10 has the potential to supersede the established benefit of 5-FU in PDAC treatment and indicate novel combination approaches that should be validated in vivo and may be beneficial in established regimens that include 5-FU.
{"title":"The polymeric fluoropyrimidine CF10 overcomes limitations of 5-FU in pancreatic ductal adenocarcinoma cells through increased replication stress.","authors":"Jennifer M Finan, Roberto Di Niro, Soon Young Park, Kang Jin Jeong, Madeline D Hedberg, Alexander Smith, Grace A McCarthy, Alex O Haber, John Muschler, Rosalie C Sears, Gordon B Mills, William H Gmeiner, Jonathan R Brody","doi":"10.1080/15384047.2024.2421584","DOIUrl":"10.1080/15384047.2024.2421584","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease soon to become the second leading cause of cancer deaths in the US. Beside surgery, current therapies have narrow clinical benefits with systemic toxicities. FOLFIRINOX is the current standard of care, one component of which is 5- Fluorouracil (5-FU), which causes serious gastrointestinal and hematopoietic toxicities and is vulnerable to resistance mechanisms. Recently, we have developed polymeric fluoropyrimidines (F10, CF10) which unlike 5-FU, are, in principle, completely converted to the thymidylate synthase inhibitory metabolite FdUMP, without generating appreciable levels of ribonucleotides that cause systemic toxicities while displaying much stronger anti-cancer activity. Here, we confirm the potency of CF10 and investigate enhancement of its efficacy through combination with inhibitors in vitro targeting replication stress, a hallmark of PDAC cells. CF10 is 308-times more potent as a single agent than 5-FU and was effective in the nM range in primary patient derived models. Further, we find that activity of CF10, but not 5-FU, is enhanced through combination with inhibitors of ATR and Wee1 that regulate the S and G2 DNA damage checkpoints and can be reversed by addition of dNTPs indicative of CF10 acting, at least in part, through inducing replication stress. Our results indicate CF10 has the potential to supersede the established benefit of 5-FU in PDAC treatment and indicate novel combination approaches that should be validated in vivo and may be beneficial in established regimens that include 5-FU.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2421584"},"PeriodicalIF":5.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-31Epub Date: 2024-11-08DOI: 10.1080/15384047.2024.2425127
Shujuan Jin, Mengjiao Zhang, Xiaoting Qiao
Cyclophilin A (CypA), a member of the immunophilin family, stands out as the most prevalent among the cyclophilins found in humans. Beyond serving as the intracellular receptor for the immunosuppressive drug cyclosporine A (CsA), CypA exerts critical functions within the cell via its peptidyl-prolyl cis-trans isomerase (PPIase) activity, which is crucial for processes, such as protein folding, trafficking, assembly, modulation of immune responses, and cell signaling. Increasing evidence indicates that CypA is up-regulated in a variety of human cancers and it may be a novel potential therapeutic target for cancer treatment. Therefore, gaining a thorough understanding of CypA's contribution to cancer could yield fresh perspectives and inform the development of innovative therapeutic approaches. This review delves into the multifaceted roles of CypA in cancer biology and explores the therapeutic potential of targeting CypA.
