110 results on '"Charalampos Pontikoglou"'
Search Results
2. A Comparative Sentiment Analysis of Greek Clinical Conversations Using BERT, RoBERTa, GPT-2, and XLNet
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Maria Evangelia Chatzimina, Helen A. Papadaki, Charalampos Pontikoglou, and Manolis Tsiknakis
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sentiment analysis ,healthcare ,clinical dialogues ,cancer ,hematologic malignancies ,Greek ,Technology ,Biology (General) ,QH301-705.5 - Abstract
In addressing the critical role of emotional context in patient–clinician conversations, this study conducted a comprehensive sentiment analysis using BERT, RoBERTa, GPT-2, and XLNet. Our dataset includes 185 h of Greek conversations focused on hematologic malignancies. The methodology involved data collection, data annotation, model training, and performance evaluation using metrics such as accuracy, precision, recall, F1-score, and specificity. BERT outperformed the other methods across all sentiment categories, demonstrating its effectiveness in capturing the emotional context in clinical interactions. RoBERTa showed a strong performance, particularly in identifying neutral sentiments. GPT-2 showed promising results in neutral sentiments but exhibited a lower precision and recall for negatives. XLNet showed a moderate performance, with variations across categories. Overall, our findings highlight the complexities of sentiment analysis in clinical contexts, especially in underrepresented languages like Greek. These insights highlight the potential of advanced deep-learning models in enhancing communication and patient care in healthcare settings. The integration of sentiment analysis in healthcare could provide insights into the emotional states of patients, resulting in more effective and empathetic patient support. Our study aims to address the gap and limitations of sentiment analysis in a Greek clinical context, an area where resources are scarce and its application remains underexplored.
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- 2024
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3. Cell Instructive Behavior of Composite Scaffolds in a Co-Culture of Human Mesenchymal Stem Cells and Peripheral Blood Mononuclear Cells
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Georgia-Ioanna Kontogianni, Amedeo Franco Bonatti, Carmelo De Maria, Raasti Naseem, Catarina Coelho, Kalliopi Alpantaki, Aristea Batsali, Charalampos Pontikoglou, Paulo Quadros, Kenneth Dalgarno, Giovanni Vozzi, Chiara Vitale-Brovarone, and Maria Chatzinikolaidou
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PLLA ,PCL ,PHBV ,3D-printed scaffolds ,osteogenesis ,osteoclastogenesis ,Biotechnology ,TP248.13-248.65 ,Medicine (General) ,R5-920 - Abstract
The in vitro evaluation of 3D scaffolds for bone tissue engineering in mono-cultures is a common practice; however, it does not represent the native complex nature of bone tissue. Co-cultures of osteoblasts and osteoclasts, without the addition of stimulating agents for monitoring cellular cross-talk, remains a challenge. In this study, a growth factor-free co-culture of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and human peripheral blood mononuclear cells (hPBMCs) has been established and used for the evaluation of 3D-printed scaffolds for bone tissue engineering. The scaffolds were produced from PLLA/PCL/PHBV polymeric blends, with two composite materials produced through the addition of 2.5% w/v nanohydroxyapatite (nHA) or strontium-substituted nanohydroxyapatite (Sr-nHA). Cell morphology data showed that hPBMCs remained undifferentiated in co-culture, while no obvious differences were observed in the mono- and co-cultures of hBM-MSCs. A significantly increased alkaline phosphatase (ALP) activity and osteogenic gene expression was observed in co-culture on Sr-nHA-containing scaffolds. Tartrate-resistant acid phosphatase (TRAP) activity and osteoclastogenic gene expression displayed significantly suppressed levels in co-culture on Sr-nHA-containing scaffolds. Interestingly, mono-cultures of hPBMCs on Sr-nHA-containing scaffolds indicated a delay in osteoclasts formation, as evidenced from TRAP activity and gene expression, demonstrating that strontium acts as an osteoclastogenesis inhibitor. This co-culture study presents an effective 3D model to evaluate the regenerative capacity of scaffolds for bone tissue engineering, thus minimizing time-consuming and costly in vivo experiments.
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- 2024
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4. Caplacizumab for immune thrombotic thrombocytopenic purpura: real-world multicenter data
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Eleni Gavriilaki, Emmanuel Nikolousis, Eudoxia-Evaggelia Koravou, Sotiria Dimou-Besikli, Charalampos Kartsios, Anna Papakonstantinou, Anastasia Mpanti, Charalampos Pontikoglou, Christina Kalpadaki, Aikaterini Bitsani, Ilianna Tassi, Tasoula Touloumenidou, Thomas Chatziconstantinou, Maria Papathanasiou, Antonia Syrigou, Eleutheria Ztriva, Georgia Kaiafa, Evdokia Mandala, Zois Mellios, Dimitrios Karakasis, Alexandra Kourakli, Argiris Symeonidis, Eleni Kapsali, Helen H. Papadaki, Chrysavgi Lalayanni, and Ioanna Sakellari
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caplacizumab ,thrombotic thrombocytopenic purpura ,plasma exchange ,ADAMTS13 ,multicenter real-world study ,Medicine (General) ,R5-920 - Abstract
Given the limited real-world data of caplacizumab, our multicenter real-world study was designed to assess the safety and efficacy of caplacizumab in immune thrombotic thrombocytopenic pupura (iTTP), compared to historic controls. We have studied 70 patients: 23 in the caplacizumab and 47 in the historic control group. Plasma exchange was applied in all episodes except for two patients that denied plasma exchange. Rituximab as first-line treatment was more common in the caplacizumab group compared to historic control. Caplacizumab (10 mg daily) was given at a median on day 7 (1–43) from initial diagnosis for 32 (6–47) dosages. In the caplacizumab group, a median of 12 (8–23) patients required plasma exchange sessions versus 14 (6–32) in the control group. Caplacizumab administration did not produce any grade 3 complications or major hemorrhagic events. After a median of 19.0 (2.6–320) months since the iTTP diagnosis, 5 deaths occurred (4 in the control group and 1 in the caplacizumab group, p = 0.310). Caplacizumab patients achieved early platelet normalization and ADAMTS13 activity normalization at the end of treatment. Relapse was observed only in 2/23 (9%) caplacizumab patients, compared to 29/47 (62%) historic controls (p
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- 2023
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5. P752: TRANSCRIPTOMIC ANALYSIS OF MYELOID-DERIVED SUPPRESSOR CELLS (MDSCS) IN THE PERIPHERAL BLOOD OF PATIENTS WITH CHRONIC IDIOPATHIC NEUTROPENIA (CIN)
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Nikoleta Bizymi, Athina Damianaki, Matthieu Lavigne, Emmanuel Dialynas, Niki Gounalaki, Eirini Stratidaki, Grigoris Tsaknakis, Irene Mavroudi, Charalampos Pontikoglou, Panagiotis Verginis, and Helen A. Papadaki
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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6. P1606: PRIMARY AND SECONDARY IMMUNE THROMBOCYTOPENIA (ITP) IN ADULTS: REAL WORLD COMPARATIVE RETROSPECTIVE STUDY FROM THE ITP REGISTRY OF THE HELLENIC SOCIETY OF HEMATOLOGY
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Emily Stavroulaki, Charalampos Pontikoglou, Theodora Chatzilygeroudi, Alexandra Kouraklis-Symeonidis, Argiris Symeonidis, Maria Dimou, Panayiotis Panayiotidis, Giorgos Drakos, Aspasia Koudouna, Athanasios Galanopoulos, Vasileia Kaliafentaki, Angelos Matheakakis, Christina Lekarakou, Peggy Kanellou, Eleni Gavriilaki, Syrigou Antonia, Ioanna Sakellari, Dimitra Liapi, Georgios Tsirakis, Anna Kolovou, Sofia Chatzileontiadou, Maria Papaioannou, Aikaterini Souravla, Maria Dellatola, Maria Pagoni, Maria Bobola, Panagiotis Diamantopoulos, Marina Mantzourani, Nora-Athina Viniou, Aikaterini Megalakaki, Ioanna Christodoulou, Efthymia Vlachaki, Stavroula Giannouli, Vasiliki Gkalea, Charis Matsouka, Ioannis Kotsianidis, George Vassilopoulos, Maria Protopappa, Eleftheria Hatzimichael, Panagiotis Zikos, Marianna Politou, George N Chalkiadakis, and Helen Papadaki
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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7. Real world data on the prognostic significance of monocytopenia in myelodysplastic syndrome
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Panagiotis T. Diamantopoulos, Emmanouil Charakopoulos, Argiris Symeonidis, Ioannis Kotsianidis, Nora-Athina Viniou, Vassiliki Pappa, Charalampos Pontikoglou, Dimitrios Tsokanas, Georgios Drakos, Alexandra Kourakli, Elena Solomou, Eleftheria Hatzimichael, Anastasia Pouli, Maria Kotsopoulou, Evangelos Asmanis, Maria Dimou, Panayiotis Panayiotidis, Sotirios Papageorgiou, Georgios Vassilopoulos, Achilles Anagnostopoulos, Theodoros Vassilakopoulos, Helen Papadaki, and Athanasios Galanopoulos
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Medicine ,Science - Abstract
Abstract Monocytopenia is a common finding in patients with myelodysplastic syndrome (MDS), but although monocytes may exhibit prognostic significance in MDS due to their role in innate immunity, they have not been incorporated in any prognostic scoring system for MDS. In this study, we analyzed national registry data from 1719 adults with MDS. Monocytopenia was present in 29.5% of the patients and was correlated with the presence of excess blasts and higher revised international prognostic scoring system categories. Univariate analysis showed that monocytopenia was prognostic of a lower overall survival [(OS), 32.0 versus 65.0 months, p
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- 2022
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8. miRkit: R framework analyzing miRNA PCR array data
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Maria Tsagiopoulou, Anastasis Togkousidis, Nikolaos Pechlivanis, Maria Christina Maniou, Aristea Batsali, Angelos Matheakakis, Charalampos Pontikoglou, and Fotis Psomopoulos
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miRNA ,qPCR ,RT-PCR ,PCR array ,GO ,KEGG ,Medicine ,Biology (General) ,QH301-705.5 ,Science (General) ,Q1-390 - Abstract
Abstract Objective The characterization of microRNAs (miRNA) in recent years is an important advance in the field of gene regulation. To this end, several approaches for miRNA expression analysis and various bioinformatics tools have been developed over the last few years. It is a common practice to analyze miRNA PCR Array data using the commercially available software, mostly due to its convenience and ease-of-use. Results In this work we present miRkit, an open source framework written in R, that allows for the comprehensive analysis of RT-PCR data, from the processing of raw data to a functional analysis of the produced results. The main goal of the proposed tool is to provide an assessment of the samples’ quality, perform data normalization by endogenous and exogenous miRNAs, and facilitate differential and functional enrichment analysis. The tool offers fast execution times with low memory usage, and is freely available under a ΜΙΤ license from https://bio.tools/mirkit . Overall, miRkit offers the full analysis from the raw RT-PCR data to functional analysis of targeted genes, and specifically designed to support the popular miScript miRNA PCR Array (Qiagen) technology.
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- 2021
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9. Erythrodermic psoriasis after rituximab treatment in a patient with autoimmune hemolytic anemia
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Dimitra Koumaki, Vasiliki Koumaki, Vrettos Haniotis, Alexander Katoulis, Sotirios Boumpoucheropoulos, Maria Stefanidou, Charalampos Pontikoglou, George Bertsias, George Evangelou, Kyriaki Zografaki, Aikaterini Mantaka, Sabine Elke Krueger-Krasagakis, and Konstantinos Krasagakis
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Dermatology ,RL1-803 - Published
- 2021
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10. MyPal ADULT study protocol: a randomised clinical trial of the MyPal ePRO-based early palliative care system in adult patients with haematological malignancies
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Sheila Payne, Paolo Ghia, Lydia Scarfò, Richard Rosenquist, Christina Karamanidou, Tina Garani-Papadatos, Kostas Stamatopoulos, Cathy Payne, Christos Maramis, Julie Ling, Michael Doubek, Jana Didi, Charalampos Pontikoglou, Helen Α Papadaki, Niki Stavroyianni, and Pantelis Natsiavas
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Medicine - Abstract
Introduction The systematic collection of electronic patient-reported outcome (ePRO) in the routine care of patients with chronic haematological malignancies such as chronic lymphocytic leukaemia (CLL) and myelodysplasia syndromes (MDS) can constitute a very ambitious but worthwhile challenge. MyPal is a Horizon 2020 Research & Innovation Action aiming to meet this challenge and foster palliative care for patients with CLL or MDS by leveraging ePRO systems to adapt to the personal needs of patients and caregiver(s).Methods and analysis In this interventional randomised trial, 300 patients with CLL or MDS will be recruited across Europe. Patients will be randomly allocated to early palliative care using the MyPal system (n=150) versus standard care including general palliative care if needed (n=150). Patients in the experimental arm will be given access to the MyPal digital health platform which consists of purposely designed software available on smartphones and/or tablets. The platform entails different functionalities including physical and psychoemotional symptom reporting via regular questionnaire completion, spontaneous self-reporting, motivational messages, medication management and a personalised search engine for health information. Data on patients’ activity (daily steps and sleep quality) will be automatically collected via wearable devices.Ethics and dissemination The integration of ePROs via mobile applications has raised ethical concerns regarding inclusion criteria, information provided to participants, free and voluntary consent, and respect for their autonomy. These have been carefully addressed by a multidisciplinary team. Data processing, dissemination and exploitation of the study findings will take place in full compliance with European Union data protection law. A participatory design was adopted in the development of the digital platform involving focus groups and discussions with patients to identify needs and preferences. The protocol was approved by the ethics committees of San Raffaele (8/2020), Thessaloniki ‘George Papanikolaou’ Hospital (849), Karolinska Institutet (20.10.2020), University General Hospital of Heraklion (07/15.4.2020) and University of Brno (01-120220/EK).Trial registration number NCT04370457.
