Article
Allergy
Cem Akin, Michel Arock, Peter Valent
Summary: Indolent systemic mastocytosis (ISM) is the most common form of systemic mastocytosis, and many patients experience symptoms related to mast cell mediators. Conventional medication may effectively control symptoms in some patients, but there is a subset of patients who do not respond to these treatments. Tyrosine kinase inhibitors directed against specific gene mutations may be an alternative option for these patients.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Oncology
Lina Degenfeld-Schonburg, Susanne Gamperl, Gabriele Stefanzl, Anna-Katharina Schruef, Irina Sadovnik, Karin Bauer, Dubravka Smiljkovic, Gregor Eisenwort, Barbara Peter, Georg Greiner, Emir Hadzijusufovic, Juliana Schwaab, Wolfgang R. Sperr, Gregor Hoermann, Sonja Kopanja, Zsolt Szepfalusi, Konrad Hoetzenecker, Peter Jaksch, Andreas Reiter, Michel Arock, Peter Valent
Summary: Systemic mastocytosis (SM) is a complex hematopoietic neoplasm with clinical symptoms caused by organ infiltration by mast cells (MC) and the release of pro-inflammatory mediators. The growth and survival of MC in SM are triggered by various oncogenic mutant forms of the tyrosine kinase KIT, including the prevalent variant D816V. Two novel drugs, avapritinib and nintedanib, were found to effectively inhibit the growth and survival of neoplastic MC expressing different KIT mutant forms, including D816V, V560G, and K509I, making them potential candidates for the treatment of advanced SM.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
Review
Oncology
Kalpana K. Bhanumathy, Amrutha Balagopal, Frederick S. Vizeacoumar, Franco J. Vizeacoumar, Andrew Freywald, Vincenzo Giambra
Summary: Protein phosphorylation is a key regulatory mechanism controlling cellular responses, catalysed by members of the protein kinase superfamily. Tyrosine kinases have been extensively studied for their roles in human malignancies, leading to the development of targeted therapies. Various tyrosine kinases, both receptor and nonreceptor types, play critical roles in the pathogenesis and drug resistance of leukemia, highlighting their potential as therapeutic targets.
Review
Allergy
Peter Valent, Cem Akin, Karin Hartmann, Andreas Reiter, Jason Gotlib, Karl Sotlar, Wolfgang R. Sperr, Lina Degenfeld-Schonburg, Dubravka Smiljkovic, Massimo Triggiani, Hans-Peter Horny, Michel Arock, Stephen J. Galli, Dean D. Metcalfe
Summary: Mast cell activation plays a crucial role in allergic reactions, inflammatory states, and mast cell activation syndromes. While there is currently no treatment approach to eradicate mast cells, long-term use of drugs that inhibit KIT function may lead to a decrease in tissue mast cells and improvement in symptoms. For patients with KIT D816V-positive mastocytosis, effective KIT inhibitors like avapritinib may be used for mast cell eradication, but potential side effects need to be considered.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Won-Sik Shin, Mi-Kyung Park, Jae Hoon Kim, Si Won Oh, Ji-Yun Jang, Ho Lee, Seung-Taek Lee
Summary: In this study, we found that PTK7 plays an oncogenic role in esophageal squamous cell carcinoma (ESCC). Overexpression of PTK7 enhanced the proliferation, adhesion, wound healing, and migration of ESCC cells, and important signaling pathways were activated during this process. Furthermore, mouse models confirmed the importance of PTK7 in tumor formation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Vanessa Marensi, Karen R. Keeshan, David J. MacEwan
Summary: AML is an aggressive blood cancer with a high mortality rate, especially for patients with FLT3 gene mutations, leading to difficulties in developing personalized therapeutic strategies due to mutation-driven drug resistance. Targeting FLT3 receptor tyrosine kinase has become a treatment strategy, but limited clinical impact has been observed with current tyrosine kinase inhibitors against FLT3-ITD.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Oncology
Ying-Chen Chen, Chu-Yen Chien, Chia-Chen Hsu, Chien-Hsing Lee, Yu-Ting Chou, Shine-Gwo Shiah, Shyun-Yeu Liu, Ching-Yu Yen, Alexander Cheng-Ting Hsieh, Martin Wabitsch, Yi-Shing Shieh
Summary: This study demonstrates that leptin-mediated AXL signaling pathway activation contributes to 5-FU resistance in colorectal cancer, suggesting a novel therapeutic strategy for colorectal cancer treatment.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Vignesh Sivaganesh, Varsha Sivaganesh, Christina Scanlon, Alexander Iskander, Salma Maher, Thu Le, Bela Peethambaran
Summary: Protein tyrosine phosphatases (PTPs) have emerged as a new target in cancer therapy, with both tumor-suppressive and oncogenic properties. This review focuses on key PTPs investigated in various cancers and explores the different mechanisms underlying pro-cancerous and anti-cancerous effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Hematology
Melody C. Carter, Dean D. Metcalfe
Summary: Historically, understanding of human mast cells has lagged behind other cell lineages, and there is currently no identified pharmacological agent that can completely and selectively inhibit human MC function. Mast cell diseases are categorized as intrinsic or extrinsic to the MC compartment, with mediators playing a key role in MC activation disorders.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Biochemical Research Methods
Raiha Tahir, Santosh Renuse, Savita Udainiya, Anil K. Madugundu, Jevon A. Cutler, Raja Sekhar Nirujogi, Chan Hyun Na, Yaoyu Xu, Xinyan Wu, Akhilesh Pandey
Summary: This study reveals significant signaling differences between two common KRAS mutations, highlighting distinct signaling mechanisms implicated in G12D and G13D mutations. By targeting a cell surface molecule MPZL1 and confirming its impact on proliferation of G12D cells, the study underscores the potential for individualized treatments based on subtle differences between related oncogenic mutants.
