Pub Date : 2026-01-06DOI: 10.1016/j.tranon.2025.102659
Sara Cherradi , Salomé Roux , Marie Dupuy , Eric Assenat , Hong Tuan Duong
Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal cancer, largely due to late diagnosis, tumor heterogeneity, and a dense, immunosuppressive stroma that limits therapeutic efficacy. While regimens like FOLFIRINOX and gemcitabine-based therapies offer some benefit, treatment selection remains empirical, with no reliable predictive models to guide personalized decisions. We adapted our previously validated serum-derived educated spheroid technology creating 3D spheroids using PDAC patient serum. These spheroids maintained structural integrity, viability, and consistent size over eight days, avoiding overgrowth. They also exhibited extracellular matrix deposition such as type I collagen, and expressed key genes involved in drug resistance and tumor progression including COL1A1, FN1, MMP2, CXCL1, and CXCL2. Using the Target-Independent Cell Killing (TICK) strategy, we established individualized chemograms to assess true therapeutic response helping clinicians in refining the optimal treatment protocol. In a 16-case study, our model achieved high concordance with clinical responses across gemcitabine, Gem-Pac, and FOLFIRINOX treatments supporting its utility in personalized care. Finally, we demonstrated that predictive accuracy was highest when patient serum was collected within a short window prior to treatment initiation. These findings support PDAC patient serum-educated spheroids as a rapid, non-invasive, and physiologically relevant tool for guiding personalized chemotherapy and monitoring treatment response in real time.
{"title":"A serum-derived 3D tumor model platform for personalized prediction and monitoring of chemotherapeutic response in pancreatic ductal adenocarcinoma","authors":"Sara Cherradi , Salomé Roux , Marie Dupuy , Eric Assenat , Hong Tuan Duong","doi":"10.1016/j.tranon.2025.102659","DOIUrl":"10.1016/j.tranon.2025.102659","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal cancer, largely due to late diagnosis, tumor heterogeneity, and a dense, immunosuppressive stroma that limits therapeutic efficacy. While regimens like FOLFIRINOX and gemcitabine-based therapies offer some benefit, treatment selection remains empirical, with no reliable predictive models to guide personalized decisions. We adapted our previously validated serum-derived educated spheroid technology creating 3D spheroids using PDAC patient serum. These spheroids maintained structural integrity, viability, and consistent size over eight days, avoiding overgrowth. They also exhibited extracellular matrix deposition such as type I collagen, and expressed key genes involved in drug resistance and tumor progression including <em>COL1A1, FN1, MMP2, CXCL1</em>, and <em>CXCL2</em>. Using the Target-Independent Cell Killing (TICK) strategy, we established individualized chemograms to assess true therapeutic response helping clinicians in refining the optimal treatment protocol. In a 16-case study, our model achieved high concordance with clinical responses across gemcitabine, Gem-Pac, and FOLFIRINOX treatments supporting its utility in personalized care. Finally, we demonstrated that predictive accuracy was highest when patient serum was collected within a short window prior to treatment initiation. These findings support PDAC patient serum-educated spheroids as a rapid, non-invasive, and physiologically relevant tool for guiding personalized chemotherapy and monitoring treatment response in real time.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102659"},"PeriodicalIF":5.0,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-06DOI: 10.1016/j.tranon.2025.102646
Jinhui Bai , Mei Deng , Xueting Wu , Chao Xiong , Huixian Wu , Li Wang , Jie Qin
Background
Malignant proliferation and invasion of tumor cells are the primary causes of death among patients with breast cancer, yet the molecular mechanisms orchestrating cancer metastasis are not well elucidated. Ubiquitin-conjugating enzyme E2C (UBE2C) has been reported to be involved in the tumorigenesis and development of various malignant tumors; however, the biological roles and underlying mechanisms of UBE2C in breast cancer remain unclear.
Methods
UBE2C expression was analyzed in breast cancer tissue and cell lines using immunohistochemistry, quantitative reverse transcription PCR (RT-qPCR) and Western blot. The biological roles of UBE2C and its transcription factor MAZ were investigated in vitro using CCK-8, plate cloning, scratch, Transwell, cell cycle and apoptosis assays, while a nude mouse subcutaneous tumorigenic model was employed for the in vivo studies. Dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were conducted to validate the binding relationship between MAZ and UBE2C.
