Frontiers in Oncology最新文献

{"title":"Endoscopic ultrasound-guided fine-needle aspiration in diagnosing primary medistinal large B-cell lymphoma: a case report.","authors":"Jingyan Tang, Yuchen Guan, Jianfeng Zhang, Chengqi Guan","doi":"10.3389/fonc.2025.1404211","DOIUrl":"https://doi.org/10.3389/fonc.2025.1404211","url":null,"abstract":"<p><strong>Background: </strong>Mediastinal tumors present diagnostic challenges due to their unique location. This case report presents a patient diagnosed with primary mediastinal large B-cell lymphoma (PMBCL) using endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), demonstrating the utility of this minimally invasive technique in detecting and confirming PMBCL.</p><p><strong>Case description: </strong>A 34-year-old previously healthy woman came to our hospital complaining of dysphagia for 3 months. The gastroscopy showed a huge submucosal bulge in the middle of the esophagus, and a contrast-enhanced computed tomography scan of the chest revealed a left main bronchus nodule measuring 15 mm, mediastinal lymph node enlargement, and fusion with necrosis. Subsequently, we obtained the tissue from the mediastinal mass through EUS-FNA and the tissue from the left main bronchus nodule through transbronchoscope biopsy. According to the pathologic findings, we made a clear diagnosis: primary mediastinal large B-cell lymphoma.</p><p><strong>Conclusion: </strong>As a minimally invasive technique, EUS-FNA is highly safe, repeatable, and accurate for lymphoma diagnosis. Although there are some limitations, it can play an important role in diagnosing mediastinal tumors.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1404211"},"PeriodicalIF":3.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811108","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}

{"title":"Single-cell sequencing and spatial transcriptomics reveal the evolution of glucose metabolism in hepatocellular carcinoma and identify G6PD as a potential therapeutic target.","authors":"Deyang Xi, Yinshuang Yang, Jiayi Guo, Mengjiao Wang, Xuebing Yan, Chunyang Li","doi":"10.3389/fonc.2025.1553722","DOIUrl":"https://doi.org/10.3389/fonc.2025.1553722","url":null,"abstract":"<p><strong>Background: </strong>Glucose metabolism reprogramming provides significant insights into the development and progression of malignant tumors. This study aims to explore the temporal-spatial evolution of the glucose metabolism in HCC using single-cell sequencing and spatial transcriptomics (ST), and validates G6PD as a potential therapeutic target for HCC.</p><p><strong>Methods: </strong>We collected single-cell sequencing data from 7 HCC and adjacent non-cancerous tissues from the GSE149614 database, and ST data from 4 HCC tissues from the HRA000437 database. Pseudotime analysis was performed on the single-cell data, while ST data was used to analyze spatial metabolic activity. High-throughput sequencing and experiments, including wound healing, CCK-8, and transwell assays, were conducted to validate the role and regulatory mechanisms of G6PD in HCC.</p><p><strong>Results: </strong>Our study identified a progressive upregulation of PPP-related genes during tumorigenesis. ST analysis revealed elevated PPP metabolic scores in the central and intermediate tumor regions compared to the peripheral zones. High-throughput sequencing and experimental validation further suggested that G6PD-mediated regulation of HCC cell proliferation, migration, and invasion is likely associated with glutathione metabolism and ROS production. Finally, Cox regression analysis cofirmed G6PD as an independent prognostic factor for overall survival in HCC patients.</p><p><strong>Conclusion: </strong>Our study provides novel insights into the changes in glucose metabolism in HCC from both temporal and spatial perspectives. We experimentally demonstrated that G6PD regulates proliferation, migration, and invasion in HCC and propose G6PD as a prognostic marker and therapeutic metabolic target for the HCC.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1553722"},"PeriodicalIF":3.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811159","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}

