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JOURNAL ARTICLE
Derya Bakırdöğen, Kıvanç Görgülü, Hana Algül
Advances in the digital pathology field have facilitated the characterization of histology samples for both clinical and preclinical research. However, uncovering subtle correlations between bioimaging, clinical and molecular parameters requires extensive statistical analysis. As a user-friendly software, Hourglass, simplifies multiparametric dataset analysis through intuitive data visualization and statistical tools. Systemic analysis of interleukin-6 (IL-6)/pStat3 signaling pathway through Hourglass revealed differences in regional immune cell composition within tumors...
February 25, 2024: Journal of Pathology
#22
JOURNAL ARTICLE
Zhaohua Cai, Yangjing Jiang, Huan Tong, Min Liang, Yijie Huang, Liang Fang, Feng Liang, Yunwen Hu, Xin Shi, Jian Wang, Zi Wang, Qingqi Ji, Huanhuan Huo, Linghong Shen, Ben He
Liver kinase B1 (Lkb1), encoded by serine/threonine kinase (Stk11), is a serine/threonine kinase and tumor suppressor that is strongly implicated in Peutz-Jeghers syndrome (PJS). Numerous studies have shown that mesenchymal-specific Lkb1 is sufficient for the development of PJS-like polyps in mice. However, the cellular origin and components of these Lkb1-associated polyps and underlying mechanisms remain elusive. In this study, we generated tamoxifen-inducible Lkb1flox/flox ;Myh11-Cre/ERT2 and Lkb1flox/flox ;PDGFRα-Cre/ERT2 mice, performed single-cell RNA sequencing (scRNA-seq) and imaging-based lineage tracing, and aimed to investigate the cellular complexity of gastrointestinal polyps associated with PJS...
February 23, 2024: Journal of Pathology
#23
JOURNAL ARTICLE
Kaifeng Jin, Jingtong Xu, Xiaohe Su, Ziyue Xu, Bingyu Li, Ge Liu, Hailong Liu, Yiwei Wang, Yu Zhu, Le Xu, Weijuan Zhang, Zhaopei Liu, Zewei Wang, Yuan Chang, Jiejie Xu
TP53 mutation is one of the most common genetic alterations in urothelial carcinoma (UrCa), and heterogeneity of TP53 mutants leads to heterogeneous clinical outcomes. This study aimed to investigate the clinical relevance of specific TP53 mutations in UrCa. In this study, a total of eight cohorts were enrolled, along with matched clinical annotation. TP53 mutations were classified as disruptive and nondisruptive according to the degree of disturbance of p53 protein function and structure. We evaluated the clinical significance of TP53 mutations in our local datasets and publicly available datasets...
February 21, 2024: Journal of Pathology
#24
JOURNAL ARTICLE
Ewa Rajpert-De Meyts, Anne Goriely, Kristian Almstrup
Testicular germ cell tumours (TGCTs) derived from immature (type I) and pluripotent germ cell neoplasia in situ (GCNIS, type II) are characterised by remarkable phenotypic heterogeneity and plasticity. In contrast, the rare spermatocytic tumour (SpT, type III), derived from mature spermatogonia, is considered a homogenous and benign tumour but may occasionally present as an anaplastic or an aggressive sarcomatoid tumour. While various oncogenic processes had been proposed, the precise mechanism driving malignant progression remained elusive until the molecular characterisation of a series of atypical SpTs described in a recent issue of The Journal of Pathology...
February 16, 2024: Journal of Pathology
#25
JOURNAL ARTICLE
Kenta Makino, Takamichi Ishii, Haruhiko Takeda, Yoichi Saito, Yukio Fujiwara, Masakazu Fujimoto, Takashi Ito, Satoshi Wakama, Ken Kumagai, Fumiaki Munekage, Hiroshi Horie, Katsuhiro Tomofuji, Yu Oshima, Elena Yukie Uebayashi, Takayuki Kawai, Satoshi Ogiso, Ken Fukumitsu, Atsushi Takai, Hiroshi Seno, Etsuro Hatano
Cholangiolocarcinoma (CLC) is a primary liver carcinoma that resembles the canals of Hering and that has been reported to be associated with stem cell features. Due to its rarity, the nature of CLC remains unclear, and its pathological classification remains controversial. To clarify the positioning of CLC in primary liver cancers and identify characteristics that could distinguish CLC from other liver cancers, we performed integrated analyses using whole-exome sequencing (WES), immunohistochemistry, and a retrospective review of clinical information on eight CLC cases and two cases of recurrent CLC...
