journal
https://read.qxmd.com/read/38537936/a-deep-learning-based-assessment-pipeline-for-intraepithelial-and-stromal-tumor-infiltrating-lymphocytes-in-high-grade-serous-ovarian-carcinoma
#1
JOURNAL ARTICLE
Kohei Hamada, Ryusuke Murakami, Akihiko Ueda, Yoko Kashima, Chiho Miyagawa, Mana Taki, Koji Yamanoi, Ken Yamaguchi, Junzo Hamanishi, Sachiko Minamiguchi, Noriomi Matsumura, Masaki Mandai
Tumor-infiltrating lymphocytes (TILs) are associated with improved survival in patients with epithelial ovarian cancer. However, the evaluation of TILs has not been applied to routine clinical practice due to reproducibility issues. We developed two convolutional neural network models to detect TILs and to determine their spatial location in whole-slide images, and established a spatial assessment pipeline to objectively quantify intraepithelial and stromal TILs in patients with high-grade serous ovarian carcinoma...
March 25, 2024: American Journal of Pathology
https://read.qxmd.com/read/38537935/cryptochrome-2-suppresses-epithelial-mesenchymal-transition-by-promoting-trophoblastic-ferroptosis-in-unexplained-recurrent-spontaneous-abortion
#2
JOURNAL ARTICLE
Faminzi Li, Liantao Guo, Mengqi Zhou, Lu Han, Shujuan Wu, Lianzhi Wu, Jing Yang
Unexplained recurrent spontaneous abortion (URSA) is a serious reproductive issue that affects women of childbearing age. Studies have shown a close association between disrupted circadian rhythm and impaired epithelial-mesenchymal transition (EMT) process in trophoblasts during URSA, though the underlying mechanism has not been elaborated. This study aims to investigate the regulatory relationship between circadian rhythm gene cryptochrome 2 (CRY2) and ferroptosis on the migratory ability of trophoblast cells...
March 25, 2024: American Journal of Pathology
https://read.qxmd.com/read/38537934/different-oncogenes-and-reproductive-histories-shape-the-progression-of-distinct-premalignant-clones-in-multistage-mouse-breast-cancer-models
#3
JOURNAL ARTICLE
Maryknoll Linscott, Jerry Ruizhe Ren, Shelley Gestl, Edward J Gunther
A remote carcinogen exposure can predispose to breast cancer onset decades later, suggesting carcinogen-induced mutations generate long-lived premalignant clones. How subsequent events influence the progression of specific premalignant clones remains poorly understood. Here, we generated multistage mouse models of mammary carcinogenesis by combining chemical carcinogen exposure (using 7,12-dimethylbenzanthracene, DMBA) with transgenes that enable inducible expression of one of two clinically relevant mammary oncogenes: c-MYC (MYC) or PIK3CAH1047R (PIK)...
March 25, 2024: American Journal of Pathology
https://read.qxmd.com/read/38537933/serum-fusion-transcripts-to-assess-the-risk-of-hepatocellular-carcinoma-and-the-impact-of-cancer-treatment-through-machine-learning
#4
JOURNAL ARTICLE
Yan-Ping Yu, Silvia Liu, David Geller, Jian-Hua Luo
Hepatocellular carcinoma (HCC) is one of the most lethal malignancies for human. Early diagnosis of HCC is crucial in reducing the mortality of the disease. In this study, a panel of 9 fusion transcripts in the serum samples from 136 individuals using TaqMan qRT-PCR was analyzed. Seven fusion genes were frequently detected in the serum samples of HCC patients, including MAN2A1-FER (100%), SLC45A2-AMACR (62.3%), ZMPSTE24-ZMYM4 (62.3%), PTEN-NOLC1 (57.4%), CCNH-C5orf30 (55.7%), STAMBPL1-FAS (26.2%) and PCMTD1-SNTG1 (16...
March 25, 2024: American Journal of Pathology
https://read.qxmd.com/read/38537932/tnf-receptor-2-signals-clear-cell-renal-carcinoma-proliferation-via-phosphorylated-4ebp1-and-mitochondrial-gene-translation
#5
JOURNAL ARTICLE
Rafia S Al-Lamki, Aviva M Tolkovsky, Mohammad Alawwami, WanHua Lu, Sarah F Field, Jun Wang, Jordan S Pober, John R Bradley
Clear cell renal cell carcinoma (ccRCC), a tubular epithelial malignancy, secretes tumor necrosis factor (TNF) which signals ccRCC cells in an autocrine manner via two cell surface receptors, TNFR1 and TNFR2, to activate shared and distinct signalling pathways. Selective ligation of TNFR2 was shown to drive cell cycle entry of malignant cells via a signalling pathway involving Etk, VEGFR2, PI3K, Akt, pSer727 -Stat3 and mTOR. In this study, phosphorylated-4EBP1 serine 65 (pSer65 -4EBP1) is identified as a downstream target of this TNFR2 signalling pathway...