{"title":"Advantages of time-dependent diffusion MRI for quantitative microstructural mapping in breast tumors.","authors":"Lei Bao, Sijie Li, Zhuo Wang, Yang Sun, Ying Qiu, Zhiwei Shen, Xiaoxiao Zhang, Xue Chen, Xiaoxiao Zhang, Junyu Zhang, Tiefeng Ji","doi":"10.3389/fonc.2025.1537529","DOIUrl":"https://doi.org/10.3389/fonc.2025.1537529","url":null,"abstract":"<p><strong>Objectives: </strong>Time-dependent diffusion MRI (TD-MRI) can measure tumor tissue microstructure, but its effectiveness in differentiating benign from malignant breast tumors is unclear. This study aims to investigate the diagnostic value of TD-MRI microstructural features for distinguishing between benign and malignant breast tumors.</p><p><strong>Methods: </strong>This prospective study included 44 patients with malignant breast tumors and 28 with benign tumors. All subjects underwent the IMPULSED protocol on a 3.0-T MRI scanner. Imaging data were analyzed using least squares fitting in MATLAB, yielding Dex (extracellular diffusivity), Vin (intracellular volume fraction), Dmean (cell diameter), Vin/Dmean, and ADC values. The molecular subtypes of breast cancer are classified based on immunohistochemistry (IHC) results.</p><p><strong>Results: </strong>Malignant tumors exhibited significantly lower Dmean (17.37 ± 2.74 µm <i>vs.</i> 22.47 ± 3.85µm, p<0.0001), higher Vin (0.41 ± 0.13% <i>vs.</i> 0.19 ± 0.10%, p<0.0001), and higher Vin/Dmean (2.13 ± 0.66 <i>vs.</i> 0.93 ± 0.61, p<0.0001) compared to benign tumors. No significant difference was found in Dex (2.15 ± 0.28 um²/ms <i>vs.</i> 2.25 ± 0.31 um²/ms, p>0.05). Strong correlations were observed: positive between ADC and Dmean, and negative between ADC and both Vin and Vin/Dmean. AUC values for Vin (0.92; 95% CI: 0.86-0.99), and Vin/Dmean (0.91; 95% CI: 0.83-0.98) surpassed those for ADC.</p><p><strong>Conclusion: </strong>TD-MRI microstructure mapping effectively differentiates benign from malignant breast tumors, highlighting its potential to improve diagnostic accuracy for lesions.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1537529"},"PeriodicalIF":3.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811092","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}

{"title":"Learning curve of transanal minimally invasive surgery for rectal neoplasm.","authors":"Xingwang Li, Shaoqing Guo, Kunhou Yao, Zheng Ge, Yuewei Li, Junhong Hu, Hongping Xia","doi":"10.3389/fonc.2025.1545589","DOIUrl":"https://doi.org/10.3389/fonc.2025.1545589","url":null,"abstract":"<p><strong>Objectives: </strong>The field of view through transanal endoscopic provides new treatment approaches for solving complex clinical problems. TAMIS belongs to single-port endoscopic surgery, and the operation is complex. Analyzing the learning curve of TAMIS aims to facilitate its better clinical promotion.</p><p><strong>Methods: </strong>A retrospective cohort study analyzed the clinical data of 58 patients who underwent TAMIS by the same surgeon from January 2018 to October 2024. The learning curve of TAMIS was obtained using the cumulative sum (CUSUM) analysis, and the optimal number of surgeries was determined based on the peak value of the curve, Clinical indicators such as operative time, intraoperative blood loss, positive rate of circumferential margin, length of postoperative hospital stay, and incidence of postoperative complications were compared at different stages.</p><p><strong>Results: </strong>All 58 patients successfully underwent TAMIS. The optimum curve equation was y=0.016<i>x</i> ³-2.0556<i>x</i> ²+67.240<i>x</i>-150.103, <i>R</i> ² = 0.950, <i>P</i><0.05. According to the peak value of the curve, 22 cases were determined as the minimum cumulative required cases for surgeons to cross the TAMIS learning curve. 58 cases were divided into two groups: the learning improvement group (Pre-proficiency) of the first 22 cases, and the proficiency group (Post-proficiency) of the latter 36 cases. Compared with Pre-proficiency stage, the Post-proficiency stage had shorter surgery duration, less intraoperative blood loss, and shorter length of postoperative hospital stay (<i>P</i><0.05). There was no statistically significant difference in the observation indicators including positive rate of circumferential margin and incidence of postoperative complications between the two groups (<i>P</i>>0.05).</p><p><strong>Conclusions: </strong>The learning curve of TAMIS can be divided into Pre-proficiency stage and Post-proficiency stage. 22 surgeries may be the number of surgeries required to cross the TAMIS learning curve.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1545589"},"PeriodicalIF":3.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811132","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}