{"title":"Cyclophilin A: promising target in cancer therapy.","authors":"Shujuan Jin, Mengjiao Zhang, Xiaoting Qiao","doi":"10.1080/15384047.2024.2425127","DOIUrl":"10.1080/15384047.2024.2425127","url":null,"abstract":"<p><p>Cyclophilin A (CypA), a member of the immunophilin family, stands out as the most prevalent among the cyclophilins found in humans. Beyond serving as the intracellular receptor for the immunosuppressive drug cyclosporine A (CsA), CypA exerts critical functions within the cell via its <i>peptidyl-prolyl cis-trans isomerase</i> (<i>PPIase</i>) activity, which is crucial for processes, such as protein folding, trafficking, assembly, modulation of immune responses, and cell signaling. Increasing evidence indicates that CypA is up-regulated in a variety of human cancers and it may be a novel potential therapeutic target for cancer treatment. Therefore, gaining a thorough understanding of CypA's contribution to cancer could yield fresh perspectives and inform the development of innovative therapeutic approaches. This review delves into the multifaceted roles of CypA in cancer biology and explores the therapeutic potential of targeting CypA.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2425127"},"PeriodicalIF":5.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-31Epub Date: 2024-11-08DOI: 10.1080/16549716.2024.2426348
Peter Dambach, Valérie R Louis, Claire J Standley, Carlos Alberto Montenegro-Quiñonez
Dengue fever, a mosquito-borne viral illness transmitted by Aedes mosquitoes, continues to be a significant public health burden in tropical and subtropical regions. Traditional vector control methods, primarily reliant on insecticides and larvicides, face challenges because of emerging insecticide resistance and limited community engagement. This narrative review explores co-creation as a collaborative approach to dengue control, where communities actively participate in designing and implementing solutions. Through an examination of existing literature, we discuss the rationale for co-creation, the various methods employed, evidence for effectiveness, challenges, and other items. Findings from previous studies suggest that co-creation can empower communities by fostering a sense of ownership and responsibility for dengue control efforts. Using local knowledge and insights, co-creation approaches have also been shown to identify and address specific community needs and preferences, leading to more contextually relevant interventions. Additionally, co-creation initiatives have demonstrated success in promoting behavior change within communities, leading to increased uptakes of preventive measures such as proper waste management and use of personal protective measures. However, challenges such as building trust and collaboration, addressing power dynamics, and ensuring long-term sustainability remain critical factors that are essential to foster collaboration, empower communities, and develop sustainable strategies for dengue control in affected regions.
{"title":"Beyond top-down: community co-creation approaches for sustainable dengue vector control.","authors":"Peter Dambach, Valérie R Louis, Claire J Standley, Carlos Alberto Montenegro-Quiñonez","doi":"10.1080/16549716.2024.2426348","DOIUrl":"10.1080/16549716.2024.2426348","url":null,"abstract":"<p><p>Dengue fever, a mosquito-borne viral illness transmitted by <i>Aedes</i> mosquitoes, continues to be a significant public health burden in tropical and subtropical regions. Traditional vector control methods, primarily reliant on insecticides and larvicides, face challenges because of emerging insecticide resistance and limited community engagement. This narrative review explores co-creation as a collaborative approach to dengue control, where communities actively participate in designing and implementing solutions. Through an examination of existing literature, we discuss the rationale for co-creation, the various methods employed, evidence for effectiveness, challenges, and other items. Findings from previous studies suggest that co-creation can empower communities by fostering a sense of ownership and responsibility for dengue control efforts. Using local knowledge and insights, co-creation approaches have also been shown to identify and address specific community needs and preferences, leading to more contextually relevant interventions. Additionally, co-creation initiatives have demonstrated success in promoting behavior change within communities, leading to increased uptakes of preventive measures such as proper waste management and use of personal protective measures. However, challenges such as building trust and collaboration, addressing power dynamics, and ensuring long-term sustainability remain critical factors that are essential to foster collaboration, empower communities, and develop sustainable strategies for dengue control in affected regions.</p>","PeriodicalId":49197,"journal":{"name":"Global Health Action","volume":"17 1","pages":"2426348"},"PeriodicalIF":4.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606947","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}
Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis and lack of effective treatments. In recent years, peptide vaccines that use sequences based on tumor-specific or tumor-associated antigens to activate immune responses against tumor cells have emerged as a new therapeutic strategy. In this study, we developed a novel therapeutic polypeptide vaccine targeting the tumor-associated antigen Fibrinogen-Like Protein 2 (FGL2), whose dominant epitope peptide was tandemly linked to the C-terminus of HCMV-IE1mut via a linker. We used this vaccine to compare the therapeutic efficacy of HCMV-IE1mut alone versus HCMV-IE1mut-FGL2172-220 and investigate the potential mechanism of action of HCMV-IE1mut-FGL2172-220 in glioma treatment. An in situ GBM model (GL261-IE1-luc cells) was used to determine the efficacy of the vaccine. Treatment with HCMV-IE1mut-FGL2172-220 exerted antitumor effects and extended the survival of the GL261 animal model. We observed reduced proportions of microglia, regulatory T cells (Treg), and myeloid-derived suppressor cells (MDSC) in the tumor microenvironment (TME) by immunofluorescence. Flow cytometry showed that compared to HCMV-IE1mut alone, treatment with HCMV-IE1mut-FGL2172-220 increased the proportion of CD8+ T cells and tissue-resident memory T cells (TRM). ELISA analysis showed that it improved the secretion of tumor-specific IFN-γ and TNF-α by these cells and downregulated the expression of IL-6 and IL-10. Our study demonstrates that the long-peptide FGL2172-220 improves the antitumor efficacy of HCMV-IE1mut, possibly by reshaping immune cells in the glioma microenvironment. These findings lay the groundwork for the development of therapeutic antigenic peptide vaccines to improve antitumor effects for cancer.
