Review
Biochemistry & Molecular Biology
Lili Liang, Andreas M. Kaufmann
Summary: Cancer stem cells (CSCs) have been identified and characterized in both hematopoietic and solid tumors. They possess unique properties, including slow proliferation, self-renewal, differentiation, and the ability to undergo epithelial-mesenchymal transition (EMT) and its reverse process. CSCs play a crucial role in tumor growth, therapy resistance, and cancer metastasis. Strategies targeting CSCs are being developed for novel anti-metastasis treatments, aiming to improve therapeutic efficiency and prognosis with fewer side effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Linxiang Lan, Theodore Evan, Huafu Li, Aasia Hussain, E. Josue Ruiz, May Zaw Thin, Rute M. M. Ferreira, Hari Ps, Eva M. Riising, Yoh Zen, Jorge Almagro, Kevin W. Ng, Pablo Soro-Barrio, Jessica Nelson, Gabriela Koifman, Joana Carvalho, Emma L. Nye, Yulong He, Changhua Zhang, Anguraj Sadanandam, Axel Behrens
Summary: This study identifies BMP inhibitor GREM1 as a key regulator of cellular heterogeneity in pancreatic cancer. Continuous activity of GREM1 is required to maintain the stability of the epithelial PDAC subpopulations, while high activity of GREM1 can revert the mesenchymal fate of PDAC cells. By inhibiting the expression of epithelial-mesenchymal transition transcription factors, GREM1 restricts the epithelial-mesenchymal plasticity of pancreatic cancer cells.
Review
Oncology
Tuan Luu
Summary: Pancreatic cancer, known for its high mortality and insensitivity to existing therapies, has attracted increasing scholarly attention for its progression mechanisms, particularly the role of epithelial-mesenchymal transition (EMT) in cancer genesis and metastasis. Recent discoveries on EMT-regulating factors in pancreatic cancer have shed light on the relationship between EMT and this cancer type, marking a key advancement in research on EMT in pancreatic cancer.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Meena U. Rajagopal, Shivani Bansal, Prabhjit Kaur, Shreyans K. Jain, Tatiana Altadil, Charles P. Hinzman, Yaoxiang Li, Joanna Moulton, Baldev Singh, Sunil Bansal, Siddheshwar Kisan Chauthe, Rajbir Singh, Partha P. Banerjee, Mark Mapstone, Massimo S. Fiandaca, Howard J. Federoff, Keith Unger, Jill P. Smith, Amrita K. Cheema
Summary: Pancreatic cancer is an aggressive disease with poor outcomes due to late diagnosis. Metabolomics approach revealed metabolic changes that could potentially improve clinical outcomes.
Review
Oncology
Jingwen Jiang, Jiayu Li, Xiumei Zhou, Xueqin Zhao, Biao Huang, Yuan Qin
Summary: Exosomes play an important role in intercellular communication and can regulate the EMT process in tumor cells. They have potential applications in cancer diagnosis and treatment.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Xin Zhao, Xiaoshi Zhang, Xinxue Zhang, Tao Jiang, Jialei Zhai, Huaguang Wang, Mengxiu Huang, Ren Lang, Qiang He
Summary: This study revealed that miR-374b-5p is downregulated in pancreatic cancer (PC) and its overexpression can inhibit the proliferation, migration, and invasion of PC cells by suppressing the expression of KDM5B, thereby reducing epithelial-mesenchymal transition (EMT) in PC. The findings suggest that miR-374b-5p could potentially serve as a prognostic biomarker and therapeutic target for EMT induced by KDM5B in PC.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Multidisciplinary Sciences
Shunhao Wang, Jingchao Li, Mei Chen, Liting Ren, Wenya Feng, Lining Xu, Xiaolan Chen, Tian Xia, Nanfeng Zheng, Sijin Liu
Summary: Palladium nanoplates inhibit lung metastasis by suppressing EMT signaling in breast cancer cells and interacting with TGF-beta proteins, leading to reduced downstream signaling activation. NIR irradiation enhances the inhibitory effects of PdPL on both primary tumors and metastasis.
