Article
Pathology
Karen J. Fritchie, Baptiste Ameline, Vanghelita Andrei, Christopher Griffith, Akeesha A. Shah, Josephine K. Dermawan, Matteo Trucco, Thomas Budd, Judith J. Thangaiah, Jeremy Molligan, Rumeal D. Whaley, Kelly Magliocca, Elizabeth Azzato, Annemieke van Zante, Vickie Jo, Bin Xu, Justin A. Bishop, Lisa Rooper, Daniel Baumhoer
Summary: This study explored the relationship between Ewing sarcoma and ALES using DNA methylation profiling. The results showed that ALES has a distinct methylation signature from conventional Ewing sarcoma. This finding strengthens the understanding that ALES should be considered a separate entity from Ewing sarcoma.
Article
Oncology
Matthew T. T. Houdek, Mark J. J. Heidenreich, Safia K. K. Ahmed, Wendy Allen-Rhoades, Brittany L. L. Siontis, Steven I. I. Robinson, Ivy A. A. Petersen, Peter S. S. Rose
Summary: The study evaluated the treatment experience of EES patients and found that chemotherapy and surgery can achieve excellent local control.
JOURNAL OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Logan G. Spector, Aubrey K. Hubbard, Brandon J. Diessner, Mitchell J. Machiela, Beau Webber, Joshua D. Schiffman
Summary: Ewing sarcoma is the second most common primary bone tumor in children and adolescents, with few known epidemiological or genetic risk factors. Studies show significant variation in ES incidence across different geographic regions, indicating potential ancestral influence on disease risk.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Editorial Material
Radiology, Nuclear Medicine & Medical Imaging
Junhao Wu, Ya Liu, Weidong Gong, Taiping Liao, Chunyin Zhang
Summary: Subcutaneous Ewing sarcoma is rare and often presents as a mass. Diagnosis is typically confirmed through PET/CT scans and histopathological tests.
CLINICAL NUCLEAR MEDICINE
(2021)
Review
Oncology
Ajay Gupta, Richard F. Riedel, Chirag Shah, Scott C. Borinstein, Michael S. Isakoff, Rashmi Chugh, Jeremy M. Rosenblum, Erin S. Murphy, Shauna R. Campbell, Catherine M. Albert, Stacey Zahler, Stefanie M. Thomas, Matteo Trucco
Summary: Ewing sarcoma is a common malignant tumor in adolescents and young adults. This review focuses on the experience of the National Ewing Sarcoma Tumor Board and aims to provide guidelines and recommendations for the upfront management of Ewing sarcoma patients.
Article
Oncology
Bree R. Eaton, Line Claude, Daniel J. Indelicato, Ralph Vatner, Brian Yeh, Rudolf Schwarz, Nadia Laack
Summary: Ewing sarcoma requires complex multidisciplinary management, with standard treatment involving a combination of chemotherapy, surgery, and radiation followed by consolidation local treatment. Data support the efficacy of these treatment modalities.
PEDIATRIC BLOOD & CANCER
(2021)
Review
Oncology
Daria Fayzullina, Sergey Tsibulnikov, Mikhail Stempen, Brett A. Schroeder, Naveen Kumar, Rajesh Kumar Kharwar, Arbind Acharya, Peter Timashev, Ilya Ulasov
Summary: Ewing sarcoma is a rare malignant bone tumor with a high recurrence rate. This study identifies new therapeutic targets, particularly the EWSR1/FLI1 fusion protein, and proposes experimental therapy targeting multiple signaling pathways for improved patient survival.
Article
Oncology
David Boyce-Fappiano, B. Ashleigh Guadagnolo, Ravin Ratan, Wei-Lien Wang, Michael J. Wagner, Shreyaskumar Patel, John A. Livingston, Patrick P. Lin, Kevin Diao, Devarati Mitra, Ahsan Farooqi, Alexander J. Lazar, Christina L. Roland, Andrew J. Bishop
Summary: This study reviewed the treatment experience of 60 patients with localized extraskeletal Ewing sarcoma and found that combined-modality local therapy did not provide a local control advantage compared to single-modality local therapy. Single-modality local therapy may be sufficient for local control in select patients with favorable disease features.