{"title":"FGL2<sub>172-220</sub> peptides improve the antitumor effect of HCMV-IE1mut vaccine against glioblastoma by modulating immunosuppressive cells in the tumor microenvironment.","authors":"Shan Wang, Shasha Jiang, Xu Li, Huan Huang, Xu Qiu, Meng Yu, Xiaoli Yang, Fengjun Liu, Chen Wang, Wen Shen, Yunyang Wang, Bin Wang","doi":"10.1080/2162402X.2024.2423983","DOIUrl":"10.1080/2162402X.2024.2423983","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis and lack of effective treatments. In recent years, peptide vaccines that use sequences based on tumor-specific or tumor-associated antigens to activate immune responses against tumor cells have emerged as a new therapeutic strategy. In this study, we developed a novel therapeutic polypeptide vaccine targeting the tumor-associated antigen Fibrinogen-Like Protein 2 (FGL2), whose dominant epitope peptide was tandemly linked to the C-terminus of HCMV-IE1mut via a linker. We used this vaccine to compare the therapeutic efficacy of HCMV-IE1mut alone versus HCMV-IE1mut-FGL2<sub>172-220</sub> and investigate the potential mechanism of action of HCMV-IE1mut-FGL2<sub>172-220</sub> in glioma treatment. An in situ GBM model (GL261-IE1-luc cells) was used to determine the efficacy of the vaccine. Treatment with HCMV-IE1mut-FGL2<sub>172-220</sub> exerted antitumor effects and extended the survival of the GL261 animal model. We observed reduced proportions of microglia, regulatory T cells (Treg), and myeloid-derived suppressor cells (MDSC) in the tumor microenvironment (TME) by immunofluorescence. Flow cytometry showed that compared to HCMV-IE1mut alone, treatment with HCMV-IE1mut-FGL2<sub>172-220</sub> increased the proportion of CD8+ T cells and tissue-resident memory T cells (TRM). ELISA analysis showed that it improved the secretion of tumor-specific IFN-γ and TNF-α by these cells and downregulated the expression of IL-6 and IL-10. Our study demonstrates that the long-peptide FGL2<sub>172-220</sub> improves the antitumor efficacy of HCMV-IE1mut, possibly by reshaping immune cells in the glioma microenvironment. These findings lay the groundwork for the development of therapeutic antigenic peptide vaccines to improve antitumor effects for cancer.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2423983"},"PeriodicalIF":5.3,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neoantigen-reactive CD4+ T cells play a key role in the anti-tumor immune response. However, the majority of epithelial tumors are negative for HLA class II (HLA-II) surface expression, and less is known about the processing of HLA-II antigens. Here, we directly identified naturally presented HLA-II neoantigens in HLA-II negative colorectal cancer (CRC) tissue using a proteogenomic approach. The neoantigens were immunogenic and induced patient CD4+ T cells with a Th1-like memory phenotype that produced IFN-γ, IL2 and TNF-α. Multiplex immunohistochemistry (IHC) demonstrated an interaction between Th cells and HLA-II-positive antigen-presenting cells (APCs) at the invasive margin and within the tertiary lymphoid structures (TLS). In our CRC cohort, the density of stromal APCs was associated with HLA-II antigen presentation in the tumor microenvironment (TME), and the number of TLS was positively correlated with the number of somatic mutations in the tumors. These results demonstrate the presence of neoantigen-specific CD4+ surveillance in HLA-II-negative CRC and suggest a potential role for macrophages and dendritic cells (DCs) at the invasive margin and in TLS for antigen presentation. Stromal APCs in the TME can potentially be used as a source for HLA-II neoantigen identification.
