Article
Multidisciplinary Sciences
Maalavika Pillai, Mohit Kumar Jolly
Summary: Studying the network of transcription factors in melanoma reveals the dynamics that drive cell state transitions and phenotypic switching, offering new insights into melanoma heterogeneity.
Article
Dermatology
Gil S. Leichner, Inbal Schweitzer, Shani Dror, Lotan Levin, Polina Geva, Tamar Golan, Laureen Zaremba, Guy Shapira, Roma Parikh, Noam Shomron, Aviv Barzilai, Jorg D. Hoheisel, Carmit Levy, Shoshana Greenberger
Summary: Melanoma, the deadliest cutaneous tumor, spreads through the lymphatic and blood system, and an increased density of dermal lymphatic vessels is observed before invasion into the dermis. In this study, melanoma cells were found to secrete extracellular vesicles termed melanosomes at the primary stage, which led to pro-lymphangiogenic changes in dermal lymphatic cells. These changes were mediated by the transfer of mature let-7i from melanoma-derived melanosomes to lymphatic endothelial cells, inducing type I IFN signaling and enhancing IFI6 expression.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Liying Wang, Dan Lu, Minfeng Huo, Huixiong Xu
Summary: Mitochondrial-targeted therapies have shown effectiveness in inducing programmed cell death in malignant melanoma, with potential clinical applications in triggering the switch from apoptosis to pyroptosis for cancer treatment.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Olga Grigorieva, Mikhail Arbatskiy, Ekaterina Novoseletskaya, Uliana Dyachkova, Alexander Ishkin, Natalia Kalinina, Anastasia Efimenko
Summary: The activation of multipotent mesenchymal stromal cells (MSCs) by PDGF-BB was found to induce the expression of genes associated with senescence, but further experimental validation demonstrated that PDGF-BB still exerted mitogenic and pro-migratory effects on MSCs, enhancing their pro-angiogenic activity without significantly stimulating MSC senescence.
Article
Biochemistry & Molecular Biology
Dong-Hee Han, Min Kyoung Shin, Jin Wook Oh, Junha Lee, Jung-Suk Sung, Min Kim
Summary: This study aims to identify the mechanism of tumorigenesis in bronchial epithelial cells induced by chronic TDI exposure. Transcriptome analysis confirmed that TDI increases TGF-beta 1 expression and regulates genes associated with cancerous characteristics. Our results indicate that chronic TDI exposure leads to EMT and other cancer properties through upregulation of TGF-beta 1 secretion and activation of TGF-beta 1 signal transduction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Yurun Gan, Tao Zhang, Xiaodong Chen, Wei Cao, Liangyu Lin, Liming Du, Yu Wang, Fei Zhou, Xuefeng He, Yulong He, Jianhe Gan, Huiming Sheng, Lydia Sorokin, Yufang Shi, Ying Wang
Summary: The study demonstrates that co-administration of steroids interferes with the efficacy of mesenchymal stromal cells (MSCs) in treating acute graft-versus-host disease (aGvHD), with vascular endothelial growth factor C (VEGF-C) inducing immune responses and exacerbating disease progression. This suggests that steroids can reverse the immunosuppressive effect of MSCs by promoting VEGF-C-augmented CD8(+) T cell response, providing new insights for designing effective MSC-based therapies.