{"title":"GART promotes the proliferation and migration of human non-small cell lung cancer cell lines A549 and H1299 by targeting PAICS-Akt-β-catenin pathway.","authors":"Zhuo Chen, Yu-Heng Ding, Mei-Qi Zhao, Yong-Jun Zhang, Meng-Ying Sun, Ai-Qin Zhang, Xiang Qian, Xu-Ming Ji","doi":"10.3389/fonc.2025.1543463","DOIUrl":"https://doi.org/10.3389/fonc.2025.1543463","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is the primary subtype of Non-small cell lung cancer (NSCLC) and a serious threat to human health. However, the precise molecular mechanisms in lung cancer remain largely unexplored.</p><p><strong>Methods: </strong>Herein, we performed proteomic analysis in a cohort of 20 LC primary tumors and their paired normal tissues. The expression levels and prognostic value of hub proteins were also explored in LUAD using public databases. Glycinamide ribonucleotide transformylase (GART) expression was detected by qRT-PCR in LC cell lines. The roles of GART were assessed by CCK-8, colony formation, Wound healing assays, and xenograft tumor model. Expression levels of the PAICS-Akt-β-catenin pathway were estimated through qRT-PCR and western blot assays.</p><p><strong>Results: </strong>The proteomic analysis of tumor tissues of LC indicated that 263 proteins were upregulated and 194 were downregulated. Bioinformatics analysis showed that differentially expressed proteins were mainly associated with the regulation of apoptotic process and cell adhesion, PI3K-Akt signaling pathway, Purine metabolism, and Wnt signaling pathway. The expression of hub proteins EPRS, GART, HSPE1, and RPS6 was much higher in LUAD tissues than in normal tissues analyzed by the Ualcan database. Overexpression of GART represented a poor prognosis in LUAD patients. Additionally, the knockdown of GART effectively inhibited the cell proliferation and migration of LC cells both <i>in vitro</i> and <i>in vivo.</i> Mechanistically, qRT-PCR and western blot analyses suggested that GART deletion could inhibit the activation of the PAICS-Akt-β-catenin pathway <i>in vivo</i>.</p><p><strong>Conclusions: </strong>Our study indicated a tumor-promoting function of GART in LC through the regulation of the PAICS-Akt-β-catenin axis, and it may be used as a therapeutic target for NSCLC.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1543463"},"PeriodicalIF":3.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811114","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}

{"title":"Prognostic and predictive value of tumor infiltration proportion within lymph nodes in N1 colorectal cancer.","authors":"Rujie Chen, Jun Zhu, Dong Xu, Xiaoyan Fan, Yihuan Qiao, Xunliang Jiang, Jun Hao, Yongtao Du, Xihao Chen, Guo Yuan, Jipeng Li","doi":"10.3389/fonc.2025.1512960","DOIUrl":"https://doi.org/10.3389/fonc.2025.1512960","url":null,"abstract":"<p><strong>Introduction: </strong>Lymph node metastasis is a crucial determinant of prognosis in colorectal cancer (CRC), significantly impacting survival outcomes and treatment decision-making. This study aims to evaluate the prognostic value of tumor infiltration proportion within lymph nodes (TIPLN) in N1 CRC patients and to develop a TIPLN-based nomogram to predict prognosis.</p><p><strong>Methods: </strong>A total of 416 N1 CRC patients who underwent radical resection were enrolled and divided into training and validation cohorts. Whole-slide images of lymph nodes were annotated to assess the TIPLN. Univariable and multivariable Cox regression analyses were conducted to identify independent prognostic factors and to develop a nomogram for predicting patient outcomes. The precision and discrimination of the nomogram were evaluated using the area under the receiver operating characteristic curve (AUC), concordance index (C-index), and calibration curve. Decision curve analysis (DCA) was performed to compare the net benefit of the nomogram at different threshold probabilities. Additionally, net reclassification index (NRI) and integrated discrimination improvement (IDI) were used to evaluate the nomogram's clinical utility.</p><p><strong>Results: </strong>High TIPLN levels were significantly associated with poorer overall survival (OS). Five variables, including TIPLN, were selected to construct the nomogram. The C-index in OS prediction was 0.739 and 0.753 for the training and validation cohorts, respectively. Additionally, strong precision and discrimination were demonstrated through AUC and calibration curves. The NRI (training cohort: 0.191 for 3-year and 0.436 for 5-year OS prediction; validation cohort: 0.180 for 3-year and 0.439 for 5-year OS prediction) and IDI (training cohort: 0.079 for 3-year and 0.094 for 5-year OS prediction; validation cohort: 0.078 for 3-year and 0.098 for 5-year OS prediction) suggest that the TIPLN-based nomogram significantly outperformed the clinicopathological nomogram. Furthermore, DCA demonstrated the high clinical applicability of the TIPLN-based nomogram for predicting OS.</p><p><strong>Conclusions: </strong>TIPLN could serve as a prognostic predictor for N1 CRC patients. The TIPLN-based nomogram enhances survival prediction accuracy and facilitates more informed, individualized clinical decision-making.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1512960"},"PeriodicalIF":3.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811139","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}