NATIONAL SCIENCE REVIEW
(2021)
Review
Biochemistry & Molecular Biology
Ming-Yu Chou, Muh-Hwa Yang
Summary: The interplay between EMT and immune metabolic changes in cancer cells during tumor metastasis has gained interest among researchers. Understanding how they influence each other may provide novel explanations for immune surveillance during metastasis. Studying immunometabolism in the regulatory loop between tumor-infiltrating immune cells and EMT is crucial for cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Shuang Lu, Hong Sun Kim, Yubo Cao, Karan Bedi, Lili Zhao, Ishwarya Venkata Narayanan, Brian Magnuson, Yumei Gu, Jing Yang, Zhujun Yi, Sepideh Babaniamansour, Sargis Shameon, Chang Xu, Michelle T. Paulsen, Ping Qiu, Sivakumar Jeyarajan, Mats Ljungman, Dafydd Thomas, Yali Dou, Howard Crawford, Marina Pasca di Magliano, Kai Ge, Bo Yang, Jiaqi Shi
Summary: In this study, a novel signaling axis mediated by KMT2D linking TGF-beta to the activin A pathway was discovered. Loss of KMT2D induces the expression and secretion of activin A, which activates a noncanonical p38 MAPK-mediated pathway to enhance tumor invasion and metastasis in pancreatic cancer.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Immunology
Junquan Song, Rongyuan Wei, Shiying Huo, Jianpeng Gao, Xiaowen Liu
Summary: Through the analysis of differentially expressed genes between metastatic gastric cancer and primary gastric cancer, a metastasis-related epithelial-mesenchymal transition signature (MEMTS) was constructed. High MEMTS indicates a poor prognosis in patients with gastric cancer, and patients with low MEMTS may benefit more from adjuvant chemoradiotherapy. MEMTS reliably predicts the response to immunotherapy in gastric cancer and is significantly associated with cancer-associated fibroblasts and stromal score in the tumor microenvironment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Pelin Balcik-Ercin, Laure Cayrefourcq, Rama Soundararajan, Sendurai A. Mani, Catherine Alix-Panabieres
Summary: Metastasis is a complex and not fully understood process in cancer, where circulating tumor cells (CTCs) play a crucial role. CTCs possess a unique ability to transition between epithelial and mesenchymal states, known as epithelial-to-mesenchymal plasticity (EMP), which aids in their metastatic potential. This study focuses on the EMP phenotype of colon CTC lines, showing that these cells have minimal mesenchymal features but exhibit an increase in mesenchymal-epithelial transition (MET) markers, suggesting a quick reversion to the epithelial state for successful metastasis.
Article
Medicine, Research & Experimental
Yunhui Zhou, Xinyi Zhou, Qiwen Ben, Ningning Liu, Jiahui Wang, Yongpeng Zhai, Yichen Bao, Lin Zhou
Summary: PDAC is characterized by a hypoxic microenvironment, high heterogeneity, and high recurrence rate. This study found that GATA6-AS1 expression is significantly decreased in PDAC and low expression is associated with unfavorable clinicopathologic characteristics and poor prognosis. Functional studies showed that GATA6-AS1 can suppress the proliferation, invasion, migration, and EMT process of PDAC cells under hypoxia.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Biotechnology & Applied Microbiology
Zhenglei Xu, Zeming Chen, Minsi Peng, Zhuliang Zhang, Weixiang Luo, Ruiyue Shi, Lisheng Wang, Yingcai Hong
Summary: Pancreatic cancer is difficult to treat, and the main reasons for poor prognosis are cell invasion and migration. In this study, researchers found that miR-490-5p is abnormally low-expressed in pancreatic cancer and downregulation of miR-490-5p enhances the viability, migration, and invasion of pancreatic cancer cells. Additionally, miR-490-5p regulates the protein expression of MMP2, MMP9, and N-cadherin, and upregulates the protein expression of E-cadherin. The expression of MAGI2-AS3 is also associated with cell viability, migration, and invasion in pancreatic cancer. The study reveals that miR-490-5p plays an anti-cancer role in pancreatic cancer by targeting MAGI2-AS3 and regulating EMT.
