American Journal of Pathology最新文献_第7页

Early Endosome Disturbance and Endolysosomal Pathway Dysfunction in Duchenne Muscular Dystrophy 杜氏肌营养不良的早期内溶酶体紊乱和内溶酶体通路功能障碍。

IF 3.6 2区医学

American Journal of Pathology Pub Date : 2025-06-09 DOI: 10.1016/j.ajpath.2025.05.007

Julie Chassagne , Nathalie Da Silva , Ines Akrouf , Bruno Cadot , Laura Julien , Ines Barthélémy , Stéphane Blot , Caroline Le Guiner , Mai Thao Bui , Norma B. Romero , Jeanne Lainé , France Pietri-Rouxel , Pierre Meunier , Kamel Mamchaoui , Stéphanie Lorain , Marc Bitoun , Sofia Benkhelifa-Ziyyat

{"title":"Early Endosome Disturbance and Endolysosomal Pathway Dysfunction in Duchenne Muscular Dystrophy","authors":"Julie Chassagne , Nathalie Da Silva , Ines Akrouf , Bruno Cadot , Laura Julien , Ines Barthélémy , Stéphane Blot , Caroline Le Guiner , Mai Thao Bui , Norma B. Romero , Jeanne Lainé , France Pietri-Rouxel , Pierre Meunier , Kamel Mamchaoui , Stéphanie Lorain , Marc Bitoun , Sofia Benkhelifa-Ziyyat","doi":"10.1016/j.ajpath.2025.05.007","DOIUrl":"10.1016/j.ajpath.2025.05.007","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD) is a lethal dystrophy characterized by the progressive loss of muscle fibers caused by mutations in <em>DMD</em> gene and absence of the dystrophin protein. Although autophagy and lysosome biogenesis defects have been described in DMD muscles, the endosomal pathway has never been studied. The current study revealed an association of impaired lysosome formation with altered acidification and reduced degradative function of the endolysosomal pathway in muscle cells derived from patients with DMD. Early endosomes were increased in these cells as well as in muscle biopsies from patients with DMD and two animal models of DMD, <em>mdx</em> mice and golden retriever muscular dystrophy dogs. These abnormalities occurred due to the lack of dystrophin per se and could be correlated with disease progression and severity. An abnormal up-regulation of the Rab5 GTPase protein, one key actor of early endosomal biogenesis and fusion, was identified in the three DMD models, which may underlie the endosomal defects. Finally, Rab5 knockdown in human DMD muscle cells as well as dystrophin restoration in golden retriever muscular dystrophy dogs normalized Rab5 expression levels and rescued endosomal abnormalities. This study unveiled a defect in a pathway essential for muscle homeostasis and for the efficacy of DMD therapies.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 9","pages":"Pages 1627-1642"},"PeriodicalIF":3.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273986","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}

引用次数: 0

Nitric Oxide May Adversely Affect the Metabolism and Viability of Retinal Organoids Derived from Patients with Leber Hereditary Optic Neuropathy 一氧化氮可能对Leber遗传性视神经病变患者视网膜类器官的代谢和活力产生不利影响。

IF 3.6 2区医学

American Journal of Pathology Pub Date : 2025-06-09 DOI: 10.1016/j.ajpath.2025.05.006

Fumio Takano, Megumi Kitamura, Kaori Ueda, Makoto Nakamura

{"title":"Nitric Oxide May Adversely Affect the Metabolism and Viability of Retinal Organoids Derived from Patients with Leber Hereditary Optic Neuropathy","authors":"Fumio Takano, Megumi Kitamura, Kaori Ueda, Makoto Nakamura","doi":"10.1016/j.ajpath.2025.05.006","DOIUrl":"10.1016/j.ajpath.2025.05.006","url":null,"abstract":"<div><div>Leber hereditary optic neuropathy (LHON) is a bilateral optic neuropathy associated with mitochondrial DNA (mtDNA) mutations characterized by parapapillary telangiectasia during the acute phase. However, its precise mechanism remains unclear. This study evaluated the effects of nitric oxide (NO) on retinal organoids (ROs) generated from induced pluripotent stem cells derived from patients with LHON. Established induced pluripotent stem cells from three patients with the m.11778G>A mutation (patient group) and three healthy individuals (control group) were differentiated into ROs. Changes in cell death ratios, mtDNA copy number, and metabolite profiles in the ROs following exposure to sodium nitroprusside (SNP), which was an NO donor, were compared between the two groups. At baseline, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling–positive cell ratios did not differ significantly, whereas the mtDNA copy number was significantly higher in the patient group. SNP exposure significantly increased the proportion of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling–positive cells in the patient group but did not affect the mtDNA copy number. Relative concentrations of metabolites, including taurine and γ-aminobutyric acid, were initially reduced in the patient group, but increased following SNP exposure. These findings suggest that NO may promote retinal cell death and disrupt metabolite profiles in ROs derived from patients with LHON.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 9","pages":"Pages 1693-1706"},"PeriodicalIF":3.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273989","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}

