Thijmen Sijnesael, François Richard, Max Ak Rätze, Thijs Koorman, Blessing Bassey-Archibong, Christa Rohof, Juliet Daniel, Christine Desmedt, Patrick Wb Derksen
Invasive lobular carcinoma (ILC) is a low- to intermediate-grade histological breast cancer type caused by mutational inactivation of E-cadherin function, resulting in the acquisition of anchorage independence (anoikis resistance). Most ILC cases express estrogen receptors, but options are limited in relapsed endocrine-refractory disease as ILC tends to be less responsive to standard chemotherapy. Moreover, ILC can relapse after >15 years, an event that currently cannot be predicted. E-cadherin inactivation leads to p120-catenin-dependent relief of the transcriptional repressor Kaiso (ZBTB33) and activation of canonical Kaiso target genes...
September 22, 2023: Journal of Pathology
Mohamed Elnagdy, Yali Wang, Walter Rodriguez, JingWen Zhang, Philip Bauer, Daniel W Wilkey, Michael Merchant, Jianmin Pan, Zainab Farooqui, Robert Cannon, Shesh Rai, Claudio Maldonado, Shirish Barve, Craig J McClain, Leila Gobejishvili
Activation and transdifferentiation of hepatic stellate cells (HSC) into migratory myofibroblasts is a key process in liver fibrogenesis. Cell migration requires an active remodeling of the cytoskeleton, which is a tightly regulated process coordinated by Rho-specific guanine nucleotide exchange factors (GEFs) and the Rho family of small GTPases. Rho-associated kinase (ROCK) promotes assembly of focal adhesions and actin stress fibers by regulating cytoskeleton organization. GEF exchange protein directly activated by cAMP 1 (EPAC1) has been implicated in modulating TGFβ1 and Rho signaling; however, its role in HSC migration has never been examined...
September 21, 2023: Journal of Pathology
Jeppe Thorlacius-Ussing, Christina Jensen, Neel I Nissen, Thomas R Cox, Raghu Kalluri, Morten Karsdal, Nicholas Willumsen
Cancer-associated fibroblasts (CAFs) deposit and remodel collagens in the tumor stroma, impacting cancer progression and efficacy of interventions. CAFs are the focus of new therapeutics with the aim of normalizing the tumor microenvironment. To do this, a better understanding of CAF heterogeneity and collagen composition in cancer is needed. In this study, we sought to profile the expression of collagens at multiple levels with the goal of identifying cancer biomarkers. We investigated the collagen expression pattern in various cell types and CAF subtypes in a publicly available single-cell RNA sequencing (RNA-seq) dataset of pancreatic ductal adenocarcinoma...
September 20, 2023: Journal of Pathology
Kamran Abbasi, Parveen Ali, Virginia Barbour, Kirsten Bibbins-Domingo, Marcel Gm Olde Rikkert, Andy Haines, Ira Helfand, Richard Horton, Bob Mash, Arun Mitra, Carlos Monteiro, Elena N Naumova, Eric J Rubin, Tilman Ruff, Peush Sahni, James Tumwine, Paul Yonga, Chris Zielinski
No abstract text is available yet for this article.
September 19, 2023: Journal of Pathology
Simone van de Weerd, Arezo Torang, Liselotte W Zwager, Pim J Koelink, Jan Koster, Barbara Aj Bastiaansen, Veerle Lammers, Ciro Longobardi, Jeanine Ml Roodhart, J Han van Krieken, Arantza Farina Sarasqueta, Evelien Dekker, Jan Paul Medema
The consensus molecular subtype (CMS) classification divides colorectal cancer (CRC) into four distinct subtypes based on RNA expression profiles. The biological differences between CMSs are already present in CRC precursor lesions, but not all CMSs pose the same risk of malignant transformation. To fully understand the path to malignant transformation and to determine whether CMS is a fixed entity during progression, genomic and transcriptomic data from two regions of the same CRC lesion were compared: the precursor region and the carcinoma region...
