Advanced biology最新文献

COL12A1 rs970547 Polymorphism Predisposes Anterior Cruciate Ligament Injury by Inducing ER Stress and Impairing Fibroblast Function. COL12A1 rs970547多态性通过诱导内质网应激和损害成纤维细胞功能而易导致前交叉韧带损伤。

IF 2.6 3区生物学

Advanced biology Pub Date : 2026-05-01 DOI: 10.1002/adbi.202500655

Wenchuan Zhao, Hong Chen, Junwei Wang, Yixin Li, Rui Chen, Jingyi Zhou

引用次数: 0

Copper Overload Affects α-Synuclein Clearance Mechanisms in a Parkinson's Disease In Vitro Model. 铜超载影响帕金森病体外模型中α-突触核蛋白清除机制

IF 2.6 3区生物学

Advanced biology Pub Date : 2026-05-01 DOI: 10.1002/adbi.202500274

Debora Musarò, Marina Damato, Chiara Coppola, Marco Greco, Michele Maffia

{"title":"Copper Overload Affects α-Synuclein Clearance Mechanisms in a Parkinson's Disease In Vitro Model.","authors":"Debora Musarò, Marina Damato, Chiara Coppola, Marco Greco, Michele Maffia","doi":"10.1002/adbi.202500274","DOIUrl":"10.1002/adbi.202500274","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta and the formation of Lewy bodies, abnormal protein aggregates primarily composed of α-synuclein. Copper, an essential trace element, plays a role in α-synuclein aggregation and PD pathogenesis. This study examines the effects of copper overload on α-synuclein clearance pathways, focusing on autophagy and the ubiquitin-proteasome system (UPS) in dopaminergic SH-SY5Y neuroblastoma cells. Copper exposure enhances autophagosome formation, as indicated by increased Beclin-1 and LC3-II levels, and impairs autophagic flux, evidenced by LC3-II accumulation in the presence of chloroquine. Concurrently, copper increases polyubiquitinated proteins, suggesting UPS dysfunction, which is confirmed through MG132 treatment. These disruptions lead to the accumulation and aggregation of α-synuclein, particularly in its phosphorylated form. Immunofluorescence reveals neurite-localized α-synuclein aggregates, consistent with copper's role in α-synuclein pathology. This study highlights copper dyshomeostasis as a contributor to impaired α-synuclein clearance through autophagy and UPS dysfunction, advancing the understanding of PD's molecular basis.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"10 5","pages":"e00274"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13136777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cibotii Rhizoma Extract Mitigates LPS-Induced Inflammatory Bone Loss by Inhibiting the RANK Signaling Pathway to Suppress Osteoclastogenesis and Bone Resorption. 黄芪提取物通过抑制RANK信号通路抑制破骨细胞生成和骨吸收来减轻脂多糖诱导的炎症性骨丢失。

IF 2.6 3区生物学

Advanced biology Pub Date : 2026-05-01 DOI: 10.1002/adbi.202500599

Jin Young Hong, Wan-Jin Jeon, Hyunseong Kim, Junseon Lee, Hyun Kim, Changhwan Yeo, Yoon Jae Lee, In-Hyuk Ha

{"title":"Cibotii Rhizoma Extract Mitigates LPS-Induced Inflammatory Bone Loss by Inhibiting the RANK Signaling Pathway to Suppress Osteoclastogenesis and Bone Resorption.","authors":"Jin Young Hong, Wan-Jin Jeon, Hyunseong Kim, Junseon Lee, Hyun Kim, Changhwan Yeo, Yoon Jae Lee, In-Hyuk Ha","doi":"10.1002/adbi.202500599","DOIUrl":"https://doi.org/10.1002/adbi.202500599","url":null,"abstract":"<p><p>Bone homeostasis is maintained through balanced interactions between osteoblasts and osteoclasts, whereas chronic inflammation disrupts this balance by enhancing osteoclast activity and bone loss. This study investigated the protective effects of Cibotii Rhizoma (CR) on inflammatory bone destruction and its underlying mechanisms. In vitro, CR suppressed receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis in bone marrow-derived monocyte/macrophage (BMM) cultures by downregulating NFATc1, c-Src, and TRAF6, thereby inhibiting osteoclast formation, podosomal actin ring assembly, and cell fusion. In vivo, administration of CR in an LPS-induced bone loss mouse model preserved bone microarchitecture, as confirmed by micro-CT and histological analyses, and significantly reduced osteoclast numbers and calvarial bone erosion. Immunohistochemical staining further revealed decreased RANK and NFATc1 activity in calvarial bone tissue following CR treatment. Collectively, these findings indicate that CR mitigates inflammatory bone loss by targeting RANK signaling to inhibit osteoclastogenesis and bone resorption, highlighting its potential as a therapeutic agent for inflammatory bone diseases.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"10 5","pages":"e00599"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