Results
UBE2C expression is elevated in breast cancer, and higher levels of UBE2C are associated with poorer survival among patients with breast cancer. UBE2C promotes the progression of breast cancer both in vivo and in vitro. Additionally, UBE2C is a direct transcriptional target of MAZ, which also accelerates malignant development of breast cancer. Furthermore, UBE2C exerts its oncogenic effects dependent on the MAPK signaling pathway.
Conclusion
Our findings highlight the critical role of the MAZ/UBE2C/MAPK signaling axis in the progression of breast cancer and identify potential novel therapeutic targets for its treatment.
{"title":"MAZ-Mediated ubiquitin-conjugating enzyme E2C upregulation promotes breast cancer progression via the MAPK signaling pathway","authors":"Jinhui Bai , Mei Deng , Xueting Wu , Chao Xiong , Huixian Wu , Li Wang , Jie Qin","doi":"10.1016/j.tranon.2025.102646","DOIUrl":"10.1016/j.tranon.2025.102646","url":null,"abstract":"<div><h3>Background</h3><div>Malignant proliferation and invasion of tumor cells are the primary causes of death among patients with breast cancer, yet the molecular mechanisms orchestrating cancer metastasis are not well elucidated. Ubiquitin-conjugating enzyme E2C (UBE2C) has been reported to be involved in the tumorigenesis and development of various malignant tumors; however, the biological roles and underlying mechanisms of UBE2C in breast cancer remain unclear.</div></div><div><h3>Methods</h3><div>UBE2C expression was analyzed in breast cancer tissue and cell lines using immunohistochemistry, quantitative reverse transcription PCR (RT-qPCR) and Western blot. The biological roles of UBE2C and its transcription factor MAZ were investigated in vitro using CCK-8, plate cloning, scratch, Transwell, cell cycle and apoptosis assays, while a nude mouse subcutaneous tumorigenic model was employed for the in vivo studies. Dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were conducted to validate the binding relationship between MAZ and UBE2C.</div></div><div><h3>Results</h3><div>UBE2C expression is elevated in breast cancer, and higher levels of UBE2C are associated with poorer survival among patients with breast cancer. UBE2C promotes the progression of breast cancer both in vivo and in vitro. Additionally, UBE2C is a direct transcriptional target of MAZ, which also accelerates malignant development of breast cancer. Furthermore, UBE2C exerts its oncogenic effects dependent on the MAPK signaling pathway.</div></div><div><h3>Conclusion</h3><div>Our findings highlight the critical role of the MAZ/UBE2C/MAPK signaling axis in the progression of breast cancer and identify potential novel therapeutic targets for its treatment.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102646"},"PeriodicalIF":5.0,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-06DOI: 10.1016/j.tranon.2025.102653
Wei Ye , Wei Su , Chang Lei , Chenjun Huang , Mingjun Du
Esophageal squamous cell carcinoma (ESCC) exhibits marked heterogeneity and poor prognosis, but the contribution of stemness‑related tumor cells remains unclear. Using single‑cell RNA sequencing, we identified eight tumor subpopulations in ESCC, among which one cluster displayed prominent stem‑like and proliferative features with high expression of MKI67, STMN1, and UBE2C. Based on its marker genes, we established a stemness‑associated scoring model (SASM). Validation in independent TCGA and GSE53624 cohorts confirmed that higher SASM scores predicted shorter overall survival and reduced immune infiltration, particularly of CD8⁺ T cells. SASM scores were positively correlated with tumor mutational burden (TMB), and patients with high SASM and low TMB exhibited the poorest outcomes. Further analysis identified TFDP1 as a key gene associated with SASM and adverse prognosis, which was upregulated in tumor tissues and promoted ESCC cell proliferation in vitro. Overall, our study delineates stemness‑related tumor heterogeneity in ESCC, proposes a prognostic scoring system with immunological relevance, and highlights TFDP1 as a potential therapeutic target.