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- 2021
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11. New Perspectives on Myeloid-Derived Suppressor Cells and Their Emerging Role in Haematology
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Nikoleta Bizymi, Andreas M. Matthaiou, Angelos Matheakakis, Ioanna Voulgari, Nikoletta Aresti, Konstantina Zavitsanou, Anastasios Karasachinidis, Irene Mavroudi, Charalampos Pontikoglou, and Helen A. Papadaki
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myeloid-derived suppressor cell (MDSC) ,haematology ,immunology ,cancer ,infection ,autoimmunity ,Medicine - Abstract
Myeloid-derived suppressor cells (MDSCs) are immature cells of myeloid origin that have gained researchers’ attention, as they constitute promising biomarkers and targets for novel therapeutic strategies (i.e., blockage of development, differentiation, depletion, and deactivation) in several conditions, including neoplastic, autoimmune, infective, and inflammatory diseases, as well as pregnancy, obesity, and graft rejection. They are characterised in humans by the typical immunophenotype of CD11b+CD33+HLA-DR–/low and immune-modulating properties leading to decreased T-cell proliferation, induction of T-regulatory cells (T-regs), hindering of natural killer (NK) cell functionality, and macrophage M2-polarisation. The research in the field is challenging, as there are still difficulties in defining cell-surface markers and gating strategies that uniquely identify the different populations of MDSCs, and the currently available functional assays are highly demanding. There is evidence that MDSCs display altered frequency and/or functionality and could be targeted in immune-mediated and malignant haematologic diseases, although there is a large variability of techniques and results between different laboratories. This review presents the current literature concerning MDSCs in a clinical point of view in an attempt to trigger future investigation by serving as a guide to the clinical haematologist in order to apply them in the context of precision medicine as well as the researcher in the field of experimental haematology.
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- 2022
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12. Oncology and complications
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Giuseppe Giordano, Evangelia Kyriazi, Charalampos Mavridis, Francesco Persico, Charalampos Fragkoulis, Piergiorgio Gatto, George Georgiadis, Irene Giagourta, Ioannis Glykas, Rodolfo Hurle, Massimo Lazzeri, Giovanni Lughezzani, Vincenzo Magnano San Lio, Charalampos Mamoulakis, Diego Meo, Helen A. Papadaki, George Piaditis, Charalampos Pontikoglou, and Georgios Stathouros
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Ureter-arterial fistula ,BCG ,Pneumonitis ,Bladder tumors ,Cystectomy ,Paraganglioma ,Thrombotic thrombocytopenic purpura ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
This collection of cases describes some unusual urological tumors and complications related to urological tumors and their treatment. Case 1: A case of uretero-arterial fistula in a patient with long-term ureteral stenting for ureteral oncological stricture and a second case associated to retroperitoneal fibrosis were described. Abdominal CT, pyelography, cystoscopy were useful to show the origin of the bleeding. Angiography is useful for confirming the diagnosis and for subsequent positioning of an endovascular prosthesis which represents a safe approach with reduced post-procedural complications. Case 2: A case of patient who suffered from interstitial pneumonitis during a cycle of intravesical BCG instillations for urothelial cancer. The patient was hospitalized for more than two weeks in a COVID ward for a suspected of COVID-19 pneumonia, but he did not show any evidence of SARS-CoV-2 infection during his hospital stay. Case 3: A case of a young man with a functional urinary bladder paraganglioma who was successfully managed with complete removal of the tumor, leaving the urinary bladder intact. Case 4: A case of a 61 year old male suffering from muscle invasive bladder cancer who was admitted for a radical cystectomy and on the eighth postoperative day developed microangiopathic hemolytic anemia and thrombocytopenia, which clinically defines thrombotic microangiopathy.
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- 2021
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13. Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species
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Angeliki M. Andrianaki, Irene Kyrmizi, Kalliopi Thanopoulou, Clara Baldin, Elias Drakos, Sameh S. M. Soliman, Amol C. Shetty, Carrie McCracken, Tonia Akoumianaki, Kostas Stylianou, Petros Ioannou, Charalampos Pontikoglou, Helen A. Papadaki, Maria Tzardi, Valerie Belle, Emilien Etienne, Anne Beauvais, George Samonis, Dimitrios P. Kontoyiannis, Evangelos Andreakos, Vincent M. Bruno, Ashraf S. Ibrahim, and Georgios Chamilos
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Science - Abstract
Mucormycosis is a life-threatening respiratory fungal infection that typically occurs in patients with abnormalities in iron metabolism. Here the authors show that iron restriction inside the phagosome of macrophages is an essential component of the host defense against Rhizopus, the main species causing mucormycosis.
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- 2018
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14. Differential expression of cell cycle and WNT pathway-related genes accounts for differences in the growth and differentiation potential of Wharton’s jelly and bone marrow-derived mesenchymal stem cells
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Aristea K. Batsali, Charalampos Pontikoglou, Dimitrios Koutroulakis, Konstantia I. Pavlaki, Athina Damianaki, Irene Mavroudi, Kalliopi Alpantaki, Elisavet Kouvidi, George Kontakis, and Helen A. Papadaki
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Bone marrow ,Wharton’s jelly ,Mesenchymal stem cells ,Cell cycle ,WNT pathway ,Medicine (General) ,R5-920 ,Biochemistry ,QD415-436 - Abstract
Abstract Background In view of the current interest in exploring the clinical use of mesenchymal stem cells (MSCs) from different sources, we performed a side-by-side comparison of the biological properties of MSCs isolated from the Wharton’s jelly (WJ), the most abundant MSC source in umbilical cord, with bone marrow (BM)-MSCs, the most extensively studied MSC population. Methods MSCs were isolated and expanded from BM aspirates of hematologically healthy donors (n = 18) and from the WJ of full-term neonates (n = 18). We evaluated, in parallel experiments, the MSC immunophenotypic, survival and senescence characteristics as well as their proliferative potential and cell cycle distribution. We also assessed the expression of genes associated with the WNT- and cell cycle-signaling pathway and we performed karyotypic analysis through passages to evaluate the MSC genomic stability. The hematopoiesis-supporting capacity of MSCs from both sources was investigated by evaluating the clonogenic cells in the non-adherent fraction of MSC co-cultures with BM or umbilical cord blood-derived CD34+ cells and by measuring the hematopoietic cytokines levels in MSC culture supernatants. Finally, we evaluated the ability of MSCs to differentiate into adipocytes and osteocytes and the effect of the WNT-associated molecules WISP-1 and sFRP4 on the differentiation potential of WJ-MSCs. Results Both ex vivo-expanded MSC populations showed similar morphologic, immunophenotypic, survival and senescence characteristics and acquired genomic alterations at low frequency during passages. WJ-MSCs exhibited higher proliferative potential, possibly due to upregulation of genes that stimulate cell proliferation along with downregulation of genes related to cell cycle inhibition. WJ-MSCs displayed inferior lineage priming and differentiation capacity toward osteocytes and adipocytes, compared to BM-MSCs. This finding was associated with differential expression of molecules related to WNT signaling, including WISP1 and sFRP4, the respective role of which in the differentiation potential of WJ-MSCs was specifically investigated. Interestingly, treatment of WJ-MSCs with recombinant human WISP1 or sFRP4 resulted in induction of osteogenesis and adipogenesis, respectively. WJ-MSCs exhibited inferior hematopoiesis-supporting potential probably due to reduced production of stromal cell-Derived Factor-1α, compared to BM-MSCs. Conclusions Overall, these data are anticipated to contribute to the better characterization of WJ-MSCs and BM-MSCs for potential clinical applications.
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- 2017
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15. Myeloid-Derived Suppressor Cells in Hematologic Diseases: Promising Biomarkers and Treatment Targets
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Nikoleta Bizymi, Sunčica Bjelica, Astrid Olsnes Kittang, Slavko Mojsilovic, Maria Velegraki, Charalampos Pontikoglou, Mikael Roussel, Elisabeth Ersvær, Juan Francisco Santibañez, Marie Lipoldová, and Helen A. Papadaki
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Abstract. Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immature myeloid cells that exist at very low numbers in healthy subjects but can expand significantly in malignant, infectious, and chronic inflammatory diseases. These cells are characterized as early-MDSCs, monocytic-MDSCs, and polymorphonuclear-MDSCs and can be studied on the basis of their immunophenotypic characteristics and their functional properties to suppress T-cell activation and proliferation. MDSCs have emerged as important contributors to tumor expansion and chronic inflammation progression by inducing immunosuppressive mechanisms, angiogenesis and drug resistance. Most experimental and clinical studies concerning MDSCs have been mainly focused on solid tumors. In recent years, however, the implication of MDSCs in the immune dysregulation associated with hematologic malignancies, immune-mediated cytopenias and allogeneic hemopoietic stem cell transplantation has been documented and the potential role of these cells as biomarkers and therapeutic targets has started to attract a particular interest in hematology. The elucidation of the molecular and signaling pathways associated with the generation, expansion and function of MDSCs in malignant and immune-mediated hematologic diseases and the clarification of mechanisms related to the circulation and the crosstalk of MDSCs with malignant cells and other components of the immune system are anticipated to lead to novel therapeutic strategies. This review summarizes all available evidence on the implication of MDSCs in hematologic diseases highlighting the challenges and perspectives arising from this novel field of research.
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- 2019
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16. Author Correction: Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species
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Angeliki M. Andrianaki, Irene Kyrmizi, Kalliopi Thanopoulou, Clara Baldin, Elias Drakos, Sameh S. M. Soliman, Amol C. Shetty, Carrie McCracken, Tonia Akoumianaki, Kostas Stylianou, Petros Ioannou, Charalampos Pontikoglou, Helen A. Papadaki, Maria Tzardi, Valerie Belle, Emilien Etienne, Anne Beauvais, George Samonis, Dimitrios P. Kontoyiannis, Evangelos Andreakos, Vincent M. Bruno, Ashraf S. Ibrahim, and Georgios Chamilos
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Science - Abstract
The original version of this Article contained an error in the spelling of the author Emilien Etienne, which was incorrectly given as Emilien Ettiene. These errors have now been corrected in both the PDF and HTML versions of the Article.
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- 2018
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17. Mesenchymal Stem Cells in Immune-Mediated Bone Marrow Failure Syndromes
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Maria-Christina Kastrinaki, Konstantia Pavlaki, Aristea K. Batsali, Elisavet Kouvidi, Irene Mavroudi, Charalampos Pontikoglou, and Helen A. Papadaki
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2013
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18. CD200R/CD200 inhibits osteoclastogenesis: new mechanism of osteoclast control by mesenchymal stem cells in human.
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Audrey Varin, Charalampos Pontikoglou, Elodie Labat, Frédéric Deschaseaux, and Luc Sensebé
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Medicine ,Science - Abstract
Bone homeostasis is maintained by the balance between bone-forming osteoblasts and bone-degrading osteoclasts. Osteoblasts have a mesenchymal origin whereas osteoclasts belong to the myeloid lineage. Osteoclast and osteoblast communication occurs through soluble factors secretion, cell-bone interaction and cell-cell contact, which modulate their activities. CD200 is an immunoglobulin superfamilly member expressed on various types of cells including mesenchymal stem cells (MSCs). CD200 receptor (CD200R) is expressed on myeloid cells such as monocytes/macrophages. We assume that CD200 could be a new molecule involved in the control of osteoclastogenesis and could play a role in MSC-osteoclast communication in humans. In this study, we demonstrated that soluble CD200 inhibited the differentiation of osteoclast precursors as well as their maturation in bone-resorbing cells in vitro. Soluble CD200 did not modify the monocyte phenotype but inhibited the receptor activator of nuclear factor kappa-B ligand (RANKL) signaling pathway as well as the gene expression of osteoclast markers such as osteoclast-associated receptor (OSCAR) and nuclear factor of activated T cells cytoplasmic 1 (NFATc1). Moreover, MSCs inhibited osteoclast formation, which depended on cell-cell contact and was associated with CD200 expression on the MSC surface. Our results clearly demonstrate that MSCs, through the expression of CD200, play a major role in the regulation of bone resorption and bone physiology and that the CD200-CD200R couple could be a new target to control bone diseases.