KAT6A Promotes Lung Cancer Proliferation and Invasion via Keap1-Nrf2 Signaling. KAT6A通过Keap1-Nrf2信号促进肺癌的增殖和侵袭。

IF 2.6 3区生物学

Advanced biology Pub Date : 2026-05-01 DOI: 10.1002/adbi.202500503

Qian Ning, Weichao Bai, Hong Li, Jing Xue, Dan Li, Tianjun Chen

{"title":"KAT6A Promotes Lung Cancer Proliferation and Invasion via Keap1-Nrf2 Signaling.","authors":"Qian Ning, Weichao Bai, Hong Li, Jing Xue, Dan Li, Tianjun Chen","doi":"10.1002/adbi.202500503","DOIUrl":"https://doi.org/10.1002/adbi.202500503","url":null,"abstract":"<p><p>This study aimed to investigate the role of lysine acetyltransferase 6A (KAT6A) in lung cancer progression and its potential involvement in Nrf2-related oxidative stress regulation. KAT6A was overexpressed or silenced in A549 and H1299 lung cancer cells. KAT6A expression was verified by quantitative reverse transcription polymerase chain reaction and Western blot. Cell Counting Kit-8 and Transwell assays showed that KAT6A overexpression promoted cell proliferation and invasion, whereas KAT6A silencing suppressed cell proliferation. KAT6A overexpression decreased the expression of Keap1 protein and enhanced Nrf2 signaling activity. Oxidative stress evaluation using 2',7'-dichlorodihydrofluorescein diacetate staining, malondialdehyde (MDA) detection, and superoxide dismutase (SOD) activity assays indicated decreased reactive oxygen species levels, reduced MDA content, and elevated SOD activity. Co-immunoprecipitation confirmed the interaction between KAT6A and Nrf2, and dual-luciferase reporter assays showed enhanced Nrf2 transcriptional activity on the heme oxygenase-1 promoter. Silencing Nrf2 reversed the effects of KAT6A on proliferation. Immunohistochemistry of clinical lung adenocarcinoma samples showed that high KAT6A expression correlated with advanced tumor stage and shorter overall survival. These findings suggest that KAT6A regulates oxidative stress via the Keap1-Nrf2 pathway, thereby promoting malignant progression in lung adenocarcinoma, and may serve as a potential prognostic biomarker.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"10 5","pages":"e00503"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mir-301b-3p Targets Alx4 to Suppress Cisplatin Sensitivity in Breast Cancer through DNA Damage Mir-301b-3p通过DNA损伤靶向Alx4抑制乳腺癌顺铂敏感性

