Article
Biochemistry & Molecular Biology
Salome Ruiz-Demoulin, Eva Trenquier, Sanaa Dekkar, Sebastien Deshayes, Prisca Boisguerin, Cesar Serrano, Pascal de Santa Barbara, Sandrine Faure
Summary: Gastrointestinal stromal tumor (GIST) is mainly caused by a KIT receptor tyrosine kinase oncogenic mutation. Targeting KIT using tyrosine kinase inhibitors provides benefit, but resistance eventually develops. This study shows that LIX1 is upregulated in response to imatinib or sunitinib treatment in GIST cells and silencing LIX1 enhances the anti-tumor effect of imatinib by inhibiting MAPK signaling reactivation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Manali Tilak, Jennifer Holborn, Laura A. New, Jasmin Lalonde, Nina Jones
Summary: Glioblastoma multiforme (GBM) is a deadly cancer with limited response to existing therapies. Subtypes of GBM with distinct genetic signatures show aberrant activation of signal transduction pathways. Current research focuses on understanding these molecular alterations to develop more efficient targeted therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Alberto Servetto, Luigi Formisano, Carlos L. Arteaga
Summary: FGFR signaling abnormalities play a role in breast cancer development and drug resistance. Clinical trials with FGFR inhibitors have faced challenges, with lack of established patient selection criteria identified as a potential reason for failure.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2021)
Review
Biochemistry & Molecular Biology
Mai Tanaka, Dietmar W. Siemann
Summary: Dysregulated signaling pathways in cancer cells and the tumor microenvironment, including the Axl and Gas6 pathways, have led to the development of therapeutic agents targeting the Gas6/Axl pathway. Promising results have been observed in both preclinical and clinical settings, indicating potential clinical efficacy of targeting Gas6 and Axl.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Andrea Napolitano, Alexandra E. Ostler, Robin L. Jones, Paul H. Huang
Summary: FGFR pathway alterations have been identified in various sarcoma subtypes, suggesting potential therapeutic targets. However, clinical trials have shown low efficacy of selective FGFR inhibitors, highlighting the need for further research to identify patients who will benefit most from this targeted therapy.
Article
Polymer Science
Tahir Mehmood, Rath Pichyangkura, Chatchai Muanprasat
Summary: This study demonstrates that chitosan oligosaccharide can reduce the diarrhea induced by afatinib and regulate the tight junctions and chloride secretion in intestinal epithelial cells by activating AMPK. This study provides a promising natural polymer-derived compound for further development of treatment for afatinib-associated diarrhea.
Review
Pharmacology & Pharmacy
Yazan Haddad, Marek Remes, Vojtech Adam, Zbynek Heger
Summary: The study utilized variations in 110 crystal structures to assemble eight distinct families highlighting the C-helix orientation in the N-lobe of the EGFR kinase domain. These families shared similar mutational profiles, ligand R-groups facing the C-helix, mutation sites, and DFG domain.
DRUG DISCOVERY TODAY
(2021)
Article
Pharmacology & Pharmacy
Elisa Herraez, Ruba Al-Abdulla, Meraris Soto, Oscar Briz, Dominik Bettinger, Heike Bantel, Sofia del Carmen, Maria A. Serrano, Andreas Geier, Jose J. G. Marin, Rocio I. R. Macias
Summary: Impaired function of organic cation transporter 1 (OCT1) in hepatocellular carcinoma (HCC) has been associated with unsatisfactory response to sorafenib. However, some patients lacking OCT1 at the plasma membrane (PM) of HCC cells still respond to sorafenib, suggesting that another transporter may contribute to take up this drug. The aim of this study was to investigate whether OCT3 could contribute to the uptake of sorafenib and other tyrosine kinase inhibitors (TKIs) and whether OCT3 determination can predict HCC response to sorafenib. Functional in vitro studies revealed that OCT3 is also able to mediate sorafenib uptake. Other TKIs, such as regorafenib, lenvatinib, and cabozantinib can also interact with this transporter. In HCC samples, OCT3 was expressed at the PM of cancer cells, and its presence, detected in 26% of tumors, was associated with better outcomes in patients treated with sorafenib. Analysis by immunohistochemistry of OCT3 in the PM of tumor cells may help to predict the response of HCC patients to sorafenib and potentially to other TKIs.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Oncology
Yan Sun, Liang Zhu, Pian Liu, Huan Zhang, Feng Guo, Xin Jin
Summary: In this study, researchers found that the upregulation of palmitoyl acyltransferase ZDHHC2 is associated with TKI resistance in ccRCC. ZDHHC2 mediates AGK S-palmitoylation to activate the PI3K-AKT-mTOR signaling pathway, which modulates sunitinib sensitivity. These findings suggest that targeting ZDHHC2 may improve the efficacy of sunitinib in treating ccRCC.
