Review
Oncology
Jin Wu, Guanting Lu, Xinjiang Wang
Summary: MDM4, originally named MDMX, is an oncogene that plays critical roles in promoting cancer cell growth and inhibiting apoptosis by blocking the p53 pathway. Different splicing isoforms of MDM4 show potential therapeutic value in cancer treatment, making them attractive targets for therapy.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Review
Oncology
Mosebo Armstrong Manabile, Rodney Hull, Richard Khanyile, Thulo Molefi, Botle Precious Damane, Nigel Patrick Mongan, David Owen Bates, Zodwa Dlamini
Summary: Colorectal cancer is a leading cause of cancer-related deaths globally, with increasing incidence in developing countries. Dysregulated alternative splicing processes in colorectal cancer can promote its development and progression by producing proteins that activate cancer-promoting genes or deactivate cancer-inhibiting genes. It is important to identify these dysregulated alternative splicing genes in order to develop targeted treatments and diagnostics to stop cancer development and progression.
Article
Chemistry, Multidisciplinary
Samia M. M. Al-Muntaser, Ahmed A. A. Al-Karmalawy, Abeer M. M. El-Naggar, Ali Khalil Ali, Nour E. A. Abd El-Sattar, Eslam M. M. Abbass
Summary: In this study, new 4-thiophenyl-pyrazole, pyridine, and pyrimidine derivatives were designed as dual EGFR/VEGFR-2 inhibitors and evaluated for their anticancer and antimicrobial activities. Some of the compounds showed promising anticancer activities and significant dual EGFR/VEGFR-2 inhibition. Additionally, most of the compounds exhibited strong to moderate antibacterial and antifungal effects.
Article
Biochemistry & Molecular Biology
Hend A. A. Ezelarab, Taha F. S. Ali, Samar H. Abbas, Ahmed M. Sayed, Eman A. M. Beshr, Heba A. Hassan
Summary: New 3-substituted oxindole derivatives were synthesized and evaluated as antiproliferative agents. Among the tested compounds, compounds 6f and 6g showed remarkable antiproliferative activity against leukemia and breast cancer cell lines. Compound 6f exhibited the most promising antiproliferative activity against MCF-7 (human breast cancer), and inhibited receptor tyrosine EGFR and tubulin polymerization.
MOLECULAR DIVERSITY
(2023)
Review
Biochemistry & Molecular Biology
James D. D. Fackenthal
Summary: Cancer is a leading cause of death worldwide. Alternative mRNA splicing has recently been recognized as a major contributor to cancer initiation and progression. Cancer cells exhibit different distribution of splicing variants compared to non-cancer cells, and they are more sensitive to drugs targeting the splicing regulatory network. Certain recurring splicing variants have been shown to contribute to tumor progression, while some disruption events result from mutations in splicing regulatory sequences or shifts in balance among naturally occurring splicing variants of mRNAs involved in cell cycle progression and apoptosis regulation. This review explores cancer-related alternative splicing events and potential therapies.
Review
Biochemistry & Molecular Biology
Altaf Ahmad Shah, Mohammad A. Kamal, Salman Akhtar
Summary: This review discusses the interplay between angiogenesis and tumor progression, focusing on therapeutic interventions targeting VEGFR-2. Tumor angiogenic pathways operate through various mechanisms, with VEGFR-2 identified as a key therapeutic target. While current anti-angiogenic drugs show good survival rates, they are also associated with serious health effects and adverse reactions, highlighting the need for more effective and safer alternative treatments.
CURRENT DRUG METABOLISM
(2021)
Article
Chemistry, Multidisciplinary
Xinyuan Xi, Fan Lei, Keliang Gao, Jingjing Li, Rihe Liu, Adam R. Karpf, Tatiana K. Bronich
Summary: Combining chemotherapeutic drugs in a single nanocarrier offers advantages in cancer treatment, including reducing toxicity, improving drug properties, and enhancing therapeutic effects. In this study, we developed functional multimodal polypeptide-based polymeric nanogels (NGs) to encapsulate a combination of drugs. These NGs exhibited selective cytotoxicity towards EGFR overexpressing ovarian cancer cells and showed preferential associations with EGFR (+) tumor cells. Furthermore, ligand-installed NGs carrying the drug combination significantly improved the treatment response of ovarian cancer xenografts compared to individual drug-loaded NGs. This work highlights the potential of our carrier system for efficient delivery of drug combinations to treat EGFR overexpressing cancers.
JOURNAL OF CONTROLLED RELEASE
(2023)
Review
Oncology
Tomohiro Enokida, Makoto Tahara
Summary: Anti-VEGFR therapy is crucial in treating thyroid cancer but can lead to dangerous adverse reactions. To minimize risks, physicians need to understand the characteristics of these reactions and take appropriate measures. The development of multitarget tyrosine kinase inhibitors has improved prognosis, but effective management of related adverse events is essential.