{"title":"Single-cell analysis identifies a stemness-associated tumor cell subpopulation and develops a prognostic scoring model in esophageal squamous cell carcinoma","authors":"Wei Ye , Wei Su , Chang Lei , Chenjun Huang , Mingjun Du","doi":"10.1016/j.tranon.2025.102653","DOIUrl":"10.1016/j.tranon.2025.102653","url":null,"abstract":"<div><div>Esophageal squamous cell carcinoma (ESCC) exhibits marked heterogeneity and poor prognosis, but the contribution of stemness‑related tumor cells remains unclear. Using single‑cell RNA sequencing, we identified eight tumor subpopulations in ESCC, among which one cluster displayed prominent stem‑like and proliferative features with high expression of MKI67, STMN1, and UBE2C. Based on its marker genes, we established a stemness‑associated scoring model (SASM). Validation in independent TCGA and GSE53624 cohorts confirmed that higher SASM scores predicted shorter overall survival and reduced immune infiltration, particularly of CD8⁺ T cells. SASM scores were positively correlated with tumor mutational burden (TMB), and patients with high SASM and low TMB exhibited the poorest outcomes. Further analysis identified TFDP1 as a key gene associated with SASM and adverse prognosis, which was upregulated in tumor tissues and promoted ESCC cell proliferation in vitro. Overall, our study delineates stemness‑related tumor heterogeneity in ESCC, proposes a prognostic scoring system with immunological relevance, and highlights TFDP1 as a potential therapeutic target.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102653"},"PeriodicalIF":5.0,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-06DOI: 10.1016/j.tranon.2025.102660
Li-Jin Xie , Li-Li Fu , Shu-Cen Liu , Chang-Sen Bai , Bai-Cheng Xu , Xiong-Wen He , Hai-Feng Lin , Yue-Can Zeng , Wen-Jun Tang
Lung cancer remains the leading cause of cancer incidence and mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for about 85% of cases. The low rate of early diagnosis and the high rate of occult metastases limit the survival benefits of conventional treatments. The current TNM staging system fails to fully reflect tumor heterogeneity or the dynamic molecular evolution of the disease, thus affecting the prediction of recurrence and the prognostic stratification. Some recent advances in minimal residual disease (MRD) detection, such as ultra-sensitive liquid biopsy technologies, have largely overcome the limitations of traditional imaging and offered a transformative approach for continuous, precision-based management of lung cancer. This review systematically summarized the technological evolution of MRD detection and highlighted its clinical significance in guiding adaptive therapy for NSCLC, including treatment escalation, de-escalation, and the emerging concept of precision-guided drug holidays. Moreover, the authors comprehensively discussed the “Four-Dimensional TNMB Staging System,” which incorporates continuous molecular monitoring to address the static limitations of conventional staging and enhance the accuracy of prognostic stratification.
Although ongoing challenges, such as the lack of standardized interpretation criteria and limited detection sensitivity, the combinations with the third-generation liquid biopsy platforms, multi-omics analyses, and multi-center prospective validation studies are expected to advance the clinical implementation of MRD-guided strategies. The paradigm change will enable the transition of NSCLC management from conventional standardized models to a precision-guided, closed-loop system of “monitoring-intervention-remonitoring,” establishing a solid theoretical and practical foundation for comprehensive, molecularly driven management strategies.
{"title":"Adaptive therapy for perioperative non–small cell lung cancer: strategies guided by dynamic minimal residual disease adjustment","authors":"Li-Jin Xie , Li-Li Fu , Shu-Cen Liu , Chang-Sen Bai , Bai-Cheng Xu , Xiong-Wen He , Hai-Feng Lin , Yue-Can Zeng , Wen-Jun Tang","doi":"10.1016/j.tranon.2025.102660","DOIUrl":"10.1016/j.tranon.2025.102660","url":null,"abstract":"<div><div>Lung cancer remains the leading cause of cancer incidence and mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for about 85% of cases. The low rate of early diagnosis and the high rate of occult metastases limit the survival benefits of conventional treatments. The current TNM staging system fails to fully reflect tumor heterogeneity or the dynamic molecular evolution of the disease, thus affecting the prediction of recurrence and the prognostic stratification. Some recent advances in minimal residual disease (MRD) detection, such as ultra-sensitive liquid biopsy technologies, have largely overcome the limitations of traditional imaging and offered a transformative approach for continuous, precision-based management of lung cancer. This review systematically summarized the technological evolution of MRD detection and highlighted its clinical significance in guiding adaptive therapy for NSCLC, including treatment escalation, de-escalation, and the emerging concept of precision-guided drug holidays. Moreover, the authors comprehensively discussed the “Four-Dimensional TNMB Staging System,” which incorporates continuous molecular monitoring to address the static limitations of conventional staging and enhance the accuracy of prognostic stratification.</div><div>Although ongoing challenges, such as the lack of standardized interpretation criteria and limited detection sensitivity, the combinations with the third-generation liquid biopsy platforms, multi-omics analyses, and multi-center prospective validation studies are expected to advance the clinical implementation of MRD-guided strategies. The paradigm change will enable the transition of NSCLC management from conventional standardized models to a precision-guided, closed-loop system of “monitoring-intervention-remonitoring,” establishing a solid theoretical and practical foundation for comprehensive, molecularly driven management strategies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102660"},"PeriodicalIF":5.0,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-06DOI: 10.1016/j.tranon.2025.102662
Yihao Liu , Yizhu Gao , Chenyu Huo , Tao Zeng , Wenjun Meng , Haoling Zhang , Qinqin He
Lung cancer ranks first among all malignancies in incidence, with current treatment strategies including surgery, chemotherapy, immunotherapy, and targeted therapy. Despite these advances, drug resistance in advanced non-small cell lung cancer (NSCLC) remains a major obstacle and innovative therapeutic approaches are imperative to address it. Chimeric antigen receptor T-cell (CAR-T) therapy has shown impressive and long-lasting results in blood cancers, but its success in solid tumors such as lung cancer remains limited. This review summarizes recent advances and future directions of CAR-T therapy in NSCLC, focusing on major therapeutic targets such as EGFR, MSLN, PD-L1, MUC1, CEA, and ROR1, as well as on the efficacy and potential of combining CAR-T therapy with other treatment modalities. Additionally, we discuss adverse events in NSCLC patients undergoing CAR-T therapy, emphasizing cytokine release syndrome (CRS) and cardiovascular complications—their incidence, pathophysiology, interrelation, and management strategies.