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- 2013
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19. Effect of lenalidomide therapy on hematopoiesis of patients with myelodysplastic syndrome associated with chromosome 5q deletion
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Maria Ximeri, Athanasios Galanopoulos, Mirjam Klaus, Agapi Parcharidou, Krinio Giannikou, Maria Psyllaki, Argyrios Symeonidis, Vasiliki Pappa, Zafiris Kartasis, Dimitra Liapi, Eleftheria Hatzimichael, Styliani Kokoris, Penelope Korkolopoulou, Constantina Sambani, Charalampos Pontikoglou, and Helen A. Papadaki
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Background Lenalidomide improves erythropoiesis in patients with low/intermediate-1 risk myelodysplastic syndrome and interstitial deletion of the long arm of chromosome 5 [del(5q)]. The aim of this study was to explore the effect of lenalidomide treatment on the reserves and functional characteristics of bone marrow hematopoietic progenitor/precursor cells, bone marrow stromal cells and peripheral blood lymphocytes in patients with low/intermediate-1 risk myelodysplastic syndrome with del(5q).Design and Methods We evaluated the number and clonogenic potential of bone marrow erythroid/myeloid/megakaryocytic progenitor cells using clonogenic assays, the apoptotic characteristics and adhesion molecule expression of CD34+ cells by flow cytometry, the hematopoiesis-supporting capacity of bone marrow stromal cells using long-term bone marrow cultures and the number and activation status of peripheral blood lymphocytes in ten patients with low/intermediate-1 risk myelodysplastic syndrome with del(5q) receiving lenalidomide.Results Compared to baseline, lenalidomide treatment significantly decreased the proportion of bone marrow CD34+ cells, increased the proportion of CD36+/GlycoA+ and CD36−/GlycoA+ erythroid cells and the percentage of apoptotic cells within these cell compartments. Treatment significantly improved the clonogenic potential of bone marrow erythroid, myeloid, megakaryocytic colony-forming cells and increased the proportion of CD34+ cells expressing the adhesion molecules CD11a, CD49d, CD54, CXCR4 and the SLAM antigen CD48. The hematopoiesis-supporting capacity of bone marrow stroma improved significantly following treatment, as demonstrated by the number of colony-forming cells and the level of stromal-derived factor-1α and intercellular adhesion molecule-1 in long-term bone marrow culture supernatants. Lenalidomide treatment also increased the proportion of activated peripheral blood T lymphocytes.Conclusions The beneficial effect of lenalidomide in patients with lower risk myelodysplastic syndrome with del(5q) is associated with significant increases in the proportion of bone marrow erythroid precursor cells and in the frequency of clonogenic progenitor cells, a substantial improvement in the hematopoiesis-supporting potential of bone marrow stroma and significant alterations in the adhesion profile of bone marrow CD34+ cells.
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- 2010
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20. Sentiment Analysis in Greek Clinical Conversations: A Comparative Study of BERT, VADER, and Lexicon Approaches.
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Maria Evangelia Chatzimina, Nikolaos Oikonomou, Helen Papadaki, Manolis Tsiknakis, and Charalampos Pontikoglou
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- 2023
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21. Designing a conversational agent for patients with hematologic malignancies: Usability and Usefulness Study.
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Maria Chatzimina, Helen Papadaki, Charalampos Pontikoglou, Lefteris Koumakis, Kostas Marias, and Manolis Tsiknakis
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- 2021
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22. Using Electronic Patient Reported Outcomes to Foster Palliative Cancer Care: The MyPal Approach.
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Christos Maramis, Sheila Payne, Sarka Pospisilova, Richard Rosenquist, Paolo Ghia, Charalampos Pontikoglou, Annette Sander, Michael Doubek, Norbert M. Graf, Julie Ling, Julia Downing, Christina Karamanidou, Elpida Pavi, Vassilis Koutkias, Fatima Schera, Stephan Kiefer, Lefteris Koumakis, Konstantinos Marias, Stefan Hoffman, Heather Parker, and Jonathan Reston
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- 2019
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23. Co-Designing Smartphone Notifications According to the Clinical Routine of Cancer Patients.
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Panos Bonotis, Fatima Schera, Christina Karamanidou, Lydia Scarfo, Charalampos Pontikoglou, and Christos Maramis
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- 2021
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24. The prognostic significance of macrocytosis in patients with myelodysplastic neoplasms
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Panagiotis T. Diamantopoulos, Elena Solomou, Argiris Symeonidis, Vasiliki Pappa, Ioannis Kotsianidis, Athanasios Galanopoulos, Charalampos Pontikoglou, Achilles Anagnostopoulos, George Vassilopoulos, Panagiotis Zikos, Eleftheria Hatzimichael, Maria Papaioannou, Aekaterini Megalakaki, Theodoros Vassilakopoulos, Maria Dimou, Dimitrios Tsokanas, Menelaos‐Konstantinos Papoutselis, Sotirios Papageorgiou, Alexandra Kourakli, Helen Papadaki, Panayiotis Panayiotidis, and Nora‐Athina Viniou
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Hematology - Published
- 2023
25. Incidence and prognosis of clonal hematopoiesis in patients with chronic idiopathic neutropenia
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Gabriele Todisco, Irene Fragiadaki, Stavros Papadakis, Helen A. Papadaki, Chiara Elena, Anastasios Batas, Anna Gallì, Elisabetta Molteni, Elisa Bono, Grigorios Tsaknakis, Luca Malcovati, Peggy Kanellou, Irene Mavroudi, Charalampos Pontikoglou, Stella Maxouri, Emmanouela Linardaki, Ettore Rizzo, and Nektarios Tavernarakis
- Subjects
Adult ,Male ,medicine.medical_specialty ,Neutropenia ,Myeloid ,IDH1 ,Immunology ,Biochemistry ,Gastroenterology ,Malignant transformation ,Young Adult ,Gene Frequency ,Internal medicine ,medicine ,Humans ,Clinical significance ,Aged ,Aged, 80 and over ,Cytopenia ,business.industry ,Incidence ,Incidence (epidemiology) ,Cancer ,Cell Biology ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,medicine.anatomical_structure ,Mutation ,Female ,Clonal Hematopoiesis ,business ,Follow-Up Studies - Abstract
The incidence and prognosis of clonal hematopoiesis in patients with isolated neutropenia among patients with idiopathic cytopenia of undetermined significance (ICUS), known as ICUS-N or chronic idiopathic neutropenia (CIN) patients, is poorly defined. The current study sought to investigate the frequency and clinical significance of mutations of genes implicated in myeloid malignancies using next-generation sequencing in patients with CIN (n = 185) with a long follow-up. We found that 21 (11.35%) of 185 patients carried a total of 25 somatic mutations in 6 genes with a median variant allele frequency of 12.75%. The most frequently mutated genes were DNMT3A and TET2 involving >80% of patients, followed by IDH1/2, SRSF2, and ZRSR2. The frequency of transformation to a myeloid malignancy was low in the total group of patients (5 of 185 patients [2.70%]). However, from the transformed patients, 4 belonged to the clonal group (4 of 21 [19.05%]) and 1 to the nonclonal group (1 of 164 [0.61%]), indicating that the presence of mutation(s) confers a relative risk for transformation of 31.24 (P = .0017). The variant allele frequency of the mutant clones in the transformed patients was >10% in all cases, and the genes most frequently associated with malignant transformation were SRSF2 and IDH1. No significant differences were identified between the clonal and nonclonal groups in the severity of neutropenia. Patients with clonal disease were older compared with nonclonal patients. These data contribute to the better understanding of the heterogeneous entities underlying ICUS and highlight the importance of mutation analysis for the diagnosis and prognosis of patients with unexplained neutropenias.
- Published
- 2021
26. Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura: Real-World Multicenter Data on Re-Administration and Plasma Exchange Free Treatment
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Eleni Gavriilaki, Evdoxia Koravou, Sotiria Dimou-Mpesikli, Emmanouil Nikolousis, Anastasia Banti, Charalampos Pontikoglou, Christina Kalpadakis, Aikaterini Bitsani, Iliana Tassi, Tasoula Touloumenidou, Thomas Chatzikonstantinou, Maria Papathanassiou, Antonia Syrigou, Eleutheria Ztriva, Georgia Kaiafa, Eudokia Mandala, Zois Mellios, Dimitrios Karakasis, Alexandra Kourakli, Argyris Symeonidis, Eleni Kapsali, Eleni Papadaki, Chrysavgi Lalayanni, and Ioanna Sakellari
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
27. Oncology and complications
- Author
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Rodolfo Hurle, Charalampos Mavridis, Giovanni Lughezzani, Georgios Stathouros, Piergiorgio Gatto, Massimo Lazzeri, Diego Meo, Charalampos Pontikoglou, Ioannis Glykas, Helen A. Papadaki, Irene Giagourta, Francesco Persico, Charalampos Mamoulakis, George Piaditis, Vincenzo Magnano San Lio, George Georgiadis, Giuseppe Giordano, Charalampos Fragkoulis, and Evangelia Kyriazi
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Adult ,Male ,0301 basic medicine ,Urologic Neoplasms ,medicine.medical_specialty ,Thrombotic microangiopathy ,Fistula ,Computed Tomography Angiography ,Urology ,medicine.medical_treatment ,Cystectomy ,lcsh:RC870-923 ,Retroperitoneal fibrosis ,Ureter-arterial fistula ,BCG ,Pneumonitis ,Bladder tumors ,Paraganglioma ,Thrombotic thrombocytopenic purpura ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,medicine ,Humans ,Ureteral Diseases ,Carcinoma, Transitional Cell ,Bladder cancer ,Urinary bladder ,Purpura, Thrombotic Thrombocytopenic ,medicine.diagnostic_test ,business.industry ,COVID-19 ,Pneumonia ,Microangiopathic hemolytic anemia ,Cystoscopy ,Middle Aged ,lcsh:Diseases of the genitourinary system. Urology ,medicine.disease ,Surgery ,Administration, Intravesical ,030104 developmental biology ,medicine.anatomical_structure ,Urinary Bladder Neoplasms ,030220 oncology & carcinogenesis ,BCG Vaccine ,medicine.symptom ,business - Abstract
This collection of cases describes some unusual urological tumors and complications related to urological tumors and their treatment. Case 1: A case of uretero-arterial fistula in a patient with long-term ureteral stenting for ureteral oncological stricture and a second case associated to retroperitoneal fibrosis were described. Abdominal CT, pyelography, cystoscopy were useful to show the origin of the bleeding. Angiography is useful for confirming the diagnosis and for subsequent positioning of an endovascular prosthesis which represents a safe approach with reduced post-procedural complications. Case 2: A case of patient who suffered from interstitial pneumonitis during a cycle of intravesical BCG instillations for urothelial cancer. The patient was hospitalized for more than two weeks in a COVID ward for a suspected of COVID-19 pneumonia, but he did not show any evidence of SARS-CoV-2 infection during his hospital stay. Case 3: A case of a young man with a functional urinary bladder paraganglioma who was successfully managed with complete removal of the tumor, leaving the urinary bladder intact. Case 4: A case of a 61 year old male suffering from muscle invasive bladder cancer who was admitted for a radical cystectomy and on the eighth postoperative day developed microangiopathic hemolytic anemia and thrombocytopenia, which clinically defines thrombotic microangiopathy.
- Published
- 2021
28. The effect of 5‐azacytidine treatment delays and dose reductions on the prognosis of patients with myelodysplastic syndrome: how to optimize treatment results and outcomes
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Eleftheria Hatzimichael, Argiris Symeonidis, George Vassilopoulos, Athanasios Galanopoulos, Vasiliki Pappa, Panagiotis Zikos, Menelaos-Konstantinos Papoutselis, Alexandra Kourakli, Dimitrios Tsokanas, Marie-Christine Kyrtshonis, Maria Papaioannou, Achilles Anagnostopoulos, Maria Kotsopoulou, Maria Dimou, Helen A. Papadaki, Aekaterini Megalakaki, Nora-Athina Viniou, Panagiotis T. Diamantopoulos, Panagiotis Repousis, Panayiotis Panayiotidis, Charalampos Pontikoglou, Sotirios G. Papageorgiou, Elena E. Solomou, Ioannis Kotsianidis, and Georgios Dryllis
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Neutropenia ,Treatment results ,Disease-Free Survival ,Time-to-Treatment ,Internal medicine ,medicine ,Humans ,Registries ,Aged ,Retrospective Studies ,Aged, 80 and over ,Drug Tapering ,business.industry ,Hazard ratio ,Complete remission ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Survival Rate ,Regimen ,International Prognostic Scoring System ,Myelodysplastic Syndromes ,Azacitidine ,Female ,National registry ,Myeloid leukaemia ,business - Abstract
The regimen of 5-azacytidine for patients with myelodysplastic syndrome (MDS) has remained unchanged since its first approval. Although several modifications have since been made and delays and dose reductions are common especially during the first treatment cycles, there are minimal data on the prognostic effect of these modifications. In this study, based on data from 897 patients with MDS treated with 5-azacytidine recorded in a national registry, the effect of treatment delays and dose reductions on response, transformation to acute myeloid leukaemia, and survival (after 5-azacytidine initiation, OST ) were analysed. Delays during the first two cycles were noted in 150 patients (16·7%) and were found to adversely affect OST independently of the International Prognostic Scoring System score [hazard ratio (HR), 1·368; P = 0·033] or pre-existing neutropenia (HR, 1·42; P = 0·015). In patients achieving a response, delays before response achievement were correlated with its type (complete remission, 2·8 days/cycle; partial remission, 3·3 days/cycle; haematologic improvement, 5·6 days/cycle; P = 0·041), while delays after response achievement did not have any effect on retention of response or survival. Dose reductions were found to have no prognostic impact. Based on our results, treatment delays especially during the first cycles should be avoided, even in neutropenic patients. This strict strategy may be loosened after achieving a favourable response.