Review
Cell Biology
Maryne Dupuy, Francois Lamoureux, Mathilde Mullard, Anais Postec, Laura Regnier, Marc Baud'huin, Steven Georges, Benedicte Brounais-Le Royer, Benjamin Ory, Francoise Redini, Franck Verrecchia
Summary: Ewing sarcoma (ES) is the second most common primary malignant bone tumor in children, adolescents, and young adults in Europe, with a survival rate of 70% for localized forms using conventional treatment. However, resistance to chemotherapy and pulmonary metastases greatly reduce the survival rate. ES is characterized by a chromosomal translocation that leads to the fusion protein EWS-FLI1, which plays a crucial role in the development of ES. This review provides an overview of ES from a clinical and biological perspective.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biology
Elena Vasileva, Mikako Warren, Timothy J. Triche, James F. Amatruda
Summary: Ewing sarcoma is a malignant tumor that mainly affects children, adolescents, and young adults. The lack of a reliable genetic animal model has hindered the study of tumor cell and microenvironment interactions. By introducing human EWSR1-FLI1 gene into zebrafish, a new genetic model of Ewing sarcoma has been developed, which exhibits high penetrance and rapid tumor formation, providing a valuable tool for investigating the disease. Additionally, the study reveals the important role of the extracellular matrix in Ewing sarcoma tumor growth and suggests that targeting proteoglycan metabolism could be a potential novel therapy.
Article
Pediatrics
Chuanxi Zheng, Yong Zhou, Yi Luo, Hongying Zhang, Chongqi Tu, Li Min
Summary: A rare case of primary extra-skeletal Ewing sarcoma (EES) originating in the genitals was reported, resulting in the patient's death from sepsis and lung metastasis complications. Despite the rarity of EES, it can occur in any soft tissue site, highlighting the significance of early diagnosis and timely treatment for a favorable prognosis.
FRONTIERS IN PEDIATRICS
(2021)
Article
Oncology
Philip Heesen, Andreas Ranft, Vivek Bhadri, Benedicte Brichard, Stephane Collaud, Sona Cyprova, Hans Eich, Torben Ek, Hans Gelderblom, Jendrik Hardes, Lianne Haveman, Susanne Jabar, Wolfgang Hartmann, Dimosthenis Andreou, Peter Hauser, Josephine Kersting, Heribert Juergens, Jukka Kanerva, Thomas Kuehne, Anna Raciborska, Jelena Rascon, Arne Streitbuerger, Beate Timmermann, Yasmin Uhlenbruch, Uta Dirksen
Summary: This study analyzed the association between local therapy and event-free survival (EFS), overall survival (OS), and local recurrence (LR) in patients with Ewing sarcoma. The results showed that in certain situations, combination therapy with radiotherapy and surgery can improve the prognosis of patients. This provides important evidence for the personalized treatment of Ewing sarcoma.
EUROPEAN JOURNAL OF CANCER
(2023)
Review
Medicine, General & Internal
Stefan K. Zoellner, James E. Amatruda, Sebastian Bauer, Stephane Collaud, Enrique de Alava, Steven G. DuBois, Jendrik Hardes, Wolfgang Hartmann, Heinrich Kovar, Markus Metzler, David S. Shulman, Arne Streitbuerger, Beate Timmermann, Jeffrey A. Toretsky, Yasmin Uhlenbruch, Volker Vieth, Thomas G. P. Gruenewald, Uta Dirksen
Summary: Ewing sarcoma is a highly aggressive bone and soft-tissue cancer with a genetically simple yet specific therapeutic target. Current standard treatment involving systemic therapy and local treatment provides a realistic chance of cure for the majority of patients.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Oncology
Jessica D. Daley, Adam C. Olson, Kelly M. Bailey
Summary: Ewing sarcoma is a primary bone tumor commonly diagnosed in adolescents, and innovative therapeutic approaches are essential for patients with metastatic or relapsed Ewing sarcoma. Understanding the spectrum of DNA damage repair defects within individual Ewing tumors and the potential of DNA damage/immunotherapy combinations in treating these tumors are important for effective therapy.