February 16, 2024: Journal of Pathology
#26
JOURNAL ARTICLE
Ziqing Zeng, Weijiao Du, Fan Yang, Zhenzhen Hui, Yunliang Wang, Peng Zhang, Xiying Zhang, Wenwen Yu, Xiubao Ren, Feng Wei
This study aimed to provide more information for prognostic stratification for patients through an analysis of the T-cell spatial landscape. It involved analyzing stained tissue sections of 80 patients with stage III lung adenocarcinoma (LUAD) using multiplex immunofluorescence and exploring the spatial landscape of T cells and their relationship with prognosis in the center of the tumor (CT) and invasive margin (IM). In this study, multivariate regression suggested that the relative clustering of CT CD4+ conventional T cell (Tconv) to inducible Treg (iTreg), natural regulatory T cell (nTreg) to Tconv, terminal CD8+ T cell (tCD8) to helper T cell (Th), and IM Treg to tCD8 and the relative dispersion of CT nTreg to iTreg, IM nTreg to nTreg were independent risk factors for DFS...
February 16, 2024: Journal of Pathology
#27
JOURNAL ARTICLE
Anke Augspach, Mark A Rubin
Prostate cancer is one of the most prevalent and, upon metastasis, deadliest cancers in men. Timely identification is essential for effective treatment. Furthermore, accurate determination of prostatic origin is crucial for personalized therapy once the cancer has spread. However, current prostate cancer screening methods are lacking. A recent article in The Journal of Pathology addresses this issue by utilizing an improved antibody to reevaluate HOXB13 as a lineage marker for prostate cancer. The study's findings support the concept that, despite decreased expression in advanced prostate cancer, HOXB13 remains highly suitable for determining prostatic origin due to its androgen receptor independence, high specificity, and sensitivity...
February 9, 2024: Journal of Pathology
#28
JOURNAL ARTICLE
Natálie Klubíčková, Josephine K Dermawan, Elaheh Mosaieby, Petr Martínek, Tomáš Vaněček, Veronika Hájková, Nikola Ptáková, Petr Grossmann, Petr Šteiner, Marián Švajdler, Zdeněk Kinkor, Květoslava Michalová, Peter Szepe, Lukáš Plank, Stanislava Hederová, Alexandra Kolenová, Neofit Juriev Spasov, Kemal Kosemehmetoglu, Leo Pažanin, Zuzana Špůrková, Martin Baník, Luděk Baumruk, Anders Meyer, Antonina Kalmykova, Olena Koshyk, Michal Michal, Michael Michal
Alterations in kinase genes such as NTRK1/2/3, RET, and BRAF underlie infantile fibrosarcoma (IFS), the emerging entity 'NTRK-rearranged spindle cell neoplasms' included in the latest WHO classification, and a growing set of tumors with overlapping clinical and pathological features. In this study, we conducted a comprehensive clinicopathological and molecular analysis of 22 cases of IFS and other kinase gene-altered spindle cell neoplasms affecting both pediatric and adult patients. Follow-up periods for 16 patients ranged in length from 10 to 130 months (mean 38 months)...
February 9, 2024: Journal of Pathology
#29
JOURNAL ARTICLE
Na Zhang, Fuchen Liu, Yuying Zhao, Xiaohan Sun, Bing Wen, Jian-Qiang Lu, Chuanzhu Yan, Duoling Li
Pompe disease is a lysosomal storage disorder that preferentially affects muscles, and it is caused by GAA mutation coding acid alpha-glucosidase in lysosome and glycophagy deficiency. While the initial pathology of Pompe disease is glycogen accumulation in lysosomes, the special role of the lysosomal pathway in glycogen degradation is not fully understood. Hence, we investigated the characteristics of accumulated glycogen and the mechanism underlying glycophagy disturbance in Pompe disease. Skeletal muscle specimens were obtained from the affected sites of patients and mouse models with Pompe disease...