Review
Biochemistry & Molecular Biology
Skye Montoya, Deborah Soong, Nina Nguyen, Maurizio Affer, Sailasya P. Munamarty, Justin Taylor
Summary: Development of targeted therapies has provided nonchemotherapeutic options for patients, with small molecule kinase inhibitors being a key focus. However, resistance to these therapies may develop, necessitating multiple lines of treatment. Combinations of therapies targeting complimentary pathways may be more effective in overcoming drug resistance.
Article
Oncology
Nikolaus Magios, Farastuk Bozorgmehr, Anna-Lena Volckmar, Daniel Kazdal, Martina Kirchner, Felix J. Herth, Claus-Peter Heussel, Florian Eichhorn, Michael Meister, Thomas Muley, Rami A. Elshafie, Jurgen R. Fischer, Martin Faehling, Mark Kriegsmann, Peter Schirmacher, Helge Bischoff, Albrecht Stenzinger, Michael Thomas, Petros Christopoulos
Summary: This study retrospectively analyzed EGFR(+) non-small-cell lung cancer patients who received osimertinib after first/second-generation TKI therapy, showing that osimertinib may prolong survival, but approximately 15% and 30% of patients forego molecular retesting and subsequent treatment, respectively, mainly due to rapid disease deterioration.
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Michael D. Paul, Kalina Hristova
Summary: This study proposes a provocative hypothesis that active, ligand-bound RTK dimers from unrelated subfamilies can associate into heterooligomers with novel signaling properties, supported by quantitative FRET study. Direct interactions between EGFR and VEGFR2 are observed in the absence of ligand and in the presence of both ligands, suggesting a novel mechanism for signal diversification.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Virginia S. Hahn, Kathleen W. Zhang, Lova Sun, Vivek Narayan, Daniel J. Lenihan, Bonnie Ky
Summary: The growing use of targeted therapies in oncology has led to significant improvements in survival rates, but also presents challenges in managing toxicities associated with long-term treatment. Overlapping signaling pathways may result in systemic toxicities, with cardiovascular toxicities being of particular concern.
CIRCULATION RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Mona H. Ibraheim, Ibrahim Maher, Ibrahim Khater
Summary: The study aims to find novel inhibitors for EGFR and VEGFR-2 kinases through molecular docking, pharmacokinetic analysis, interaction analysis, and molecular dynamic simulation. Compound 2C showed good docking performance, drug-likeness, and interactions, and it can stably bind to the kinases. Therefore, compound 2C may be a promising option to slow the spread of cancer.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Chemistry, Medicinal
Adileh Ayati, Setareh Moghimi, Mahsa Toolabi, Alireza Foroumadi
Summary: Despite advancements in cancer treatment, EGFR inhibitors have shown significant improvement in targeted therapy. However, the emergence of epigenetic mutation and resistance issues have limited their effectiveness, leading to the need for further research in this field. Recent studies have focused on genetic alterations in the EGFR tyrosine kinase domain, resulting in the development of more selective and effective inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Genetics & Heredity
Jan Lejman, Grzegorz Zielinski, Piotr Gawda, Monika Lejman
Summary: Alternative splicing is a crucial mechanism that increases genetic diversity and can be a therapeutic target. Spinal Muscular Atrophy (SMA) is a neurodegenerative disease mainly caused by the homozygous deletion in the SMN1 gene, with 95% of cases attributed to this mutation.
Article
Biochemistry & Molecular Biology
Asma Boudria, Cherine Abou Faycal, Tao Jia, Stephanie Gout, Michelle Keramidas, Chloe Didier, Nicolas Lemaitre, Sandra Manet, Jean-Luc Coll, Anne-Claire Toffart, Denis Moro-Sibilot, Corinne Albiges-Rizo, Veronique Josserand, Eva Faurobert, Christian Brambilla, Elisabeth Brambilla, Sylvie Gazzeri, Beatrice Eymin
Article
Multidisciplinary Sciences
Cherine Abou Faycal, Sylvie Gazzeri, Beatrice Eymin
SCIENTIFIC REPORTS
(2019)
Review
Genetics & Heredity
Florence de Fraipont, Sylvie Gazzeri, William C. Cho, Beatrice Eymin
FRONTIERS IN GENETICS
(2019)
Article
Biochemistry & Molecular Biology
Zhen Sun, Ines Velazquez-Ouesada, Devadarssen Murdamoothoo, Constance Ahowesso, Alev Yilmaz, Caroline Spenle, Gerlinde Averous, William Erne, Felicitas Oberndorfer, Andre Oszwald, Renate Kain, Catherine Bourdon, Pierre Mangin, Claire Deligne, Kim Midwood, Cherine Abou-Faycal, Olivier Lefebvre, Annick Klein, Michael van der Heyden, Marie-Pierre Chenard, Gerhard Christofori, Carole Mathelin, Thomas Loustau, Thomas Hussenet, Gertraud Orend