FRONTIERS IN ONCOLOGY
(2022)
Review
Cell Biology
Manideep C. Pachva, Horton Lai, Andy Jia, Melanie Rouleau, Poul H. Sorensen
Summary: Ewing sarcoma is a highly aggressive cancer, with poor prognosis for patients with metastatic disease. Intercellular communication within the tumor microenvironment is crucial for cancer cells to establish immunosuppressive and cancer-permissive environments. Additional research on this communication mechanism may lead to new therapeutic strategies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Chemistry, Medicinal
Luca Filippi, Alessandro Pini, Maurizio Cammalleri, Paola Bagnoli, Massimo Dal Monte
Summary: The role of beta-adrenoceptors in hypoxia-driven diseases, such as infantile hemangiomas and retinopathy of prematurity, has been highlighted. The upregulation of beta 3-ARs by hypoxia in both cancer and embryo development suggests potential similarities in their functions.
MEDICINAL RESEARCH REVIEWS
(2022)
Article
Chemistry, Medicinal
Mahmoud A. Ragab, Wagdy M. Eldehna, Alessio Nocentini, Alessandro Bonardi, Hazem E. Okda, Bahaa Elgendy, Tarek S. Ibrahim, Mohammad M. Abd-Alhaseeb, Paola Gratteri, Claudiu T. Supuran, Ahmed A. Al-Karmalawy, Mohamed Elagawany
Summary: In the current medical era, the traditional single target inhibition paradigm of drug discovery is being replaced by the multi-target design concept. A novel series of 4-(5-amino-pyrazol-1-yl)benzenesulfonamide derivatives was designed and synthesized as potential multi-target anti-inflammatory agents. The compounds showed inhibitory activities against COX-2, 5-LOX, and carbonic anhydrase (CA) isoforms, suggesting their potential application in treating inflammatory diseases with a multi-target approach.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Infectious Diseases
Alessio Nocentini, Clemente Capasso, Claudiu T. Supuran
Summary: Resistance to antibiotic treatment occurs when microorganisms resist clinically approved antibiotics. Medication repurposing/repositioning is a strategy that can help find new antibiotics. Among them, Zn2+ ion binders, such as sulfonamides and their bioisosteres, are considered promising compounds for obtaining novel antibacterials.
Article
Chemistry, Medicinal
Davide Ialongo, Antonella Messore, Valentina Noemi Madia, Valeria Tudino, Alessio Nocentini, Paola Gratteri, Simone Giovannuzzi, Claudiu T. T. Supuran, Alice Nicolai, Susanna Scarpa, Samanta Taurone, Michele Camarda, Marco Artico, Veronica Papa, Francesco Saccoliti, Luigi Scipione, Roberto Di Santo, Roberta Costi
Summary: Solid tumors create a hostile environment for surrounding cells by decreasing pH through producing metabolic acids. Carbonic anhydrases (CAs) play a role in acid/base regulation and are clinically relevant in cancer therapy. This study describes new diketo acid derivatives as nanomolar inhibitors of the CA IX and XII isoforms, with selectivity over CAs I and II. These compounds showed antiproliferative activity in tumor cell lines overexpressing CA IX and XII, with no effect on normal cells.