March 25, 2024: American Journal of Pathology
https://read.qxmd.com/read/38493927/sortilin-in-biliary-epithelial-cells-promotes-ductular-reaction-and-fibrosis-during-cholestatic-injury
#6
JOURNAL ARTICLE
Einav Hubel, Anat Neuman, Sigal Fishman, Ortal Schaffer, Noam Erez, Bander Abu Shrkihe, Yuval Shteingard, Tamar Gross, Oren Shibolet, Chen Varol, Isabel Zvibel
Cholestatic injuries are accompanied by a ductular reaction, initiated by proliferation and activation of biliary epithelial cells (BEC), leading to fibrosis. Sortilin (Sort1) facilitates IL-6 secretion and leukemia inhibitory factor (LIF) signaling. This study investigated the interplay between sortilin, IL-6 and LIF in cholestatic injury-induced ductular reaction, morphogenesis of new ducts and fibrosis. Cholestatic injury was induced by bile duct ligation (BDL) in WT and Sort1-/- mice, with or without augmentation of IL-6 or LIF...
March 15, 2024: American Journal of Pathology
https://read.qxmd.com/read/38493926/prediction-of-met-overexpression-in-lung-adenocarcinoma-from-hematoxylin-and-eosin-images
#7
JOURNAL ARTICLE
Kshitij Ingale, Sun Hae Hong, Josh S K Bell, Abbas Rizvi, Amy Welch, Lingdao Sha, Irvin Ho, Kunal Nagpal, Aïcha Bentaieb, Rohan P Joshi, Martin C Stumpe
MET protein overexpression is a targetable event in non-small cell lung cancer (NSCLC) and is the subject of active drug development. Challenges in identifying patients for these therapies include lack of access to validated testing, such as standardized immunohistochemistry (IHC) assessment, and consumption of valuable tissue for a single gene/protein assay. Development of pre-screening algorithms using routinely available digitized hematoxylin and eosin (H&E)-stained slides to predict MET overexpression could promote testing for those who will benefit most...
March 15, 2024: American Journal of Pathology
https://read.qxmd.com/read/38492733/developmental-dopaminergic-signaling-modulates-neural-circuit-formation-and-contributes-to-autism-spectrum-disorder-asd-related-phenotypes
#8
JOURNAL ARTICLE
Xiaojuan Lu, Yixing Song, Jiaqi Wang, Yunyun Cai, Siwan Peng, Jiaqi Lin, Biqin Lai, Junjie Sun, Tianqing Liu, Gang Chen, Lingyan Xing
Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with a complex etiology. Recent evidence suggests that dopamine plays a crucial role in neural development. However, it remains unclear whether and how disrupted dopaminergic signaling during development contributes to ASD. In this study, human brain RNA-seq transcriptome analysis revealed a significant correlation between changes in dopaminergic signaling pathways and neural developmental signaling in ASD patients. In the zebrafish model, disrupted developmental dopaminergic signaling led to neural circuit abnormalities and behavior reminiscent of autism...
March 14, 2024: American Journal of Pathology
https://read.qxmd.com/read/38467190/this-month-in-ajp
#9
JOURNAL ARTICLE
(no author information available yet)
No abstract text is available yet for this article.
March 9, 2024: American Journal of Pathology
https://read.qxmd.com/read/38442804/deletion-of-myd88-in-t-cells-improves-anti-tumor-activity-in-melanoma
#10
JOURNAL ARTICLE
Abraham L Bayer, Darwing Padilla-Rolon, Sasha Smolgovsky, Philip Hinds, Pilar Alcaide
Cytotoxic CD8+ T-cells are central to the anti-tumor immune response by releasing cytotoxic granules that kill tumor cells. They are activated by antigen presenting cells, which become activated by DAMPs (damage associated molecular patterns) through MyD88 (myeloid differentiation response 88). However, the suppressive tumor microenvironment promotes T-cell tolerance to tumor antigens in part by enhancing the activity of immune checkpoint molecules that prevent CD8+ T-cell activation and cytotoxicity. We recently reported that MyD88 limits CD4+ T-cell activation during cardiac adaptation to stress and hypothesized that a similar mechanism exists in CD8+ T-cells which could be modulated to improve anti-tumor immunity...