Article
Oncology
Ihor Arkhypov, Feyza Gul Ozbay Kurt, Rebekka Bitsch, Daniel Novak, Vera Petrova, Samantha Lasser, Thomas Hielscher, Christopher Groth, Alisa Lepper, Xiaoying Hu, Wei Li, Jochen Utikal, Peter Altevogt, Viktor Umansky
Summary: Soluble HSP90 alpha can convert monocytes into MDSC, which inhibits the antitumor function of T and NK cells. Higher levels of HSP90 alpha in plasma of patients with melanoma are associated with increased PD-L1 expression on MDSC and shorter PFS after ICI therapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Medicine, Research & Experimental
Jieqing Zhou, Hong Jiang, Hongkun Jiang, Yan Fan, Jing Zhang, Xiaoxue Ma, Xuewei Yang, Yu Sun, Xing Zhao
Summary: ILEI facilitates renal interstitial fibrosis (RIF) via the Akt and ERK pathways and promotes renal tubular epithelial mesenchymal transition (EMT) by binding and activating leukemia inhibitory factor receptor (LIFR). Increased expression levels of ILEI and LIFR were observed in pediatric CKD patients with RIF.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Lei Huang, Xiao-Ou Zhang, Esteban J. Rozen, Xiaomei Sun, Benjamin Sallis, Odette Verdejo-Torres, Kim Wigglesworth, Daniel Moon, Tingting Huang, John P. Cavaretta, Gang Wang, Lei Zhang, Jason M. Shohet, Mary M. Lee, Qiong Wu
Summary: The protein arginine methyltransferase 5 (PRMT5) regulates the expression of metastasis-related genes by methylating Akt protein, which is required for its phosphorylation and activation, leading to the upregulation of pro-metastatic transcription factors. Moreover, inhibiting PRMT5 can attenuate primary tumor growth and block metastasis in multiple organs, suggesting it may be a potential therapeutic target for high-risk metastatic cancers.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Tommaso Colangelo, Annalucia Carbone, Francesco Mazzarelli, Roberto Cuttano, Elisa Dama, Teresa Nittoli, Jacopo Albanesi, Giovannina Barisciano, Nicola Forte, Orazio Palumbo, Paolo Graziano, Alessandra di Masi, Vittorio Colantuoni, Lina Sabatino, Fabrizio Bianchi, Gianluigi Mazzoccoli
Summary: The study reveals the functional role of the circadian gene Timeless (TIM) in colorectal cancer (CRC). Loss of TIM expression is associated with cancer development, metastasis, and accumulation of DNA damage. The unedited TIM-ZEB1 axis is involved in malignant phenotype acquisition in colorectal carcinogenesis, and TIM-ZEB1 expression profiling could serve as a prognostic biomarker in CRC.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biochemistry & Molecular Biology
Yang Li, Lei Li, Jun Qin, Junyi Wu, Xueming Dai, Junming Xu
Summary: This study reveals the critical role of OSR1 in breast cancer by promoting EMT and metastasis, suggesting its potential as a promising therapeutic target in breast cancer treatment.
Article
Oncology
Paras Jain, Maalavika Pillai, Atchuta Srinivas Duddu, Jason A. Somarelli, Yogesh Goyal, Mohit Kumar Jolly
Summary: Phenotypic plasticity is considered a hallmark of cancer, but the dynamics of this process are still poorly understood. Recent investigations using a systems-level perspective have shed light on specific dynamical hallmarks of phenotypic plasticity in different cancers. Understanding the dynamic features of phenotypic plasticity may be crucial in shifting the paradigm of cancer treatment towards a more predictive and proactive approach.
SEMINARS IN CANCER BIOLOGY
(2023)
Article
Oncology
Jing Jia, Xinxi Zhu, Kaihua Xue, Yuanmei Huang, Menglu Wu, Yanan Yang, Wenbo Liu, Hongke Zhang, Lin He, Hong Sun
Summary: This study revealed the oncogenic role of DANCR in melanoma, showing that it promotes tumor proliferation and angiogenesis by upregulating VEGFB. Mechanistically, DANCR upregulates VEGFB through sponging miR-5194, which negatively regulates VEGFB expression and secretion. These findings suggest a new avenue for melanoma therapy by targeting the DANCR/miR-5194/VEGFB signaling pathway.
Article
Pharmacology & Pharmacy
Valentin Platel, Diane Lechevalier, Clara Bourreau, Sarah Renault, Ivana Soborova, Caroline Jeanniere, Ludovic Martin, Olivier Herault, Isabelle Corre, Nicolas Clere
Summary: The tumor microenvironment is important for the progression of melanoma, and recent studies have found that endothelial cells (EC) play a role in the endothelial-to-mesenchymal transition (EndMT). Reactive oxygen species (ROS), primarily produced by NAPDH oxidases (NOX), can control tumor growth. This study aimed to investigate the role of NOX1 and NOX2 in EndMT induced by conditioned media (CM) from melanoma cells. The results showed that NOX1 and NOX2 played important roles in EndMT.