引用次数: 0

The Angiofibrotic Switch in Retinal and Choroidal Vascular Diseases 视网膜和脉络膜血管疾病中的血管纤维化转换：血管生成和内皮-间充质转化的机制驱动因素。

IF 4.7 2区医学

American Journal of Pathology Pub Date : 2025-06-02 DOI: 10.1016/j.ajpath.2025.05.004

Fergus C. McLellan, Kelvin Huang, Elizabeth Wong, Daisy Y. Shu

{"title":"The Angiofibrotic Switch in Retinal and Choroidal Vascular Diseases","authors":"Fergus C. McLellan, Kelvin Huang, Elizabeth Wong, Daisy Y. Shu","doi":"10.1016/j.ajpath.2025.05.004","DOIUrl":"10.1016/j.ajpath.2025.05.004","url":null,"abstract":"<div><div>The angiofibrotic switch refers to the pathologic transition from active angiogenesis to fibrosis, a process that contributes to disease progression in retinal and choroidal neovascular diseases, such as age-related macular degeneration and proliferative diabetic retinopathy. This switch marks the replacement of newly formed, fragile blood vessels with fibrotic tissue, ultimately leading to scarring and permanent vision loss. Understanding this process is crucial, as fibrosis results in severe visual impairment and, currently, no anti-fibrotic therapies exist. Central to the angiofibrotic switch is endothelial-mesenchymal transition, a process where endothelial cells lose their vascular endothelial identity and acquire mesenchymal properties, contributing to extracellular matrix deposition and fibrosis. This review explores the cellular and molecular mechanisms underlying the angiofibrotic switch, emphasizing the interplay between angiogenesis, endothelial-mesenchymal transition, and metabolic dysregulation in driving fibrosis. Key mediators, such as transforming growth factor-β and vascular endothelial growth factor, are discussed in the context of their dual roles in promoting angiogenesis and fibrosis. This review underlines the need for early detection methods and targeted therapies to mitigate the angiofibrotic switch and improve outcomes in patients with neovascular retinal and choroidal diseases. By unraveling the complexities of this transition, this review aims to provide a framework for developing innovative diagnostic and therapeutic strategies to prevent fibrosis and mitigate vision loss in retinal and choroidal neovascular diseases.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 8","pages":"Pages 1363-1375"},"PeriodicalIF":4.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224033","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}

引用次数: 0

Mitochondrial Protease AFG3L2 Inhibits Ferroptosis of Intestinal Epithelial Cells through PPARA/GPX4 Signaling Pathway to Improve Experimental Enteritis 线粒体蛋白酶AFG3L2通过PPARA/GPX4信号通路抑制肠上皮细胞铁下垂，改善实验性肠炎。

IF 4.7 2区医学

American Journal of Pathology Pub Date : 2025-05-30 DOI: 10.1016/j.ajpath.2025.05.002

