Article
Medicine, General & Internal
Peter Hillmen, Jeff Szer, Ilene Weitz, Alexander Roeth, Britta Hoechsmann, Jens Panse, Kensuke Usuki, Morag Griffin, Jean-Jacques Kiladjian, Carlos de Castro, Hisakazu Nishimori, Lisa Tan, Mohamed Hamdani, Pascal Deschatelets, Cedric Francois, Federico Grossi, Temitayo Ajayi, Antonio Risitano, Regis Peffault de la Tour
Summary: The study demonstrated that Pegcetacoplan was superior to eculizumab in improving hemoglobin and clinical and hematologic outcomes in patients with PNH by providing broad hemolysis control, including control of intravascular and extravascular hemolysis.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Hematology
Gloria F. Gerber, Robert A. Brodsky
Summary: This article discusses the theoretical basis and clinical studies of using C3 inhibitors in the treatment of PNH, as well as provides suggestions for treatment sequencing.
Review
Hematology
Robert A. Brodsky
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare complement-mediated hemolytic anemia with diverse manifestations, requiring differentiated treatment approaches; terminal complement inhibition is effective for intravascular hemolysis treatment but not bone marrow failure; novel complement inhibitors under clinical development show promising prospects for future applications.
Review
Immunology
Chenyuan Li, Xifeng Dong, Huaquan Wang, Zonghong Shao
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired genetic mutation disease caused by defects in the PIG-A gene, leading to hemolysis of erythrocyte membranes.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Melissa A. Colden, Sushant Kumar, Bolormaa Munkhbileg, Daria V. Babushok
Summary: Paroxysmal Nocturnal Hemoglobinuria (PNH) is a disease that involves mutations in a specific gene, leading to hemolysis and abnormal clonal expansion of blood cells. The mechanisms behind this expansion are still debated, but recent advancements in research and technology offer new opportunities for understanding the disease.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Balraj Singh, Nazia Khan, Parminder Kaur, Michael Maroules
Summary: This study reports an unusual presentation of the coexistence of two clonal disorders, PNH and APL. The literature review shows that AML is derived from the PNH clone, but the PNH phenotype disappears with the onset of AML. This case contributes to our understanding that AML in the setting of PNH is a separate disorder.
JOURNAL OF CANCER RESEARCH AND THERAPEUTICS
(2022)
Review
Hematology
Jens Panse
Summary: In the past 20 years, therapy for paroxysmal nocturnal hemoglobinuria (PNH) mainly relied on antibody-based terminal complement inhibition. PNH is a disease characterized by a mutation that causes the absence or deficiency of complement-regulatory proteins on blood cells, leading to intravascular hemolysis and related complications. Recently, there has been a development of new drugs targeting the proximal and terminal complement cascade, with the approval of the first proximal complement inhibitor targeting C3 in 2021. This article aims to provide an overview of the progress made in PNH treatment and discuss the approved therapeutic options, as well as the potential impact and consequences of current and future treatments on patients' lives.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Review
Hematology
Austin G. Kulasekararaj, Ioanna Lazana
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder characterized by deficiency of GPI-linked complement regulators. Despite the introduction of C5 inhibitors, residual hemolysis still occurs, leading to anemia and transfusion dependency in some patients. The development of longer-acting and subcutaneous formulations of C5 inhibitors, as well as proximal complement inhibitors, have shown promising results in improving hemoglobin levels and reducing hemolysis. Combination treatments have also been explored. This review discusses the current therapeutic options and emerging approaches for PNH.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Review
Medicine, General & Internal
Bruno Fattizzo, Fabio Serpenti, Juri Alessandro Giannotta, Wilma Barcellini
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is an intriguing disease with ongoing research on its pathophysiology, diagnostics, and treatment. Advanced flow cytometry techniques have enabled detection of small PNH clones, but data interpretation remains challenging. New complement inhibitors may improve patients' quality of life and response rates, but questions regarding their use and long-term safety need further investigation.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Medicine, Research & Experimental
Bo Xu
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening blood disease. The new targeted C3 therapy Empaveli (pegcetacoplan) has been approved by the US FDA for adult PNH patients. Pegcetacoplan targets C3 and effectively controls the complement cascade, resulting in improved hemoglobin levels and reduced need for blood transfusions.