March 3, 2024: American Journal of Pathology
https://read.qxmd.com/read/38442803/ficolin-a-2-aggravated-severe-lung-injury-through-nets-mediated-by-gsdmd-induced-pyroptosis
#11
JOURNAL ARTICLE
Li Huang, Xiaowu Tan, Weixia Xuan, Qing Luo, Li Xie, Yunzhu Xi, Rong Li, Li Li, Feifan Li, Meiyun Zhao, Yongliang Jiang, Xu Wu
Neutrophil extracellular traps (NETs) and pyroptosis are critical events in lung injury. We aimed to investigate whether Ficolin-A influences NET formation through pyroptosis to exacerbate lipopolysaccharides (LPS)-induced lung injury. The expression of Ficolin-A/2, NETs, and pyroptosis-related molecules was investigated in animal and cell models. Knockout and knockdown (recombinant protein) methods were employed to elucidate regulatory mechanisms. Pearson's correlation coefficient was utilized to analyze the correlation between Ficolins and pyroptosis- and NET-related markers in clinical samples...
March 3, 2024: American Journal of Pathology
https://read.qxmd.com/read/38432512/tumor-necrosis-factor-alpha-induced-protein-8-like-1-binds-to-protein-arginine-methyltransferase-1-to-suppress-the-methylation-of-signal-transducer-and-activator-of-transcription-3-and-cell-growth-in-oral-squamous-cell-carcinoma
#12
JOURNAL ARTICLE
Bing Liu, Wen Si, Bo Wei, Xuan Zhang, Peng Chen
Tumor necrosis factor alpha-induced protein 8 (TIPE/TNFAIP8/OXi-α) family are a newly discovered series of proteins involved in immune regulation and tumorigenesis. TIPE1, as the member of TIPE/TNFAIP8/OXi-α family, has emerged as an anti-cancer drug target as it is promotes cancer cell apoptosis and inhibits cell proliferation. Here, the current study aimed to systematically reveal that TIPE1 regulates the activity of protein arginine methyltransferase 1 (PRMT1) and the subsequent methylation of signal transducer and activator of transcription 3 (STAT3) to suppress oral squamous cell carcinoma (OSCC) growth...
March 1, 2024: American Journal of Pathology
https://read.qxmd.com/read/38417699/the-unrecognized-role-of-ninjurin-2-in-inflammation-metabolism-and-pyroptosis
#13
JOURNAL ARTICLE
Juan Liu, Wenwei Hu, Zhaohui Feng
No abstract text is available yet for this article.
February 28, 2024: American Journal of Pathology
https://read.qxmd.com/read/38423356/reg%C3%AE-mitigates-radiation-induced-enteritis-by-preserving-mucin-secretion-and-sustaining-microbiome-homeostasis
#14
JOURNAL ARTICLE
Xiangzhan Zhu, Ya Li, Xue Tian, Yiming Jing, Zimeng Wang, Lingling Yue, Jianhui Li, Ling Wu, Xinkui Zhou, Zhidan Yu, Yaodong Zhang, Fangxia Guan, Minglei Yang, Bianhong Zhang
Radiation-induced enteritis, a significant concern in abdominal radiation therapy, is closely associated with gut microbiota dysbiosis. The critical mucus layer plays a pivotal role in preventing the translocation of commensal and pathogenic microbes. While the significant expression of REGγ in intestinal epithelial cells is well established, its role in modulating mucus layer and gut microbiota remains enigmatic. Current study revealed notable changes in gut microorganisms and metabolites in irradiated mice lacking REGγ, as opposed to wild-type mice...
February 27, 2024: American Journal of Pathology
https://read.qxmd.com/read/38423355/decreased-proteasomal-function-exacerbates-er-stress-induced-chronic-inflammation-in-obese-adipose-tissue
#15
JOURNAL ARTICLE
Shimpei Nakagawa, Aya Fukui-Miyazaki, Takuma Yoshida, Yasushi Ishii, Eri Murata, Koji Taniguchi, Akihiro Ishizu, Masanori Kasahara, Utano Tomaru
Low-grade chronic inflammation contributes to both aging and the pathogenesis of age-related diseases. White adipose tissue (WAT) in obese individuals exhibits chronic inflammation, which is associated with obesity-related disorders. Aging exacerbates obesity-related inflammation in WAT; however, the molecular mechanisms underlying chronic inflammation and its exacerbation by aging remain unclear. Age-related decline in activity of the proteasome, a multi-subunit proteolytic complex, has been implicated in age-related diseases...
February 27, 2024: American Journal of Pathology
https://read.qxmd.com/read/38417698/the-role-of-microrna-and-long-non-coding-rna-in-cholestatic-liver-diseases
#16
REVIEW
Yudian Zhang, Ying Liu, Wen Huo, Longfei He, Bowen Li, Hui Wang, Fanyin Meng, Chenggang Duan, Bingru Zhou, Jinbo Wu, Rong Chen, Juan Xing, Ying Wan
Cholestatic liver diseases encompass a range of organic damages, metabolic disorders, and dysfunctions within the hepatobiliary system, arising from various pathogenic causes. These factors contribute to disruptions in bile production, secretion, and excretion. Cholestatic liver diseases can be classified into intrahepatic and extrahepatic cholestasis according to the location of occurrence. The etiology of cholestatic liver diseases are complex, which include drugs, poisons, viruses, parasites, bacteria, autoimmune responses, tumors and genetic metabolism...