JOURNAL OF PROTEOME RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Roberta Parente, Valentina Giudice, Chiara Cardamone, Bianca Serio, Carmine Selleri, Massimo Triggiani
Summary: Mast cells (MCs) are immune cells that play a significant role in allergic and inflammatory diseases, releasing pro-inflammatory mediators. MC disorders, including mastocytosis and MC activation syndromes, are heterogeneous conditions characterized by abnormal MC proliferation and hyperactivity. The diagnosis of MC disorders is challenging due to the transient and unspecific symptoms and the similarity with other diseases. Tryptase is currently used as a biomarker for MC activation, but there is a need for further research to identify more reliable biomarkers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Fuli Fan, Hyeon Joo Yoo, Sophia Stock, Lei Wang, Yibin Liu, Maria-Luisa Schubert, Sanmei Wang, Brigitte Neuber, Angela Hueckelhoven-Krauss, Ulrike Gern, Anita Schmitt, Carsten Mueller-Tidow, Peter Dreger, Michael Schmitt, Leopold Sellner
Summary: The use of ibrutinib has been shown to improve the viability and expansion of CART cells derived from CLL patients, enriching them with less-differentiated naive-like T cell subsets and reducing exhaustion marker expression. Additionally, ibrutinib enhances the cytokine release capacity of CLL patient-derived CART cells, suggesting it can improve the yield and function of these cell products.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Elizabeth Proano-Perez, Laia Olle, Yanru Guo, Cristina Aparicio, Mario Guerrero, Rosa Munoz-Cano, Margarita Martin
Summary: Activating mutations in KIT (CD117) are associated with various diseases, and recent research found that the SH3BP2 pathway regulates MITF through miR-1246 and miR-5100, suggesting that MITF may be a potential therapeutic target for gastrointestinal stromal tumors and mastocytosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jixian Luo, Huiguang Zheng, Sen Wang, Dingyun Li, Wenli Ma, Lan Wang, M. James C. Crabbe
Summary: The fusion gene of ABL1 is associated with tumor proliferation, invasion, and migration. The ABL1 inhibitor Nilotinib shows potential for T-ALL leukemia treatment by inhibiting leukemia cell migration induced by CXCL12. Cofilin1 is identified as a novel ABL1 binding partner and is involved in the migration of leukemia cells induced by CXCL12.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2021)
Article
Immunology
Qingya Cui, Peiqi Liang, Haiping Dai, Wei Cui, Mengjie Cai, Zixuan Ding, Qinfen Ma, Jia Yin, Zheng Li, Sining Liu, Liqing Kang, Li Yao, Jiannong Cen, Hongjie Shen, Mingqing Zhu, Lei Yu, Depei Wu, Xiaowen Tang
Summary: Resistance to TKIs and chemotherapy in CML-BP may be overcome by CAR-T-38 cell therapy, targeting CD38 antigen, leading to significant therapeutic responses.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Ilona Berestjuk, Margaux Lecacheur, Alexandrine Carminati, Serena Diazzi, Christopher Rovera, Virginie Prod'homme, Mickael Ohanna, Ana Popovic, Aude Mallavialle, Frederic Larbret, Sabrina Pisano, Stephane Audebert, Thierry Passeron, Cedric Gaggioli, Christophe A. Girard, Marcel Deckert, Sophie Tartare-Deckert
Summary: The study reveals that physical and structural signals from fibroblast-derived ECM can cause the antiproliferative responses to BRAF/MEK inhibitors to fail in melanoma. Drug-induced linear clustering of DDR1 and DDR2 mediates ECM-mediated drug resistance. Targeting DDR1 and DDR2 can overcome resistance to BRAF-targeted therapy mediated by ECM.