CLINICAL AND EXPERIMENTAL MEDICINE
(2023)
Article
Medicine, General & Internal
Runsen Du, Lihua Zheng, Peng Liu, Yaheng Zhao, Yan Yang, Lei Zhang, Zengren Zhao
Summary: We report a case of a female who was cured of hemorrhagic esophageal varices caused by paroxysmal nocturnal hemoglobinuria (PNH) through transjugular intrahepatic portosystemic shunt (TIPS) treatment. PNH complicated by portal vein and visceral veins thrombosis without hepatic veins is extremely rare, and it can be easily misdiagnosed due to lack of awareness. Hemorrhagic esophageal varices due to PNH with portal vein thrombosis have only been reported in one previous case in 1974, and this report presents the second case.
FRONTIERS IN MEDICINE
(2023)
Article
Hematology
Raymond Siu Ming Wong, Juan Ramon Navarro-Cabrera, Narcisa Sonia Comia, Yeow Tee Goh, Henry Idrobo, Daolada Kongkabpan, David Gomez-Almaguer, Mohammed Al-Adhami, Temitayo Ajayi, Paulo Alvarenga, Jessica Savage, Pascal Deschatelets, Cedric Francois, Federico Grossi, Teresita Dumagay
Summary: PNH is a rare disease characterized by complement-mediated hemolysis. Pegcetacoplan, the first C3-targeted therapy, has shown superior efficacy and safety compared to supportive care in complement inhibitor-naive patients with PNH, leading to significant stabilization of hemoglobin levels and reduction in lactate dehydrogenase levels.
Article
Biochemistry & Molecular Biology
Ioanna Lazana, Sean Apap Mangion, Selma Babiker, Joanna Large, Roochi Trikha, Mark Zuckerman, Shreyans Gandhi, Austin G. Kulasekararaj
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is a disease characterized by hemolysis and thrombosis, with a significant impact on morbidity and mortality. This study investigated the association between respiratory virus infections and breakthrough hemolysis (BTH) in PNH patients on eculizumab treatment. The results indicate that respiratory virus infections pose a significant risk for BTH in PNH patients and highlight the need for regular screening and close monitoring of patients with respiratory symptoms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Lijie Zeng, Hui Liu, Zhaoyun Liu, Liyan Li, Honglei Wang, Yingying Chen, Junshu Wu, Guanrou Wang, Lijuan Li, Rong Fu
Summary: Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal disorder caused by somatic PIGA mutations, resulting in a deficiency in GPI-AP. PNH cells have a defect in lipid raft formation and display increased levels of IFN-alpha. The reduced IFN alpha signal transduction in PNH cells mediated by lipid rafts may be explained by the suppressed STAT2 activation and the inflammatory response caused by defected endocytosis of IFN alpha/beta Rs in lipid rafts. Cavin1 may be a potential target for suppressing IFN-alpha inflammatory signaling in PNH cells.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Chemistry, Analytical
Kaan Batu Soysal, Seyma Parlatan, Metban Mastanzade, Murat Ozbalak, Mustafa Nuri Yenerel, Mehmet Burcin Unlu, Gunay Basar, Ugur Parlatan
Summary: The study proposed a combined approach using Raman spectroscopy and machine learning to analyze blood samples from volunteers with and without PNH conditions. Results showed a significant difference between the two groups, with a specificity of 81.8% and a sensitivity of 78.3% in the training performed by support vector machine (SVM) analysis. This method demonstrates the potential for immediate and high accuracy testing for PNH disease.
ANALYTICAL METHODS
(2021)
Article
Hematology
Kanagaraju Ponnusamy, Maria Myrsini Tzioni, Murshida Begum, Mark E. Robinson, Valentina S. Caputo, Alexia Katsarou, Nikolaos Trasanidis, Xiaolin Xiao, Ioannis Kostopoulos, Deena Iskander, Irene Roberts, Pritesh Trivedi, Holger W. Auner, Kikkeri Naresh, Aristeidis Chaidos, Anastasios Karadimitris
Summary: ZBP1-IRF3 axis plays a crucial role in multiple myeloma and may serve as a therapeutic target.
