journal
https://read.qxmd.com/read/38631549/stromal-rigidity-stress-accelerates-pancreatic-intraepithelial-neoplasia-progression-and-chromosomal-instability-via-nuclear-ptk2-localization
#1
JOURNAL ARTICLE
Li-Yun Ding, Chia-Jung Chang, Szu-Ying Chen, Kuan-Lin Chen, Yueh-Shan Li, Yun-Chieh Wu, Ting-Yi Hsu, Hsin-Yu Ying, Hsin-Yi Wu, Michael W Hughes, Chia-Yih Wang, Chih-Han Chang, Ming-Jer Tang, Woei-Jer Chuang, Yan-Shen Shan, Chia-Jung Chang, Po-Hsien Huang
Since the mechanotransduction by stromal stiffness stimulates the rupture and repair of the nuclear envelope in pancreatic progenitor cells, accumulated genomic aberrations are under selection in the tumor microenvironment. Analysis of cell growth, micronuclei, and γH2AX foci links to mechanotransduction pressure in vivo during serial orthotopic passages of mouse KrasLSL-G12D/+ ;Trp53flox/flox ;Pdx1-Cre (KPC) cancer cells in the tumor and in migrating through the size-restricted 3μm micropores. To search for pancreatic cancer cell-of-origin, analysis of single-cell datasets revealed that the ECM shapes an alternate route of acinar-ductal transdifferentiation of acinar cells into a central hub of elegantly restrained TOP2A-overexpressing cancer cells that spread out as unique cancer clusters with copy number amplifications in MYC-PTK2 locus and PIK3CA...
April 15, 2024: American Journal of Pathology
https://read.qxmd.com/read/38599461/differentiation-of-type-17-mait-cells-in-circulation-contributes-to-the-severity-of-sepsis
#2
JOURNAL ARTICLE
Xinying Li, Sicheng Fu, Hao Cheng, Min Ma, Zijian Song, Jun Li, Shuang Wu, Chong Zhang, Xiaoxia Wang, Maoyu Tang, Xuexue Pu, Qiang Ji, Jinquan Liang, Zhibin Zhao, Heinrich Körner, Bin Li, Min Shao, Hua Wang
Mucosal-associated invariant T (MAIT) cells are essential in defending against infection. Sepsis is a systemic inflammatory response to infection and a leading cause of death. The relationship between the overall competency of the host immune response and disease severity is not fully elucidated. This study identified a higher proportion of circulating MAIT17 with expression of IL-17A and RORγt in sepsis patients. The proportion of MAIT17 was correlated with the severity of sepsis. Single-cell RNA sequencing (scRNA-seq) analysis revealed an enhanced expression of lactate dehydrogenase A (LDHA) in MAIT17 in sepsis patients...
April 8, 2024: American Journal of Pathology
https://read.qxmd.com/read/38599460/this-month-in-ajp
#3
JOURNAL ARTICLE
(no author information available yet)
No abstract text is available yet for this article.
April 8, 2024: American Journal of Pathology
https://read.qxmd.com/read/38588853/graph-perceiver-network-for-lung-tumor-and-bronchial-premalignant-lesion-stratification-from-histopathology
#4
JOURNAL ARTICLE
Rushin H Gindra, Yi Zheng, Emily J Green, Mary E Reid, Sarah A Mazzilli, Daniel T Merrick, Eric J Burks, Vijaya B Kolachalama, Jennifer E Beane
Bronchial premalignant lesions (PMLs) precede the development of invasive lung squamous carcinoma (LUSC), posing a significant challenge in distinguishing those likely to advance to LUSC from those that might regress without intervention. In this context, we present a novel computational approach, the Graph Perceiver Network (GRAPE-Net), leveraging hematoxylin and eosin (H&E) stained whole slide images (WSIs) to stratify endobronchial biopsies of PMLs across a spectrum from normal to tumor lung tissues...
April 6, 2024: American Journal of Pathology
https://read.qxmd.com/read/38588852/role-of-hnf4alpha-cmyc-interaction-in-cde-diet-induced-liver-injury-and-regeneration
#5
JOURNAL ARTICLE
Manasi Kotulkar, Julia Barbee, Diego Paine-Cabrera, Dakota Robarts, Maura O'Neil, Udayan Apte
Hepatocyte nuclear factor 4 alpha (HNF4α) is a nuclear factor essential for liver function that regulates the expression of cMyc and plays an important role in proliferation and differentiation during liver regeneration. This study investigated the role of HNF4α-cMyc interaction in regulating liver injury and regeneration using the choline-deficient and ethionine-supplemented (CDE) diet model. WT, hepatocyte-specific HNF4α-KO, cMyc-KO, and HNF4α-cMyc double knockout (DKO) mice were fed a CDE diet for one week to induce subacute liver injury...