{"title":"Combination of MLo-1508 with sunitinib for the experimental treatment of papillary renal cell carcinoma.","authors":"Ângela Marques-Magalhães, Filipa Moreira-Silva, Inês Graça, Paula C Dias, Margareta P Correia, Maria Ana Alzamora, Rui Henrique, Marie Lopez, Paola B Arimondo, Vera Miranda-Gonçalves, Carmen Jerónimo","doi":"10.3389/fonc.2025.1399956","DOIUrl":"10.3389/fonc.2025.1399956","url":null,"abstract":"<p><p>Renal cell carcinoma (RCC) is the 14^th most incident cancer worldwide, and no curative therapeutic options are available for advanced and metastatic disease. Hence, new treatment alternatives are urgently needed to tackle disease management and drug resistance. Herein, we explored the use of MLo-1508 as an anti-tumoral agent in RCC and further assessed its combination with sunitinib for the treatment of papillary RCC. For that, different RCC cell lines were treated with both drugs, alone or in combination, and different phenotypic assays were performed. Moreover, global DNA methylation levels and specific DNMT3a activity were measured, and gene-specific CpG methylation and transcript levels were quantified after treatment. Finally, the combinatory potential of MLo-1508 and sunitinib were asses both in vitro and in vivo using the ACHN cell line. We found that MLo-1508 significantly decreased RCC cell viability while inducing apoptosis in a dose-dependent manner without cytotoxicity for non-malignant cells. Moreover, the treatment induced morphometric alterations and DNA damage in all RCC cell lines. MLo-1508 decreased <i>DNMT1</i> and <i>DNMT3A</i> transcript levels in 786-O and ACHN cells, inhibited DNMT3A activity, and reduced the global DNA methylation content of ACHN cells. When combined with sunitinib, a reduction in ACHN cell viability, as well as cell cycle arrest at G2/M was observed. Importantly, MLo-1508 decreased the sunitinib effective anti-tumoral concentration against ACHN cell viability. In an <i>in vivo</i> ACHN CAM model, the combination induced cell necrosis. Thus, MLo-1508 might improve sensitivity to sunitinib treatment by decreasing the required concentration and delaying resistance acquisition.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1399956"},"PeriodicalIF":3.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802957","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}

{"title":"Editorial: The role of AI in GU oncology.","authors":"Sungun Bang, Kazumi Taguchi, Martin King, Kyo Chul Koo","doi":"10.3389/fonc.2025.1588967","DOIUrl":"https://doi.org/10.3389/fonc.2025.1588967","url":null,"abstract":"","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1588967"},"PeriodicalIF":3.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802815","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}