September 8, 2023: Journal of Pathology
Rami S Vanguri, James W Smithy, Yanyun Li, Mingqiang Zhuang, Colleen A Maher, Nathaniel Aleynick, Xiyu Peng, Hikmat Al-Ahmadie, Samuel A Funt, Jonathan E Rosenberg, Gopa Iyer, Dean Bajorin, James C Mathews, Saad Nadeem, Katherine S Panageas, Ronglai Shen, Margaret K Callahan, Travis J Hollmann
As predictive biomarkers of response to immune checkpoint inhibitors (ICIs) remain a major unmet clinical need in patients with urothelial carcinoma (UC), we sought to identify tissue-based immune biomarkers of clinical benefit to ICIs using multiplex immunofluorescence and to integrate these findings with previously identified peripheral blood biomarkers of response. Fifty-five pretreatment and 12 paired on-treatment UC specimens were identified from patients treated with nivolumab with or without ipilimumab...
September 5, 2023: Journal of Pathology
Jorge García-Giménez, Gina Córdoba-David, Sandra Rayego-Mateos, Pablo Cannata-Ortiz, Susana Carrasco, Marta Ruiz-Ortega, Beatriz Fernandez-Fernandez, Alberto Ortiz, Adrián M Ramos
Rapidly progressive/crescentic glomerulonephritis (RPGN/CGN) involves the formation of glomerular crescents by maladaptive differentiation of parietal epithelial cells that leads to rapid loss of renal function. The molecular mechanisms of crescent formation are poorly understood. Therefore, new insights into molecular mechanisms could identify alternative therapeutic targets for RPGN/CGN. Analysis of kidney biopsies from patients with RPGN revealed increased interstitial, glomerular, and tubular expression of STING1, an accessory protein of the c-GAS-dependent DNA-sensing pathway, which was also observed in murine nephrotoxic nephritis induced by an anti-GBM antibody...
August 31, 2023: Journal of Pathology
Samantha Morón-Ros, Albert Blasco-Roset, Artur Navarro-Gascon, Celia Rupérez, Monica Zamora, Fatima Crispi, Iker Uriarte, Maite G Fernández-Barrena, Matias Avila, Gemma Ferrer-Curriu, Josep Lupón, Antoni Bayés-Genis, Francesc Villarroya, Aleix Gavaldà-Navarro, Anna Planavila
FGF15 and its human orthologue, FGF19, are members of the endocrine FGF family and are secreted by ileal enterocytes in response to bile acids. FGF15/19 mainly targets the liver, but recent studies indicate that it also regulates skeletal muscle mass and adipose tissue plasticity. The aim of this study was to determine the role(s) of the enterokine FGF15/19 during the development of cardiac hypertrophy. Studies in a cohort of humans suffering from heart failure showed increased circulating levels of FGF19 compared with control individuals...
August 31, 2023: Journal of Pathology
Tom van den Ende, Ymke van der Pol, Aafke Creemers, Norbert Moldovan, Dries Boers, Mark I van Berge Henegouwen, Maarten Ccm Hulshof, Saskia Agm Cillessen, Nicole Ct van Grieken, D Michiel Pegtel, Sarah Derks, Maarten F Bijlsma, Florent Mouliere, Hanneke Wm van Laarhoven
Circulating tumor DNA (ctDNA) holds promise in resectable esophageal adenocarcinoma (EAC) to predict patient outcome but is not yet sensitive enough to be clinically applicable. Our aim was to combine ctDNA mutation data with shallow whole-genome sequencing (sWGS)-derived copy number tumor fraction estimates (ichorCNA) to improve pathological response and survival prediction in EAC. In total, 111 stage II/III EAC patients with baseline (n = 111), post-neoadjuvant chemoradiotherapy (nCRT) (n = 68), and pre-surgery (n = 92) plasma samples were used for ctDNA characterization...