April 6, 2024: American Journal of Pathology
https://read.qxmd.com/read/38588851/tfe3-pi3k-akt-mtor-axis-in-renal-cell-carcinoma-affects-tumor-microenvironment
#6
JOURNAL ARTICLE
Chung Su Hwang, Yun Kyung Kang, Ji Yun Kim, So Hyun Shin, Joon Young Park, Ji Sun Song, So Young Kim, Se Jin Jung, Jung Hee Lee, Ju-Young Na, Dong Hoon Shin, Jee Yeon Kim, Sung Woo Park, Hyun Jung Lee
The role of the PI3K/Akt pathway in renal cell carcinoma (RCC) progression, metastasis, and resistance to therapies has not been thoroughly investigated. Transcription factor E3 (TFE3) expression is related to poorer prognosis and tumor microenvironment in patients with RCC. We aimed to determine the relationship between TFE3 and the PI3K/Akt pathway. TFE3 downregulation was achieved by transient transfection of small interfering RNA (siRNA) and short hairpin RNA (shRNA) in UOK146 cells. TFE3 overexpression was induced by transient transfection with pcDNA3...
April 6, 2024: American Journal of Pathology
https://read.qxmd.com/read/38548270/glut1-promotes-nlrp3-inflammasome-activation-of-airway-epithelium-in-lipopolysaccharide-induced-acute-lung-injury
#7
JOURNAL ARTICLE
Jiehong Li, Yijian Li, Guanjin Chen, Yan Liang, Jianpeng Xie, Shuiying Zhang, Kai Zhong, Tong Jiang, Haisu Yi, Haixiong Tang, Xin Chen
Acute lung injury (ALI) is a devastating clinical disease caused by different factors, with high morbidity and mortality. It has been shown that lung injury and inflammation caused by lipopolysaccharide (LPS) can be modulated by NLRP3 inflammasome activation, yet its exact function within the airway epithelium is still unknown. Meanwhile, glucose transporter protein 1 (GLUT1) has been shown to contribute to a number of inflammatory illnesses, including ALI. The present study was aimed to assess GLUT1's function in NLRP3 inflammasome activation of airway epithelium in LPS-induced acute lung injury...
March 26, 2024: American Journal of Pathology
https://read.qxmd.com/read/38548269/enhanced-optic-nerve-expansion-and-altered-ultrastructure-of-elastic-fibers-induced-by-lysyl-oxidase-inhibition-in-a-mouse-model-of-marfan-syndrome
#8
JOURNAL ARTICLE
Hang-Jing Wu, Evan Krystofiak, John Kuchtey, Rachel W Kuchtey
Two major constituents of exfoliation material (XFM), fibrillin- 1 and lysyl oxidase-like 1 (encoded by FBN1 and LOXL1) are implicated in exfoliation glaucoma (XFG), yet their individual contributions to ocular phenotype are minor. To test the hypothesis that a combination of FBN1 mutation and LOXL1 deficiency exacerbates ocular phenotypes, pan-LOX inhibitor, β-aminopropionitrile (BAPN) was used to treat adult wild-type (wt) and Fbn1C1041G/+ mice for 8 weeks and their eyes were examined. Although intraocular pressure was not changed and XFM not detected in the eyes, BAPN treatment worsened optic nerve and axon expansion in Fbn1C1041G/+ mice, an early sign of axonal damage in rodent models of glaucoma...
March 26, 2024: American Journal of Pathology
https://read.qxmd.com/read/38548268/tgf%C3%AE-1-drives-integrin-dependent-pericyte-migration-and-microvascular-destabilization-in-fibrotic-disease
#9
JOURNAL ARTICLE
Amanda S Pellowe, Michelle J Wu, Tae-Yun Kang, Tracy D Chung, Adrian Ledesma-Mendoza, Erica Herzog, Andre Levchenko, Ian Odell, John Varga, Anjelica L Gonzalez
Interactions between endothelial cells (EC) and mural pericytes (PC) are critical to maintaining the stability and function of the microvascular wall. Abnormal interactions between these two cell types are a hallmark of progressive fibrotic diseases, such as systemic sclerosis (SSc, scleroderma). However, the role that PCs play in signaling microvascular dysfunction remains underexplored. It is hypothesized that integrin-matrix interactions contribute to PC migration from the vascular wall and conversion into interstitial myofibroblasts...
March 26, 2024: American Journal of Pathology
https://read.qxmd.com/read/38548267/poorly-differentiated-hepatocellular-carcinoma-cells-avoid-apoptosis-by-interacting-with-t-cells-via-cd40-cd40l-linkage
#10
JOURNAL ARTICLE
Hanh Vinh Ngo, Thuy Thi Thanh Le, Hieu Ngoc Vu, Hai Hoang, Hiroko Ikenaga, Misako Sato-Matsubara, Sawako Uchida-Kobayashi, Hayato Urushima, Khanh Van Nguyen, Ha Thi Nguyen, Hiroji Shinkawa, Shoji Kubo, Naoko Ohtani, Masaru Enomoto, Akihiro Tamori, Norifumi Kawada
Hepatocellular carcinoma (HCC) is associated with elevated soluble CD40 levels in our previous study. Here we aimed to investigate CD40's role in liver tumor progression. We examined CD40 levels in HCC patient tissues and various HCC cell lines, studying their interaction with CD4+ T cells. RNA sequencing analysis was performed to explore the mechanisms of CD40 induction. Poorly differentiated HCC tumour tissues exhibited high membrane-bound CD40 (mCD40) expression, in contrast to non-tumour areas. Poorly differentiated HCC cell lines showed high expression of mCD40 with low CD40 promoter methylation which were opposite of well-differentiated ones...
March 26, 2024: American Journal of Pathology
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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