PHARMACOLOGICAL RESEARCH
(2022)
Review
Oncology
Serena Diazzi, Sophie Tartare-Deckert, Marcel Deckert
Summary: Advanced cutaneous melanoma is the deadliest form of skin cancer, and targeted therapies and immune checkpoint blockade therapies have revolutionized its treatment. However, therapy-driven resistance remains a significant challenge. Recent studies have shown that phenotypic plasticity of melanoma cells, particularly their ability to adapt mechanically, is a key factor in treatment resistance and tumor relapse. Targeting dedifferentiated cells and mechanotransduction pathways in the extracellular matrix (ECM) may hold promise in overcoming melanoma cross-resistance.
Article
Neurosciences
Huijie Feng, Yukun Yuan, Michael R. Williams, Alex J. Roy, Jeffery R. Leipprandt, Richard R. Neubig
Summary: This study investigates the electrophysiological mechanisms of a movement disorder animal model with monoallelic Gnao1 loss. It reveals the role of G alpha(o) protein in regulating GABA release in the mouse cerebellum. The findings could lead to the discovery of new drugs or the repurposing of existing drugs for GNAO1-associated disorders. Additionally, targeting GNAO1 could have implications for the treatment of other monogenic movement disorders.
JOURNAL OF NEUROPHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Tereza Vaclova, Atanu Chakraborty, James Sherwood, Sarah Ross, Danielle Carroll, J. Carl Barrett, Julian Downward, Elza C. de Bruin
Summary: The study investigates the co-occurrence of additional KRAS mutations with KRAS G12C in non-small cell lung cancer (NSCLC) tumors and its impact on cellular response to G12C-specific inhibitors. The results show that KRAS c.35G>T mutation most frequently co-occurred with KRAS G12C and led to cellular resistance to G12C inhibitors. Therefore, comprehensive genotyping of KRAS tumors is necessary for optimal patient selection for treatment with a KRAS G12C inhibitor.
SCIENTIFIC REPORTS
(2022)
Article
Medicine, Research & Experimental
Elizabeth A. Kuczynski, Giulia Morlino, Alison Peter, Anna M. L. Coenen-Stass, Jennifer Moss, Neha Wali, Oona Delpuech, Avinash Reddy, Anisha Solanki, Charles Sinclair, Dinis P. Calado, Larissa S. Carnevalli
Summary: This study established a novel mouse model of PTCL by transplanting lymphoma cells into immune-competent mice, which exhibited similar B-cell activation and lymphomagenesis as observed in human PTCL. Molecular profiling identified specific gene expressions and mutations related to high-risk PTCL subtype. Targeting the DNA damage response pathway led to prolonged treatment responses in vivo, suggesting the potential of DDR inhibition as an effective therapy for PTCL.
EMBO MOLECULAR MEDICINE
(2022)
Editorial Material
Medicine, General & Internal
Miriam Molina-Arcas, Julian Downward
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Multidisciplinary Sciences
Philip East, Gavin P. Kelly, Dhruva Biswas, Michaela Marani, David C. Hancock, Todd Creasy, Kris Sachsenmeier, Charles Swanton, Julian Downward, Sophie de Carne Trecesson
Summary: The study found that 84% of patients with lung adenocarcinoma have oncogenic activation of the RAS signaling pathway, with a high proportion of activation even in KRAS wild-type tumors; patient groups with high RAS activity show adverse clinical outcomes and reduced response to chemotherapy. Stratifying patients based on oncogenic RAS transcriptional activity may ultimately assist in clinical decision-making.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Isobelle Wall, Victoire Boulat, Aekta Shah, Kim R. M. Blenman, Yin Wu, Elena Alberts, Dinis Pedro Calado, Roberto Salgado, Anita Grigoriadis
Summary: The tumor microenvironment (TME), lymph nodes (LNs), and peripheral blood form the interconnected immune sites in breast cancer. Understanding the dynamic interaction between these immune sites is crucial for improving anti-cancer responses and therapeutic outcomes in breast cancer patients.