{"title":"CAR-T therapy in non-small cell lung cancer: Clinical prospects, potential, and strategies for cardiotoxicity management","authors":"Yihao Liu , Yizhu Gao , Chenyu Huo , Tao Zeng , Wenjun Meng , Haoling Zhang , Qinqin He","doi":"10.1016/j.tranon.2025.102662","DOIUrl":"10.1016/j.tranon.2025.102662","url":null,"abstract":"<div><div>Lung cancer ranks first among all malignancies in incidence, with current treatment strategies including surgery, chemotherapy, immunotherapy, and targeted therapy. Despite these advances, drug resistance in advanced non-small cell lung cancer (NSCLC) remains a major obstacle and innovative therapeutic approaches are imperative to address it. Chimeric antigen receptor T-cell (CAR-T) therapy has shown impressive and long-lasting results in blood cancers, but its success in solid tumors such as lung cancer remains limited. This review summarizes recent advances and future directions of CAR-T therapy in NSCLC, focusing on major therapeutic targets such as EGFR, MSLN, PD-L1, MUC1, CEA, and ROR1, as well as on the efficacy and potential of combining CAR-T therapy with other treatment modalities. Additionally, we discuss adverse events in NSCLC patients undergoing CAR-T therapy, emphasizing cytokine release syndrome (CRS) and cardiovascular complications—their incidence, pathophysiology, interrelation, and management strategies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102662"},"PeriodicalIF":5.0,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-30DOI: 10.1016/j.tranon.2025.102656
Yuhan Jia , Feng Zhang , Kun Zou , Lijuan Zou
{"title":"Corrigendum to “A Clinical Study on the Efficacy of Concurrent Chemoradiotherapy Combined with Targeted Therapy and Hyperthermia in Patients with Locally Advanced Cervical Cancer” [Translational Oncology,Volume61, November 2025, 102516]","authors":"Yuhan Jia , Feng Zhang , Kun Zou , Lijuan Zou","doi":"10.1016/j.tranon.2025.102656","DOIUrl":"10.1016/j.tranon.2025.102656","url":null,"abstract":"","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102656"},"PeriodicalIF":5.0,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-19DOI: 10.1016/j.tranon.2025.102649
Yun Jin, Tongyu Wang, Junyan Ma, Jiao Quan, Ning Zhou
Hyaluronidase 1 (HYAL1), a key enzyme in hyaluronic acid (HA) metabolism, exhibits a perplexing paradoxical character in tumor biology. This review systematically delineates the dual roles of HYAL1 in cancer: on one hand, by degrading HA to generate low-molecular-weight fragments with pro-angiogenic and immunomodulatory activities, HYAL1 promotes tumor progression and metastasis in various malignancies, including prostate cancer, esophageal carcinoma, and osteosarcoma; on the other hand, it demonstrates tumor-suppressive properties in specific contexts such as colorectal cancer models. This functional contradiction underscores the context-dependent nature of HYAL1, whose activity and effects are profoundly influenced by tumor type, microenvironmental features, and epigenetic regulation.