February 9, 2024: Journal of Pathology
#30
JOURNAL ARTICLE
Lara Sanoguera-Miralles, Inés Llinares-Burguet, Elena Bueno-Martínez, Lobna Ramadane-Morchadi, Cristiana Stuani, Alberto Valenzuela-Palomo, Alicia García-Álvarez, Pedro Pérez-Segura, Emanuele Buratti, Miguel de la Hoya, Eladio A Velasco-Sampedro
Splicing is controlled by a large set of regulatory elements (SREs) including splicing enhancers and silencers, which are involved in exon recognition. Variants at these motifs may dysregulate splicing and trigger loss-of-function transcripts associated with disease. Our goal here was to study the alternatively spliced exons 8 and 10 of the breast cancer susceptibility gene CHEK2. For this purpose, we used a previously published minigene with exons 6-10 that produced the expected minigene full-length transcript and replicated the naturally occurring events of exon 8 [Δ(E8)] and exon 10 [Δ(E10)] skipping...
February 9, 2024: Journal of Pathology
#31
JOURNAL ARTICLE
Song Ling, Doyun Kwak, Yoh Takuwa, Chunxi Ge, Renny Franceschi, Kevin K Kim
Pulmonary fibrosis, especially idiopathic pulmonary fibrosis (IPF), portends significant morbidity and mortality, and current therapeutic options are suboptimal. We have previously shown that type I collagen signaling through discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase expressed by fibroblasts, is critical for the regulation of fibroblast apoptosis and progressive fibrosis. However, the downstream signaling pathways for DDR2 remain poorly defined and could also be attractive potential targets for therapy...
February 9, 2024: Journal of Pathology
#32
JOURNAL ARTICLE
Aritra Bhattacharyya, Ranjha Khan, Joanna Y Lee, Gizachew Tassew, Babak Oskouian, Maria L Allende, Richard L Proia, Xiaoyang Yin, Javier G Ortega, Mallar Bhattacharya, Julie D Saba
Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease of the lung that leads rapidly to respiratory failure. Novel approaches to treatment are urgently needed. The bioactive lipid sphingosine-1-phosphate (S1P) is increased in IPF lungs and promotes proinflammatory and profibrotic TGF-β signaling. Hence, decreasing lung S1P represents a potential therapeutic strategy for IPF. S1P is degraded by the intracellular enzyme S1P lyase (SPL). Here we find that a knock-in mouse with a missense SPL mutation mimicking human disease resulted in reduced SPL activity, increased S1P, increased TGF-β signaling, increased lung fibrosis, and higher mortality after injury compared to wild type (WT)...
February 9, 2024: Journal of Pathology
#33
JOURNAL ARTICLE
Braydon Meyer, Clare Stirzaker, Sonny Ramkomuth, Kate Harvey, Belinda Chan, Cheok Soon Lee, Rooshdiya Karim, Niantao Deng, Kelly A Avery-Kiejda, Rodney J Scott, Sunil Lakhani, Stephen Fox, Elizabeth Robbins, Joo-Shik Shin, Jane Beith, Anthony Gill, Loretta Sioson, Charles Chan, Mrudula Krishnaswamy, Caroline Cooper, Sanjay Warrier, Cindy Mak, John Ej Rasko, Charles G Bailey, Alexander Swarbrick, Susan J Clark, Sandra O'Toole, Ruth Pidsley
Phyllodes tumours (PTs) are rare fibroepithelial lesions of the breast that are classified as benign, borderline, or malignant. As little is known about the molecular underpinnings of PTs, current diagnosis relies on histological examination. However, accurate classification is often difficult, particularly for distinguishing borderline from malignant PTs. Furthermore, PTs can be misdiagnosed as other tumour types with shared histological features, such as fibroadenoma and metaplastic breast cancers. As DNA methylation is a recognised hallmark of many cancers, we hypothesised that DNA methylation could provide novel biomarkers for diagnosis and tumour stratification in PTs, whilst also allowing insight into the molecular aetiology of this otherwise understudied tumour...
February 1, 2024: Journal of Pathology
#34
JOURNAL ARTICLE
Celia Barrio-Alonso, Alicia Nieto-Valle, Elena García-Martínez, Alba Gutiérrez-Seijo, Verónica Parra-Blanco, Iván Márquez-Rodas, José Antonio Avilés-Izquierdo, Paloma Sánchez-Mateos, Rafael Samaniego
During cancer evolution, tumor cells attract and dynamically interact with monocytes/macrophages. To find biomarkers of disease progression in human melanoma, we used unbiased RNA sequencing and secretome analyses of tumor-macrophage co-cultures. Pathway analysis of genes differentially modulated in human macrophages exposed to melanoma cells revealed a general upregulation of inflammatory hallmark gene sets, particularly chemokines. A selective group of chemokines, including CCL8, CCL15, and CCL20, was actively secreted upon melanoma-macrophage co-culture...