Article
Pediatrics
Rosa Teresa Scaramuzzo, Paola Bagnoli, Massimo Dal Monte, Maurizio Cammalleri, Alessandro Pini, Sandy Ballini, Anna Bendinelli, Ielizza Desideri, Massimiliano Ciantelli, Luca Filippi
Article
Biochemistry & Molecular Biology
Monica Martinez-Montiel, Laura L. Romero-Hernandez, Simone Giovannuzzi, Paloma Begines, Adrian Puerta, Ana I. Ahuja-Casarin, Miguel X. Fernandes, Penelope Merino-Montiel, Sara Montiel-Smith, Alessio Nocentini, Jose M. Padron, Claudiu T. Supuran, Jose G. Fernandez-Bolanos, Oscar Lopez
Summary: The development of new inhibitors for carbonic anhydrases (CAs), which are involved in a variety of biological events, is a hot topic in current Medicinal Chemistry. In particular, CA IX and XII, as membrane-bound enzymes, play important roles in tumor survival and chemoresistance. In this study, a bicyclic carbohydrate-based hydrophilic tail was added to a CA-targeting pharmacophore to investigate the influence of tail conformation on CA inhibition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Waleed A. A. Badawi, Mahmoud Rashed, Alessio Nocentini, Alessandro Bonardi, Mohammad M. M. Abd-Alhaseeb, Sara T. T. Al-Rashood, Giri Babu Veerakanellore, Taghreed A. A. Majrashi, Eslam B. B. Elkaeed, Bahaa Elgendy, Paola Gratteri, Claudiu T. T. Supuran, Wagdy M. M. Eldehna, Mohamed Elagawany
Summary: In this study, new pyridazine-based sulphonamides were developed as potential multi-target anti-inflammatory drugs, which can inhibit the CA, COX-2, and 5-LOX enzymes simultaneously, avoiding the drawbacks of using NSAIDs alone.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Simone Giovannuzzi, Alessandro Bonardi, Paola Gratteri, Alessio Nocentini, Claudiu T. T. Supuran
Summary: A structure-based drug design was used to identify potent and selective inhibitors of hCA III by considering its unique active site and substitution. New aliphatic primary sulfonamides with 1,2,3-triazole linkers were designed to coordinate the zinc(II) ion and improve contacts at the active site entrance. These compounds showed nanomolar potency and selectivity for hCA III, and molecular simulations provided insights into ligand/target interactions and the physio-pathological roles of hCA III.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Nora Astrain-Redin, Niccolo Paoletti, Daniel Plano, Alessandro Bonardi, Paola Gratteri, Andrea Angeli, Carmen Sanmartin, Claudiu T. Supuran
Summary: In the search for new cancer treatments, organoselenium compounds and carbonic anhydrase inhibitors have shown promise. Selenium-containing compounds, especially selenols, have demonstrated potent inhibition of tumor-associated CA isoforms. In this study, selenoesters combining NSAIDs and natural product fragments were evaluated as nonclassical inhibitors of tumor-associated CA isoforms.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Alessio Nocentini, Alessandro Bonardi, Carla Bazzicalupi, Vincenzo Alterio, Davide Esposito, Simona Maria Monti, Michael Smietana, Giuseppina De Simone, Claudiu T. Supuran, Paola Gratteri, Jean-Yves Winum
Summary: In this study, substituted 6-(1H-1,2,3-triazol-1-yl)benzoxaboroles were synthesized and characterized using in silico design. The 6-azidobenzoxaborole was introduced as a molecular platform for preparing libraries of inhibitors through a click chemistry strategy. Compound 20 showed high selectivity as hCAVII and IX inhibitors with inhibition constants below 30 nM. Crystallographic investigation validated the design hypothesis and provided explanations for the different inhibition behavior observed against five hCA isoforms. Overall, compound 20 was identified as a promising lead compound to develop novel anticancer agents targeting hCA IX and potent neuropathic pain relievers targeting hCA VII.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Morteza Abdoli, Alessandro Bonardi, Niccolo Paoletti, Ashok Aspatwar, Seppo Parkkila, Paola Gratteri, Claudiu T. Supuran, Raivis Zalubovskis
Summary: A library of structurally diverse N-((4-sulfamoylphenyl)carbamothioyl) amides was synthesized by selectively acylating 4-thioureidobenzenesulfonamide with various acyl chlorides. The inhibitory effects of these sulfonamides on human carbonic anhydrase (hCA) and bacterial beta-carbonic anhydrase from Mycobacterium tuberculosis (MtCA) were investigated in vitro and in silico. The compounds showed better inhibition against hCA I, hCA II, hCA VII, as well as MtCA1 and MtCA2, but poor inhibition against MtCA3.