August 24, 2023: Journal of Pathology
Huimei Zou, Min Chen, Xiuhong Wang, Jie Yu, Xiaoying Li, Ying Xie, Jun Liu, Miao Liu, Lifen Xu, Qiong Zhang, Xiaoxue Tian, Fan Zhang, Bing Guo
As an essential factor in the prognosis of systemic lupus erythematosus (SLE), lupus nephritis (LN) can accelerate the rate at which patients with SLE can transition to chronic kidney disease or even end-stage renal disease. Podocytes now appear to be a possible direct target in LN in addition to being prone to collateral damage from glomerular capillary lesions induces by immune complexes and inflammatory processes. The NLRP3 inflammasome is regulated by CCAAT/enhancer-binding protein β (C/EBPβ), which is involved in the pathogenesis of SLE...
August 21, 2023: Journal of Pathology
Shefali Thakur, Syed Haider, Rachael Natrajan
Tumour heterogeneity is pervasive amongst many cancers and leads to disease progression, and therapy resistance. In this review, using breast cancer as an exemplar, we focus on the recent advances in understanding the interplay between tumour cells and their microenvironment using single cell sequencing and digital spatial profiling technologies. Further, we discuss the utility of lineage tracing methodologies in pre-clinical models of breast cancer, and how these are being used to unravel new therapeutic vulnerabilities and reveal biomarkers of breast cancer progression...
August 16, 2023: Journal of Pathology
Jingyu Zang, Ruiyun Zhang, Di Jin, Feng Xie, Akezhouli Shahatiaili, Guangyu Wu, Yue Zhang, Zhixin Zhao, Pan Du, Shidong Jia, Haige Chen, Guanglei Zhuang
Non-invasive biomarkers for immunotherapy response remain a compelling unmet medical need. POLARIS-03 is a multicenter phase II trial to evaluate the safety and efficacy of toripalimab (anti-programmed cell death 1) in refractory metastatic urothelial carcinoma (mUC). We assessed the predictive utility of longitudinal circulating tumor DNA (ctDNA) analysis from a single-institution biomarker cohort. Twenty-seven mUC patients receiving toripalimab (3 mg/kg Q2W) at Ren Ji Hospital were enrolled. Serial plasma specimens were obtained at baseline and then every two cycles during treatment...
August 16, 2023: Journal of Pathology
J Louise Jones, Richard Poulsom, Philip J Coates
The 2023 Annual Review Issue of The Journal of Pathology, Recent Advances in Pathology, contains 12 invited reviews on topics of current interest in pathology. This year, our subjects include immuno-oncology and computational pathology approaches for diagnostic and research applications in human disease. Reviews on the tissue microenvironment include the effects of apoptotic cell-derived exosomes, how understanding the tumour microenvironment predicts prognosis, and the growing appreciation of the diverse functions of fibroblast subtypes in health and disease...
August 14, 2023: Journal of Pathology
Gregory Verghese, Jochen K Lennerz, Danny Ruta, Wen Ng, Selvam Thavaraj, Kalliopi P Siziopikou, Threnesan Naidoo, Swapnil Rane, Roberto Salgado, Sarah E Pinder, Anita Grigoriadis
Computational pathology refers to applying deep learning techniques and algorithms to analyse and interpret histopathology images. Advances in artificial intelligence (AI) have led to an explosion in innovation in computational pathology, ranging from the prospect of automation of routine diagnostic tasks to the discovery of new prognostic and predictive biomarkers from tissue morphology. Despite the promising potential of computational pathology, its integration in clinical settings has been limited by a range of obstacles including operational, technical, regulatory, ethical, financial, and cultural challenges...
August 14, 2023: Journal of Pathology
Marta Persson, Mattias K Andersson, Per-Erik Sahlin, Yoshitsugu Mitani, Margaret S Brandwein-Weber, Henry F Frierson, Christopher Moskaluk, Isabel Fonseca, Renata Ferrarotto, Werner Boecker, Thomas Loening, Adel K El-Naggar, Göran Stenman
Adenoid cystic carcinoma (ACC) is a MYB-driven head and neck malignancy with high rates of local recurrence and distant metastasis and poor long-term survival. New effective targeted therapies and clinically useful biomarkers for patient stratification are needed to improve ACC patient survival. Here, we present an integrated copy number and transcriptomic analysis of ACC to identify novel driver genes and prognostic biomarkers. A total of 598 ACCs were studied. Clinical follow-up was available from 366 patients, the largest cohort analyzed to date...
