Article
Multidisciplinary Sciences
Constantin Schmitt, Dieter Saur, Stefanie Baerthel, Chiara Falcomata
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a complex disease with a heterogeneous tumor microenvironment. Mouse models, such as immunocompetent and cell line-based orthotopic allograft models, are widely used for preclinical studies. This protocol provides a reproducible and robust method for injecting PDAC cells into the mouse pancreas.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Geriatrics & Gerontology
Wouter R. P. H. van de Worp, Jan Theys, Alba Sanz Gonzalez, Brent van der Heyden, Frank Verhaegen, Duncan Hauser, Florian Caiment, Hubertus J. M. Smeets, Annemie M. W. J. Schols, Ardy van Helvoort, Ramon C. J. Langen
Summary: A syngeneic, orthotopic lung cancer mouse model was evaluated to see if it replicates the systemic and muscle-specific alterations associated with human lung cancer cachexia.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2023)
Article
Respiratory System
Tomoyuki Nakagiri, Sabine Wrenger, Kokilavani Sivaraman, Fabio Ius, Tobias Goecke, Patrick Zardo, Veronika Grau, Tobias Welte, Axel Haverich, Ann-Kathrin Knofel, Sabina Janciauskiene
Summary: Therapy with AAT suppresses acute rejection after LuTx in a mouse model, with beneficial effects involving anti-protease and immunomodulatory activities of AAT.
RESPIRATORY RESEARCH
(2021)
Article
Oncology
Tsukasa Ishiwata, Takeshi Seki, Alexander Gregor, Masato Aragaki, Yamato Motooka, Tomonari Kinoshita, Terunaga Inage, Nicholas Bernards, Hideki Ujiie, Zhenchian Chen, Andrew Effat, Juan Chen, Gang Zheng, Koichiro Tatsumi, Kazuhiro Yasufuku
Summary: The study utilized an ultra-small composite optical fiberscope for phototherapy of lung cancer with a high success rate. This method could serve as a versatile preclinical research platform for evaluating photosensitizers in lung cancer treatment, offering a novel in vivo research approach.
TRANSLATIONAL LUNG CANCER RESEARCH
(2021)
Article
Immunology
Wen Luo, Hai Hoang, Yanling Liao, Jian Pan, Janet Ayello, Mitchell S. Cairo
Summary: A humanized mouse model for Ewing sarcoma has been developed, allowing for functional reconstitution of the human immune system and evaluation of immunotherapy. This model holds promise for translational research in bone malignancies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Iris Kamer, Elizabeta Bab-Dinitz, Oranit Zadok, Efrat Ofek, Teodor Gottfried, Inbal Daniel-Meshulam, Goni Hout-Siloni, Alon Ben Nun, Iris Barshack, Amir Onn, Jair Bar
Summary: A lack of robust, accessible experimental models is a major obstacle in advancing cancer immunotherapy. This study aimed to develop an ex-vivo organ culture (EVOC) model for non-small cell lung cancer (NSCLC) immunotherapy, which reflected original tissue features and showed promising correlations with immune checkpoint inhibitor response. The study provides valuable insights into biomarkers for ICI-induced response in early stage NSCLC.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Medicine, General & Internal
Anis Krache, Charlotte Fontan, Carine Pestourie, Manuel Bardies, Yann Bouvet, Pierre Payoux, Etienne Chatelut, Melanie White-Koning, Anne-Sophie Salabert
Summary: Anti-PDL1 is a monoclonal antibody that restores the immune system response in several tumors by targeting PD-L1. Non-invasive imaging enables whole-body mapping of PD-L1 sites and could improve the assessment of tumor PD-L1 expression.