Mechanistically, HYAL1 functions not only through the classical HA-CD44 signaling axis but also by regulating the MMPs/TIMPs balance, integrin activation, and cytoskeletal reorganization. Recent studies reveal that HYAL1 expression is directly controlled by epigenetic regulators like BRD2, while its activity can be monitored in real-time using novel bioluminescent probes, providing powerful tools for investigating its dynamic functions. Notably, HYAL1-based therapeutic strategies have shown considerable promise, particularly in oncolytic virotherapy, where HYAL1-expressing recombinant viruses significantly enhance the penetration and efficacy of chemotherapeutic agents and immune cells within tumors.
Key challenges persist, including HA metabolic complexity, functional redundancy among hyaluronidases, and HA fragment instability. Future research must decipher HYAL1′s context-specific roles within tumor heterogeneity, elucidate its epigenetic regulation, and develop targeted strategies. A deeper understanding of this HYAL1 paradox is essential to leverage its potential for precision cancer therapies targeting HA metabolism.
{"title":"The HYAL1 paradox in cancer: From complex tumor biology to novel therapeutic strategies","authors":"Yun Jin, Tongyu Wang, Junyan Ma, Jiao Quan, Ning Zhou","doi":"10.1016/j.tranon.2025.102649","DOIUrl":"10.1016/j.tranon.2025.102649","url":null,"abstract":"<div><div>Hyaluronidase 1 (HYAL1), a key enzyme in hyaluronic acid (HA) metabolism, exhibits a perplexing paradoxical character in tumor biology. This review systematically delineates the dual roles of HYAL1 in cancer: on one hand, by degrading HA to generate low-molecular-weight fragments with pro-angiogenic and immunomodulatory activities, HYAL1 promotes tumor progression and metastasis in various malignancies, including prostate cancer, esophageal carcinoma, and osteosarcoma; on the other hand, it demonstrates tumor-suppressive properties in specific contexts such as colorectal cancer models. This functional contradiction underscores the context-dependent nature of HYAL1, whose activity and effects are profoundly influenced by tumor type, microenvironmental features, and epigenetic regulation.</div><div>Mechanistically, HYAL1 functions not only through the classical HA-CD44 signaling axis but also by regulating the MMPs/TIMPs balance, integrin activation, and cytoskeletal reorganization. Recent studies reveal that HYAL1 expression is directly controlled by epigenetic regulators like BRD2, while its activity can be monitored in real-time using novel bioluminescent probes, providing powerful tools for investigating its dynamic functions. Notably, HYAL1-based therapeutic strategies have shown considerable promise, particularly in oncolytic virotherapy, where HYAL1-expressing recombinant viruses significantly enhance the penetration and efficacy of chemotherapeutic agents and immune cells within tumors.</div><div>Key challenges persist, including HA metabolic complexity, functional redundancy among hyaluronidases, and HA fragment instability. Future research must decipher HYAL1′s context-specific roles within tumor heterogeneity, elucidate its epigenetic regulation, and develop targeted strategies. A deeper understanding of this HYAL1 paradox is essential to leverage its potential for precision cancer therapies targeting HA metabolism.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102649"},"PeriodicalIF":5.0,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-19DOI: 10.1016/j.tranon.2025.102643
Diana Lourenço , Raquel Lopes , Joana Caetano , Filipa Barahona , Jessica Rodrigues , Ana C. Queirós , Emilie Arnault Carneiro , Cristina João
Preclinical models for multiple myeloma (MM) often fail to recapitulate the complexity of the bone marrow (BM) microenvironment, limiting their utility for drug testing and translational research. There is an urgent need for physiologically relevant, patient-adaptable platforms to support personalized therapeutic evaluation.
We developed BioMarrow, a 3D ex vivo BM culture system using unmanipulated patient BM aspirates embedded in Matrigel. Culture conditions were optimized to sustain diverse hematopoietic, stromal and immune populations for up to 7 days. Spatial distribution, cytokine secretion and treatment responses were assessed via flow cytometry, immunohistochemistry, multiplex ELISA and cell viability assays.
The model maintained key BM components characteristics of MM, supported stromal network formation and preserved cytokines such as IL-6 and TGF-β. Immune-effector cytokines were reduced, consistent with a tumour-permissive microenvironment. Drug testing with MM cell lines confirmed BioMarrow's ability to discriminate treatment sensitivity.
BioMarrow captures essential features of the MM niche and offers a clinically relevant, short-term platform for ex vivo therapeutic screening. Its scalability and immune component preservation support future integration into personalized treatment workflows, including immunotherapy evaluation.