Article
Pharmacology & Pharmacy
Tao Jia, Jeremy Ciccione, Thibault Jacquet, Manon Maurel, Titouan Montheil, Ahmad Mehdi, Jean Martinez, Beatrice Eymin, Gilles Subra, Jean-Luc Coll
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2019)
Article
Immunology
Mariska T. Meijer, Alex F. de Vos, Brendon P. Scicluna, Joris J. Roelofs, Cherine Abou Faycal, Gertraud Orend, Fabrice Uhel, Tom van der Poll
Summary: While TNC plays a role in shaping the immune response during lipopolysaccharide-induced inflammation, its role may be superseded by other factors during pneumosepsis caused by a common gram-negative pathogen.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Raphael Clere-Jehl, Hamid Merdji, Mohamad Kassem, Cecile Macquin, Aurore De Cauwer, Alicia Sibony, Kei Kurihara, Laetitia Minniti, Cherine Abou Faycal, Seiamak Bahram, Ferhat Meziani, Julie Helms, Philippe Georgel
Summary: This study investigates the role of circulating IFN-alpha in patients with septic shock-induced DIC and the potential therapeutic target of endothelial Stat1 in a mouse model of sepsis. Type I IFNs were found to play key roles in septic shock-induced DIC, with endothelial Stat1 possibly serving as a therapeutic target.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Devadarssen Murdamoothoo, Zhen Sun, Alev Yilmaz, Gilles Riegel, Cherine Abou-Faycal, Claire Deligne, Ines Velazquez-Quesada, William Erne, Marine Nascimento, Matthias Morgelin, Gerard Cremel, Nicodeme Paul, Raphael Carapito, Romain Veber, Helene Dumortier, Jingping Yuan, Kim S. Midwood, Thomas Loustau, Gertraud Orend
Summary: The study found that tenascin-C inhibits CD8 T cell infiltration by inducing CXCL12, which may contribute to the low response rates of immune checkpoint therapy in cancer treatment. Blocking the CXCR4 receptor of CXCL12 enhances macrophage and CD8 T cell infiltration, reducing tumor growth and metastasis.
EMBO MOLECULAR MEDICINE
(2021)
Article
Immunology
Sayda Dhaouadi, Rahma Ben Abderrazek, Thomas Loustau, Cherine Abou-Faycal, Ayoub Ksouri, William Erne, Devadarssen Murdamoothoo, Matthias Morgelin, Andreas Kungl, Alain Jung, Sonia Ledrappier, Zakaria Benlasfar, Sandrine Bichet, Ruth Chiquet-Ehrismann, Ismail Hendaoui, Gertraud Orend, Balkiss Bouhaouala-Zahar
Summary: The newly generated Nb3 and Nb4 nanobodies show high specificity for human TNC and have been characterized to interact with TNC through various methods.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Caroline Spenle, Thomas Loustau, Helene Burckel, Gilles Riegel, Cherine Abou Faycal, Chengbei Li, Alev Yilmaz, Luciana Petti, Fanny Steinbach, Constance Ahowesso, Camille Jost, Nicodeme Paul, Raphael Carapito, Georges Noel, Fabienne Anjuere, Nathalie Salome, Gertraud Orend
Summary: The study using a novel syngeneic tongue OSCC grafting model found high TNC expression and TIL infiltration in irradiated tumors, while TNC knockout host showed less immune suppressive TME and tendency towards more tumor regression, which could be significant for future anti-cancer targeting of OSCC.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Microbiology
Mariska T. Meijer, Alex F. de Vos, Hessel Peters Sengers, Brendon P. Scicluna, Joris J. Roelofs, Cherine Abou Faycal, Fabrice Uhel, Gertraud Orend, Tom van der Poll
Summary: The study found that TNC plays a moderate protective role against tissue pathology during the acute inflammatory phase of MRSA-induced pneumonia, but not during the bacterial clearance phase, suggesting a context-dependent effect of TNC. Contrary to previous descriptions, TNC does not seem to play a major role in disease outcome during MRSA-induced pneumonia.
MICROBIOLOGY SPECTRUM
(2021)
Article
Biochemistry & Molecular Biology
Cherine Abou Faycal, Andre Oszwald, Tobias Feilen, Miguel Cosenza-Contreras, Oliver Schilling, Thomas Loustau, Fanny Steinbach, Helga Schachner, Brigitte Langer, Peter Heeringa, Andrew J. Rees, Gertraud Orend, Renate Kain
Summary: This study established a severe FNGN mouse model by combined administration of antibodies and bacterial lipopolysaccharides, which replicated acute injury and investigated the process of glomerular and interstitial scarring. Mass-spectrometric proteome analysis revealed detailed changes in the extracellular matrix and cells. The study observed tissue infiltration by neutrophils, macrophages, T cells, and myofibroblasts.
Article
Medicine, Research & Experimental
Alexandre Mariotte, Aurore De Cauwer, Chrystelle Po, Cherine Abou-Faycal, Angelique Pichot, Nicodeme Paul, Ismael Aouadi, Raphael Carapito, Benoit Frisch, Cecile Macquin, Emmanuel Chatelus, Jean Sibilia, Jean-Paul Armspach, Seiamak Bahram, Philippe Georgel