IF 2.6 3区生物学

Advanced biology Pub Date : 2026-04-07 DOI: 10.1002/adbi.202500715

Yan Yan, Jianhong Xia, Tingting Ma, Liqing Zhou

{"title":"Mir-301b-3p Targets Alx4 to Suppress Cisplatin Sensitivity in Breast Cancer through DNA Damage","authors":"Yan Yan, Jianhong Xia, Tingting Ma, Liqing Zhou","doi":"10.1002/adbi.202500715","DOIUrl":"10.1002/adbi.202500715","url":null,"abstract":"<div>\u0000 \u0000 <p><b>Objective</b>: To elucidate how ALX Homeobox 4 (ALX4) modulates cisplatin sensitivity via DNA damage regulation in breast cancer (BC), this study explored the established role of mRNA-mediated DNA repair in driving chemoresistance. <b>Methods</b>: Integrated bioinformatics and molecular experiments identified ALX4 and miR-301b-3p expression patterns in BC cells. Potential binding sites between them were predicted and verified by dual-luciferase assays. Cellular experiments determined cisplatin IC50 via CCK-8 assays, while functional impacts of the miR-301b-3p/ALX4 axis on proliferation, apoptosis, and cisplatin-induced DNA damage were assessed using CCK-8, flow cytometry, alkaline comet assays, and western blot. <b>Results</b>: Our study identified downregulated ALX4 and upregulated miR-301b-3p in BC tissues. miR-301b-3p directly targeted ALX4, as confirmed by dual-luciferase assays. Overexpression of ALX4 inhibited BC cell proliferation, promoted apoptosis, enhanced cisplatin-induced DNA damage, and increased cisplatin sensitivity. Conversely, miR-301b-3p negatively regulated ALX4, thereby modulating DNA damage and cellular response to cisplatin. <b>Conclusion</b>: This study demonstrates that miR-301b-3p promotes BC proliferation and reduces cisplatin sensitivity by suppressing ALX4, a mechanism mediated through the regulation of DNA damage pathways. These findings offer new insights into cisplatin resistance and suggest potential therapeutic targets for overcoming chemoresistance in BC.</p>\u0000 </div>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"10 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Burden, Trends and Prediction of NAFLD/MAFLD Attributable to Smoking From 1990 to 2021: GBD 2021 Analysis 1990 - 2021年吸烟所致NAFLD/MAFLD的负担、趋势和预测：GBD 2021分析

IF 2.6 3区生物学

Advanced biology Pub Date : 2026-03-31 DOI: 10.1002/adbi.202500232

Lijuan Chen, Ziyi Zhu, Yishu Wang, Lin Guo, Zhenzhen Fu, Xianyong Yin, John Zhong Li, Yingyun Gong, Hongwen Zhou

{"title":"Burden, Trends and Prediction of NAFLD/MAFLD Attributable to Smoking From 1990 to 2021: GBD 2021 Analysis","authors":"Lijuan Chen, Ziyi Zhu, Yishu Wang, Lin Guo, Zhenzhen Fu, Xianyong Yin, John Zhong Li, Yingyun Gong, Hongwen Zhou","doi":"10.1002/adbi.202500232","DOIUrl":"10.1002/adbi.202500232","url":null,"abstract":"<div>\u0000 \u0000 <p>Smoking is a risk factor for non-alcoholic fatty liver disease (NAFLD, recently proposed as metabolic dysfunction‑associated fatty liver disease, MAFLD), but the global smoking-attributable NAFLD/MAFLD burden remains unclear. Using GBD 2021 data, this study quantified the burden by age, sex, socio-demographic index (SDI), and region, computed average annual percent changes (AAPC) via Joinpoint regression, and projected 2022–2036 burden using the Bayesian age-period-cohort (BAPC) model. During 1990–2021, the AAPC of the age-standardized DALY rate (ASDR) and mortality rate (ASMR) was 0.0223 [95% uncertainty interval (UI): −0.1432, 0.1880, <i>p</i> = 0.79] and 0.2660 (95%UI: 0.1666, 0.3655, <i>p</i> < 0.001), suggesting that the death-related burden increased mostly. Notably, males contributed the most to this trend, with the sharpest upward trend recorded in low-middle SDI regions. Global cross-country inequality revealed that this death-related burden is widening, especially among females. In contrast to this historical trajectory, predictive models suggest a steady decline by 2036. In conclusion, global ASMR of smoking-attributable NAFLD/MAFLD increased during 1990–2021, especially in low-middle SDI regions and male populations. Despite a projected gradual burden decline over the next 15 years, it still emphasizes the need for strengthened tobacco control and NAFLD/MAFLD prevention in low-middle SDI regions and male populations.</p>\u0000 </div>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"10 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic Potential of Stem Cells From Human Exfoliated Deciduous Teeth and Their Derivatives in Immune-Mediated Inflammatory Diseases: Mechanisms and Perspectives 人脱落乳牙干细胞及其衍生物在免疫介导炎性疾病中的治疗潜力：机制和观点。

IF 2.6 3区生物学

Advanced biology Pub Date : 2026-03-24 DOI: 10.1002/adbi.202500443

Wenbo Cui, Dandan Zheng, Anqi Liu, Meiling Wu, Qing Liu, Hao Guo, Xiaowei Cai, Zhenlai Zhu