Article
Multidisciplinary Sciences
Takefumi Kimura, Sai P. Pydi, Lei Wang, Dhanush Haspula, Yinghong Cui, Huiyan Lu, Gabriele M. Koenig, Evi Kostenis, Gregory R. Steinberg, Oksana Gavrilova, Juergen Wess
Summary: This study found that by activating adipocyte G(q) signaling, the increased lipolysis in obese individuals can be prevented, leading to improved glucose and lipid homeostasis. This has important implications for the development of novel anti-diabetic drugs based on GPCR.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Kai Li, Zi-Yang Peng, Shan Gao, Qing-Shi Wang, Rui Wang, Xiang Li, Guo-Dong Xiao, Jing Zhang, Hong Ren, Shou-Ching Tang, Xin Sun
Summary: The study revealed that m6A controlled the interference of EMT features, the miR-146a/Notch signaling pathway was highly activated in an m6A-dependent manner, and TUSC7 regulation of miR-146a affected Notch signaling functions, influencing lung cancer progression and stem cell renewal.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
John Lee, Rongbing Chen, T. Mohanakumar, Ross Bremner, Sumeet Mittal, Timothy P. Fleming
Summary: The study identified activated EGFR, ErbB2, and ErbB3 receptors in esophageal cancer cells, and found that treatment with the pan-EGFR family inhibitor afatinib could inhibit tumor cell proliferation and growth in both in vitro and animal xenograft models. Targeting activated TKRs may serve as a personalized treatment strategy for EC tumors.
ONCOTARGETS AND THERAPY
(2021)
Article
Multidisciplinary Sciences
Youqian Wu, Chao Zhang, Xiaolan Liu, Zhengfu He, Bing Shan, Qingxin Zeng, Qingwei Zhao, Huaying Zhu, Hongwei Liao, Xufeng Cen, Xiaoyan Xu, Mengmeng Zhang, Tingjun Hou, Zhe Wang, Huanhuan Yan, Shuying Yang, Yaqin Sun, Yanying Chen, Ronghai Wu, Tingxue Xie, Wei Chen, Ayaz Najafov, Songmin Ying, Hongguang Xia
Summary: The study identifies compounds inducing PD-L1 degradation, with EGFR inhibitors promoting PD-L1 degradation through GSK3 alpha-mediated phosphorylation. ARIH1 is identified as the E3 ubiquitin ligase targeting PD-L1 for degradation and plays a critical role in anti-tumor immunity. This research suggests that GSK3 alpha and ARIH1 may be potential drug targets to enhance anti-tumor immunity and immunotherapies.
NATURE COMMUNICATIONS
(2021)
Review
Oncology
Maria Saigi, Enric Carcereny, Teresa Moran, Marc Cucurull, Ainhoa Hernandez, Eva Pros, Montse Sanchez-Cespedes, Marta Domenech, Anna Martinez-Cardus
Summary: Identifying molecular oncogenic drivers is crucial for precision oncology. Genetic rearrangements, including gene fusions and gene amplification, involving and activating receptor tyrosine kinases (RTKs) are recurrent in solid tumors, particularly in non-small cell lung cancer. Advances in the tools to detect these alterations have deepened our understanding of the underlying biology and tumor characteristics and have prompted the development of novel inhibitors targeting activated RTKs. The review focuses on the genetic and molecular structure of oncogenic RTKs, methods for diagnosis, therapeutic implications of tyrosine kinase inhibitors, and the use of liquid biopsies for monitoring the disease.