- Published
- 2020
29. Characteristics of Long-Term Survival in Patients With Myelodysplastic Syndrome Treated With 5-Azacyditine: Results From the Hellenic 5-Azacytidine Registry
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Maria Papaioannou, Eleftheria Hatzimichael, Menelaos-Konstantinos Papoutselis, Alexandra Kourakli, George Vassilopoulos, Panayiotis Panayiotidis, Vasiliki Pappa, Helen A. Papadaki, Eleni Solomou, Panagiotis Zikos, Argiris Symeonidis, Nora-Athina Viniou, Sotirios G. Papageorgiou, Georgios Kyriakakis, Maria Dimou, Achilles Anagnostopoulos, Panagiotis T. Diamantopoulos, Athanasios Galanopoulos, Aekaterini Megalakaki, Panagiotis Repousis, Ioannis Kotsianidis, Charalampos Pontikoglou, Maria Kotsopoulou, and Dimitrios Tsokanas
- Subjects
Male ,Antimetabolites, Antineoplastic ,Cancer Research ,medicine.medical_specialty ,Percentile ,Treatment response ,Multivariate analysis ,03 medical and health sciences ,0302 clinical medicine ,Stable Disease ,Internal medicine ,Long term survival ,medicine ,Humans ,In patient ,Registries ,Aged ,Aged, 80 and over ,business.industry ,Hematology ,Middle Aged ,Prognosis ,Oncology ,Quartile ,International Prognostic Scoring System ,Myelodysplastic Syndromes ,030220 oncology & carcinogenesis ,Azacitidine ,Female ,business ,030215 immunology - Abstract
Background Hypomethylating agents have altered the prognosis of myelodysplastic syndrome (MDS) so that long-term survival is now a feasible treatment goal. Patients and Methods We analyzed data from patients with MDS treated with 5-azacytidine recorded in the Hellenic 5-azacytidine registry. We divided patients, on the basis of their survival after 5-azacytidine initiation (OST), in groups of long-term survivors (Q3 and P90 group with OST above the third quartile and the 90th percentile of the whole group, respectively) and short-term survivors comprising the remaining patients, and compared the characteristics between the groups. The study included 626 patients, 157 in the Q3 group and 63 in the P90 group. Results Categorization per the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R), and World Health Organization–based prognostic scoring system (WPSS) was found to predict long-term survival, while multivariate analysis revealed that response to 5-azacytidine was the strongest predictor of long-term survival. Nevertheless, patients with hematologic improvement (HI) and stable disease (SD) were equally distributed in the groups of short- and long-term survival. Conclusion SD should not be considered a poor treatment response and should not be grouped with failure, while HI offers similar prognosis to SD and thus should not be grouped with complete and partial remission. Patients with SD should continue treatment with 5-azacytidine.
- Published
- 2020
30. MyPal ADULT study protocol: a randomised clinical trial of the MyPal ePRO-based early palliative care system in adult patients with haematological malignancies
- Author
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Helen Α Papadaki, Christos Maramis, Niki Stavroyianni, Charalampos Pontikoglou, Kostas Stamatopoulos, Tina Garani-Papadatos, Richard Rosenquist, Pantelis Natsiavas, Cathy Payne, Michael Doubek, Lydia Scarfò, Sheila Payne, Paolo Ghia, Jana Didi, Julie Ling, Christina Karamanidou, Scarfo, L., Karamanidou, C., Doubek, M., Garani-Papadatos, T., Didi, J., Pontikoglou, C., Ling, J., Payne, C., Papadaki, H. A., Rosenquist, R., Stavroyianni, N., Payne, S., Ghia, P., Natsiavas, P., Maramis, C., and Stamatopoulos, K.
- Subjects
Adult ,Palliative care ,Health informatics ,adult palliative care ,Participatory design ,Humans ,Medicine ,media_common.cataloged_instance ,European union ,health informatics ,Randomized Controlled Trials as Topic ,media_common ,Protocol (science) ,business.industry ,Palliative Care ,General Medicine ,Focus Groups ,medicine.disease ,Focus group ,Digital health ,Clinical trial ,Sleep Quality ,Hematologic Neoplasms ,leukaemia ,Medical emergency ,business ,Software - Abstract
IntroductionThe systematic collection of electronic patient-reported outcome (ePRO) in the routine care of patients with chronic haematological malignancies such as chronic lymphocytic leukaemia (CLL) and myelodysplasia syndromes (MDS) can constitute a very ambitious but worthwhile challenge. MyPal is a Horizon 2020 Research & Innovation Action aiming to meet this challenge and foster palliative care for patients with CLL or MDS by leveraging ePRO systems to adapt to the personal needs of patients and caregiver(s).Methods and analysisIn this interventional randomised trial, 300 patients with CLL or MDS will be recruited across Europe. Patients will be randomly allocated to early palliative care using the MyPal system (n=150) versus standard care including general palliative care if needed (n=150). Patients in the experimental arm will be given access to the MyPal digital health platform which consists of purposely designed software available on smartphones and/or tablets. The platform entails different functionalities including physical and psychoemotional symptom reporting via regular questionnaire completion, spontaneous self-reporting, motivational messages, medication management and a personalised search engine for health information. Data on patients’ activity (daily steps and sleep quality) will be automatically collected via wearable devices.Ethics and disseminationThe integration of ePROs via mobile applications has raised ethical concerns regarding inclusion criteria, information provided to participants, free and voluntary consent, and respect for their autonomy. These have been carefully addressed by a multidisciplinary team. Data processing, dissemination and exploitation of the study findings will take place in full compliance with European Union data protection law. A participatory design was adopted in the development of the digital platform involving focus groups and discussions with patients to identify needs and preferences. The protocol was approved by the ethics committees of San Raffaele (8/2020), Thessaloniki ‘George Papanikolaou’ Hospital (849), Karolinska Institutet (20.10.2020), University General Hospital of Heraklion (07/15.4.2020) and University of Brno (01-120220/EK).Trial registration numberNCT04370457.
- Published
- 2021
31. Therapeutic Implications of Mesenchymal Stromal Cells and Their Extracellular Vesicles in Autoimmune Diseases: From Biology to Clinical Applications
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Aristea Batsali, Charalampos Pontikoglou, Angelos Matheakakis, and Helen A. Papadaki
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QH301-705.5 ,Cell ,Review ,exosomes ,Biology ,Mesenchymal Stem Cell Transplantation ,immunomodulation ,Catalysis ,autoimmune disorders ,Autoimmune Diseases ,Inorganic Chemistry ,Stroma ,medicine ,Animals ,Humans ,Physical and Theoretical Chemistry ,Biology (General) ,Molecular Biology ,QD1-999 ,Spectroscopy ,Organic Chemistry ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,General Medicine ,Microvesicles ,Computer Science Applications ,Cell biology ,Chemistry ,medicine.anatomical_structure ,Multipotent Stem Cell ,Bone marrow ,mesenchymal stromal cells ,extracellular vesicles ,Intracellular ,Homing (hematopoietic) - Abstract
Mesenchymal stromal cells (MSCs) are perivascular multipotent stem cells originally identified in the bone marrow (BM) stroma and subsequently in virtually all vascularized tissues. Because of their ability to differentiate into various mesodermal lineages, their trophic properties, homing capacity, and immunomodulatory functions, MSCs have emerged as attractive candidates in tissue repair and treatment of autoimmune disorders. Accumulating evidence suggests that the beneficial effects of MSCs may be primarily mediated via a number of paracrine-acting soluble factors and extracellular vesicles (EVs). EVs are membrane-coated vesicles that are increasingly being acknowledged as playing a key role in intercellular communication via their capacity to carry and deliver their cargo, consisting of proteins, nucleic acids, and lipids to recipient cells. MSC-EVs recapitulate the functions of the cells they originate, including immunoregulatory effects but do not seem to be associated with the limitations and concerns of cell-based therapies, thereby emerging as an appealing alternative therapeutic option in immune-mediated disorders. In the present review, the biology of MSCs will be outlined and an overview of their immunomodulatory functions will be provided. In addition, current knowledge on the features of MSC-EVs and their immunoregulatory potential will be summarized. Finally, therapeutic applications of MSCs and MSC-EVs in autoimmune disorders will be discussed.
- Published
- 2021
32. miRkit: R Framework Analyzing miRNA PCR Array Data
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Fotis Psomopoulos, Maria Christina Maniou, Nikolaos Pechlivanis, Charalampos Pontikoglou, Aristea Batsali, Maria Tsagiopoulou, Angelos Matheakakis, and Anastasis Togkousidis
- Subjects
Science (General) ,QH301-705.5 ,Computer science ,RT-PCR ,Computational biology ,Polymerase Chain Reaction ,General Biochemistry, Genetics and Molecular Biology ,Field (computer science) ,Database normalization ,Q1-390 ,Software ,Mirna expression ,microRNA ,Biology (General) ,KEGG ,miRNA ,PCR array ,business.industry ,Gene Expression Profiling ,Computational Biology ,General Medicine ,MicroRNAs ,Research Note ,qPCR ,Open source ,Gene Expression Regulation ,GO ,Medicine ,Raw data ,business - Abstract
Objective The characterization of microRNAs (miRNA) in recent years is an important advance in the field of gene regulation. To this end, several approaches for miRNA expression analysis and various bioinformatics tools have been developed over the last few years. It is a common practice to analyze miRNA PCR Array data using the commercially available software, mostly due to its convenience and ease-of-use. Results In this work we present miRkit, an open source framework written in R, that allows for the comprehensive analysis of RT-PCR data, from the processing of raw data to a functional analysis of the produced results. The main goal of the proposed tool is to provide an assessment of the samples’ quality, perform data normalization by endogenous and exogenous miRNAs, and facilitate differential and functional enrichment analysis. The tool offers fast execution times with low memory usage, and is freely available under a ΜΙΤ license from https://bio.tools/mirkit. Overall, miRkit offers the full analysis from the raw RT-PCR data to functional analysis of targeted genes, and specifically designed to support the popular miScript miRNA PCR Array (Qiagen) technology.
- Published
- 2021
33. Multiple Sites of Arterial Thrombosis in A 35-Year Old Patient after ChAdOx1 (AstraZeneca) Vaccination, Requiring Emergent Femoral and Carotid Surgical Thrombectomy
- Author
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Thomas Pappas, Charis Matsouka, Christos V. Ioannou, Nikolaos Kontopodis, Stella Lioudaki, Vasiliki Gkalea, Eleni Papadaki, and Charalampos Pontikoglou
- Subjects
medicine.medical_specialty ,business.industry ,General Medicine ,medicine.disease ,Thrombosis ,Surgery ,Vaccination ,Stenosis ,Venous thrombosis ,Intracranial Thrombosis ,medicine ,Platelet ,Thrombus ,Cardiology and Cardiovascular Medicine ,Complication ,business - Abstract
Background Vaccine Induced Thrombotic Thrombocytopenia (VITT) is a rare complication following ChAdOx1 (AstraZeneca) vaccination. Venous thrombosis in unusual sites such as splachnic or intracranial thrombosis, is the commonest manifestation. Case report We report a 35-year-old male patient who presented with acute left leg ischemia and thrombocytopenia 11-days after vaccination requiring emergent thrombectomy. During work-up, a localized thrombus was detected in the left carotid bifurcation mandating carotid thrombectomy. Localized right iliac thrombus causing a non-limiting flow stenosis was treated conservatively. The platelet aggregating capacity of patient's plasma was confirmed in a functional assay, thereby establishing VITT. Conclusion To the best of our knowledge this is the first case presenting multiple arterial thromboses requiring surgical treatment after ChAdOx1 vaccination.