Article
Chemistry, Medicinal
Mudasir Nabi Peerzada, Daniela Vullo, Niccolo Paoletti, Alessandro Bonardi, Paola Gratteri, Claudiu T. Supuran, Amir Azam
Summary: For the discovery of novel carbonic anhydrase inhibitors for cancer treatment, a series of 4-{4-[(hydroxyimino)-methyl]piperazin-1-yl}benzenesulfonamides were designed and synthesized. The compounds 27-34 showed inhibition against human isoforms hCA I, hCA II, hCA IX, and hCA XII. Compound 29 inhibited hCA I with a Ki value of 3.0 nM, while compound 32 inhibited hCA II with a Ki value of 4.4 nM. Compound 30 effectively inhibited the tumor-associated hCA IX isoform with a Ki value of 43 nM, and compounds 29 and 31 significantly inhibited hCA XII with a Ki value of 5 nM. Molecular modeling revealed the hydrophobic and hydrogen bond interactions of drug molecule 30 with the active site of the investigated hCAs, as well as its binding to zinc through the deprotonated sulfonamide group.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biochemistry & Molecular Biology
Paloma Begines, Alessandro Bonardi, Alessio Nocentini, Paola Gratteri, Simone Giovannuzzi, Roberto Ronca, Camilla Tavani, Maria Luisa Massardi, Oscar Lopez, Claudiu T. Supuran
Summary: This study successfully synthesized a variety of compounds that conjugate biotin with sulfonamide motifs and tested their efficacy as carbonic anhydrase inhibitors in vitro. Most of the synthesized compounds showed interesting inhibition profiles in the nanomolar range, and some compounds exhibited good selectivity towards tumor-associated enzymes. One compound demonstrated anti-proliferative activity in multiple tumor cell lines.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Luca Filippi, Francesca Pascarella, Alessandro Pini, Maurizio Cammalleri, Paola Bagnoli, Riccardo Morganti, Francesca Innocenti, Nicola Castagnini, Alice Melosi, Rosa Teresa Scaramuzzo
Summary: The embryo and fetus grow in a hypoxic environment and intrauterine oxygen levels fluctuate throughout pregnancy. A retrospective study on healthy newborns with gestational age < 37 weeks showed a progressive decrease in oxygen levels starting from the 23rd week until the 33-34th week of gestation, followed by an increase in fetal oxygenation until birth. This biphasic trend indicates the role of placenta in regulating oxygen availability to promote stemness and differentiation at specific times and tissues.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Marjan Sobati, Morteza Abdoli, Alessandro Bonardi, Paola Gratteri, Claudiu T. Supuran, Raivis Zalubovskis
Summary: A series of novel sulfonamide-incorporated α-aminophosphonate derivatives were synthesized, utilizing a one-pot, two-step FeCl3-catalyzed coupling reaction. These compounds were tested for inhibition against four different isoforms of carbonic anhydrase, including human cytosolic (h) hCA I and II (off-targets), as well as transmembrane cancer-related hCA IX and XII (targets). Among the synthesized compounds, derivative 23 exhibited the highest selectivity towards the cancer-associated isoforms over the off-target hCA I and hCA II, and the binding mode of both enantiomers R and S was investigated using in silico studies.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)