Review
Biochemistry & Molecular Biology
Ying Xu, Qing Zhu
Summary: Pancreatic cancer is a lethal disease characterized by high invasiveness, early metastasis, rapid progression, and late diagnosis. The ability of pancreatic cancer cells to undergo EMT plays a crucial role in their tumorigenic and metastatic potential, as well as therapeutic resistance. Histone modifications, a central epigenetic modification, are closely involved in EMT. In this review, we discuss the mechanisms by which histone-modifying enzymes regulate EMT in pancreatic cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Xiuyuan Zhang, Yiming Li, Pengbo Hu, Liang Xu, Hong Qiu
Summary: In this study, the joint role of epithelial-mesenchymal transition (EMT) and the immune microenvironment in gastric cancer (GC) progression was investigated. A model called EIRG_score was developed to predict prognosis and immunotherapeutic response. The results showed that the EIRG_score was significantly associated with prognosis, immune infiltration, gene mutation, chemotherapeutic drug sensitivity, and immunotherapy response.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Surgery
Dilmurodjon Eshmuminov, Debora J. Studer, Victor Lopez Lopez, Marcel A. Schneider, Jan Lerut, Mary Lo, Linda Sher, Thomas J. Musholt, Oana Lozan, Nabila Bouzakri, Carlo Sposito, Rosalba Miceli, Shoma Barat, David Morris, Helga Oehler, Teresa Schreckenbach, Peri Husen, Charles B. Rosen, Gregory J. Gores, Toshihiko Masui, Tan-To Cheung, Corina Kim-Fuchs, Aurel Perren, Philipp Dutkowski, Henrik Petrowsky, Espen Thiis-Evensen, Pal-Dag Line, Michal Grat, Stefano Partelli, Massimo Falconi, Lulu Tanno, Ricardo Robles-Campos, Vincenzo Mazzaferro, Pierre-Alain Clavien, Kuno Lehmann
Summary: This multicenter study compares the outcomes of liver resection (LR) and liver transplantation (LT) in patients with neuroendocrine liver metastasis (NELM). The results suggest that LT provides a survival benefit over LR, but adherence to selection criteria is important.
Article
Endocrinology & Metabolism
Marco Schiavo Lena, Stefano Partelli, Valentina Andreasi, Francesca Muffatti, Miriam Redegalli, Emanuela Brunetto, Beatrice Maghini, Monika Falke, Maria Giulia Cangi, Aurel Perren, Massimo Falconi, Claudio Doglioni
Summary: The incidence of well-differentiated non-functioning pancreatic neuroendocrine tumors (NF-PanNET) has been increasing. A reliable predictive model based on prognostic characteristics is urgently needed for tailoring a follow-up strategy. In this study, the infiltrative growth pattern of NF-PanNET was found to be strongly associated with a poorer survival and could provide additional prognostic information.
ENDOCRINE PATHOLOGY
(2023)
Article
Pathology
Amjad Khan, Nelleke Brouwer, Annika Blank, Felix Mueller, Davide Soldini, Aurelia Noske, Elisabeth Gaus, Simone Brandt, Iris Nagtegaal, Heather Dawson, Jean-Philippe Thiran, Aurel Perren, Alessandro Lugli, Inti Zlobec
Summary: This study proposes a deep learning-based workflow for evaluating lymph node metastases in colorectal cancer. The method achieved high accuracy after training on a dataset of 100 whole-slide images. The fine-tuned models showed significant improvements in metastasis detection and achieved excellent performance in the validation cohorts.
Article
Pathology
Magdalena Skoworonska, Annika Blank, Irene Centeno, Caroline Hammer, Aurel Perren, Inti Zlobec, Tilman T. Rau
Summary: The standardized preanalytical code (SPREC) is a precise format for aggregating warm ischemia (WIT), cold ischemia (CIT), and fixation times (FIT). Through empirical research, the Tissue Bank Bern has developed a fully informative SPREC code and identified its dual role as a sample characteristic and a traceable process parameter. The study also reveals specific differences in WIT, CIT, and FIT values in various organs, as well as the potential to optimize the SPREC fixation and adapt its categories based on real-life data.
JOURNAL OF PATHOLOGY CLINICAL RESEARCH
(2023)
Article
Endocrinology & Metabolism
Matthias S. S. Dettmer, Sandra Huerlimann, Lukas Scheuble, Erik Vassella, Aurel Perren, Corinna Wicke
Summary: A 44-year-old female patient with familial adenomatous polyposis (FAP) had a diagnosis of cribriform morular thyroid carcinoma (CMTC). Next generation sequencing revealed a homozygous APC mutation and a TERT promoter mutation in both components. TP53 mutation was exclusive to the CMTC part, while the poorly differentiated component showed clonal evolution with an activating PIK3CA mutation and copy number gains of BRCA2, FGF23, FGFR1, and PIK3CB alterations typically seen in squamous cell carcinoma. The patient, after total thyroidectomy and radioiodine ablation, remained disease-free with no residual tumor burden on 2-year follow-up.