January 30, 2024: Journal of Pathology
#35
REVIEW
Chowdhury Arif Jahangir, David B Page, Glenn Broeckx, Claudia A Gonzalez, Caoimbhe Burke, Clodagh Murphy, Jorge S Reis-Filho, Amy Ly, Paul W Harms, Rajarsi R Gupta, Michael Vieth, Akira I Hida, Mohamed Kahila, Zuzana Kos, Paul J van Diest, Sara Verbandt, Jeppe Thagaard, Reena Khiroya, Khalid Abduljabbar, Gabriela Acosta Haab, Balazs Acs, Sylvia Adams, Jonas S Almeida, Isabel Alvarado-Cabrero, Farid Azmoudeh-Ardalan, Sunil Badve, Nurkhairul Bariyah Baharun, Enrique R Bellolio, Vydehi Bheemaraju, Kim Rm Blenman, Luciana Botinelly Mendonça Fujimoto, Octavio Burgues, Alexandros Chardas, Maggie Chon U Cheang, Francesco Ciompi, Lee Ad Cooper, An Coosemans, Germán Corredor, Flavio Luis Dantas Portela, Frederik Deman, Sandra Demaria, Sarah N Dudgeon, Mahmoud Elghazawy, Claudio Fernandez-Martín, Susan Fineberg, Stephen B Fox, Jennifer M Giltnane, Sacha Gnjatic, Paula I Gonzalez-Ericsson, Anita Grigoriadis, Niels Halama, Matthew G Hanna, Aparna Harbhajanka, Steven N Hart, Johan Hartman, Stephen Hewitt, Hugo M Horlings, Zaheed Husain, Sheeba Irshad, Emiel Am Janssen, Tatsuki R Kataoka, Kosuke Kawaguchi, Andrey I Khramtsov, Umay Kiraz, Pawan Kirtani, Liudmila L Kodach, Konstanty Korski, Guray Akturk, Ely Scott, Anikó Kovács, Anne-Vibeke Laenkholm, Corinna Lang-Schwarz, Denis Larsimont, Jochen K Lennerz, Marvin Lerousseau, Xiaoxian Li, Anant Madabhushi, Sai K Maley, Vidya Manur Narasimhamurthy, Douglas K Marks, Elizabeth S McDonald, Ravi Mehrotra, Stefan Michiels, Durga Kharidehal, Fayyaz Ul Amir Afsar Minhas, Shachi Mittal, David A Moore, Shamim Mushtaq, Hussain Nighat, Thomas Papathomas, Frederique Penault-Llorca, Rashindrie D Perera, Christopher J Pinard, Juan Carlos Pinto-Cardenas, Giancarlo Pruneri, Lajos Pusztai, Nasir Mahmood Rajpoot, Bernardo Leon Rapoport, Tilman T Rau, Joana M Ribeiro, David Rimm, Anne Vincent-Salomon, Joel Saltz, Shahin Sayed, Evangelos Hytopoulos, Sarah Mahon, Kalliopi P Siziopikou, Christos Sotiriou, Albrecht Stenzinger, Maher A Sughayer, Daniel Sur, Fraser Symmans, Sunao Tanaka, Timothy Taxter, Sabine Tejpar, Jonas Teuwen, E Aubrey Thompson, Trine Tramm, William T Tran, Jeroen van der Laak, Gregory E Verghese, Giuseppe Viale, Noorul Wahab, Thomas Walter, Yannick Waumans, Hannah Y Wen, Wentao Yang, Yinyin Yuan, John Bartlett, Sibylle Loibl, Carsten Denkert, Peter Savas, Sherene Loi, Elisabeth Specht Stovgaard, Roberto Salgado, William M Gallagher, Arman Rahman
Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples...