FRONTIERS IN MEDICINE
(2022)
Article
Immunology
Mihaly Balogh, Jixiang Zhang, Caitlyn M. Gaffney, Neha Kalakuntla, Nicholas T. Nguyen, Ronnie T. Trinh, Clarissa Aguilar, Hoang Vu Pham, Bojana Milutinovic, James M. Nichols, Rajasekaran Mahalingam, Andrew J. Shepherd
Summary: This study demonstrates that colon cancer is associated with latent sensory neuron dysfunction and implicates cytokine/chemokine signaling in this process. These findings may have implications for determining risk factors and treatment responsiveness related to neuropathy in colorectal cancer.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Chemistry, Multidisciplinary
Qishuai Feng, Wenming Fang, Yuedong Guo, Ping Hu, Jianlin Shi
Summary: Cancer stem cells (CSCs) play a critical role in the initiation and progression of early lung cancer. By modulating the communication between tumor-associated macrophages (TAMs) and CSCs, we developed a nebulized therapeutic strategy that triggers CSC ferroptosis, leading to the suppression of early lung cancer.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Oncology
Arta M. Monjazeb, Ziming Wang, Logan V. Vick, Cordelia Dunai, Christine Minnar, Lam T. Khuat, William J. Murphy
Summary: The study emphasizes the importance of using species appropriate reagents to evaluate the efficacy and toxicity of cancer immunotherapy in mouse models. The use of a mouse anti-mouse PD-1 antibody can prevent lethal anaphylaxis and show superior antitumor effects compared to xenogeneic reagents.
Review
Oncology
Reihaneh Alsadat Mahmoudian, Moein Farshchian, Fatemeh Fardi Golyan, Parvaneh Mahmoudian, Ali Alasti, Vahid Moghimi, Mina Maftooh, Majid Khazaei, Seyed Mahdi Hassanian, Gordon A. Ferns, Hanie Mahaki, Soodabeh Shahidsales, Amir Avan
Summary: Preclinical models in cancer research can be manipulated to mimic human behavior and conditions through environmental, genomic, molecular, organ system, and physical activity modifications. Recent developments in genetic engineering, such as CRISPR/Cas9, transposable elements, epigenome modifications, and liquid biopsies, have advanced the creation of mouse models for studying cancer. This review focuses on the production and usage of xenografts, chemical-induced models, and genetically engineered mouse models (GEMMs), specifically for esophageal cancer research, and briefly discusses potential gene-editing tools.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2023)
Review
Zoology
Sergey Karakashev, Ru-Gang Zhang
Summary: Epithelial ovarian cancer is the leading cause of gynecological cancer-related mortality in developed countries, with multiple histological and molecular subtypes. Research focusing on animal models that consider the heterogeneity of the disease is crucial for studying novel therapies.
ZOOLOGICAL RESEARCH
(2021)
Review
Oncology
Adedeji K. Adebayo, Harikrishna Nakshatri
Summary: Oxygen levels play a crucial role in cellular homeostasis, but can be disrupted in pathological conditions. Despite this, routine in vitro cellular manipulations are typically carried out in ambient air, which may have negative effects on stem and cancer cells.
Article
Oncology
Wouter R. P. H. van de Worp, Brent van der Heyden, Georgios Lappas, Ardy van Helvoort, Jan Theys, Annemie M. W. J. Schols, Frank Verhaegen, Ramon C. J. Langen
Summary: Lung cancer is the leading cause of cancer related deaths worldwide, and orthotopic mouse models represent the disease more realistically compared to subcutaneous tumor models. A deep learning algorithm was developed to automatically segment and quantify lung tumor volume and mass in whole-body mouse CT scans, providing a fast and highly accurate tool for noninvasive detection and analysis of tumor development in these models.
Article
Oncology
Maicol Mancini, Quentin-Dominique Thomas, Sylvia Bourdel, Laura Papon, Emilie Bousquet, Prisca Jalta, Silvia La Monica, Camille Travert, Roberta Alfieri, Xavier Quantin, Marta Canamero, Antonio Maraver
Summary: The use of targeted therapy has improved the clinical management of lung cancer patients, but resistance remains a common issue. Combining different therapies may help delay or eliminate the development of resistance.
Letter
Hematology
Giovanni Rindone, Andrea Aroldi, Elisa Bossi, Luisa Verga, Giovanni Zambrotta, Sara Tarantino, Rocco Piazza, Lara Mussolin, Roberto Chiarle, Carlo Gambacorti-Passerini
Article
Oncology
Jiajin Chen, Yunjie Song, Yi Li, Yongyue Wei, Sipeng Shen, Yang Zhao, Dongfang You, Li Su, Maria Moksnes Bjaanaes, Anna Karlsson, Maria Planck, Johan Staaf, Aslaug Helland, Manel Esteller, Hongbing Shen, David C. C. Christiani, Ruyang Zhang, Feng Chen
Summary: This study identified significant gene-gene interactions associated with non-small-cell lung cancer survival through a three-step analytic strategy. Two interactions were found at both the epigenetic and transcriptional levels, providing potential clues for precision treatment of NSCLC.