{"title":"BioMarrow: An accessible and reproducible 3D patient-derived bone marrow model for advancing research and clinical applications","authors":"Diana Lourenço , Raquel Lopes , Joana Caetano , Filipa Barahona , Jessica Rodrigues , Ana C. Queirós , Emilie Arnault Carneiro , Cristina João","doi":"10.1016/j.tranon.2025.102643","DOIUrl":"10.1016/j.tranon.2025.102643","url":null,"abstract":"<div><div>Preclinical models for multiple myeloma (MM) often fail to recapitulate the complexity of the bone marrow (BM) microenvironment, limiting their utility for drug testing and translational research. There is an urgent need for physiologically relevant, patient-adaptable platforms to support personalized therapeutic evaluation.</div><div>We developed BioMarrow, a 3D <em>ex vivo</em> BM culture system using unmanipulated patient BM aspirates embedded in Matrigel. Culture conditions were optimized to sustain diverse hematopoietic, stromal and immune populations for up to 7 days. Spatial distribution, cytokine secretion and treatment responses were assessed via flow cytometry, immunohistochemistry, multiplex ELISA and cell viability assays.</div><div>The model maintained key BM components characteristics of MM, supported stromal network formation and preserved cytokines such as IL-6 and TGF-β. Immune-effector cytokines were reduced, consistent with a tumour-permissive microenvironment. Drug testing with MM cell lines confirmed BioMarrow's ability to discriminate treatment sensitivity.</div><div>BioMarrow captures essential features of the MM niche and offers a clinically relevant, short-term platform for <em>ex vivo</em> therapeutic screening. Its scalability and immune component preservation support future integration into personalized treatment workflows, including immunotherapy evaluation.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102643"},"PeriodicalIF":5.0,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-19DOI: 10.1016/j.tranon.2025.102641
Qiao Huang , Tao Hou , Yi Ren , Wei Xing Liao, Ang Zi Zhu, Ying Liu, Xiao Lin Zhan, Hua Shi Yin
Background
Nasopharyngeal carcinoma (NPC) is a subtype of head and neck carcinoma. This study aimed to investigate the diagnostic and prognostic significance of EphB2 in NPC.
Methods
Serum and nasopharyngeal tissue samples were collected from 159 NPC patients and 159 individuals with chronic nasopharyngeal mucosal inflammation (control group). EphB2 expression in tissue samples was assessed by western blotting (WB) and immunofluorescence (IF); its concentration in serum was measured by enzyme-linked immunosorbent assay (ELISA). Survival rate differences were evaluated using Kaplan–Meier analysis and the log-rank test. Multivariate Cox regression was performed to identify prognosis-related factors. The diagnostic performance of EphB2 was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC).
Results
EphB2 expression was significantly elevated in both serum and tissue samples of NPC patients compared to controls. High EphB2 levels were significantly associated with TNM stage, tumor invasion depth, lymph node metastasis, distant metastases, EBV infection, and recurrence status. Kaplan–Meier survival curves showed that NPC patients with high levels of EphB2 or EBV(+) or recurrence had the poorest disease-free survival. Cox regression identified high EphB2 expression, EBV(+), and recurrence as independent predictors of poor prognosis in NPC. ROC analysis demonstrated that at an optimal cutoff of 7.079 ng/mL, serum EphB2 effectively distinguished NPC patients from controls, with an AUC of 0.904 (95 % CI: 0.866–0.942, P < 0.001), sensitivity of 79.9 %, and specificity of 98.7 %. The AUC for EBV infection alone was 0.767 (95 % CI: 0.714–0.821, P < 0.001), with a sensitivity of 71.1 % and specificity of 82.4 %. Combined detection of EphB2 and EBV infection improved the AUC to 0.922 (95 % CI: 0.891–0.954, P < 0.001), with 78.6 % sensitivity and 97.5 % specificity.
Conclusions
Serum EphB2 represents a promising diagnostic and prognostic biomarker for NPC. The combination of EBV seropositivity and high EphB2 expression may be valuable for early NPC screening.