- Published
- 2022
34. Increased proportion and altered properties of intermediate monocytes in the peripheral blood of patients with lower risk Myelodysplastic Syndrome
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Lydia Kalaitzaki, Maria Velegraki, Irene Mavroudi, Helen A. Papadaki, Maria Tsagiopoulou, Charalampos Pontikoglou, Nikos Papakonstantinou, Stamatia Laidou, Stavroula Ntoufa, Athina Damianaki, and Nikoleta Bizymi
- Subjects
Male ,Lipopolysaccharide ,Lipopolysaccharide Receptors ,CD16 ,Monocytes ,Transcriptome ,Pathogenesis ,chemistry.chemical_compound ,Leukocyte Count ,Immune system ,Risk Factors ,Medicine ,Humans ,Molecular Biology ,Aged ,Aged, 80 and over ,business.industry ,Tumor Necrosis Factor-alpha ,Monocyte ,Receptors, IgG ,Cell Biology ,Hematology ,Middle Aged ,Haematopoiesis ,medicine.anatomical_structure ,chemistry ,Myelodysplastic Syndromes ,Immunology ,Molecular Medicine ,Tumor necrosis factor alpha ,Female ,business - Abstract
Immune deregulation has a critical role in the pathogenesis of lower risk myelodysplastic syndromes (MDS). The cells of the macrophage/monocyte lineage have been reported to contribute to the inflammatory process in MDS through impaired phagocytosis of the apoptotic hemopoietic cells and abnormal production of cytokines. In the present study we assessed the number of peripheral blood (PB) monocyte subsets, namely the classical CD14bright/CD16−, intermediate CD14bright/CD16+ and non-classical CD14dim/CD16+ cells, in patients with lower risk (low/intermediate-I) MDS (n = 32). We also assessed the production of tumor necrosis factor (TNF)α by patient PB monocytes in response to immune stimulus as well as their transcriptome profile. Compared to age- and sex-matched healthy individuals (n = 19), MDS patients had significantly lower number of classical and increased number of intermediate monocytes. Patient intermediate monocytes displayed increased production of TNFα following stimulation with lipopolysaccharide, compared to healthy individuals. Transcriptional profiling comparison of CD16+ monocytes from patients and controls revealed 43 differentially expressed genes mostly associated with biological pathways/processes relevant to hemopoiesis, immune signaling and cell adhesion. These data provide evidence for the first-time that distinct monocyte subsets display abnormal quantitative and functional characteristics in lower risk MDS substantiating their role in the immune deregulation associated with the disease.
- Published
- 2020
35. Osteogenic differentiation of bone marrow mesenchymal stem cells on chitosan/gelatin scaffolds: gene expression profile and mechanical analysis
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Anthie Georgopoulou, Charalampos Pontikoglou, Athanasios Mantalaris, Michail E. Klontzas, Maria Chatzinikolaidou, Aristea Batsali, Maria M. Karabela, Nikolaos E. Zafeiropoulos, and Fotios Papadogiannis
- Subjects
Stromal cell ,0206 medical engineering ,Integrin ,Biomedical Engineering ,Bioengineering ,Biocompatible Materials ,Bone Marrow Cells ,02 engineering and technology ,Immunophenotyping ,Biomaterials ,Extracellular matrix ,Osteogenesis ,Cell Adhesion ,Pressure ,Humans ,Cell adhesion ,Thrombospondins ,Cell Proliferation ,Chitosan ,biology ,Tissue Scaffolds ,Chemistry ,Cell adhesion molecule ,Gene Expression Profiling ,Mesenchymal stem cell ,Cell Differentiation ,Mesenchymal Stem Cells ,021001 nanoscience & nanotechnology ,020601 biomedical engineering ,Matrix Metalloproteinases ,Cell biology ,Extracellular Matrix ,RUNX2 ,biology.protein ,Gelatin ,Polystyrenes ,Collagen ,0210 nano-technology ,Transcriptome - Abstract
In the present study we explore the extracellular matrix (ECM) produced by human bone marrow mesenchymal stem/stromal cells (BM-MSCs) induced to undergo osteogenic differentiation within porous chitosan/gelatin (CS:Gel) scaffolds by investigating their multiple gene expression profile and mechanical behavior. Initially, the efficiency of the BM-MSCs osteogenic differentiation within the constructs was confirmed by the significant rise in the expression of the osteogenesis associated genes DLX5, RUNX2, ALP and OSC. In line with these findings, OSC and Col1A1 protein expression was also detected in BM-MSCs on the CS:Gel scaffolds at day 14 of osteogenic differentiation. We then profiled, for the first time, the expression of 84 cell adhesion and ECM molecules using PCR arrays. The arrays, which were conducted at day 14 of osteogenic differentiation, demonstrated that 49 genes including collagens, integrins, laminins, ECM proteases, catenins, thrombospondins, ECM protease inhibitors and cell-cell adhesion molecules were differentially expressed in BM-MSCs seeded on scaffolds compared to tissue culture polystyrene control. Moreover, we performed dynamic mechanical analysis of the cell-loaded scaffolds on days 0, 7 and 14 to investigate the correlation between the biological results and the mechanical behavior of the constructs. Our data demonstrate a significant increase in the stiffness of the constructs with storage modulus values of 2 MPa on day 7, compared to 0.5 MPa on day 0, following a drop of the stiffness at 0.8 MPa on day 14, that may be attributed to the significant increase of specific ECM protease gene expression such as MMP1, MMP9, MMP11 and MMP16 at this time period.
- Published
- 2020
36. The Role of Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles (MSC-EVs) in Normal and Abnormal Hematopoiesis and Their Therapeutic Potential
- Author
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Angelos Matheakakis, Helen A. Papadaki, Anthie Georgopoulou, Charalampos Pontikoglou, Irene Mavroudi, and Aristea Batsali
- Subjects
0301 basic medicine ,Population ,lcsh:Medicine ,Review ,exosomes ,03 medical and health sciences ,0302 clinical medicine ,medicine ,hematological malignancies ,education ,micro-vesicles (MVs) ,education.field_of_study ,mesenchymal stem cells (MSCs) ,business.industry ,Mesenchymal stem cell ,lcsh:R ,hematopoietic stem cell transplantation (HSCT) ,General Medicine ,medicine.disease ,Microvesicles ,MSC-EVs ,Haematopoiesis ,030104 developmental biology ,Graft-versus-host disease ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer research ,Bone marrow ,Stem cell ,extracellular vesicles (EVs) ,business ,Homeostasis - Abstract
Mesenchymal stem cells (MSCs) represent a heterogeneous cellular population responsible for the support, maintenance, and regulation of normal hematopoietic stem cells (HSCs). In many hematological malignancies, however, MSCs are deregulated and may create an inhibitory microenvironment able to induce the disease initiation and/or progression. MSCs secrete soluble factors including extracellular vesicles (EVs), which may influence the bone marrow (BM) microenvironment via paracrine mechanisms. MSC-derived EVs (MSC-EVs) may even mimic the effects of MSCs from which they originate. Therefore, MSC-EVs contribute to the BM homeostasis but may also display multiple roles in the induction and maintenance of abnormal hematopoiesis. Compared to MSCs, MSC-EVs have been considered a more promising tool for therapeutic purposes including the prevention and treatment of Graft Versus Host Disease (GVHD) following allogenic HSC transplantation (HSCT). There are, however, still unanswered questions such as the molecular and cellular mechanisms associated with the supportive effect of MSC-EVs, the impact of the isolation, purification, large-scale production, storage conditions, MSC source, and donor characteristics on MSC-EV biological effects as well as the optimal dose and safety for clinical usage. This review summarizes the role of MSC-EVs in normal and malignant hematopoiesis and their potential contribution in treating GVHD.
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- 2020
37. Increased Frequency of Mutations in the Gene Responsible for Familial Mediterranean Fever (MEFV) in a Cohort of Patients with Chronic Idiopathic Neutropenia
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Panagiotis Skendros, Peggy Kanellou, Charalampos Pontikoglou, Stavros Papadakis, Grigorios Tsaknakis, George N. Goulielmos, Erasmia Boutakoglou, Konstantinos Ritis, Helen A. Papadaki, and Irene Mavroudi
- Subjects
medicine.medical_specialty ,Chronic idiopathic neutropenia ,business.industry ,Immunology ,Familial Mediterranean fever ,Cell Biology ,Hematology ,medicine.disease ,MEFV ,Biochemistry ,Gastroenterology ,Internal medicine ,Cohort ,Medicine ,business ,Gene - Abstract
Introduction-Aim: Chronic idiopathic neutropenia (CIN) is a neutrophil disorder characterized by the prolonged and unexplained reduction in the number of peripheral blood (PB) absolute neutrophil counts (ANC). The underlying pathogenesis in CIN implicates the production of proinflammatory cytokines by activated lymphocytes and monocytes that induce excessive apoptotic death of the bone marrow (BM) granulocytic progenitor cells. Clonal hematopoiesis identified by next generation sequencing (NGS) of myeloid genes is found in 11% of CIN patients conferring an increased risk for MDS/AML transformation whereas the non-clonal patients display usually a benign course. The basis for the immune cell activation and proinflammatory cytokine production in CIN remains obscure. Based on previously reported data showing increased frequency of mutations of the MEFV gene encoding pyrin in patients with idiopathic inflammatory conditions other than typical Familial Mediterranean Fever (FMF), we sought to investigate the common MEFV mutations in a cohort of well characterized CIN patients. Patients-Methods: We have studied 50 patients fulfilling the previously reported diagnostic criteria of CIN (median ANC 1.5x10 9/L, range 0.2-1.7 x10 9/L), 44 females and 6 males with a median age of 56 years (range 25-87 years) and a long-follow-up (median 132 months, range 8-336 months) in the Department of Hematology of the University Hospital of Heraklion, Crete, Greece. Nonisotopic RNase cleavage assay (NIRCA) analysis was used as first screening method to detect MEFV exons 10 and 2 mutations in DNA extracted from PB or BM samples from CIN patients, confirmed by direct NGS analysis. These sequences contain the main disease-related mutations and polymorphisms. Results: Genetics alterations of MEFV were detected in 22 out of 50 CIN patients (44%). Pathogenic mutations (variants associated with typical or "atypical" FMF phenotype in Greek population) were identified in 10/50 CIN patients (20%). The 20% frequency of MEFV mutations in exon 10 and/or exon 2 in CIN patients is significantly higher compared to the carrier rate of common MEFV mutations in the healthy Greek population (0.7%) according to our previously reported data (PATG; Ile>Met), two patients with heterozygous A744S (GCC>TCC; Ala>Ser) and one with homozygosity, one patient with heterozygous M694V (ATG>GTG; Met>Val), one with heterozygous K695R (AAG>AGG; Lys>Arg) and one with heterozygous M680I (ATG>ATC; Met>Ile), all in exon 10, and (b) four patients with homozygous R202Q mutation in exon 2 (one patient with homozygous A744S co-mutation in exon 10) and two patients with R202Q heterozygosity combined with heterozygosity of I720M and A744S of exons 10, respectively. None of the patients displayed any symptoms/signs of FMF or other systemic inflammatory disease. No statistically significant differences were identified between MEFV mutated and non-mutated CIN patients in the severity of neutropenia or in lymphocyte, monocyte, hemoglobin and platelet counts. A significant difference was identified between the two patient groups in serum IgG (1440±264 vs 1133±245 mg/dl; P = 0.0023, Mann-Whitney test) but not IgA or IgM levels. Discussion: This study reports for the first time that 20% of unselected, consecutive patients with CIN carry mutations of the MEFV gene without clinical manifestations of FMF. Whether these patients represent atypical cases of FMF or the identified MEFV genetic alterations have a pathogenetic/modifying effect in the inflammatory responses associated with CIN is an open/novel field of research. As a first step we are currently investigating the neutrophil autophagic status, IL-1β production and the neutrophil extracellular trap (NET) formation in CIN patients with mutations in MEFV to clarify their potential effect in the immune deregulation known to characterize CIN. Disclosures No relevant conflicts of interest to declare.