MOLECULAR ONCOLOGY
(2023)
Review
Genetics & Heredity
Ines Orsolic, Arnaud Carrier, Manel Esteller
Summary: Cancer was once believed to be solely genetic, but now it is known that dysregulated genetic and epigenetic mechanisms work together in cancer development. Recently, the epitranscriptome, which refers to chemical modifications of RNA molecules, has been found to play a role in regulating RNA function. Specific enzymes responsible for these modifications, known as RMPs, are being investigated for their potential as therapeutic targets or diagnostic markers in cancer. The study of epitranscriptomics has revealed the critical role of RNA modifications in cellular pathways and their potential importance in cancer treatment.
TRENDS IN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Aleix Noguera-Castells, Carlos A. Garcia-Prieto, Damiana Alvarez-Errico, Manel Esteller
Summary: DNA methylation, a well-studied epigenetic mark, plays a critical role in gene regulation and is altered in cancer and other diseases. The newly developed 900K EPIC v2 microarray provides significant improvements in coverage and includes additional probes for DNA cis-regulatory regions. Validation studies demonstrate the reproducibility and versatility of this updated tool for studying the DNA methylome.
Article
Biochemistry & Molecular Biology
David Ortega-Alarcon, Rafael Claveria-Gimeno, Sonia Vega, Olga C. Jorge-Torres, Manel Esteller, Olga Abian, Adrian Velazquez-Campoy
Summary: Hydroxymethylated cytosine (5hmC) is a stable DNA epigenetic mark that interacts with MeCP2 in a distinct mode with a specific thermodynamic signature. Mutations associated with Rett syndrome alter the interaction between MeCP2 and dsDNA in a cytosine modification-specific manner, which may be correlated with disease onset time and clinical severity score.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Oncology
Gregory J. Riely, Egbert F. Smit, Myung-Ju Ahn, Enriqueta Felip, Suresh S. Ramalingam, Anne Tsao, Melissa Johnson, Francesco Gelsomino, Raymond Esper, Ernest Nadal, Michael Offin, Mariano Provencio, Jeffrey Clarke, Maen Hussain, Gregory A. Otterson, Ibiayi Dagogo-Jack, Jonathan W. Goldman, Daniel Morgensztern, Ann Alcasid, Tiziana Usari, Paul Wissel, Keith Wilner, Nuzhat Pathan, Svitlana Tonkovyd, Bruce E. Johnson
Summary: The combination of encorafenib and binimetinib showed clinical efficacy and acceptable safety in patients with BRAF(V600E)-mutant metastatic NSCLC.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Biochemical Research Methods
Zeliha Yalcin, Danielle Koot, Karel Bezstarosti, Daniel Salas-Lloret, Onno B. Bleijerveld, Vera Boersma, Mattia Falcone, Roman Gonzalez-Prieto, Maarten Altelaar, Jeroen A. A. Demmers, Jacqueline J. L. Jacobs
Summary: Ubiquitination plays a crucial role in cellular processes, but dysregulation of ubiquitin machinery enzymes can lead to pathogenesis. Defining in vivo substrates of individual ubiquitin-conjugating enzymes is challenging. In this study, we used proteomics methods to identify in vivo targets of UBE2D3, an E2 enzyme with unclear roles. UBE2D3 depletion affected the global proteome and the ubiquitinome, especially molecular pathways related to mRNA translation. Our findings show that UBE2D3 is involved in ribosome-associated protein quality control and autophagic protein quality control.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Immunology
Qian Hao, Chuanzong Zhan, Chaoyang Lian, Simin Luo, Wenyi Cao, Binbin Wang, Xia Xie, Xiaofei Ye, Tuantuan Gui, Claudia Voena, Chiara Pighi, Yanyan Wang, Ying Tian, Xin Wang, Pengfei Dai, Yanni Cai, Xiaojing Liu, Shengqun Ouyang, Shiqi Sun, Qianwen Hu, Jun Liu, Youqiong Ye, Jingkun Zhao, Aiguo Lu, Ji-Yang Wang, Chuanxin Huang, Bing Su, Fei-Long Meng, Roberto Chiarle, Qiang Pan-Hammarstrom, Leng-Siew Yeap
Summary: Insertions and deletions (indels) are low-frequency deleterious genomic DNA alterations, and indels leading to long CDR3 are crucial for antibody functions. The mechanism that generates indels during immunoglobulin diversification remains poorly understood. Through deep profiling of indels in mouse models, the study unveils the prevalent +/- 1-bp indels that bias deleterious outcomes and the rare longer in-frame indels. The research also reveals the involvement of DNA repair and processing factors in indel generation and suggests potential strategies for generating antibodies with long CDR3.