{"title":"Therapeutic Potential of Stem Cells From Human Exfoliated Deciduous Teeth and Their Derivatives in Immune-Mediated Inflammatory Diseases: Mechanisms and Perspectives","authors":"Wenbo Cui, Dandan Zheng, Anqi Liu, Meiling Wu, Qing Liu, Hao Guo, Xiaowei Cai, Zhenlai Zhu","doi":"10.1002/adbi.202500443","DOIUrl":"10.1002/adbi.202500443","url":null,"abstract":"<div>\u0000 \u0000 <p>Stem cells from human exfoliated deciduous teeth (SHED) and their derivatives have emerged as promising therapeutic agents for treating immune-mediated inflammatory diseases (IMIDs). IMIDs are characterized by dysregulated immune responses, leading to chronic inflammation and tissue damage. The current treatment landscape for IMIDs faces challenges, including the complexity of disease mechanisms and the limitations of existing therapies, which frequently fail to achieve long-term remission and are often associated with significant side effects. Consequently, there is a pressing need for innovative therapies that not only alleviate symptoms but also address the underlying immune dysfunction and promote the repair of damaged tissues. In this context, SHED and their derivatives offer a dual therapeutic advantage by harnessing both immunomodulatory and regenerative capacities. Research highlighted in this review demonstrates the therapeutic potential of SHED and their derivatives in multiple IMIDs, such as systemic lupus erythematosus, Sjögren's syndrome, multiple sclerosis, and rheumatoid arthritis. Critically, the aim of this review is not only to synthesize recent progress in SHED research for IMID treatment but also to highlight the strategic significance of innovative therapies emerging from the intersection of regenerative medicine and immunology.</p>\u0000 </div>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"10 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

iMSCs vs MSCs: Comparative Features and Therapeutic Potential in Wound Healing 间充质干细胞与间充质干细胞：伤口愈合的比较特征和治疗潜力。

IF 2.6 3区生物学

Advanced biology Pub Date : 2026-03-24 DOI: 10.1002/adbi.202500623

Avinash Sanap, Akshaya Ashok, Kaustubh Raundal, Supriya Kheur, Ravindra Badhe, Ramesh Bhonde

{"title":"iMSCs vs MSCs: Comparative Features and Therapeutic Potential in Wound Healing","authors":"Avinash Sanap, Akshaya Ashok, Kaustubh Raundal, Supriya Kheur, Ravindra Badhe, Ramesh Bhonde","doi":"10.1002/adbi.202500623","DOIUrl":"10.1002/adbi.202500623","url":null,"abstract":"<div>\u0000 \u0000 <p>Regenerative medicine is evolving exponentially due to the wide range of therapeutic applications of mesenchymal stromal cells (MSCs), including wound healing. Although the translation of tissue-derived primary MSCs (tMSCs) into clinical practice remains scarce despite preclinical success. The primary causes are donor-associated and batch-to-batch variations, replicative senescence, and the inability of large-scale manufacturing. Recent studies show that the induced MSCs (iMSCs) derived from reprogrammed induced pluripotent stem cells (iPSCs) offer distinct advantages over conventional tMSCs. This review aims to provide a comprehensive comparative analysis of the cellular characteristics, secretome composition (including growth factors, cytokines, and exosome cargo), regenerative capacities, and therapeutic potentials of tMSCs and iMSCs, with a specific focus on their applications in wound healing and tissue regeneration. The iMSCs surpass tMSCs by providing superior regenerative, immunomodulatory, and angiogenic benefits, along with unmatched consistency and scalability. iMSCs and their derivatives have exhibited remarkable capacities to promote angiogenesis, ECM production, re-epithelialization, tissue regeneration, and scarless wound healing in diabetic, cutaneous, mucosal, and burn wounds. These advantages position iMSCs as a next-generation cell therapy for managing both acute and chronic wounds, promising improved clinical outcomes and broader applicability.</p>\u0000 </div>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"10 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Application and Research Progress of Carbonated Hydroxyapatite in Bone Tissue Regeneration 碳酸羟基磷灰石在骨组织再生中的应用与研究进展。