- Published
- 2021
38. Follow-up Next Generation Sequencing (NGS) Analyses on Clonal Chronic Idiopathic Neutropenia (CIN) Patients: Insights in the Natural History of the Disease
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Charalampos Pontikoglou, Anna Gallì, Helen A. Papadaki, Irene Fragiadaki, Grigorios Tsaknakis, Stavros Papadakis, Peggy Kanellou, Irene Mavroudi, and Luca Malcovati
- Subjects
Oncology ,medicine.medical_specialty ,Chronic idiopathic neutropenia ,business.industry ,Immunology ,Cell Biology ,Hematology ,Disease ,Biochemistry ,DNA sequencing ,Natural history ,Internal medicine ,Medicine ,business - Abstract
Background: We have previously performed NGS analysis of genes that are recurrently mutated in myeloid malignancies in a cohort of patients with the diagnosis of chronic idiopathic neutropenia (CIN) according to previously reported criteria that largely overlap with those proposed for idiopathic cytopenia/neutropenia of undetermined significance (ICUS-N). We have thus estimated for the first time the frequency of clonal hematopoiesis in patients with CIN/ICUS-N (11.54%) and found that clonal CIN patients have a significantly higher risk of developing a myeloid neoplasm than those with no evidence of clonality (non-clonal). 1 However more longitudinal follow-up NGS studies are required for the tracking of clonal evolution and delineation of clonal CIN natural history. Aims: To conduct longitudinal follow-up NGS analyses in order to assess clonal evolution and associate the clinical significance of detected clonal aberrations with the risk of transforming to myeloid malignancy in clonal CIN clinical outcome. Methods: Genomic DNA was extracted from patients' BM or PB samples, sequencing libraries were prepared and subjected to targeted next generation sequencing (NGS) on an Ion S5 Prime Sequencer (Thermo Fisher Scientific) using a panel of 38 genes recurrently mutated in myeloid malignancies. Results: Follow-up analysis by NGS was performed in 16 clonal CIN patients (Figure 1). (Out of these 16 patients, follow-up NGS data has already been published in 9 patients, however additional timepoints were tested in 3 of them). 1 The median time between the first and subsequent analysis was 28.5 months (range 8-164 months). Ten of these patients carried the initial somatic mutations with only subtle changes in the size of clone as estimated by the variant allele frequency (VAF); the patients displayed absence of additional mutations and did not develop myeloid malignancy (Figure 1A-C, E-G, I, K, L, P). Two patients acquired a second mutation at follow-up. One of them still displayed stable disease course (Figure 1D) whereas the second eventually progressed to CMML (Figure 1H). The analysis also revealed that one patient lost the initial detected mutation at follow-up after 98 months (Figure 1J). Two patients who progressed to MDS/MPN and AML respectively, displayed a notable clonal expansion with additional mutations at the time of progression (Figure 1M and Figure 1N, respectively). Specifically, the patient who progressed to MDS/MPN acquired a mutation in JAK2 and ASXL1 while the patient who progressed to AML acquired the typical NPM1 p.L287fs mutation. The patient who developed MDS with multilineage dysplasia, carrying three mutations in DNMT3A and IDH1, showed a moderate increase in the VAF of these mutations at first follow-up (Figure 1O). The patient progressed to acute lymphoblastic leukemia (2 nd follow-up) with acquisition of additional truncating mutation in ETV6. Following treatment (3 rd and 4 th follow-up) mutation in ETV6 was lost, however the three mutations in DNMT3A and IDH1 persisted and their clone size increased. Conclusions: In the majority of patients tested for clonal evolution over time, most mutant clones appeared to be remarkably stable, with minimal VAF change, no acquisition of new molecular alterations and no progression to overt myeloid malignancy. Two CIN patients who transformed to a myeloid malignancy displayed a clonal expansion as was reflected by the increase of VAF and the development of additional mutations whereas in the third patient only a modest VAF increase was identified before malignant transformation. Finally in the patient bearing 4 mutations no progression to overt malignancy was observed after 12 months of follow-up. This ongoing study of sequential NGS analysis of CIN patients is anticipated to contribute to the better understanding and enrich further the knowledge on the natural history of this rare disease. References: Tsaknakis G, Galli A, Papadakis S et al. Incidence and Prognosis of Clonal Hematopoiesis in patients with Chronic Idiopathic Neutropenia. Blood. 2021 Jun 24:blood.2021010815. doi: 10.1182/blood.2021010815. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
- Published
- 2021
39. Myelodysplastic Syndromes (MDS) Presenting with Isolated Thrombocytopenia: Characteristics, Outcomes, and Clinical Presentation Differences from Immune Thrombocytopenic Purpura (ITP)
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Vassiliki Pappa, Vasileios Papadopoulos, Flora N. Kontopidou, Eleftheria Hatzimichael, Alexandra Kourakli, Ioannis Adamopoulos, Panagiotis Zikos, Stamatis Karakatsanis, Athanasios Galanopoulos, Konstantina Papathanasiou, Argiris Symeonidis, Panagiotis T. Diamantopoulos, Sotirios G. Papageorgiou, Dimitris Tsokanas, Kotsianidis Ioannis, Menelaos Papoutselis, Helen A. Papadaki, Nora-Athina Viniou, Emily Stavroulaki, Anna Vardi, Maria Dimou, Konstantinos Liapis, Christina Misidou, Epameinondas Koumpis, Maria Ximeri, Charalampos Pontikoglou, George Vrachiolias, Theodoros P. Vassilakopoulos, Eleni Bouronikou, Nikolaos Charchalakis, Aikaterini Megalakaki, and Panayiotis Panayiotidis
- Subjects
business.industry ,Myelodysplastic syndromes ,Immunology ,Isolated thrombocytopenia ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Thrombocytopenic purpura ,Immune system ,medicine ,Presentation (obstetrics) ,business - Abstract
Introduction: Less than 5% of patients with MDS present with thrombocytopenia as an isolated abnormality (MDS-IT). There have been few systematic studies on MDS-IT and data regarding its course and prognosis are conflicting. Previous studies have defined MDS-IT based on the IPSS thresholds (Hb ≥10 g/dL; ANC ≥1.8×10 9/L; PLT Methods: We identified patients who had PLT 13 g/dL (men) or >12 g/dL (women), and ANC ≥1.8 ×10 9/L, registered in the Hellenic National Registry of Myelodysplastic and Hypoplastic Syndromes which includes 2792 patients (analysis cut-off date; July 7, 2016). Patients were divided into 4 groups: group 1 had PLT 149-100 ×10 9/L; group 2, 99-50 ×10 9/L; group 3, Results: A total of 77 patients (45 men; 32 women) with MDS-IT were identified (2.9% of total MDS cohort). Of these, 28.6% were classified in group 1; 49.4% in group 2; 14.3% in group 3; and 7.8% in group 4. Median PLT count was 87 ×10 9/L (12-139 ×10 9/L), WBC count 4.6 ×10 9/L, and Hb 13.6 g/dL. Bone marrow (BM) blasts ranged from 0-9% (median, 2%). Median follow-up was 51.0 months (41.6-60.4), during which 15 (19.5%) patients died. AML developed in 9 patients (11.7%). Histologically, MDS with multilineage dysplasia (MLD) was seen in 77.6% whereas MDS with excess blasts (EB) and MDS with single lineage dysplasia (SLD) comprised 10.7% and 11.9% of cases, respectively. Most patients (73.5%) had lower-risk MDS on the IPSS-R (i.e. IPSS-R ≤3.5). Of the 59 patients with cytogenetic data, 83.1% had favorable, 13.5% intermediate, and 3.4% poor risk cytogenetics. Most (40) had a normal karyotype followed by isolated del(20q) (6). All patients with del(20q) showed a characteristic set of clinical features: age >60 years, blasts 0-3%, bilineage (erythroid/megakaryocytic) dysplasia, and increased reticulin fibrosis. There were no significant differences between any of the 4 PLT groups regarding age, sex, IPSS-R, cytogenetics, BM blasts, and histology. Median OS was 109 months (95% CI 103-115) and LFS 108 months (101-115). Our results showed no significant difference in OS (P=0.891) and LFS (P=0.871) between the 4 PLT groups. As compared with total MDS cohort, MDS-IT occurred at younger age (64.7 vs. 72.4 years, P In comparing MDS-IT with ITP, the median age at diagnosis was 66.0 years for MDS-IT and 49.0 years for ITP (P80 years. Its incidence reached a peak between the ages of 70-79 years, whereas ITP occurred at a more constant level over time (Figure 1B). Women predominated in ITP and men in MDS-IT (P=0.007). Overall, ITP was associated with more marked thrombocytopenia than MDS-IT (15.0 ×10 9/L vs. 87.0 ×10 9/L) (P Conclusions: In one of the largest reported series, we conclude that MDS-IT is associated with MDS-MLD, favorable cytogenetics, lower-risk IPSS-R, high survival rate, and a low risk of AML evolution. Our data suggest that the superior prognosis in MDS-IT than general MDS may have intrinsic genomic underpinnings as survival curves remained unchanged after correcting for age, sex, blasts and IPSS-R. Importantly, no significant differences in OS and LFS were noted between the 4 PLT subgroups, suggesting that the degree of thrombocytopenia does not correlate with mortality in MDS-IT. From the diagnostic standpoint, age 80 years and PLT Figure 1 Figure 1. Disclosures Viniou: Sandoz: Research Funding; Takeda: Research Funding; Novartis: Honoraria, Research Funding; Sanofi: Research Funding; Janssen: Honoraria, Research Funding; Pfizer: Research Funding; Abbvie: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Roche: Research Funding; Astellas: Research Funding; Celgene: Research Funding. Vassilakopoulos: Dr. Reddy's: Research Funding; Amgen: Honoraria, Research Funding; GlaxoSmithKline: Honoraria, Other: Travel; AbbVie: Consultancy, Honoraria; Integris: Honoraria; Pfizer: Research Funding; Roche: Consultancy, Honoraria, Other: Travel; Takeda: Consultancy, Honoraria, Other: Travel, Research Funding; Genesis Pharma: Consultancy, Honoraria, Other: Travel; Merck: Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Karyopharm: Research Funding; AstraZeneca: Honoraria. Hatzimichael: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Honoraria; Gilead: Honoraria; Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genesis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Pharmathen- Innovis: Honoraria; GSK: Honoraria; Bristol Myersr Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Symeonidis: Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi/Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Demo: Research Funding; MSD: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; WinMedica: Research Funding; Astellas: Consultancy, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GenesisPharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.
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- 2021
40. Immunoglobulin and B-cell disturbances in patients with chronic idiopathic neutropenia
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Maria I. Zervou, Peggy Kanellou, Irene Mavroudi, Semeli Mastrodemou, Maria Ximeri, Helen A. Papadaki, Katerina Pyrovolaki, Helen Koutala, Aristides G. Eliopoulos, Athina Damianaki, Charalampos Pontikoglou, and George N. Goulielmos
- Subjects
Adult ,Male ,0301 basic medicine ,Neutropenia ,Adolescent ,Increased IgM level ,CD40 Ligand ,Immunology ,B-Lymphocyte Subsets ,Immunoglobulins ,chemical and pharmacologic phenomena ,Immunoglobulin D ,Immunoglobulin G ,Young Adult ,03 medical and health sciences ,medicine ,Humans ,Immunology and Allergy ,CD40 Antigens ,B cell ,Aged ,B-Lymphocytes ,biology ,business.industry ,hemic and immune systems ,Middle Aged ,medicine.disease ,Immunoglobulin Class Switching ,Tumor Necrosis Factor Receptor Superfamily, Member 7 ,030104 developmental biology ,medicine.anatomical_structure ,Immunoglobulin M ,Immunoglobulin class switching ,Case-Control Studies ,Chronic Disease ,biology.protein ,Female ,Antibody ,business ,Signal Transduction - Abstract
Chronic idiopathic neutropenia (CIN) is a granulocytic disorder associated with presence of activated, myelosuppressive T-lymphocytes. In the present study we have evaluated constituents of humoral immunity in CIN patients (n=48) compared to healthy controls (n=52). CIN patients displayed lower serum IgG levels due to a reduction in IgG1, IgG3, IgG4 but not IgG2, lower IgA and increased IgM levels compared to controls. The proportion of CD19+ cells did not differ between patients and controls; however the proportion of the naive IgD+/CD27- B-cells was increased and the proportion of class-switched memory IgD-/CD27+ B-cells was decreased in the patients. The percentage of CD40+ B-cells did not differ between patients and controls and no aberrations in the CD40-meadiated signal transduction pathway or in CD40-gene polymorphisms were identified. These data provide further evidence that immune disturbances are associated with the pathophysiology of CIN and point out for the first time the implication of the B-cell system.
- Published
- 2017
41. Thoracoabdominal Resection of Mucormycosis Lesions in a Leukemic Patient
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Charalampos Pontikoglou, George Chalkiadakis, George Lazopoulos, Paris-Dimitrios Kalogerakos, Michael Kiparakis, and Kostantia Pavlaki
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Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Thorax ,Posaconazole ,medicine.medical_specialty ,030106 microbiology ,Risk Assessment ,Severity of Illness Index ,Immunocompromised Host ,03 medical and health sciences ,Rare Diseases ,Amphotericin B ,medicine ,Humans ,Mucormycosis ,Laparotomy ,Rib cage ,Lung Diseases, Fungal ,business.industry ,Middle Aged ,medicine.disease ,Diaphragm (structural system) ,Surgery ,Leukemia, Myeloid, Acute ,Leukemia ,Treatment Outcome ,medicine.anatomical_structure ,Thoracotomy ,Abdomen ,Tomography, X-Ray Computed ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies ,medicine.drug - Abstract
Mucormycosis is a rare fungal infection that poses a severe threat to immunocompromised patients. In the case presented herein, a 56-year-old leukemic patient, who was treated with amphotericin B and posaconazole, was scheduled for surgical resection of mucormycosis lesions that had spread to the thorax and abdomen. Surgery was aggressive and the resection involved the left lateral thoracoabdominal wall, 2 ribs, the left diaphragm, and the spleen. The patient tolerated the procedure well and the leukemia went into remission. Aggressive surgery can benefit immunocompromised patients with mucormycosis.