ENDOCRINE PATHOLOGY
(2023)
Article
Gastroenterology & Hepatology
Eva Karamitopoulou, Anna Silvia Wenning, Animesh Acharjee, Inti Zlobec, Pauline Aeschbacher, Aurel Perren, Beat Gloor
Summary: The study investigates spatially organised immune determinants of pancreatic ductal adenocarcinoma (PDAC) recurrence and finds distinct inflammatory/stromal responses in each recurrence group. PDACs with no recurrence show high immunogenicity, adaptive immune responses, and pro-inflammatory chemokines. PDACs with liver and/or peritoneal recurrences display low immunogenicity and innate immune responses. PDACs with local and/or lung recurrences display interferon-gamma signaling and mixed adaptive and innate immune responses.
Article
Pathology
Nicole Schaad, Sabina Berezowska, Aurel Perren, Ekkehard Hewer
Summary: Synoptic reporting improves the completeness and standardization of surgical pathology reports, enhancing the quality of clinical cancer care. Implementing this reporting system, however, poses challenges due to the required effort for database setup and maintenance. A template-based, database-free approach was found to significantly increase the completeness of surgical pathology reports compared to narrative reports, making it a viable alternative during the implementation of synoptic reporting.
Article
Gastroenterology & Hepatology
Patcharamon Seubnooch, Matteo Montani, Sofia Tsouka, Emmanuelle Claude, Umara Rafiqi, Aurel Perren, Jean-Francois Dufour, Mojgan Masoodi
Summary: This study investigated the spatial distribution of hepatic lipid metabolism in different zones of the liver using mass spectrometry imaging. The results showed heterogeneous distribution of lipids across liver zones, with fatty acids mainly located in the periportal zone, phospholipids in both the periportal and pericentral zones, and triacylglycerols and diacylglycerols in the pericentral zone. This research provides important insights into lipid metabolism during the progression of liver disease.
Article
Biochemistry & Molecular Biology
Oxana (Sachenkova) Lundstrom, Max Adriaan Verbiest, Feifei Xia, Helyaneh Ziaei Jam, Inti Zlobec, Maria Anisimova, Melissa Gymrek
Summary: Short tandem repeats (STRs), consisting of repeated one to six nucleotide motifs, have been shown to influence various traits in humans. However, the study of STRs has been limited due to technical challenges. Recent advancements in genome-wide analysis tools have enabled large-scale analysis of STR variations in populations.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Letter
Oncology
Reto M. Kaderli, Cedric Nesti, Konstantin Braeutigam, Marcel Zwahlen, Aurel Perren
Letter
Oncology
Reto M. Kaderli, Cedric Nesti, Konstantin Brautigam, Marcel Zwahlen, Aurel Perren
Meeting Abstract
Medicine, Research & Experimental
Amjad Khan, Nelleke Brouwer, Annika Blank, Felix Muller, Davide Soldini, Aurelia Noske, Elisabeth Gaus, Simone Brandt, Iris Nagtegaal, Heather Dawson, Jean-Philippe Thiran, Aurel Perren, Alessandro Lugli, Inti Zlobec
LABORATORY INVESTIGATION
(2023)
Meeting Abstract
Medicine, Research & Experimental
Erik Vassella, Lisa Holer, Aurel Perren, Stefanie Hayoz, Peter Thuss-Patience, Wolfgang Eisterer, Walter Mingrone, Sabina Schacher, Viviane Hess, Thomas Ruhstaller, Rupert Langer
LABORATORY INVESTIGATION
(2023)
Article
Pathology
Ana Leni Frei, Raphael Oberson, Elias Baumann, Aurel Perren, Rainer Grobholz, Alessandro Lugli, Heather Dawson, Christian Abbet, Ibai Lertxundi, Stefan Reinhard, Aart Mookhoek, Johann Feichtinger, Rossella Sarro, Gallus Gadient, Corina Dommann-Scherrer, Jessica Barizzi, Sabina Berezowska, Katharina Glatz, Susanne Dertinger, Yara Banz, Rene Schoenegg, Laura Rubbia-Brandt, Achim Fleischmann, Guenter Saile, Pierre Mainil-Varlet, Ruggero Biral, Luca Giudici, Alex Soltermann, Audrey Baur Chaubert, Sylvia Stadlmann, Joachim Diebold, Kristof Egervaril, Charles Beniere, Francesca Saro, Andrew Janowczyk, Inti Zlobec
Summary: Estimating tumor cell fraction (TCF) is a common clinical task with high variability among pathologists. This study evaluated the impact of using a tumor cell fraction computer-aided diagnostic (TCFCAD) tool to support pathologists' evaluation. The results showed that with the assistance of TCFCAD, interobserver variability decreased and estimates were closer to the ground truth. Pathologists also reported increased confidence in their assessments when aided by the TCFCAD tool.