Article
Biochemical Research Methods
May Zaw Thin, Christopher Moore, Thomas Snoeks, Tammy Kalber, Julian Downward, Axel Behrens
Summary: In this paper, a method of lung nodule image acquisition and analysis using a micro-computed tomography scanner is introduced for translational research in lung cancer that closely mimics clinical environments. The method has the advantages of low radiation dose, high resolution, and high-throughput imaging, and utilizes specific image analysis tools for identifying different types of lung tumors.
Article
Multidisciplinary Sciences
Mohamed Ismail, Stephen R. Martin, Roger George, Francesca Houghton, Geoff Kelly, Raphael A. G. Chaleil, Panayiotis Anastasiou, Xinyue Wang, Nicola O'Reilly, Stefania Federico, Dhira Joshi, Hemavathi Nagaraj, Rachel Cooley, Ning Sze Hui, Miriam Molina-Arcas, David C. Hancock, Ali Tavassoli, Julian Downward
Summary: A cyclic peptide inhibitor (cyclo-CRVLIR) was discovered that interacts with the p110 alpha-RBD and blocks its interaction with KRAS. This inhibitor effectively blocks the p110 alpha/KRAS interaction and reduces phospho-AKT levels in several oncogenic KRAS cell lines.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Mohamed Abdelgied, Katie Uhl, Oliver G. Chen, Chad Schultz, Kaylie Tripp, Angela M. Peraino, Shreya Paithankar, Bin Chen, Maximiliano Tamae Kakazu, Alicia Castillo Bahena, Tara E. Jager, Cameron Lawson, Dave W. Chesla, Nikolay Pestov, Nikolai N. Modyanov, Jeremy Prokop, Richard R. Neubig, Bruce D. Uhal, Reda E. Girgis, Xiaopeng Li
Summary: Idiopathic pulmonary fibrosis (IPF) is a pathological condition with unknown cause that leads to lung injury and fibrotic response, resulting in thickening of alveolar walls and obliteration of alveolar space. Small airway disease and mucus accumulation are prominent in IPF lungs, similar to cystic fibrosis lung disease. Overexpression of the ATP12A protein in distal small airways of IPF patients and in mouse lungs exacerbates pulmonary fibrosis, which can be prevented by vonoprazan, a potassium competitive proton pump blocker. Inhibiting ATP12A protein may serve as a novel therapeutic strategy for IPF.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Kevin Ng, Jesse Boumelha, Katey S. S. Enfield, Jorge L. Almagro, Hongui M. Cha, Oriol Pich, Takahiro Karasaki, David Moore, Roberto Salgado, Monica Sivakumar, George Young, Miriam L. Molina-Arcas, Sophie de Carne Trecesson, Panayiotis Anastasiou, Annika C. Fendler, Lewis Au, Scott T. C. Shepherd, Carlos Martinez-Ruiz, Clare Puttick, James R. M. Black, Thomas B. K. Watkins, Hyemin Kim, Seohee Shim, Nikhil Faulkner, Jan A. Attig, Selvaraju Veeriah, Neil J. Magno, Sophia T. Ward, Alexander Frankell, Maise Al Bakir, Emilia Lim, Mark Hill, Gareth Wilson, Daniel Cook, Nicolai Birkbak, Axel Behrens, Nadia Yousaf, Sanjay Popat, Allan Hackshaw, TRACERx Consortium, CAPTURE Consortium, Crispin T. Hiley, Kevin Litchfield, Nicholas McGranahan, Mariam Jamal-Hanjani, James Larkin, Se-Hoon Lee, Samra Turajlic, Charles Swanton, Julian Downward, George Kassiotis
Summary: This study reveals that lung adenocarcinomas in both humans and mice elicit local germinal center responses and tumour-binding antibodies, with endogenous retrovirus (ERV) envelope glycoproteins as the dominant anti-tumour antibody target. ERV-targeting B cell responses are enhanced by immune checkpoint blockade (ICB) and targeted inhibition of KRAS(G12C). ERV-reactive antibodies have anti-tumour activity and improve survival in a mouse model, and ERV expression predicts the response to ICB in human lung adenocarcinoma. Furthermore, the study demonstrates that effective immunotherapy in the mouse model requires CXCL13-dependent tertiary lymphoid structure (TLS) formation, and therapeutic CXCL13 treatment enhances anti-tumour immunity and synergizes with ICB. These findings provide a potential mechanistic basis for the association between TLS and immunotherapy response.