- Published
- 2018
42. Frequency and Functional Analysis of Myeloid-Derived Suppressor Cells (MDSCs) in the Peripheral Blood and Bone Marrow of Patients with Chronic Idiopathic Neutropenia (CIN)
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Helen A. Papadaki, Maria Velegraki, George M. Kontakis, Anthie Georgopoulou, Irene Mavroudi, Charalampos Pontikoglou, Konstantina Zavitsanou, John Sperelakis, Athina Damianaki, Nikoleta Bizymi, and Anastasios Karasachinidis
- Subjects
Chronic idiopathic neutropenia ,Functional analysis ,business.industry ,Immunology ,Cell Biology ,Hematology ,Biochemistry ,Peripheral blood ,medicine.anatomical_structure ,medicine ,Cancer research ,Myeloid-derived Suppressor Cell ,Bone marrow ,business - Abstract
Myeloid-derived suppressor cells (MDSCs) are myeloid cells with immunoregulatory properties characterized mainly by suppression of T-cell responses (Bizymi et al, HemaSphere 2019). They are divided in HLA-DRlow/-/CD11b+/CD33+/CD15+ polymorphonuclear (PMN-MDSCs) and HLA-DRlow/-/CD11b+/CD33+/CD14+ monocytic (M-MDSCs) subsets and they are implicated in inflammatory and malignant diseases. Chronic idiopathic neutropenia (CIN), is a (usually benign) neutrophil disorder characterized by persistent and unexplained neutropenia following a detailed clinical/laboratory investigation including anti-neutrophil antibody testing, bone marrow (BM) biopsy and karyotype (Dale & Bolyard, Curr Opin Hematol 2017). Previous studies have shown that neutropenia in CIN is associated with increased apoptosis of BM granulocytic progenitor cells due to an inflammatory BM microenvironment consisting of oligoclonal T-lymphocytes, proinflammatory monocytes and proapoptotic cytokines. The aim of the present study is to explore the possible involvement of the MDSCs in the pathophysiology of CIN by investigating their number in peripheral blood (PB) and BM in association with their functional characteristics. We have studied 100 CIN patients and 49 age- and sex-matched healthy controls. The patients fulfilled the previously described diagnostic criteria for CIN (Papadaki et al, Blood 2003) and had mean neutrophil counts 1095.67 ± 479.52 (median 1215, range 100-1700). MDSC subsets were quantitated by flow cytometry in the PB mononuclear cell (PBMC) fraction using the combination of CD33PC7/CD15PC5/HLA-DRECD/CD14PE/CD11bFITC monoclonal antibodies and the Kaluza analysis software. MDSC subsets were also studied in the BMMC fraction of 24 CIN patients and 8 healthy controls from the study population. The T-cell suppression function of patient MDSCs was evaluated in coculture experiments of immunomagnetically sorted, CFSE stained, normal CD3+ cells with immunomagnetically sorted M-MDSCs and PMN-MDSCs from 4 patients and 4 healthy donors using recombinant human IL-2 as activating factor. CFSE staining was detected in the CD3+ cells on day 0 and day 3 of coculture and analysis was performed with the Fcs Express 7 software. Statistical analysis was performed with the Statistica software. We found that the proportion of PB M-MDSCs was statistically significant lower in CIN patients (1.45% ± 1.82%) compared to controls (3.68% ± 3.12%, Mann-Whitney test, p < 0.0001) (Figure a) whereas the proportion of PB PMN-MDSCs, although lower in patients, did not differ significantly from the controls. The proportion of BM M-MDSCs did not differ significantly between CIN patients and controls whereas the proportion of BM PMN-MDSCs was statistically significant lower in patients (13.27% ± 11.27%) compared to controls (19.49% ± 4.46%; Mann-Whitney test, p = 0.0291) (Figure b). Paired analysis showed that the proportion of PMN-MDSCs were higher in the BMMC compared to PBMC fraction in both CIN patients (13.27% ± 11.27% vs 1.14% ± 1.64%, respectively; Wilcoxon test, p = 0.005) (Figure c) and healthy controls (19.49% ± 4.46% vs 9.92% ± 9.08%, respectively; Wilcoxon test, p = 0.0118). Interestingly, the proportion of increase of PMN-MDSCs (in BMMC vs PBMC fraction) was significantly higher in patients (86.71% ± 21.26%) compared to controls (55.95% ± 38.59%; Mann-Whitney test, p = 0.0357) (Figure d). The above data indicate low production of PMN-MDSCs in CIN patients compared to controls but a trend for accumulation of these cells in patients' BM. No statistically significant difference was documented in paired analysis of M-MDSCs between BMMC and PBMC fractions in either CIN patients or healthy controls. Patient PMN-MDSCs and M-MDSCs displayed normal capacity to suppress T-cell proliferation as was indicated by the T-cell generations in coculture experiments of normal CD3+ cells in the presence or absence of patient MDSCs (Figure e). In conclusion, CIN patients display low proportion of MDSCs in the PB and lower proportion of PMN-MDSC in the BM compared to normal individuals. Patient MDSCs display normal capacity to suppress T-cell activation. The low proportions of MDSCs may sustain the inflammatory process associated with CIN whereas the accumulation of PMN-MDSCs in the BM represents probably a compensatory mechanism to suppress the inflammatory processes within patients' BM microenvironment. Figure Disclosures Papadaki: Genesis pharma SA: Membership on an entity's Board of Directors or advisory committees, Research Funding.
- Published
- 2020
43. Detection of L265P MYD-88 mutation in a series of clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ)
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Xanthi Yiakoumis, P. Panayiotidis, Theodoros P. Vassilakopoulos, Pantelis Tsirkinidis, Helen A. Papadaki, Sotirios Sachanas, Dimitra Rondoyianni, Maria Roumelioti, Penelope Korkolopoulou, Christina Kalpadakis, Charalampos Pontikoglou, Maria K. Angelopoulou, Gerassimos A. Pangalis, Maria Moschogiannis, and Efstathios Koulieris
- Subjects
Cancer Research ,Paraproteinemia ,Pathology ,medicine.medical_specialty ,Lymphocytosis ,Waldenstrom macroglobulinemia ,Hematology ,General Medicine ,Biology ,medicine.disease ,Marginal zone ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,Immunoglobulin M ,030220 oncology & carcinogenesis ,Mutation (genetic algorithm) ,Immunology ,medicine ,biology.protein ,Monoclonal B-cell lymphocytosis ,Bone marrow ,medicine.symptom ,030215 immunology - Abstract
Clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ) is a recently described entity characterized by the presence of clonal B cells in the blood and/or bone marrow (BM) with morphologic and immunophenotypic features consistent with marginal zone derivation in otherwise healthy individuals. CBL-MZ is commonly associated with paraproteinemia, usually immunoglobulin M (IgM), raising diagnostic difficulties from Waldenstrom macroglobulinemia (WM). The aim of the present study was to determine the presence of MYD-88 L265P mutation in a well-characterized series of CBL-MZ to identify cases that may in fact represent WM. Fifty-three CBL-MZ cases were retrospectively evaluated. MYD-88 L265P mutation was determined by allele-specific polymerase chain reaction in blood and/or BM mononuclear cells. Almost half of the CBL-MZ cases (49%) were associated with paraproteinemia mainly of the IgM type (65%). MYD-88 L265P mutation was identified in 10 cases (19%). These cases may truly represent WM, whereas 43 cases (81%) are still classified as CBL-MZ. Mutated cases were all associated with paraproteinemia compared with 37% of the nonmutated ones (P
- Published
- 2016
44. Myeloid-Derived Suppressor Cells in Hematologic Diseases: Promising Biomarkers and Treatment Targets
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Elisabeth Ersvær, Helen A. Papadaki, Marie Lipoldová, Astrid Olsnes Kittang, Charalampos Pontikoglou, Suncica Bjelica, Slavko Mojsilović, Juan F. Santibanez, Nikoleta Bizymi, Mikael Roussel, Maria Velegraki, Jonchère, Laurent, University of Crete [Heraklion] (UOC), University of Belgrade [Belgrade], University of Bergen (UiB), Medical University of South Carolina [Charleston] (MUSC), CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Western Norway University of Applied Sciences, Universidad Bernardo O'Higgins, Institute of Molecular Genetics [Prague, Czech Republic], Czech Academy of Sciences [Prague] (CAS), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
- Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,medicine.medical_specialty ,Angiogenesis ,Inflammation ,Review Article ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Internal medicine ,medicine ,Tumor Expansion ,Hematology ,lcsh:RC633-647.5 ,business.industry ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,lcsh:Diseases of the blood and blood-forming organs ,Immune dysregulation ,3. Good health ,Transplantation ,030220 oncology & carcinogenesis ,Myeloid-derived Suppressor Cell ,Cancer research ,medicine.symptom ,business ,030215 immunology - Abstract
International audience; Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immature myeloid cells that exist at very low numbers in healthy subjects but can expand significantly in malignant, infectious, and chronic inflammatory diseases. These cells are characterized as early-MDSCs, monocytic-MDSCs, and polymorphonuclear-MDSCs and can be studied on the basis of their immunophenotypic characteristics and their functional properties to suppress T-cell activation and proliferation. MDSCs have emerged as important contributors to tumor expansion and chronic inflammation progression by inducing immunosuppressive mechanisms, angiogenesis and drug resistance. Most experimental and clinical studies concerning MDSCs have been mainly focused on solid tumors. In recent years, however, the implication of MDSCs in the immune dysregulation associated with hematologic malignancies, immune-mediated cytopenias and allogeneic hemopoietic stem cell transplantation has been documented and the potential role of these cells as biomarkers and therapeutic targets has started to attract a particular interest in hematology. The elucidation of the molecular and signaling pathways associated with the generation, expansion and function of MDSCs in malignant and immune-mediated hematologic diseases and the clarification of mechanisms related to the circulation and the crosstalk of MDSCs with malignant cells and other components of the immune system are anticipated to lead to novel therapeutic strategies. This review summarizes all available evidence on the implication of MDSCs in hematologic diseases highlighting the challenges and perspectives arising from this novel field of research.
- Published
- 2019
45. Erythrodermic psoriasis after rituximab treatment in a patient with autoimmune hemolytic anemia
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Alexander C. Katoulis, George Bertsias, Sabine Krueger-Krasagakis, Vrettos Haniotis, Charalampos Pontikoglou, Konstantinos Krasagakis, George Evangelou, Sotirios Boumpoucheropoulos, Aikaterini Mantaka, Vasiliki Koumaki, Kyriaki Zografaki, Dimitra Koumaki, and Maria Stefanidou
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medicine.medical_specialty ,business.industry ,MEDLINE ,Dermatology ,lcsh:RL1-803 ,medicine.disease ,Psoriasis ,Correspondence ,lcsh:Dermatology ,Medicine ,Rituximab ,Autoimmune hemolytic anemia ,business ,medicine.drug - Published
- 2021
46. Minor populations of paroxysmal nocturnal hemoglobinuria-type cells in patients with chronic idiopathic neutropenia
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Charalampos Pontikoglou, Peggy Kanellou, Helen Koutala, Fotios Papadogiannis, Helen A. Papadaki, Irene Mavroudi, Michael Spanoudakis, Athina Damianaki, and Elias Stagakis
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Adult ,Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Neutropenia ,Adolescent ,Receptors, Antigen, T-Cell, alpha-beta ,CD14 ,Hemoglobinuria, Paroxysmal ,CD59 ,Granulopoiesis ,Immunophenotyping ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Bone Marrow ,T-Lymphocyte Subsets ,hemic and lymphatic diseases ,medicine ,Humans ,Progenitor cell ,Aged ,business.industry ,Bone marrow failure ,Hematology ,General Medicine ,Middle Aged ,Flow Cytometry ,medicine.disease ,Blood Cell Count ,030104 developmental biology ,medicine.anatomical_structure ,Chronic Disease ,Immunology ,Paroxysmal nocturnal hemoglobinuria ,Female ,Bone marrow ,business ,030215 immunology - Abstract
Chronic idiopathic neutropenia (CIN) is an acquired disorder of granulopoiesis characterized by increased apoptosis of the bone marrow (BM) granulocytic progenitor cells under the influence of pro-inflammatory mediators and oligoclonal/monoclonal T-lymphocytes. Because patients with immune-mediated BM failure display frequently paroxysmal nocturnal hemoglobinuria (PNH)-type cells in the peripheral blood (PB), we investigated the possible existence of PNH-type cells in 91 patients with CIN using flow cytometry. The patients displayed increased proportions of PNH-type glycophorin A+ /CD59dim and glycophorin A+ /CD59- red blood cells (RBCs), FLAER- /CD24- granulocytes, and FLAER- /CD14- monocytes, compared to controls (n = 55). A positive correlation was found between the proportions of PNH-type RBCs, granulocytes, and monocytes and an inverse correlation between the number of PB neutrophils and the proportions of PNH-type cell populations. The number of patients, displaying percentages of PNH-type cells above the highest percentage observed in the control group, was significantly increased among patients with skewed compared to those with normal T-cell receptor repertoire suggesting that T-cell-mediated immune processes underlie the emergence of PNH-type cells in CIN. Our findings suggest that patients with CIN display PNH-type cells in the PB at a high frequency corroborating the hypothesis that CIN belongs to the immune-mediated BM failure syndromes.