Wei Chen , Zeyan Xu , Jingjing Jiang , Wen Feng , Baiwen Li

{"title":"Mitochondrial Protease AFG3L2 Inhibits Ferroptosis of Intestinal Epithelial Cells through PPARA/GPX4 Signaling Pathway to Improve Experimental Enteritis","authors":"Wei Chen , Zeyan Xu , Jingjing Jiang , Wen Feng , Baiwen Li","doi":"10.1016/j.ajpath.2025.05.002","DOIUrl":"10.1016/j.ajpath.2025.05.002","url":null,"abstract":"<div><div>The pathogenesis of Crohn disease (CD) remains unclear, with mitochondrial dysfunction and ferroptosis emerging as important contributors. However, the specific mechanisms linking mitochondria, ferroptosis, and CD are not well understood. Through bioinformatics analysis using the Gene Expression Omnibus database, AFG3L2 was identified as a key mitochondrial gene and subjected to functional enrichment and immune infiltration analyses. Lipopolysaccharide-induced NCM460 cells were used <em>in vitro</em>. Overexpression of AFG3L2 inhibited the release of inflammatory factors, enhanced antioxidant capacity, and reduced reactive oxygen species production. In addition, AFG3L2 overexpression activated the peroxisome proliferator-activated receptor-A (PPARA) signaling pathway and promoted the nuclear translocation of PPARA. As a downstream target of PPARA, glutathione peroxidase 4 (GPX4) transcriptional activity was regulated by PPARA. AFG3L2 facilitated the binding of PPARA to the GPX4 promoter region, thereby enhancing GPX4 transcription. Importantly, the regulation of GPX4 by AFG3L2 was dependent on the activation of PPARA. 2,4,6-Trinitrobenzenesulfonic acid–induced colitis in mice was used as an <em>in vivo</em> model. Overexpression of AFG3L2 preserved mitochondrial ultrastructure, suppressed intestinal inflammation, and promoted the expression of PPARA and GPX4. In summary, the results of this study reveal the protective role of the AFG3L2/PPARA/GPX4 axis in maintaining intestinal mucosal integrity and suggest it as a potential therapeutic target for CD.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 8","pages":"Pages 1443-1456"},"PeriodicalIF":4.7,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198064","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}

引用次数: 0

Exploratory Study of Prognostic Plasma Biomarkers in Patients with Pulmonary Arterial Hypertension 肺动脉高压患者预后血浆生物标志物的探索性研究。

IF 4.7 2区医学

American Journal of Pathology Pub Date : 2025-05-30 DOI: 10.1016/j.ajpath.2025.04.018

Yukimitsu Kuwabara , Tetsuro Yokokawa , Sarah-Eve Lemay , Mélanie Sauvaget , Sandra Martineau , Sandra Breuils-Bonnet , François Potus , Sébastien Bonnet , Steeve Provencher , Olivier Boucherat

{"title":"Exploratory Study of Prognostic Plasma Biomarkers in Patients with Pulmonary Arterial Hypertension","authors":"Yukimitsu Kuwabara , Tetsuro Yokokawa , Sarah-Eve Lemay , Mélanie Sauvaget , Sandra Martineau , Sandra Breuils-Bonnet , François Potus , Sébastien Bonnet , Steeve Provencher , Olivier Boucherat","doi":"10.1016/j.ajpath.2025.04.018","DOIUrl":"10.1016/j.ajpath.2025.04.018","url":null,"abstract":"<div><div>Pulmonary arterial hypertension (PAH) is characterized by progressive pulmonary vascular lumen occlusion, ultimately leading to right ventricular failure and death. Risk stratification is essential for the management of patients with PAH. So far, B-type natriuretic peptide and its N-terminal pro-form are the only circulating biomarkers used as part of composite PAH risk assessment tools. Identification of other biomarkers of vascular or systemic origin may be valuable to provide additional information on disease severity and prognosis. Using proximity extension assay, >700 proteins related to oncology and neurology were measured in the plasma of 60 patients with PAH and 28 age- and sex-matched controls. Among the 114 proteins significantly up-regulated in patients with PAH, 14 were independently associated with death/lung transplantation after adjustment for the 2015 European Society of Cardiology/European Respiratory Society, the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) 2.0 risk scores, and the refined four-stratum risk assessment model. Among them, ectodysplasin A2 receptor (EDA2R), WAP four-disulfide core domain 2 (WFDC2), and tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) displayed incremental prognostic value on top of these predictive models. Combining previously published proteomic data sets generated from different panels with the same cohort, a set of 23 proteins was identified, many of which are strongly associated with chronological age, that predict outcome of patients with PAH after adjusting for risk assessment tools. In conclusion, proteins likely involved in the pathophysiology of the disease and potential candidates for prognostic enrichment were identified in this study.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 8","pages":"Pages 1376-1393"},"PeriodicalIF":4.7,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198063","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}