{"title":"HLA class II neoantigen presentation for CD4<sup>+</sup> T cell surveillance in HLA class II-negative colorectal cancer.","authors":"Satoru Matsumoto, Takahiro Tsujikawa, Serina Tokita, Mai Mohamed Bedeir, Kazuhiko Matsuo, Fumitake Hata, Yoshihiko Hirohashi, Takayuki Kanaseki, Toshihiko Torigoe","doi":"10.1080/2162402X.2024.2404665","DOIUrl":"10.1080/2162402X.2024.2404665","url":null,"abstract":"<p><p>Neoantigen-reactive CD4<sup>+</sup> T cells play a key role in the anti-tumor immune response. However, the majority of epithelial tumors are negative for HLA class II (HLA-II) surface expression, and less is known about the processing of HLA-II antigens. Here, we directly identified naturally presented HLA-II neoantigens in HLA-II negative colorectal cancer (CRC) tissue using a proteogenomic approach. The neoantigens were immunogenic and induced patient CD4<sup>+</sup> T cells with a Th1-like memory phenotype that produced IFN-γ, IL2 and TNF-α. Multiplex immunohistochemistry (IHC) demonstrated an interaction between Th cells and HLA-II-positive antigen-presenting cells (APCs) at the invasive margin and within the tertiary lymphoid structures (TLS). In our CRC cohort, the density of stromal APCs was associated with HLA-II antigen presentation in the tumor microenvironment (TME), and the number of TLS was positively correlated with the number of somatic mutations in the tumors. These results demonstrate the presence of neoantigen-specific CD4<sup>+</sup> surveillance in HLA-II-negative CRC and suggest a potential role for macrophages and dendritic cells (DCs) at the invasive margin and in TLS for antigen presentation. Stromal APCs in the TME can potentially be used as a source for HLA-II neoantigen identification.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2404665"},"PeriodicalIF":5.3,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-31Epub Date: 2024-11-08DOI: 10.1080/16549716.2024.2328893
Saw San Soe, Saw Thwe Paw, Mu Lwel Tha Dah, Day Mu Dah, Thae Thae Naing, K Mwee Hser, Solomon Naw, Htet Khaing Lu, Kanjana Winyoorat, Primprapaporn Thongdee, Saw Win Tun, Poe Poe, Rose McGready, Poe Christ, Htee K Poung, Win Win Cho, Hser Nay Wah, Htoo Hser, Saw Phee Do, Paw Bway Shee, Bulakorn Tinoi, Prapatsorn Misa, May Myo Thwin, Ladda Kajeechiwa
Background: Communities in which adolescent pregnancy and safe abortion care are taboo may benefit from culturally appropriate information, education, and communication.
Objective: This ethnographic and participatory action research (PAR) elicited community members' perceptions to adolescent pregnancy: which then informed dialogue-drama development in Burmese and Karen language for undocumented migrants on the Thailand-Myanmar border.
Methods: PAR was conducted in Karen and Burmese language. Interviews and discussions elicited perceptions of community members about adolescent pregnancy. These were analysed for themes and using the fishbone technique, to determine the objectives for the drama. After developing the structure and content of the drama it was piloted, revised, and performed in communities. Responses and impact of the drama were recorded. The team reflected on the drama as a method for health messaging.
Results: In 2022, themes of responsibility, communication, and experiences of adolescent pregnancy emerged from 10 interviews and 6 discussions with community members. The fishbone technique established three dramatic objectives, woven into a teenage love story with an unplanned pregnancy, to raise community awareness of i) adolescent pregnancy, ii) contraception, and iii) choice in unexpected pregnancy. Post-drama feedback from 11 migrant communities (1,238 participants) was positive although some community members voiced concerns. Given the logistical challenges of conducting the drama in person, a film will be created for wider dissemination.
Conclusions: Participatory action research resulted in a culturally-nuanced performance, with communities requesting further performances and awareness on adolescent pregnancy and safe abortion care. Video is likely to be a more sustainable option.