March 2024: Journal of Pathology
#36
JOURNAL ARTICLE
Guoliang Yang, Akezhouli Shahatiaili, Shihao Bai, Liyang Wang, Di Jin, Ming Cao, Peipei Su, Qiang Liu, Kun Tao, Qi Long, Yi Shi, Jing Xiao, Futong Tian, Lianhua Zhang, Haige Chen, Xianbin Su
Adenocarcinoma of the bladder is a rare urinary bladder carcinoma with limited therapy options due to lack of molecular characterization. Here, we aimed to reveal the mutational and transcriptomic landscapes of adenocarcinoma of the bladder and assess any relationship with prognosis. Between February 2015 and June 2021, a total of 23 patients with adenocarcinoma of the bladder were enrolled. These included 16 patients with primary bladder adenocarcinomas and seven patients with urachal adenocarcinoma. Whole exome sequencing (16 patients), whole genome sequencing (16 patients), bulk RNA sequencing (RNA-seq) (19 patients), and single-cell RNA-seq (5 patients) were conducted for the specimens...
March 2024: Journal of Pathology
#37
JOURNAL ARTICLE
Jacob Madison, Kevin Wilhelm, Daniel T Meehan, Michael Anne Gratton, Denise Vosik, Gina Samuelson, Megan Ott, John Fascianella, Noa Nelson, Dominic Cosgrove
The standard of care for patients with Alport syndrome (AS) is angiotensin-converting enzyme (ACE) inhibitors. In autosomal recessive Alport (ARAS) mice, ACE inhibitors double lifespan. We previously showed that deletion of Itga1 in Alport mice [double-knockout (DKO) mice] increased lifespan by 50%. This effect seemed dependent on the prevention of laminin 211-mediated podocyte injury. Here, we treated DKO mice with vehicle or ramipril starting at 4 weeks of age. Proteinuria and glomerular filtration rates were measured at 5-week intervals...
March 2024: Journal of Pathology
#38
JOURNAL ARTICLE
Julia Richter, Ilske Oschlies, Katharina Kock, Thomas Wüseke, Jochen Haag, Karoline Koch, Wolfram Klapper
Primary cutaneous CD4+ small or medium T-cell lymphoproliferative disorder (PCSM-LPD) is a clonal T-cell proliferation disease confined to the skin. PCSM-LPD shares expression of T follicular helper (Tfh) cell markers with various mature T-cell lymphomas. However, the benign presentation of PCSM-LPD contrasts the clinical behavior of other Tfh-lymphomas. The aim of our study was to delineate the molecular similarities and differences between PCSM-LPD and other Tfh-derived lymphomas to explain the clinical behavior and unravel possible pathological mechanisms...
February 2024: Journal of Pathology
#39
JOURNAL ARTICLE
Gil A Pastorino, Ilir Sheraj, Kerstin Huebner, Giulio Ferrero, Philipp Kunze, Arndt Hartmann, Chuanpit Hampel, Hepsen Hazal Husnugil, Arnatchai Maiuthed, Florian Gebhart, Fynn Schlattmann, Aliye Ezgi Gulec Taskiran, Goksu Oral, Ralph Palmisano, Barbara Pardini, Alessio Naccarati, Katharina Erlenbach-Wuensch, Sreeparna Banerjee, Regine Schneider-Stock
Partial epithelial-mesenchymal transition (p-EMT) has recently been identified as a hybrid state consisting of cells with both epithelial and mesenchymal characteristics and is associated with the migration, metastasis, and chemoresistance of cancer cells. Here, we describe the induction of p-EMT in starved colorectal cancer (CRC) cells and identify a p-EMT gene signature that can predict prognosis. Functional characterisation of starvation-induced p-EMT in HCT116, DLD1, and HT29 cells showed changes in proliferation, morphology, and drug sensitivity, supported by in vivo studies using the chorioallantoic membrane model...
January 18, 2024: Journal of Pathology
#40
JOURNAL ARTICLE
Suzann Duan, Travis W Sawyer, Brandon L Witten, Heyu Song, Tobias Else, Juanita L Merchant
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous malignancies that arise from complex cellular interactions within the tissue microenvironment. Here, we sought to decipher tumor-derived signals from the surrounding microenvironment by applying digital spatial profiling (DSP) to hormone-secreting and non-functional GEP-NETs. By combining this approach with in vitro studies of human-derived organoids, we demonstrated the convergence of cell autonomous immune and pro-inflammatory proteins that suggests their role in neuroendocrine differentiation and tumorigenesis...
January 17, 2024: Journal of Pathology
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