引用次数: 0

The American Journal of Pathology’s Contribution to Advancing the Understanding of the Pathogenesis of Atherosclerosis 《美国病理学杂志》对推进对动脉粥样硬化发病机制理解的贡献

IF 4.7 2区医学

American Journal of Pathology Pub Date : 2025-05-23 DOI: 10.1016/j.ajpath.2024.11.012

Avrum I. Gotlieb

引用次数: 0

Crosstalk between Hepatic Stellate Cells and Hepatic Macrophages in Metabolic Dysfunction–Associated Steatohepatitis 代谢功能障碍相关脂肪性肝炎中肝星状细胞和肝巨噬细胞间的串扰

IF 4.7 2区医学

American Journal of Pathology Pub Date : 2025-05-23 DOI: 10.1016/j.ajpath.2025.02.003

Haoran Zhong , Chen Liu , Zhiwei Huang , Peng Tan , Hao Chen , Wenguang Fu

引用次数: 0

Computationally Enabled Polychromatic Polarized Imaging Enables Mapping of Matrix Architectures that Promote Pancreatic Ductal Adenocarcinoma Dissemination 计算支持的多色偏振成像可以绘制促进胰腺导管腺癌扩散的基质结构。

IF 4.7 2区医学

American Journal of Pathology Pub Date : 2025-05-09 DOI: 10.1016/j.ajpath.2025.04.017

Guhan Qian , Hongrong Zhang , Yuming Liu , Michael Shribak , Kevin W. Eliceiri , Paolo P. Provenzano

{"title":"Computationally Enabled Polychromatic Polarized Imaging Enables Mapping of Matrix Architectures that Promote Pancreatic Ductal Adenocarcinoma Dissemination","authors":"Guhan Qian , Hongrong Zhang , Yuming Liu , Michael Shribak , Kevin W. Eliceiri , Paolo P. Provenzano","doi":"10.1016/j.ajpath.2025.04.017","DOIUrl":"10.1016/j.ajpath.2025.04.017","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDA) is a highly metastatic and lethal disease. In PDA, extracellular matrix (ECM) architectures, known as tumor-associated collagen signatures (TACSs), regulate invasion and metastatic spread in both early dissemination and late-stage disease. As such, TACS has been suggested as a biomarker to aid in pathologic assessment. However, despite its significance, approaches to quantitatively capture these ECM patterns currently require advanced optical systems with signaling processing analysis. Herein, an expansion of polychromatic polarized microscopy (PPM) with inherent angular information coupled with machine learning and computational pixel-wise analysis of TACS was used to accurately capture TACS architectures in hematoxylin and eosin–stained histology sections directly through PPM contrast. Moreover, PPM facilitated identification of transitions to dissemination architectures (ie, transitions from sequestration through expansion to dissemination from both pancreatic intraepithelial neoplasias and throughout PDA). Lastly, PPM evaluation of architectures in liver metastases, the most common metastatic site for PDA, demonstrated TACS-mediated focal and local invasion as well as identification of unique patterns anchoring aligned fibers into normal-adjacent tumor, suggesting that these patterns may be precursors to metastasis expansion and local spread from micrometastatic lesions. Combined, these findings demonstrate that PPM coupled to computational platforms is a powerful tool for analyzing ECM architecture that can be used to advance cancer microenvironment studies and provide clinically relevant diagnostic information.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 7","pages":"Pages 1242-1253"},"PeriodicalIF":4.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966629","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}

引用次数: 0

The Patatin-Like Phospholipase Domain-Containing 3 148M Variant Exacerbates Alcohol-Induced Liver Injury and Tumorigenesis in Mice. PNPLA3 148M变异加重了小鼠酒精诱导的肝损伤和肿瘤发生。

IF 3.6 2区医学

American Journal of Pathology Pub Date : 2025-05-09 DOI: 10.1016/j.ajpath.2025.04.014