SCIENCE IMMUNOLOGY
(2023)
Article
Cell Biology
Juan J. Alburquerque-Bejar, Pablo Navajas-Chocarro, Maria Saigi, Ana Ferrero-Andres, Juan M. Morillas, Andrea Vilarrubi, Antonio Gomez, JoseL. Mate, Ana M. Munoz-Marmol, Octavio A. Romero, Pedro Blecua, Veronica Davalos, Manel Esteller, Eva Pros, Paula Llabata, Manuel Torres-Diz, Anna Esteve-Codina, Montse Sanchez-Cespedes
Summary: This study reveals subsets of lung cancer that are completely refractory or show submaximal response to interferon-γ (IFNy) stimulation, which may be due to JAK2 or IFNGR1 inactivation and impaired IFNy-stimulated genes (IySGs) expression. It also suggests that MYC activation downregulates JAK2 and impairs IySGs stimulation, potentially predicting response to anti-programmed death-1/ligand-1 (PD1/L1) therapies.
CELL REPORTS MEDICINE
(2023)
Editorial Material
Oncology
Maxime Janin, Manel Esteller
Summary: Mutations in splicing factors are commonly found in CLL, but other mechanisms such as METTL3 overexpression can also lead to abnormal splicing. METTL3 deposits epitranscriptomic marks in spliceosome transcripts, causing aberrant splicing, but also vulnerability to METTL3 inhibitors.
BLOOD CANCER DISCOVERY
(2023)
Review
Oncology
Maxime Janin, Veronica Davalos, Manel Esteller
Summary: Most cancer-related deaths and illnesses can be attributed to metastasis. The role of epigenetic and epitranscriptomic changes in the origin and progression of cancer has been extensively demonstrated. These two-layer regulatory mechanisms, driven by DNA or RNA modifiers, are finely controlled in normal tissue but dysregulated in cancer. Understanding these mechanisms could have important clinical implications for prevention and management of advanced malignancies. Reversing these epi-alterations with small molecules or inhibitors against epi-modifiers could offer novel therapeutic alternatives.
CANCER AND METASTASIS REVIEWS
(2023)
Article
Oncology
Ernest Nadal, Delvys Rodriguez-Abreu, Marta Simo, Bartomeu Massuti, Oscar Juan, Gerardo Huidobro, Rafael Lopez, Javier De Castro, Anna Estival, Joaquin Mosquera, Ivana Sullivan, Enriqueta Felip, Ana Blasco, Maria Guirado, Eva Pereira, Noelia Vilarino, Valentin Navarro, Jordi Bruna
Summary: The Atezo-Brain study shows that atezolizumab alone or in combination with chemotherapy has activity in patients with untreated brain metastases in advanced nonsquamous NSCLC, and the safety profile is acceptable.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Editorial Material
Oncology
Sara Hijazo-Pechero, Cristina Munoz-Pinedo, Ernest Nadal
JOURNAL OF THORACIC ONCOLOGY
(2023)
Editorial Material
Oncology
Roberto Chiarle, Chiara Ambrogio
Summary: The development of tailored therapies has revolutionized cancer biology, allowing researchers and clinicians to delve deeper into cancer development and treatment response. By inhibiting driver oncogenes, scientists can study the adaptation and evolution of cancer cells during treatment.
MOLECULAR ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Edilene Siqueira, Bo-Hyun Kim, Larry Reser, Robert Chow, Kerry Delaney, Manel Esteller, Mark M. Ross, Jeffrey Shabanowitz, Donald F. Hunt, Sonia Guil, Juan Ausio
Summary: This study used a neural cell line derived from the human ventral mesencephalon, called ReNCell, and its MeCP2 knock out to investigate the changes in linker histones during neural cell differentiation. The results showed that MeCP2 played a crucial role in dendrite and axon development and exhibited extensive co-localization with linker histones. Additionally, the size of the nucleus decreased during differentiation, but the MeCP2 knock out cells showed a significant increase in nucleus size after differentiation.