鼻咽癌（NPC）是头颈癌的一个亚型。本研究旨在探讨EphB2在鼻咽癌中的诊断及预后意义。方法采集159例鼻咽癌患者和159例慢性鼻咽黏膜炎症患者（对照组）的血清和鼻咽组织标本。采用western blotting （WB）和免疫荧光（IF）检测组织样品中EphB2的表达；采用酶联免疫吸附试验（ELISA）测定其血清浓度。生存率差异采用Kaplan-Meier分析和log-rank检验。采用多因素Cox回归分析确定预后相关因素。采用受试者工作特征曲线（ROC）和曲线下面积（AUC）评价EphB2的诊断效能。结果鼻咽癌患者血清和组织标本中tsephb2的表达均明显高于对照组。高水平EphB2与TNM分期、肿瘤侵袭深度、淋巴结转移、远处转移、EBV感染和复发情况显著相关。Kaplan-Meier生存曲线显示，高水平EphB2或EBV（+）或复发的鼻咽癌患者无病生存期最差。Cox回归发现EphB2高表达、EBV（+）和复发是鼻咽癌预后不良的独立预测因素。ROC分析显示，在最佳截断值为7.079 ng/mL时，血清EphB2可有效区分鼻咽癌患者和对照组，AUC为0.904 (95% CI: 0.866-0.942, P < 0.001)，敏感性为79.9%，特异性为98.7%。单独EBV感染的AUC为0.767 (95% CI: 0.714-0.821, P < 0.001)，敏感性为71.1%，特异性为82.4%。联合检测EphB2和EBV感染使AUC提高到0.922 (95% CI: 0.891 ~ 0.954, P < 0.001)，敏感性78.6%，特异性97.5%。结论血清EphB2是鼻咽癌诊断和预后的良好生物标志物。EBV血清阳性和EphB2高表达的结合可能对鼻咽癌早期筛查有价值。
{"title":"Diagnostic and prognostic value of EphB2 in nasopharyngeal carcinoma","authors":"Qiao Huang , Tao Hou , Yi Ren , Wei Xing Liao, Ang Zi Zhu, Ying Liu, Xiao Lin Zhan, Hua Shi Yin","doi":"10.1016/j.tranon.2025.102641","DOIUrl":"10.1016/j.tranon.2025.102641","url":null,"abstract":"<div><h3>Background</h3><div>Nasopharyngeal carcinoma (NPC) is a subtype of head and neck carcinoma. This study aimed to investigate the diagnostic and prognostic significance of EphB2 in NPC.</div></div><div><h3>Methods</h3><div>Serum and nasopharyngeal tissue samples were collected from 159 NPC patients and 159 individuals with chronic nasopharyngeal mucosal inflammation (control group). EphB2 expression in tissue samples was assessed by western blotting (WB) and immunofluorescence (IF); its concentration in serum was measured by enzyme-linked immunosorbent assay (ELISA). Survival rate differences were evaluated using Kaplan–Meier analysis and the log-rank test. Multivariate Cox regression was performed to identify prognosis-related factors. The diagnostic performance of EphB2 was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC).</div></div><div><h3>Results</h3><div>EphB2 expression was significantly elevated in both serum and tissue samples of NPC patients compared to controls. High EphB2 levels were significantly associated with TNM stage, tumor invasion depth, lymph node metastasis, distant metastases, EBV infection, and recurrence status. Kaplan–Meier survival curves showed that NPC patients with high levels of EphB2 or EBV(+) or recurrence had the poorest disease-free survival. Cox regression identified high EphB2 expression, EBV(+), and recurrence as independent predictors of poor prognosis in NPC. ROC analysis demonstrated that at an optimal cutoff of 7.079 ng/mL, serum EphB2 effectively distinguished NPC patients from controls, with an AUC of 0.904 (95 % CI: 0.866–0.942, <em>P</em> < 0.001), sensitivity of 79.9 %, and specificity of 98.7 %. The AUC for EBV infection alone was 0.767 (95 % CI: 0.714–0.821, <em>P</em> < 0.001), with a sensitivity of 71.1 % and specificity of 82.4 %. Combined detection of EphB2 and EBV infection improved the AUC to 0.922 (95 % CI: 0.891–0.954, <em>P</em> < 0.001), with 78.6 % sensitivity and 97.5 % specificity.</div></div><div><h3>Conclusions</h3><div>Serum EphB2 represents a promising diagnostic and prognostic biomarker for NPC. The combination of EBV seropositivity and high EphB2 expression may be valuable for early NPC screening.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102641"},"PeriodicalIF":5.0,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-18DOI: 10.1016/j.tranon.2025.102648
Meiyu Liu , Junwei Huang , Mengqiao Dai , Xiaoni Gao , Zihang Ai , Wei Hu , Zanbing Li , feijie wang , Junjie Yang , Haidong Liao , Yang Xie , Yong Ying , Xiangtai Zeng
Objective
: To investigate the anti-tumor efficacy and underlying molecular mechanisms of prodigiosin (PG) in papillary thyroid cancer (PTC).