EMBO MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Jean-Hugues Guervilly, Marion Blin, Luisa Laureti, Emilie Baudelet, Stephane Audebert, Pierre-Henri Gaillard
Summary: The tumour suppressor SLX4 interacts with MSH2 and regulates the activity of MutS beta and MutS alpha, uncovering an unexpected role of SLX4 in inhibiting repair activity of MMR.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Oncology
Paul Chaintreuil, Lucie Laplane, Florian Esnault, Victoria Ghesquier, Coline Savy, Nathan Furstoss, Marie-Laure Arcangeli, Thomas Cluzeau, Guillaume Robert, Nathalie Droin, Eric Solary, Patrick Auberger, Arnaud Jacquel
Summary: Macrophages are innate immune cells that play crucial roles in various physiological and pathological processes. Caspases, previously known for their involvement in programmed cell death, are found to have non-apoptotic functions in macrophage differentiation and inflammation. Emricasan, a pan-caspase inhibitor, has shown potential in reprogramming monocyte-derived macrophages and could be an alternative therapy for diseases driven by these macrophages.
Article
Biochemistry & Molecular Biology
Victoire Gouirand, Tristan Gicquel, Evan C. Lien, Emilie Jaune-Pons, Quentin Da Costa, Pascal Finetti, Elodie Metay, Camille Duluc, Jared R. Mayers, Stephane Audebert, Luc Camoin, Laurence Borge, Marion Rubis, Julie Leca, Jeremy Nigri, Francois Bertucci, Nelson Dusetti, Juan Lucio Iovanna, Richard Tomasini, Ghislain Bidaut, Fabienne Guillaumond, Matthew G. Vander Heiden, Sophie Vasseur
Summary: Pancreatic ductal adenocarcinoma cells can activate ketone body metabolism using beta-hydroxybutyrate (beta OHB) as a fuel, which promotes PDA growth and progression. HMGCL, involved in ketogenesis, is found to be deregulated in PDA and its depletion impairs PDA migration and invasiveness. Disrupting HMGCL decreases PDA tumor growth, while beta OHB stimulates metastatic dissemination to the liver.
Letter
Oncology
Vilma Barroca, Elia Henry, Nathalie Dechamps, Laurent Renou, Paul Chaintreuil, Rohan Kulkarni, Saiyirami Devanand, Arnaud Jacquel, Guillaume Robert, Patrick Auberger, Francoise Pflumio, Marie-Laure Arcangeli
Article
Cell Biology
Avais M. Daulat, Monica S. Wagner, Steprimephane Audebert, Malgorzata Kowalczewska, Jeremy Ariey-Bonnet, Pascal Finetti, Francois Bertucci, Luc Camoin, Jean-Paul Borg
Summary: Upregulation of the developmental Wnt planar cell polarity pathway is associated with many cancers. PRICKLE1, a core component of the pathway, is phosphorylated by MINK1 kinase in triple negative breast cancer (TNBC), promoting cell motility and invasiveness. LL5 beta, a substrate of MINK1, anchors microtubules at the cell cortex to trigger focal adhesion disassembly. The upregulation of both PRICKLE1 and LL5 beta is associated with poor metastasis-free survival in TNBC patients.
JOURNAL OF CELL SCIENCE
(2022)
Article
Biotechnology & Applied Microbiology
Thi Khanh Le, Chaima Cherif, Kenneth Omabe, Clement Paris, Francois Lannes, Stephane Audebert, Emilie Baudelet, Mourad Hamimed, Dominique Barbolosi, Pascal Finetti, Cyrille Bastide, Ladan Fazli, Martin Gleave, Francois Bertucci, David Taieb, Palma Rocchi
Summary: The heat shock protein 27 (Hsp27) plays a crucial role in the progression of castration-resistant prostate cancer (CRPC), and an antisense oligonucleotide (ASO) against Hsp27 has been evaluated in clinical trials. This study demonstrates that Hsp27 regulates the expression of the human DEAD-box protein 5 (DDX5) and identifies DDX5 as a potential therapeutic target for CRPC treatment.
Article
Biochemistry & Molecular Biology
Sarah Barelier, Romain Avellan, Giri Raj Gnawali, Patrick Fourquet, Veronique Roig-Zamboni, Isabelle Poncin, Vanessa Point, Yves Bourne, Stephane Audebert, Luc Camoin, Christopher D. Spilling, Stephane Canaan, Jean-Francois Cavalier, Gerlind Sulzenbacher
Summary: We report the synthesis of new CyC alkyne-containing inhibitors (CyCyne) and their use for the direct fishing of target proteins in M. tb culture via bio-orthogonal click-chemistry activity-based protein profiling (CC-ABPP). This approach led to the capture and identification of a variety of enzymes, including HsaD, which is required for the survival of M. tb within macrophages and is a potential therapeutic target. The specificity of HsaD inhibition by the CyC analogues was confirmed through biochemical and structural approaches.