Article
Chemistry, Multidisciplinary
Sophia D. Staerz, Erika M. Lisabeth, Evert Njomen, Thomas S. Dexheimer, Richard R. Neubig, Jetze J. Tepe
Summary: The balance between protein degradation and synthesis, proteostasis, is key for proper cellular function. The majority of intracellular protein degradation occurs through the ubiquitin-proteasome system, with pathways targeting unfolded proteins playing an important role. Dysregulation of proteolysis can lead to the accumulation of intrinsically disordered proteins (IDPs), contributing to various diseases. Enhancing the activity of the 20S proteasome using small molecules, such as erlotinib, has shown potential in combating IDP accumulation.
Article
Multidisciplinary Sciences
Manuel Lauinger, Daniel Christen, Rhena F. U. Klar, Carole Roubaty, Christoph E. Heilig, Michael Stumpe, Jennifer J. Knox, Nikolina Radulovich, Laura Tamblyn, Irene Y. Xie, Peter Horak, Andrea Forschner, Michael Bitzer, Uwe A. Wittel, Melanie Boerries, Claudia R. Ball, Christoph Heining, Hanno Glimm, Martina Froehlich, Daniel Huebschmann, Steven Gallinger, Ralph Fritsch, Stefan Froehling, Grainne M. O'Kane, Joern Dengjel, Tilman Brummer
Summary: This study functionally characterizes BRAF exon 12 deletions and compares them with other BRAF ss 3-alpha C mutants. It demonstrates that BRAF(Delta ss 3-alpha C) deletion mutants form stable dimers and multiprotein complexes, and their dimerization is necessary. Some mutants with aromatic amino acid insertions at the deletion junction exhibit resistance to monomer-favoring RAF inhibitors while being sensitive to dimer-favoring inhibitors.
Article
Oncology
Marco Cefali, Isabel Scala, Giuliana Pavone, Daniel Helbling, Saskia Hussung, Ralph Fritsch, Caecilia Reiner, Soleen Stocker, Dieter Koeberle, Marc Kissling, Vito Chianca, Filippo Del Grande, Sara De Dosso, Stefania Rizzo
Summary: Malnutrition and changes in body composition such as weight loss and sarcopenia are common in pancreatic cancer patients and are associated with worse survival outcomes. However, it is unclear whether these changes are specifically linked to a higher likelihood of chemotherapy toxicity. This study retrospectively evaluated chemotherapy-related toxicity in patients with metastatic pancreatic cancer and found no significant association with body composition parameters, suggesting that other factors may play a more important role in determining prognosis.
Article
Oncology
Ruth Fluemann, Julia Hansen, Benedikt W. Pelzer, Pascal Nieper, Tim Lohmann, Ilmars Kisis, Tobias Riet, Viktoria Kohlhas, Phuong-Hien Nguyen, Martin Peifer, Nima Abedpour, Graziella Bosco, Roman K. Thomas, Moritz Kochanek, Jacqueline Knufer, Lorenz Jonigkeit, Filippo Beleggia, Alessandra Holzem, Reinhard Buttner, Philipp Lohneis, Jorn Meinel, Monika Ortmann, Thorsten Persigehl, Michael Hallek, Dinis Pedro Calado, Markus Chmielewski, Sebastian Klein, Joachim R. Goethert, Bjoern Chapuy, Branko Zevnik, F. Thomas Wunderlich, Bastian von Tresckow, Ron D. Jachimowicz, Ari M. Melnick, Hans Christian Reinhardt, Gero Knittel
Summary: Genomic profiling identified 5 subtypes of DLBCL, including the MCD/C5 cluster with MYD88, BCL2, PRDM1, and/or SPIB aberrations. Mouse models with B cell-specific Prdm1 or Spib aberrations were generated, showing molecular features of prememory and light-zone B cells. Combined BTK/BCL2 inhibition exhibited therapeutic activity in both mouse models and relapsed/refractory DLBCL patients.
BLOOD CANCER DISCOVERY
(2023)