Article
Multidisciplinary Sciences
Paula Saavedra-Garcia, Monica Roman-Trufero, Hibah A. Al-Sadah, Kevin Blighe, Elena Lopez-Jimenez, Marilena Christoforou, Lucy Penfold, Daria Capece, Xiaobei Xiong, Yirun Miao, Katarzyna Parzych, Valentina S. Caputo, Alexandros P. Siskos, Vesela Encheva, Zijing Liu, Denise Thiel, Martin F. Kaiser, Paolo Piazza, Aristeidis Chaidos, Anastasios Karadimitris, Guido Franzoso, Ambrosius P. Snijders, Hector C. Keun, Diego A. Oyarzun, Mauricio Barahona, Holger W. Auner
Summary: The study reveals the complex mechanisms of proteotoxic stress resolution in cancer cells recovering from chemotherapy-induced stress, involving extensive changes across the transcriptome, proteome, and metabolome, as well as dynamic alterations in glucose and lipid metabolism and suppression of mitochondrial function. Additionally, recovering cells are more vulnerable to specific insults, with a key vulnerability associated with cellular response to amino acid scarcity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Hematology
Nikolaos Trasanidis, Alexia Katsarou, Kanagaraju Ponnusamy, Yao-An Shen, Ioannis Kostopoulos, Bien Bergonia, Keren Keren, Paudel Reema, Xiaolin Xiao, Richard M. Szydlo, Pierangela M. R. Sabbattini, Irene A. G. Roberts, Holger W. Auner, Kikkeri N. Naresh, Aristeidis Chaidos, Tian-Li Wang, Luca Magnani, Valentina S. Caputo, Anastasios Karadimitris
Summary: This study successfully identifies adverse prognosis genes in chr1q-amp MM and reveals the important roles of PBX1 and FOXM1 in oncogenic pathways.
Article
Materials Science, Multidisciplinary
Giacomo Reina, Amalia Ruiz, Barbara Richichi, Giacomo Biagiotti, Gina E. Giacomazzo, Lucas Jacquemin, Yuta Nishina, Cecilia Menard-Moyon, Wafa T. Al-Jamal, Alberto Bianco
Summary: This study investigates the functionalisation of graphene oxide (GO) with a BODIPY derivative for glutathione (GSH) depletion and photodynamic therapy (PDT). Results show that GO-BODIPY can efficiently deplete intracellular GSH and generate reactive oxygen species, which significantly reduces cell viability after irradiation. The biocompatibility of GO and GO-BODIPY is also demonstrated in prostate adenocarcinoma cells.
Meeting Abstract
Oncology
Benedetta Conte, Chiara Molinelli, Giancarlo Bisagni, Antonio Durando, Giovanni Sanna, Stefania Gori, Ornella Garrone, Stefano Tamberi, Sabino De Placido, Francesco Schettini, Antonio Pazzola, Riccardo Ponzone, Filippo Montemurro, Gianluigi Lunardi, Rosario Notaro, Anna Turletti, Claudia Bighin, Francesca Poggio, Giulia Buzzatti, Matteo Lambertini, Luca Boni, Lucia Del Mastro
Article
Hematology
Austin G. Kulasekararaj, Morag Griffin, Saskia Langemeijer, Kensuke Usuki, Alexander Kulagin, Masayo Ogawa, Ji Yu, Arshad Mujeebuddin, Jun-ichi Nishimura, Jong Wook Lee, Regis Peffault de Latour
Summary: This study describes the long-term follow-up results of over 400 patients with PNH treated with ravulizumab for 27 weeks to 2 years, showing durable efficacy and good tolerability, highlighting the importance of C5 inhibitors as the mainstay of PNH treatment.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2022)
Review
Hematology
Franck Morschhauser, Gilles Salles, Connie Lee Batlevi, Herve Tilly, Aristeidis Chaidos, Tycel Phillips, John Burke, Ari Melnick
Summary: This review discusses the mechanisms and therapeutic targets of EZH2 in B-cell lymphomas, as well as the potential synergy of EZH2 inhibitors with existing treatments.
Article
Radiology, Nuclear Medicine & Medical Imaging
Khalil ElGendy, Tara D. Barwick, Holger W. Auner, Aristeidis Chaidos, Kathryn Wallitt, Antoni Sergot, Andrea Rockall
Summary: The study evaluated the reproducibility and intra/interobserver agreement of ADC measurements of myeloma lesions using WB-DW-MRI at 3T MRI. Results showed excellent intraobserver agreement but poorer interobserver agreement for certain lesion types. Test-retest reproducibility was high for mean ADC measurements, with some variations observed between lesion types and body regions.