Methods
: The anti-cancer effects of PG were systematically evaluated in vitro using PTC cell lines and in vivo via xenograft mouse models. Cell viability and dose-response relationships were determined by CCK-8 assays. Anti-proliferative activity was assessed through colony formation and EdU incorporation assays. The impact on metastatic potential was examined by scratch wound healing and Matrigel-based transwell migration and invasion assays. Cell cycle distribution was analyzed using flow cytometry.
Results
: In vitro, PG at 500 nM inhibited the growth of BCPAP and TPC-1 cells by 93.5 % and 89.2 %, respectively, as determined by colony formation assays. Migration and invasion of BCPAP cells were reduced by 90.7 % and 93.4 %, measured via scratch wound healing and transwell assays. PG treatment modulated epithelial-mesenchymal transition (EMT) markers both in vitro and in vivo, characterized by downregulating mesenchymal proteins and upregulating epithelial proteins, accompanied by changes in Wnt/β-catenin pathway-related proteins, indicating suppression of EMT. Flow cytometry revealed that PG induced G0/G1 cell cycle arrest in both BCPAP and TPC-1 cells. Furthermore, PG upregulated the sodium-iodide symporter (NIS), enhancing radioiodine uptake. Moreover, the treatment of PG significantly inhibited tumor growth without notable toxicity in vivo.
Conclusion
: PG exerts potent anti-tumor activity against PTC by simultaneously inhibiting proliferation, migration, and invasion, inducing cell cycle arrest, and enhancing radioiodine uptake, potentially through modulation of the Wnt/β-catenin signaling pathway. Our findings position PG as a highly promising, potentially transformative therapeutic candidate for PTC, offering a strategic approach to overcome conventional therapy resistance and improve clinical outcomes.
{"title":"Evaluation of the anti-tumor efficacy of prodigiosin in papillary thyroid cancer cell and animal models","authors":"Meiyu Liu , Junwei Huang , Mengqiao Dai , Xiaoni Gao , Zihang Ai , Wei Hu , Zanbing Li , feijie wang , Junjie Yang , Haidong Liao , Yang Xie , Yong Ying , Xiangtai Zeng","doi":"10.1016/j.tranon.2025.102648","DOIUrl":"10.1016/j.tranon.2025.102648","url":null,"abstract":"<div><h3>Objective</h3><div><strong>:</strong> To investigate the anti-tumor efficacy and underlying molecular mechanisms of prodigiosin (PG) in papillary thyroid cancer (PTC).</div></div><div><h3>Methods</h3><div><strong>:</strong> The anti-cancer effects of PG were systematically evaluated <em>in vitro</em> using PTC cell lines and <em>in vivo</em> via xenograft mouse models. Cell viability and dose-response relationships were determined by CCK-8 assays. Anti-proliferative activity was assessed through colony formation and EdU incorporation assays. The impact on metastatic potential was examined by scratch wound healing and Matrigel-based transwell migration and invasion assays. Cell cycle distribution was analyzed using flow cytometry.</div></div><div><h3>Results</h3><div><strong>:</strong> In vitro, PG at 500 nM inhibited the growth of BCPAP and TPC-1 cells by 93.5 % and 89.2 %, respectively, as determined by colony formation assays. Migration and invasion of BCPAP cells were reduced by 90.7 % and 93.4 %, measured via scratch wound healing and transwell assays. PG treatment modulated epithelial-mesenchymal transition (EMT) markers both <em>in vitro</em> and <em>in vivo</em>, characterized by downregulating mesenchymal proteins and upregulating epithelial proteins, accompanied by changes in Wnt/β-catenin pathway-related proteins, indicating suppression of EMT. Flow cytometry revealed that PG induced G0/G1 cell cycle arrest in both BCPAP and TPC-1 cells. Furthermore, PG upregulated the sodium-iodide symporter (NIS), enhancing radioiodine uptake. Moreover, the treatment of PG significantly inhibited tumor growth without notable toxicity <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div><strong>:</strong> PG exerts potent anti-tumor activity against PTC by simultaneously inhibiting proliferation, migration, and invasion, inducing cell cycle arrest, and enhancing radioiodine uptake, potentially through modulation of the Wnt/β-catenin signaling pathway. Our findings position PG as a highly promising, potentially transformative therapeutic candidate for PTC, offering a strategic approach to overcome conventional therapy resistance and improve clinical outcomes.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102648"},"PeriodicalIF":5.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145795007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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