CANCER TREATMENT REVIEWS
(2022)
Editorial Material
Genetics & Heredity
Ivona Aksentijevich
Summary: Immune responses require a delicate balance - too weak or too strong a response can cause issues. Spleen tyrosine kinase plays a crucial role in multiple signaling pathways, and its gain-of-function alterations can lead to various problems, including hypogammaglobulinemia and predisposition to B cell lymphoma.
Letter
Rheumatology
Sindhu R. Johnson, Martin Aringer
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Alexandru Garaiman, Klaus Steigmiller, Catherine Gebhard, Carina Mihai, Rucsandra Dobrota, Cosimo Bruni, Marco Matucci-Cerinic, Joerg Henes, Jeska De Vries-Bouwstra, Vanessa Smith, Andrea Doria, Yannick Allanore, Lorenzo Dagna, Branimir Anic, Carlomaurizio Montecucco, Otylia Kowal-Bielecka, Mickael Martin, Yoshiya Tanaka, Anna-Maria Hoffmann-Vold, Ulrike Held, Oliver Distler, Mike Oliver Becker
Summary: The DU-VASC model was developed and validated to assist in decision-making for the management of digital ulcers in patients with systemic sclerosis. The model showed that PI treatment was the most important predictor associated with reduced occurrence of digital ulcers.
Review
Rheumatology
Augusta Ortolan, Mara Felicetti, Mariagrazia Lorenzin, Giacomo Cozzi, Francesca Ometto, Giovanni Striani, Marta Favero, Andrea Doria, Roberta Ramonda
Summary: This study systematically reviewed the evidence and found that weight loss may have an impact on disease activity in PsA, while probiotics are not effective in SpA. The evidence for dietary behaviors is scarce and heterogeneous.
Article
Rheumatology
Alessandro Giollo, Margherita Zen, Maddalena Larosa, Davide Astorri, Mariangela Salvato, Antonia Calligaro, Konstantinos Botsios, Cristina Bernardi, Gerolamo Bianchi, Andrea Doria
Summary: The failure to optimize treatment in early rheumatoid arthritis (RA) is associated with difficult-to-treat RA (D2T-RA). Treatment delay beyond 3 months and non-discontinuation of glucocorticoids after 6 months are early predictive features of D2T-RA.
Article
Rheumatology
Margherita Zen, Laura Salmaso, Claudio Barbiellini Amidei, Ugo Fedeli, Stefania Bellio, Luca Iaccarino, Alessandro Giollo, Andrea Doria, Mario Saia
Summary: This study aimed to estimate the incidence and prevalence of SLE in northeastern Italy from 2012 to 2020. A retrospective population-based study was conducted in Veneto Region using the population registry and administrative health database. The standardized point prevalence of SLE increased from 63.5 to 70.6 per 100,000 residents during the study period, with the highest prevalence observed in females aged 60-69 years. The incidence of SLE was 2.8 per 100,000 person-years and showed a decline, with a female-to-male incidence rate ratio of 5.00.
Article
Rheumatology
Rita N. Cunha, Liliana Saraiva, Diogo Jesus, Andrea Doria, Jose P. da Silva, Luis S. Ines
Summary: This study found that anti-U1RNP, SLE-DAS score, and the need for immunosuppressants in patients with LLDAS predict a higher risk of disease flare. Remission without the use of glucocorticoids is associated with a lower risk of flare.
Article
Rheumatology
M. Lorenzin, G. Cozzi, L. Scagnellato, A. Ortolan, S. Vio, G. Striani, V Scapin, G. De Conti, A. Doria, R. Ramonda
Summary: This study aimed to examine the association between sex and clinical features, disease activity indices, and imaging features in early-stage axial spondyloarthritis (axSpA). The results showed that males were more likely to have severe inflammation and spinal progression, while females had more frequent signs of spinal inflammation on MRI. In addition, females were more likely to have involvement in peripheral and entheseal sites. Overall, there were differences in the presentation of axSpA based on sex.