{"title":"Community engagement to develop a dialogue-drama on adolescent pregnancy in a marginalised migrant population on the Thailand-Myanmar border: an ethnographic approach to participatory action research.","authors":"Saw San Soe, Saw Thwe Paw, Mu Lwel Tha Dah, Day Mu Dah, Thae Thae Naing, K Mwee Hser, Solomon Naw, Htet Khaing Lu, Kanjana Winyoorat, Primprapaporn Thongdee, Saw Win Tun, Poe Poe, Rose McGready, Poe Christ, Htee K Poung, Win Win Cho, Hser Nay Wah, Htoo Hser, Saw Phee Do, Paw Bway Shee, Bulakorn Tinoi, Prapatsorn Misa, May Myo Thwin, Ladda Kajeechiwa","doi":"10.1080/16549716.2024.2328893","DOIUrl":"10.1080/16549716.2024.2328893","url":null,"abstract":"<p><strong>Background: </strong>Communities in which adolescent pregnancy and safe abortion care are taboo may benefit from culturally appropriate information, education, and communication.</p><p><strong>Objective: </strong>This ethnographic and participatory action research (PAR) elicited community members' perceptions to adolescent pregnancy: which then informed dialogue-drama development in Burmese and Karen language for undocumented migrants on the Thailand-Myanmar border.</p><p><strong>Methods: </strong>PAR was conducted in Karen and Burmese language. Interviews and discussions elicited perceptions of community members about adolescent pregnancy. These were analysed for themes and using the fishbone technique, to determine the objectives for the drama. After developing the structure and content of the drama it was piloted, revised, and performed in communities. Responses and impact of the drama were recorded. The team reflected on the drama as a method for health messaging.</p><p><strong>Results: </strong>In 2022, themes of responsibility, communication, and experiences of adolescent pregnancy emerged from 10 interviews and 6 discussions with community members. The fishbone technique established three dramatic objectives, woven into a teenage love story with an unplanned pregnancy, to raise community awareness of i) adolescent pregnancy, ii) contraception, and iii) choice in unexpected pregnancy. Post-drama feedback from 11 migrant communities (1,238 participants) was positive although some community members voiced concerns. Given the logistical challenges of conducting the drama in person, a film will be created for wider dissemination.</p><p><strong>Conclusions: </strong>Participatory action research resulted in a culturally-nuanced performance, with communities requesting further performances and awareness on adolescent pregnancy and safe abortion care. Video is likely to be a more sustainable option.</p>","PeriodicalId":49197,"journal":{"name":"Global Health Action","volume":"17 1","pages":"2328893"},"PeriodicalIF":4.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606948","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}
Mitochondrial fission is a key trigger of cardiac ischemia-reperfusion injuries (IR). Exercise training is an efficient cardioprotective strategy, but its impact on mitochondrial fragmentation during IR remains unknown. Using isolated rat hearts, we found that exercise training limited the activation of dynamin-like protein 1 and limited mitochondrial fragmentation during IR. These results support the hypothesis that exercise training contributes to cardioprotection through its capacity to modulate the mitochondrial fragmentation during IR.
线粒体分裂是心脏缺血再灌注损伤(IR)的关键诱因。运动训练是一种有效的心脏保护策略,但它对红外损伤期间线粒体分裂的影响仍然未知。通过使用离体大鼠心脏,我们发现运动训练限制了动态样蛋白 1 的激活,并限制了线粒体在 IR 期间的破碎。这些结果支持了运动训练通过调节红外过程中线粒体破碎的能力来促进心脏保护的假设。
{"title":"Exercise training may reduce fragmented mitochondria in the ischemic-reperfused heart through DRP1.","authors":"Mathilde Dubois, Florian Pallot, Maxime Gouin-Gravezat, Doria Boulghobra, Florence Coste, Guillaume Walther, Gregory Meyer, Isabelle Bornard, Cyril Reboul","doi":"10.1085/jgp.202313485","DOIUrl":"10.1085/jgp.202313485","url":null,"abstract":"<p><p>Mitochondrial fission is a key trigger of cardiac ischemia-reperfusion injuries (IR). Exercise training is an efficient cardioprotective strategy, but its impact on mitochondrial fragmentation during IR remains unknown. Using isolated rat hearts, we found that exercise training limited the activation of dynamin-like protein 1 and limited mitochondrial fragmentation during IR. These results support the hypothesis that exercise training contributes to cardioprotection through its capacity to modulate the mitochondrial fragmentation during IR.</p>","PeriodicalId":54828,"journal":{"name":"Journal of General Physiology","volume":"156 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}