August 11, 2023: Journal of Pathology
Hong Xu, Shujun Zeng, Yingmei Wang, Tong Yang, Minmin Wang, Xuan Li, Yejun He, Xin Peng, Xia Li, Qing Qiao, Jing Zhang
Therapeutic resistance is a notable cause of death in patients with ovarian carcinoma. Polyploid giant cancer cells (PGCCs), commonly arising in tumor tissues following chemotherapy, have recently been considered to contribute to drug resistance. As a type III deacetylase, Sirtuin1 (SIRT1) plays essential roles in the cell cycle, cellular senescence, and drug resistance. Accumulating evidence has suggested that alteration in its subcellular localization via nucleocytoplasmic shuttling is a critical process influencing the functions of SIRT1...
August 11, 2023: Journal of Pathology
Katja Bieber, Siegfried Bezdek, Yask Gupta, Artem Vorobyev, Tanya Sezin, Natalie Gross, Jasper Prüssmann, Jean-Paul Sayegh, Mareike Becker, Sadegh Mousavi, Ashref Hdnah, Sven Künzel, Saleh M Ibrahim, Ralf J Ludwig, Donald Gullberg, Christian D Sadik
Psoriasis is a chronic inflammatory skin condition. Repeated epicutaneous application of Aldara® (imiquimod) cream results in psoriasiform dermatitis in mice. The Aldara®-induced psoriasiform dermatitis (AIPD) mouse model has been used to examine the pathogenesis of psoriasis. Here, we used a forward genetics approach in which we compared AIPD that developed in 13 different inbred mouse strains to identify genes and pathways that modulated disease severity. Among our primary results, we found that the severity of AIPD differed substantially between different strains of inbred mice and that these variations were associated with polymorphisms in Itga11...
August 11, 2023: Journal of Pathology
Takahiro Yamada, Taku Nakashima, Takeshi Masuda, Shinjiro Sakamoto, Kakuhiro Yamaguchi, Yasushi Horimasu, Shintaro Miyamoto, Hiroshi Iwamoto, Kazunori Fujitaka, Hironobu Hamada, Nobuhiko Kamada, Noboru Hattori
Increasing evidence indicates an interaction between the intestinal microbiota and diseases in distal organs. However, the relationship between pulmonary fibrosis and the intestinal microbiota, especially intestinal fungal microbiota, is poorly understood. Thus, this study aimed to determine the effects of changes in the intestinal fungal microbiota on the pathogenesis of pulmonary fibrosis. Mice with intestinal overgrowth of Candida albicans, which was established by oral administration of antibiotics plus C...
August 11, 2023: Journal of Pathology
Roger M Feakins, Maurice B Loughrey, Andrew Silver
Tumour budding (TB) describes single or small groups of neoplastic cells that lack continuity with an advancing tumour front. Poorly differentiated clusters (PDCs) are larger and qualitatively different. TB grade and PDCs may predict a worse outcome in colorectal carcinoma and other cancers and fall into the category of 'invasive front prognostic markers' that also includes intratumoural stroma type. Epithelial-mesenchymal transition (EMT) allows the adoption by epithelial cells of mesenchymal characteristics such as dyscohesion, migration, and stromal invasion...
August 11, 2023: Journal of Pathology
Sandra Rayego-Mateos, José Luis Morgado-Pascual, Cristina García-Caballero, Iolanda Lazaro, Aleix Sala-Vila, Lucas Opazo-Rios, Sebastian Mas-Fontao, Jesús Egido, Marta Ruiz-Ortega, Juan Antonio Moreno
Intravascular hemolysis is a common feature of different clinical entities, including sickle cell disease and malaria. Chronic hemolytic disorders are associated with hepatic damage; however, it is unknown whether heme disturbs lipid metabolism and promotes liver steatosis, thereby favoring the progression to nonalcoholic fatty liver disease (NAFLD). Using an experimental model of acute intravascular hemolysis, we report here the presence of liver injury in association with microvesicular lipid droplet deposition...
August 9, 2023: Journal of Pathology
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