SCANDINAVIAN JOURNAL OF RHEUMATOLOGY
(2023)
Article
Medicine, General & Internal
Elisabetta Zanatta, Andrea Martini, Roberto Depascale, Anna Gamba, Marta Tonello, Mariele Gatto, Chiara Giraudo, Elisabetta Balestro, Andrea Doria, Luca Iaccarino
Summary: By assessing the role of CCL18 and OX40L as biomarkers of interstitial lung disease (ILD) and/or progressive fibrosing (PF-ILD) in idiopathic inflammatory myopathies (IIMs), we found that CCL18 may be a useful biomarker in IIMs-ILD, particularly in the early identification of patients at risk of developing PF-ILD.
Article
Health Care Sciences & Services
Margherita Zen, Mariele Gatto, Roberto Depascale, Francesca Regola, Micaela Fredi, Laura Andreoli, Franco Franceschini, Maria Letizia Urban, Giacomo Emmi, Fulvia Ceccarelli, Fabrizio Conti, Alessandra Bortoluzzi, Marcello Govoni, Chiara Tani, Marta Mosca, Tania Ubiali, Maria Gerosa, Enrica P. Bozzolo, Valentina Canti, Paolo Cardinaletti, Armando Gabrielli, Giacomo Tanti, Elisa Gremese, Ginevra De Marchi, Salvatore De Vita, Serena Fasano, Francesco Ciccia, Giulia Pazzola, Carlo Salvarani, Simone Negrini, Andrea Di Matteo, Rossella De Angelis, Giovanni Orsolini, Maurizio Rossini, Paola Faggioli, Antonella Laria, Matteo Piga, Alberto Cauli, Salvatore Scarpato, Francesca Wanda Rossi, Amato De Paulis, Enrico Brunetta, Angela Ceribelli, Carlo Selmi, Marcella Prete, Vito Racanelli, Angelo Vacca, Elena Bartoloni, Roberto Gerli, Elisabetta Zanatta, Maddalena Larosa, Francesca Saccon, Andrea Doria, Luca Iaccarino
Summary: This study assessed the efficacy of belimumab in treating joint and skin manifestations in a nationwide cohort of SLE patients. The results showed that belimumab significantly improved joint and skin symptoms and reduced the use of glucocorticoids. A significant proportion of patients who did not achieve complete remission initially achieved remission during follow-up.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Materials Science, Biomaterials
Rosa Di Paola, Antonella Marucci, Davide Mangiacotti, Alessandra Antonucci, Andrea Fontana, Xuan Wang, Lu Qi, Claudia Menzaghi, Vincenzo Trischitta
Summary: Several studies have shown that downregulation of GALNT2 decreases HDL-C and increases triglycerides levels by glycosylating key enzymes of lipid metabolism. GALNT2 is also a positive modulator of insulin signaling and action. The study found that GALNT2 affects HDL-C and triglycerides levels partly through insulin sensitivity.
Article
Urology & Nephrology
Christine P. Limonte, David K. Prince, Andrew N. Hoofnagle, Andrzej Galecki, Irl B. Hirsch, Frances Tian, Sushrut S. Waikar, Helen C. Looker, Robert G. Nelson, Alessandro Doria, Michael Mauer, Bryan R. Kestenbaum, Ian H. de Boer
Summary: Biomarkers of tubular injury and inflammation were associated with kidney structural parameters in early type 1 diabetes and may be indicators of kidney disease risk.
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Correction
Endocrinology & Metabolism
Antonella Marucci, Rosa Di Paola, Irene Rutigliano, Grazia Fini, Serena Pezzilli, Claudia Menzaghi, Vincenzo Trischitta
ACTA DIABETOLOGICA
(2023)
Article
Endocrinology & Metabolism
Antonella Marucci, Rosa Di Paola, Irene Rutigliano, Grazia Fini, Serena Pezzilli, Claudia Menzaghi, Vincenzo Trischitta
ACTA DIABETOLOGICA
(2023)