- Published
- 2016
47. CD200 expression in human cultured bone marrow mesenchymal stem cells is induced by pro‐osteogenic and pro‐inflammatory cues
- Author
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Philippe Rosset, Audrey Varin, Mamadou Aliou Ba, Frédéric Deschaseaux, Pierre Charbord, Charalampos Pontikoglou, Alain Langonné, and Luc Sensebé
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Adult ,0301 basic medicine ,Stromal cell ,Bone Morphogenetic Protein 7 ,Interleukin-1beta ,Primary Cell Culture ,Bone Marrow Cells ,Core Binding Factor Alpha 1 Subunit ,Bone Morphogenetic Protein 4 ,Biology ,Dexamethasone ,Phosphates ,03 medical and health sciences ,Antigens, CD ,medicine ,Humans ,Cell Lineage ,Progenitor cell ,mesenchymal stem/stromal cells ,Cell Proliferation ,Homeodomain Proteins ,Osteoblasts ,Tumor Necrosis Factor-alpha ,Lineage markers ,NF‐κB ,Mesenchymal stem cell ,NF-kappa B ,Cell Differentiation ,Mesenchymal Stem Cells ,Original Articles ,differentiation ,Cell Biology ,cell cultures ,Extracellular Matrix ,Cell biology ,Bone morphogenetic protein 7 ,030104 developmental biology ,medicine.anatomical_structure ,Bone morphogenetic protein 4 ,Cell culture ,Immunology ,Molecular Medicine ,Original Article ,Bone marrow ,heterogeneity ,Transcription Factors - Abstract
Similar to other adult tissue stem/progenitor cells, bone marrow mesenchymal stem/stromal cells (BM MSCs) exhibit heterogeneity at the phenotypic level and in terms of proliferation and differentiation potential. In this study such a heterogeneity was reflected by the CD200 protein. We thus characterized CD200(pos) cells sorted from whole BM MSC cultures and we investigated the molecular mechanisms regulating CD200 expression. After sorting, measurement of lineage markers showed that the osteoblastic genes RUNX2 and DLX5 were up-regulated in CD200(pos) cells compared to CD200(neg) fraction. At the functional level, CD200(pos) cells were prone to mineralize the extra-cellular matrix in vitro after sole addition of phosphates. In addition, osteogenic cues generated by bone morphogenetic protein 4 (BMP4) or BMP7 strongly induced CD200 expression. These data suggest that CD200 expression is related to commitment/differentiation towards the osteoblastic lineage. Immunohistochemistry of trephine bone marrow biopsies further corroborates the osteoblastic fate of CD200(pos) cells. However, when dexamethasone was used to direct osteogenic differentiation in vitro, CD200 was consistently down-regulated. As dexamethasone has anti-inflammatory properties, we assessed the effects of different immunological stimuli on CD200 expression. The pro-inflammatory cytokines interleukin-1β and tumour necrosis factor-α increased CD200 membrane expression but down-regulated osteoblastic gene expression suggesting an additional regulatory pathway of CD200 expression. Surprisingly, whatever the context, i.e. pro-inflammatory or pro-osteogenic, CD200 expression was down-regulated when nuclear-factor (NF)-κB was inhibited by chemical or adenoviral agents. In conclusion, CD200 expression by cultured BM MSCs can be induced by both osteogenic and pro-inflammatory cytokines through the same pathway: NF-κB.
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- 2016
48. Endothelial progenitor cells as markers of severity in hypertrophic cardiomyopathy
- Author
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Maria E. Marketou, Gregory Chlouverakis, Helen A. Papadaki, Charalampos Pontikoglou, Joanna E. Kontaraki, Stylianos Petousis, Fragiskos I. Parthenakis, Athanasia Kalyva, Panos E. Vardas, and S. Maragkoudakis
- Subjects
0301 basic medicine ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,CD34 ,Hypertrophic cardiomyopathy ,Diastole ,030204 cardiovascular system & hematology ,medicine.disease ,Peripheral blood ,Pathophysiology ,Flow cytometry ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Endocrinology ,Internal medicine ,Heart failure ,cardiovascular system ,medicine ,Cardiology ,Progenitor cell ,Cardiology and Cardiovascular Medicine ,business - Abstract
Aims Endothelial progenitor cells (EPCs) are bone marrow-derived cells that are mobilized into the circulation to migrate and differentiate into mature endothelial cells contributing to post-natal physiological and pathological neovascularization. In this study, we evaluated circulating EPCs in patients with hypertrophic cardiomyopathy (HCM) and examined a potential association with clinical parameters of the disease. Methods and results We included 40 HCM patients and 23 healthy individuals. Using flow cytometry we measured EPCs in peripheral blood as two subpopulations of CD45–/CD34+/VEGFR2+ and CD45–/CD34+/CD133+ cells. Circulating CD45–/CD34+/VEGFR2+ cells were significantly increased in HCM patients in comparison with the controls (0.000238 ± 0.0003136 vs. 0.000057 ± 0.0001316, respectively, P = 0.002). However, there was no significant difference in the number of circulating CD45–/CD34+/CD133+ cells (0.003079 ± 0.0033288 vs. 0.002065 ± 0.0022173, respectively, P = 0.153). The CD45–/CD34+/VEGFR2+ subpopulation revealed a moderate correlation with LV mass index (r = 0.35, P = 0.026), while both EPC subpopulation levels showed strong positive correlations with th E/e' ratio (r = 0.423, P = 0.007 for CD45–/CD34+/VEGFR2+ and r = 0.572, P
- Published
- 2015
49. Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species
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Anne Beauvais, Charalampos Pontikoglou, Maria Tzardi, Georgios Chamilos, Petros Ioannou, Angeliki M. Andrianaki, Amol C. Shetty, Irene Kyrmizi, Kalliopi Thanopoulou, Sameh S. M. Soliman, Ashraf S. Ibrahim, Evangelos Andreakos, Emilien Ettiene, Elias Drakos, Helen A. Papadaki, George Samonis, Carrie McCracken, Kostas Stylianou, Tonia Akoumianaki, Vincent M. Bruno, Clara Baldin, Valérie Belle, Dimitrios P. Kontoyiannis, University of Crete [Heraklion] (UOC), National Hellenic Research Foundation [Athens], Academy of Athens, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, American University of Sharjah, University of Maryland School of Medicine, University of Maryland System, Bioénergétique et Ingénierie des Protéines (BIP ), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Aspergillus, Institut Pasteur [Paris], Department of Medicine, University Hospital of Heraklion, University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), University of California, Hellenic General Secretariat for Research and Technology-Excellence program (ARISTEIA), Institute Merieux, University of California (UC)-University of California (UC), Institut Pasteur [Paris] (IP), and University of California (UC)
- Subjects
Spores ,Fungal infection ,0301 basic medicine ,[SDV]Life Sciences [q-bio] ,General Physics and Astronomy ,Inbred C57BL ,Mice ,Cell Wall ,Models ,Phagosomes ,2.1 Biological and endogenous factors ,2.2 Factors relating to the physical environment ,Aetiology ,lcsh:Science ,Lung ,[SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology ,Multidisciplinary ,Spores, Fungal ,3. Good health ,Fungal ,Infectious Diseases ,Host-Pathogen Interactions ,Fungal pathogenesis ,Infection ,Rhizopus ,Intracellular ,Iron ,Science ,Phagocytosis ,Biology ,Alveolar ,Models, Biological ,Article ,General Biochemistry, Genetics and Molecular Biology ,Iron assimilation ,Microbiology ,03 medical and health sciences ,Immune system ,Immunity ,Macrophages, Alveolar ,Phagosome maturation ,medicine ,Animals ,Mucormycosis ,Author Correction ,Melanins ,Microbial Viability ,Macrophages ,Inflammatory and immune system ,General Chemistry ,Biological ,biology.organism_classification ,medicine.disease ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Fungal host response ,Mice, Inbred C57BL ,Emerging Infectious Diseases ,030104 developmental biology ,Gene Expression Regulation ,lcsh:Q - Abstract
Mucormycosis is a life-threatening respiratory fungal infection predominantly caused by Rhizopus species. Mucormycosis has incompletely understood pathogenesis, particularly how abnormalities in iron metabolism compromise immune responses. Here we show how, as opposed to other filamentous fungi, Rhizopus spp. establish intracellular persistence inside alveolar macrophages (AMs). Mechanistically, lack of intracellular swelling of Rhizopus conidia results in surface retention of melanin, which induces phagosome maturation arrest through inhibition of LC3-associated phagocytosis. Intracellular inhibition of Rhizopus is an important effector mechanism, as infection of immunocompetent mice with swollen conidia, which evade phagocytosis, results in acute lethality. Concordantly, AM depletion markedly increases susceptibility to mucormycosis. Host and pathogen transcriptomics, iron supplementation studies, and genetic manipulation of iron assimilation of fungal pathways demonstrate that iron restriction inside macrophages regulates immunity against Rhizopus. Our findings shed light on the pathogenetic mechanisms of mucormycosis and reveal the role of macrophage-mediated nutritional immunity against filamentous fungi., Mucormycosis is a life-threatening respiratory fungal infection that typically occurs in patients with abnormalities in iron metabolism. Here the authors show that iron restriction inside the phagosome of macrophages is an essential component of the host defense against Rhizopus, the main species causing mucormycosis.
- Published
- 2018
50. Prognostic Significance of Bone Marrow Cellularity in the Outcome of Patients with Myelodysplastic Syndromes Treated with Azacyitidine: A Retrospective Analysis from the Hellenic MDS Study Group
- Author
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Vassiliki Pappa, Alexandra Kourakli, Achilles Anagnostopoulos, Theodoros P. Vassilakopoulos, George Vassilopoulos, Charalampos Pontikoglou, Aikaterini Megalakaki, Panagiotis T. Diamantopoulos, Ioannis Kotsianidis, Panagiotis Zikos, Aikaterini Palla, Argiris Symeonidis, Anna Vardi, Elena E. Solomou, Athina Vyniou, Eleni Variami, Helen A. Papadaki, and Athanasios Galanopoulos
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Oncology ,medicine.medical_specialty ,business.industry ,Myelodysplastic syndromes ,education ,Immunology ,Azacitidine ,Decitabine ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Bone marrow cellularity ,medicine.anatomical_structure ,Platelet transfusion ,Internal medicine ,Oxymetholone ,medicine ,Bone marrow ,business ,health care economics and organizations ,Survival analysis ,medicine.drug - Abstract
Introduction: Clinical trials in patients with high risk myelodysplastic syndromes (MDS) have shown that these patients benefit from the available hypomethylating agents 5-azacytidine and decitabine. The majority of these patients display hypercellular bone marrow, but a small proportion despite the excess of blasts, exhibit marrow hypocellularity ( Patients & Methods: This is a retrospective multicenter study from the Hellenic National MDS Registry (EAKMYS) on behalf of the Hellenic MDS Study Group. Between 1.1.2009 and 31.12.2018 a total of 1161 MDS patients who have received treatment with azacytidine have been registered. Complete patient information and follow-up were available for 989 patients, and all these have been included in the final analysis. Statistical analysis was performed and overall survival (OS) was evaluated, using Kaplan-Meier estimates (GraphPad Prism software, CA). A p value less than 0.05 was considered statistically significant. Results: Forty nine patients had a hypocellular bone marrow (hMDS), representing the 4.95% of the whole patient population. Of these patients 39 were men (5.3% of all men included in the study) and 10 were women representing the 2.98% of all women enrolled (male to female ratio 3.9). In the non-hypoplastic group, 750 were men and 358 were women (male to female ratio 2.09). The median age at diagnosis for the hMDS group was 70.8 years, compared to 72.8 years in the non-hypoplastic group. The IPSS-R prognostic risk categorization included 15 hMDS patients in the low group, 9 in the intermediate, 14 in the high and 11 in the very high risk group. Twenty-six patients (53%) of the hMDS group had bone marrow blasts between 10 and 20%, and the remaining 23 (47%) had 5-10% blasts. The patients with hMDS received an average of 10 cycles of azacytidine treatment during the follow-up period (range 2-29 cycles). The outcomes tested were overall survival and progression to AML. The median overall survival of patients with hMDS, following azacytidine treatment start, was not significantly different from the median survival of patients with non-hypoplastic MDS [20 months versus 16 months in the non-hypoplastic group (95% CI of ratio: 0.839 to 1.863). The survival curves were not significantly different between the hMDS and non-hypoplastic MDS group (p=0.32, Figure 1). Progression to AML was also evaluated. Eleven (22.4 %) hMDS patients showed disease progression to AML. Patients with hMDS had significantly prolonged estimated median time to AML transformation, compared to the non-hypoplastic MDS population (31.7 versus 22 months respectively, p Discussion and Conclusive remarks: In this retrospective study, in which a large number of MDS patients was analyzed, we showed that bone marrow cellularity does not affect the outcome in patients treated with azacyitidine. Patients with hMDS show statistically significant slower AML progression compared to non-hypoplastic MDS. Bone marrow cellularity should not be a contraindication for using hypomethylating agents as a therapeutic option, and this type of treatment can be used safely, when indicated, also in patients with hMDS. Disclosures Pappa: Amgen: Research Funding; Gilead: Honoraria, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene / GenesisPharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Vassilakopoulos:Merck: Honoraria; Takeda Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genesis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Honoraria; Winmedica: Honoraria; Servier: Membership on an entity's Board of Directors or advisory committees. Symeonidis:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Membership on an entity's Board of Directors or advisory committees, Research Funding; Tekeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding.
- Published
- 2019
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