February 26, 2024: American Journal of Pathology
https://read.qxmd.com/read/38417697/ferroptosis-contributes-to-microvascular-dysfunction-in-diabetic-retinopathy
#17
JOURNAL ARTICLE
Qun Liu, Chao-Qun Liu, Wan-Zhao Yi, Pei-Wen Ouyang, Bo-Fan Yang, Qi Liu, Jing-Min Liu, Ya-Ni Wu, Ai-Rong Liang, Yu-Hong Cui, Jing Meng, Xiu-Yun Li, Hong-Wei Pan
Ferroptosis is a new form of cell death characterized by iron-dependent lipid peroxidation. Whether ferroptosis is involved in retinal microvascular dysfunction under diabetic condition is not known. The expression of ferroptosis related genes in patients with proliferative diabetic retinopathy (PDR) and in diabetic mice was determined with RT-qPCR. Reactive oxygen species (ROS), iron content, lipid peroxidation products, and ferroptosis-associated proteins in the cultured human retinal microvascular endothelial cells (HRMECs) and in the retina of diabetic mice were examined...
February 26, 2024: American Journal of Pathology
https://read.qxmd.com/read/38417696/serine-supports-epithelial-and-immune-cell-function-in-colitis
#18
JOURNAL ARTICLE
Ji Dong K Bai, Suchandrima Saha, Michael Wood, Bo Chen, Jinyu Li, Lukas E Dow, David C Montrose
Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract that are largely driven by immune cell activity, while mucosal healing is critical for remission. Serine is a non-essential amino acid that supports epithelial and immune cell metabolism and proliferation, however, whether these roles impact IBD pathogenesis is not well understood. Here, we show that serine synthesis increases selectively in the epithelial cells of colons from patients with IBD and murine models of colitis...
February 26, 2024: American Journal of Pathology
https://read.qxmd.com/read/38417695/metallothionein-alleviates-glutathione-depletion-induced-oxidative-cardiomyopathy-through-cisd1-dependent-regulation-of-ferroptosis-in-murine-hearts
#19
JOURNAL ARTICLE
Feng-Juan Li, Shouzhi Fu, Hua Ye, Yi-Han Hu, Jianxin Chen, Jamie R Privratsky, Wei Yu, Feng Dong, Russel J Reiter, Maolong Dong, Jun Guo, Jun Ren
This study was designed to discern the effect of heavy scavenger metallothionein on glutathione (GSH) deprivation-evoked cardiac anomalies and mechanisms involved with an emphasis on ferroptosis. WT and cardiac metallothionein transgenic mice received GSH synthase inhibitor buthionine sulfoximine (BSO, 30 mM in drinking water) for 14 days prior to assessment of myocardial morphology and function. BSO evoked cardiac remodeling and contractile anomalies including cardiac hypertrophy, interstitial fibrosis, enlarged left ventricular chambers, deranged ejection fraction, fraction shortening, cardiomyocyte contractile capacity, intracellular Ca2+ handling, sarcoplasmic reticulum Ca2+ reuptake, loss of mitochondrial integrity (mitochondrial swelling, loss of aconitase activity), mitochondrial energy deficit, carbonyl damage, lipid peroxidation, ferroptosis and apoptosis...
February 26, 2024: American Journal of Pathology
https://read.qxmd.com/read/38417694/impaired-hepatic-vldl-secretion-promotes-tumorigenesis-and-is-accelerated-with-fabp1-deletion
#20
JOURNAL ARTICLE
Elizabeth P Newberry, Elizabeth A Molitor, Allen Liu, Kamyar Chong, Xiuli Liu, Cristina Alonso, Jose M Mato, Nicholas O Davidson
Genetic polymorphisms that impair VLDL secretion are linked to hepatic steatosis, fibrosis and hepatocellular cancer (HCC). Liver-specific deletion of microsomal triglyceride transfer protein (Mttp-LKO) impairs VLDL assembly, promoting hepatic steatosis and fibrosis, which are attenuated in Mttp-LKO X Fabp1 null (Fabp1/Mttp DKO) mice. Here we examine the impact of impaired VLDL secretion in Mttp-LKO mice on HCC incidence and progression in comparison to Fabp1/Mttp DKO mice. DEN treated Mttp-LKO mice exhibited steatosis with increased tumor burden compared to flox controls, while diethylnitrosamine (DEN)- treated Fabp1/Mttp DKO mice exhibited a paradoxical increase in tumor burden and >50% mortality by 50 weeks...
February 26, 2024: American Journal of Pathology
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