BRITISH JOURNAL OF RADIOLOGY
(2022)
Review
Medicine, General & Internal
Rosario Notaro, Lucio Luzzatto
Summary: Inhibitors of proximal and terminal complement cascades can control red-cell hemolysis associated with paroxysmal nocturnal hemoglobinuria, but some patients may still experience breakthrough hemolysis.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Review
Hematology
Corrado Girmenia, Wilma Barcellini, Paola Bianchi, Eros Di Bona, Anna Paola Iori, Rosario Notaro, Simona Sica, Alberto Zanella, Antonio De Vivo, Giovanni Barosi, Antonio Risitano
Summary: This article presents the results of group discussion among experts on unmet clinical needs in managing infectious risk associated with eculizumab or new terminal complement inhibitors (CIs) in paroxysmal nocturnal hemoglobinuria (PNH). The selected clinically relevant needs were optimizing infection prevention measures, developing non-pharmacological infectious risk-mitigation strategies, and improving disease management during infectious complications. Consensus opinions and proposals for advancing clinical practice were provided for each issue. The aim is to improve CI therapy and guide future studies in this field.
Article
Chemistry, Organic
Giacomo Biagiotti, Laura Legnani, Giusi Aresta, Maria A. Chiacchio, Barbara Richichi
Summary: This study describes the synthesis and reactivity of a new class of electron-poor heterodienes in an [4+2] inverse electron demand hetero Diels-Alder reaction. The highly reactive electrophiles allow for the selective synthesis of unprecedented benzo-thiazine glyco-fused derivatives. Experimental and computational data confirm the feasibility of the reaction.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Letter
Hematology
Michela Sica, Federica Barone, Caterina Nannelli, Patrizia Ricci, Luana Marano, Maria De Angioletti, Eros Di Bona, Antonio M. Risitano, Rosario Notaro
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Chemistry, Medicinal
Jacopo Tricomi, Luca Landini, Valentina Nieddu, Ugo Cavallaro, Jillian G. Baker, Athanasios Papakyriakou, Barbara Richichi
Summary: Over the past decade, the biomedical applications of molecules that can modulate beta-adrenergic signaling have gained increasing attention, especially in cancer treatment. However, the identification of selective beta-adrenergic receptor (beta-AR) ligands for pharmacological studies and drug development remains a challenging task due to the complexity and specificity requirements of beta-ARs. In this study, we synthesized and evaluated a series of structurally diverse compounds (MC) based on the aryloxy-propanolamine scaffold of SR59230A, aiming to gain insights into the structure-activity relationships of the three beta-AR subtypes. The results provide valuable information on key structural elements and substituents that control the activity and selectivity of these compounds, which could facilitate the development of selective beta-AR drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Giacomo Reina, Giovanni Mariano Beneventi, Ramandeep Kaur, Giacomo Biagiotti, Alejandro Cadranel, Cecilia Menard-Moyon, Yuta Nishina, Barbara Richichi, Dirk M. Guldi, Alberto Bianco
Summary: Covalent functionalization of graphene oxide (GO) with boron dipyrromethenes (BODIPYs) was achieved, resulting in two different GO-BODIPY conjugates with different properties. The use of a long, flexible spacer led to strong electronic GO-BODIPY interactions, affecting light absorption and excitation. On the other hand, a short, rigid spacer resulted in minor electronic interactions and selective excitation of PBA-BODIPY, allowing the investigation of excited state interactions. Additionally, reversible covalent linkage between GO and PBA-BODIPY enabled slow release and imaging.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Multidisciplinary Sciences
Irene Cosi, Annalisa Moccia, Chiara Pescucci, Uday Munagala, Salvatore Di Giorgio, Irene Sineo, Silvestro G. G. Conticello, Rosario Notaro, Maria De Angioletti
Summary: ETV4, an overexpressed ETS protein in prostate cancer, promotes migration, invasion, and proliferation in prostate cells. This study identifies previously unknown ETV4 alternatively spliced transcripts in human prostate cell lines and confirms their presence in prostate tumors. The abundance of these transcripts may reflect tumor deranged splicing machinery and their potential interactions with canonical variants may contribute to the biology and clinics of prostate cancer. Further investigations are needed to understand the biological role of these ETV4 transcripts and their isoforms.
SCIENTIFIC REPORTS
(2023)