Article
Cell Biology
Maroua Manai, Ines EL Bini-Dhouib, Pascal Finetti, Haifa Bichiou, Carolina Reduzzi, Dorra Aissaoui, Naziha Ben-Hamida, Emilie Agavnian, Najet Srairi-Abid, Marc Lopez, Fatma Amri, Lamia Guizani-Tabbane, Khaled Rahal, Karima Mrad, Mohamed Manai, Daniel Birnbaum, Emilie Mamessier, Massimo Cristofanilli, Hamouda Boussen, Maher Kharrat, Raoudha Doghri, Francois Bertucci
Summary: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer, and protein MARCKS has been found to be associated with shorter survival in IBC patients. This study investigated the potential therapeutic target of MARCKS in IBC and found that MARCKS expression was higher in IBC than non-IBC, and MARCKS inhibition could suppress cell proliferation, migration, invasion, and mammosphere formation in IBC cells. Additionally, the study revealed that MARCKS and PTEN protein expressions were correlated with metastasis-free survival in IBC patients.
Article
Oncology
David Jeremie Birnbaum, Maelle Picard, Quentin Da Costa, Thomas Delayre, Pascal Finetti, Olivier Cabaud, Emilie Agavnian, Bernadette De Rauglaudre, Emilie Denicolai, Francois Bertucci, Emilie Mamessier
Summary: Hepatocellular carcinoma (HCC) is a common and deadly cancer, and new treatments are needed. Immune checkpoint inhibitors (ICIs) have shown promise for HCC. By analyzing a large transcriptomic database, we found that the TIGIT/DNAM-1 axis, particularly the PVRIG molecule, could be a potential therapeutic option for HCC.
Article
Oncology
Marie-Berengere Troadec, Francoise Porteu, Marie -Laure Arcangeli, Adlen Foudi, Dominique Bluteau, Paulo De Sepulveda, Christel Guillouf, Nathalie M. Mazure, Fabienne Meggetto, Philippe Brunet De La Grange, Cyril Broccardo
Summary: This article summarizes the presentations from the 2021 scientific meeting of the Club Hematopoiesis and Oncogenesis. The meeting focused on hematopoiesis and oncogenic mechanisms, covering topics such as expansion of hematopoietic stem cells, the role of stem cell niches, the intersection of hematology and immunology, the importance of metabolism in hematopoiesis, solid tumors and oncogenesis, the noncoding genome, inflammation in monocyte differentiation and leukemia, as well as recent advances in myeloid malignancies, lymphoid leukemia, and lymphoma.
BULLETIN DU CANCER
(2023)
Article
Environmental Sciences
Caroline Arcanjo, Sandrine Frelon, Olivier Armant, Luc Camoin, Stephane Audebert, Virginie Camilleri, Isabelle Cavalie, Christelle Adam-Guillermin, Beatrice Gagnaire
Summary: In this study, the effects of tritiated water (HTO) on zebrafish larvae were investigated. Transcriptomic and proteomic analyses revealed similar impacts on biological pathways such as defence response, muscle integrity and contraction, and potential visual alterations. Interestingly, these effects partly overlapped with those induced by gamma irradiation, suggesting potential common modes of action. This study provides evidence of the molecular-level effects of HTO on zebrafish larvae, and further research could explore whether these effects persist in adult organisms.
JOURNAL OF ENVIRONMENTAL RADIOACTIVITY
(2023)
Article
Medicine, General & Internal
Abdessamad El Kaoutari, Nicolas A. Fraunhoffer, Luc Camoin, Yolande Berthois, Odile Gayet, Julie Roques, Martin Bigonnet, Claire Bongrain, Joseph Ciccolini, Juan L. Iovanna, Nelson J. Dusetti, Philippe Soubeyran
Summary: Through specific proteomic tools and bioinformatics analysis, we established the ubiquitin dependent proteome of 60 PDAC, identifying 38 ubiquitination site profiles correlated with tumor phenotype and having prognostic capabilities. These findings have potential application in predicting chemotherapy response and personalized treatment in clinical settings.
Article
Biology
Clement Car, Andre Gilles, Elen Goujon, Marie-Laure Delignette Muller, Luc Camoin, Sandrine Frelon, Pablo Burraco, Samuel Granjeaud, Emilie Baudelet, Stephane Audebert, German Orizaola, Jean Armengaud, Arthur Tenenhaus, Imene Garali, Jean-Marc Bonzom, Olivier Armant
Summary: By analyzing the radar observation data from the Urumqi Satellite Receiving Station, researchers have found that the mass balance of the Yabulangsha Glacier has undergone significant changes over time. The results of the study indicate a trend of increasing mass balance of the glacier, which may be attributed to factors such as increased precipitation and decreased temperature.