IF 2.6 3区生物学

Advanced biology Pub Date : 2026-03-24 DOI: 10.1002/adbi.202500451

Yifu Bian, Xinliang Duan, Sichen Han, Yao Yuan, Jiayu Shen, Zilin Wang, Bing Han

{"title":"Application and Research Progress of Carbonated Hydroxyapatite in Bone Tissue Regeneration","authors":"Yifu Bian, Xinliang Duan, Sichen Han, Yao Yuan, Jiayu Shen, Zilin Wang, Bing Han","doi":"10.1002/adbi.202500451","DOIUrl":"10.1002/adbi.202500451","url":null,"abstract":"<div>\u0000 \u0000 <p>Carbonated Hydroxyapatite (CHA) has attracted widespread attention in bone tissue regeneration due to its chemical composition and crystal structure, which are similar to natural bone tissue. This review summarizes the basic characteristics of CHA, preparation methods, and advances in its application in bone repair. First, the crystal structure, chemical composition, and the effect of carbonate doping on its physicochemical properties are discussed, focusing on how preparation techniques such as the wet chemical method, sol–gel method, and hydrothermal synthesis regulate CHA's properties. Second, the biological mechanisms of CHA in bone tissue regeneration are outlined, including its role in promoting osteoblast proliferation and differentiation, regulating the bone repair microenvironment, and mediating related signaling pathways (e.g., Wnt/β-catenin and bone morphogenetic protein (BMP)/Smad). Furthermore, the research progress of CHA in repairing cranial, alveolar, and long bone defects is systematically reviewed through animal models and clinical studies to evaluate its bone repair capacity and biocompatibility. In addition, the composite application of CHA with polymers and bioactive glass and its potential development in frontier technologies such as 3D printing and smart drug delivery are discussed. Finally, the challenges in mechanical properties, degradation rate, and preparation processes are analyzed, and the future application prospects of CHA as an intelligent, multifunctional bone repair material are envisaged. This review aims to provide theoretical support and research insights to optimize the design and application of CHA in bone tissue engineering.</p>\u0000 </div>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"10 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tumor-Infiltrating Nociceptor Neurons in Ovarian Cancer Treatment Resistance 肿瘤浸润性伤害感受器神经元在卵巢癌治疗抵抗中的作用。

IF 2.6 3区生物学

Advanced biology Pub Date : 2026-03-09 DOI: 10.1002/adbi.202500404

Allison Jorgensen, Daniel W. Vermeer, Euihye Jung, Caitlin S. Williamson, Dalia K. Omran, Lauren E. Schwartz, Ju-Yoon Yoon, Jeffrey Barr, Ashley L. Tetlow, Camille V. Trinidad, Ronny Drapkin, Andrew K. Godwin, Paola D. Vermeer

{"title":"Tumor-Infiltrating Nociceptor Neurons in Ovarian Cancer Treatment Resistance","authors":"Allison Jorgensen, Daniel W. Vermeer, Euihye Jung, Caitlin S. Williamson, Dalia K. Omran, Lauren E. Schwartz, Ju-Yoon Yoon, Jeffrey Barr, Ashley L. Tetlow, Camille V. Trinidad, Ronny Drapkin, Andrew K. Godwin, Paola D. Vermeer","doi":"10.1002/adbi.202500404","DOIUrl":"10.1002/adbi.202500404","url":null,"abstract":"<p>Patients with densely innervated tumors suffer with poor outcomes, thus identifying them could define a cohort that could benefit from aggressive treatments. Most cases and deaths from ovarian cancer are associated with high-grade serous ovarian carcinoma (HGSOC). We immunohistochemically analyzed the histological subtypes of ovarian cancer (high-grade serous, low-grade serous, clear cell, mucinous, and endometrioid) for nerves; only HGSOCs were densely innervated. We previously defined that tumor-released small extracellular vesicles (sEVs) recruit nerves to the tumor bed and thus tested whether the difference in nerve infiltration amongst ovarian cancers was associated with sEVs. Using an in vitro neurite outgrowth assay, we found that HGSOC sEVs harbored robust neurite outgrowth activity. Importantly, sEVs from fallopian tube cell lines (the primary cell of origin of HGSOC) predominantly lacked this activity. Implantation of a syngeneic mouse model of HGSOC into transgenic mice lacking tumor-infiltrating nerves slowed tumor growth, sensitized disease to carboplatin, and improved survival. Consistent with this, we show that recurrent, treatment-resistant disease in patients is significantly more innervated than its matched naïve (untreated) malignancy. Taken together, these data identify dense nerve infiltration of HGSOCs and show that innervation contributes to treatment resistance.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"10 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13004430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0