{"title":"Exploring the mechanism of action of succinic acid in ovarian cancer via single-cell sequencing of the tumor immune microenvironment.","authors":"Jiao Zhao, Panpan Guo, Lili Zhao, Xiaobin Wang","doi":"10.3389/fonc.2025.1535504","DOIUrl":"10.3389/fonc.2025.1535504","url":null,"abstract":"<p><strong>Background: </strong>The main treatments for ovarian cancer are surgery, chemotherapy, radiotherapy, and targeted therapy. Targeted therapy is a new treatment method that has emerged in recent years and relies on specific molecular targets to treat cancer. Succinic acid is a key intermediate product in the tricarboxylic acid cycle. Research has shown that succinic acid has antioxidant properties and can alleviate oxidative stress in cells and tissues. These findings indicate the potential application of succinic acid in antioxidant therapy and the prevention of oxidative damage. This study explored the potential targets and therapeutic mechanisms of succinic acid in ovarian cancer.</p><p><strong>Methods: </strong>Using bioinformatics and single-cell sequencing technology, the hub genes related to succinic acid and ovarian cancer and the frequency and gene expression patterns of different cell types in ovarian cancer patients and normal individuals were analyzed.</p><p><strong>Results: </strong>The frequency of immune cells, including B cells, CD4⁺ cells, CD8⁺ cells, macrophages, and plasma cells, was significantly increased in ovarian cancer patients, and the frequency of other cell types, such as endothelial cells, NK cells, and pericytes/SMCs, was decreased. Further research revealed three key hub genes: SPP1, SLPI, and CD9. The expression patterns of these genes in ovarian cancer were closely related to different cell types. SPP1 was expressed mainly in macrophages, SLPI was expressed in epithelial cells, and CD9 was expressed in pericytes/SMCs and epithelial cells. SPP1, SLPI, and CD9 and their mechanisms of action may be potential targets for the treatment of ovarian cancer with succinic acid.</p><p><strong>Conclusions: </strong>This study investigated the potential therapeutic targets and mechanisms of succinic acid in ovarian cancer and the differences in immune cell infiltration and gene expression patterns, providing important insights for future tumor immunotherapy research.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1535504"},"PeriodicalIF":3.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802893","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}

{"title":"RAS70 peptide targets multiforme glioblastoma by binding to the plasma membrane heat shock protein HSP70.","authors":"Maxim Shevtsov, Natalia Yudintceva, Danila Bobkov, Ruslana Likhomanova, Anastasiya Nechaeva, Elena Mikhailova, Elena Oganesyan, Viacheslav Fedorov, Andrey Kurkin, Anastasiya Lukacheva, Georgii Fofanov, Aleksander Kim, Evegeniy Fedorov, Daria Sitovskaya, Alexey Ulitin, Natalia Mikhailova, Ilya Anufriev, Maria Istomina, Ekaterina Murashko, Elizaveta Kessenikh, Nikolay Aksenov, Yulia Vakhitova, Konstantin Samochernykh, Emil Pitkin, Evgeny Shlyakhto, Stephanie E Combs","doi":"10.3389/fonc.2025.1543657","DOIUrl":"10.3389/fonc.2025.1543657","url":null,"abstract":"<p><p>Multiforme glioblastoma-homing peptides, particularly targeting plasma membrane-bound heat shock protein mHsp70, demonstrate great application potential for tumor theranostics. In the current study, to further increase the bioavailability as well as penetration capacity through the blood-brain barrier (BBB) of the mHsp70-targeted peptide TKDNNLLGRFELSG, which is known to bind to the oligomerization sequence of mHsp70 chaperone, the latter was conjugated with tripeptide RGD (forming chimeric peptide termed RAS70). In the model BBB system RAS70 efficiently crossed the barrier accumulating in the glioblastoma cells. Subsequently, in the orthotopic glioma models, intravenous administration of the fluorescently labeled agent (RAS70-sCy7.5) resulted in the tumor retention of peptide (further confirmed by histological studies). Thus, as shown by the biodistribution studies employing epifluorescence imaging, accumulation of RAS70-sCy7.5 in C6 glioma was significantly enhanced as compared to scramble peptide. Local application of the RAS70-sCy7.5 peptide that was sprayed over the dissected brain tissues helped to efficiently delineate the tumors in glioma-bearing animals employing an intraoperative fluorescent imaging system. Tumor-specific internalization of the peptide was further confirmed on the <i>ex vivo</i> primary GBM samples obtained from adult neurooncological patients. In conclusion, RAS70 peptide demonstrated high glioma-homing properties which could be employed for the intraoperative tumor visualization as well as for developing a potential carrier for drug delivery.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1543657"},"PeriodicalIF":3.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802902","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}