Jung-Hyo Cho, Hyeong-Geug Kim, Menghao Huang, Shen Wang, Sheng Liu, Alex Lu, Kyle McCrocklin, Yang Zhang, Zhigang Fang, Juexin Wang, Wanqing Liu, Jun Wan, X Charlie Dong

{"title":"The Patatin-Like Phospholipase Domain-Containing 3 148M Variant Exacerbates Alcohol-Induced Liver Injury and Tumorigenesis in Mice.","authors":"Jung-Hyo Cho, Hyeong-Geug Kim, Menghao Huang, Shen Wang, Sheng Liu, Alex Lu, Kyle McCrocklin, Yang Zhang, Zhigang Fang, Juexin Wang, Wanqing Liu, Jun Wan, X Charlie Dong","doi":"10.1016/j.ajpath.2025.04.014","DOIUrl":"10.1016/j.ajpath.2025.04.014","url":null,"abstract":"<p><p>Patatin-like phospholipase domain-containing 3 (PNPLA3) protein 148M variant is strongly associated with cirrhosis and hepatocellular carcinoma (HCC); however, the underlying mechanisms remain elusive. This study aimed to elucidate the role of the PNPLA3<sup>148M</sup> variant in alcohol-related HCC development. Control and humanized PNPLA3<sup>148M</sup> transgenic mice were fed with an ethanol-containing diet for 12 weeks. The animals were examined for liver tumors. After the alcohol feeding, the PNPLA3<sup>148M</sup> mice had twofold higher liver cancer incidence rates and larger tumor sizes than those in the control mice. Cancer stem cell markers in the PNPLA3<sup>148M</sup> mouse livers were elevated relative to those in the control mouse livers. Alcohol detoxification was impaired in the PNPLA3<sup>148M</sup> mouse livers. Hepatic oxidative stress and DNA damage were elevated in the PNPLA3<sup>148M</sup> mice. Wnt/β-catenin and Yes-associated protein (YAP) and WW domain-containing transcription regulator 1 (TAZ) were activated in the PNPLA3<sup>148M</sup> mouse livers. The data suggest that the PNPLA3<sup>148M</sup> variant has a strong interaction with alcohol in HCC development through attenuation of alcohol detoxification and promotion of oncogenic pathways. Targeting the PNPLA3<sup>148M</sup> variant might be useful for the prevention or treatment of alcohol-associated HCC in patients carrying this variant.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deciphering the Dialogue between Brain Tumors, Neurons, and Astrocytes 破解脑肿瘤、神经元和星形胶质细胞之间的对话。

IF 4.7 2区医学

American Journal of Pathology Pub Date : 2025-05-07 DOI: 10.1016/j.ajpath.2025.04.013

Leevi H. Westerlund , Camilla K. Bergström , Pirjo M. Laakkonen , Vadim Le Joncour

{"title":"Deciphering the Dialogue between Brain Tumors, Neurons, and Astrocytes","authors":"Leevi H. Westerlund , Camilla K. Bergström , Pirjo M. Laakkonen , Vadim Le Joncour","doi":"10.1016/j.ajpath.2025.04.013","DOIUrl":"10.1016/j.ajpath.2025.04.013","url":null,"abstract":"<div><div>Glioblastoma and brain metastases from peripheral tumors account for most cases of tumors in the central nervous system while also being the deadliest. From a structural point of view, malignant brain tumors are classically characterized by hypercellularity of glioma and vascular endothelial cells. Given these atypical histologic features, glioblastoma and brain metastases have long been considered as “foreign” entities with few to no connections to the brain parenchyma. The identification of intricate connections established between glioblastoma cells and the brain parenchyma paired with the ability of peripheral metastatic cells to form functional synapses with neurons challenged the concept of brain tumors disconnected from the central nervous system. Tumor cell integration to the brain parenchyma alters brain functionality in patients and accelerates cancer progression. Next-generation precision medicine should therefore attempt to disconnect brain cancer cells from the brain. This review encompasses recent discoveries in the mechanisms underlying these relationships and discusses the impact of these connections on tumor progression. It also summarizes the therapeutic opportunities of interrupting the dialogue between healthy and neoplastic brains.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 7","pages":"Pages 1193-1208"},"PeriodicalIF":4.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964178","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}

引用次数: 0