Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

Article Types

Countries / Regions

Search Results (14)

Search Parameters:
Keywords = givinostat

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
18 pages, 690 KB  
Review
Old Therapy, New Questions: Rethinking Phlebotomy in a Pharmacologic Landscape
by Andrea Duminuco, Patrick Harrington, Vittorio Del Fabro, Elvira Scalisi, Gabriella Santuccio, Annalisa Santisi, Arianna Sbriglione, Bruno Garibaldi, Uros Markovic, Francesco Di Raimondo, Giuseppe Alberto Palumbo, Novella Pugliese and Calogero Vetro
Pharmaceuticals 2025, 18(8), 1212; https://doi.org/10.3390/ph18081212 - 16 Aug 2025
Viewed by 1541
Abstract
Therapeutic phlebotomy remains a key intervention in the management of erythrocytosis and iron overload disorders, particularly polycythemia vera (PV) and hereditary hemochromatosis. Despite its historical origins as an ancient practice, venesection continues to be recommended in international guidelines for the reduction of hematocrit [...] Read more.
Therapeutic phlebotomy remains a key intervention in the management of erythrocytosis and iron overload disorders, particularly polycythemia vera (PV) and hereditary hemochromatosis. Despite its historical origins as an ancient practice, venesection continues to be recommended in international guidelines for the reduction of hematocrit and iron burden, thereby mitigating thrombotic and organ-related complications. However, the evolving landscape of targeted pharmacologic therapies is reshaping the therapeutic paradigm. This review examines the current role of therapeutic phlebotomy, with a particular focus on PV, outlining its physiological rationale, clinical benefits, and well-documented limitations—including iron deficiency, procedural burden, and incomplete hematocrit control between sessions. Comparative insights are provided between phlebotomy and red cell apheresis, highlighting differences in efficacy, tolerability, and accessibility. The emergence of disease-modifying agents—such as interferons, JAK inhibitors, hepcidin mimetics, and epigenetic modulators like givinostat and bomedemstat—promises more sustained hematologic control with the potential to reduce or eliminate the need for repeated phlebotomies. While phlebotomy remains indispensable in early-stage or low-risk PV, its future utility will likely shift toward complementary or bridge therapy in the context of individualized, pharmacologically driven strategies, redefining the role of phlebotomy in the era of precision medicine. Full article
(This article belongs to the Section Pharmacology)
Show Figures

Graphical abstract

14 pages, 1711 KB  
Systematic Review
Histone Deacetylase Inhibitors as a Promising Treatment Against Myocardial Infarction: A Systematic Review
by Eduardo Sanchez-Fernandez, Sol Guerra-Ojeda, Andrea Suarez, Eva Serna and Maria D. Mauricio
J. Clin. Med. 2024, 13(24), 7797; https://doi.org/10.3390/jcm13247797 - 20 Dec 2024
Cited by 3 | Viewed by 2065
Abstract
Background/Objectives: Acute myocardial infarction (AMI) is a critical medical condition that requires immediate attention to minimise heart damage and improve survival rates. Early identification and prompt treatment are essential to save the patient’s life. Currently, the treatment strategy focuses on restoring blood flow [...] Read more.
Background/Objectives: Acute myocardial infarction (AMI) is a critical medical condition that requires immediate attention to minimise heart damage and improve survival rates. Early identification and prompt treatment are essential to save the patient’s life. Currently, the treatment strategy focuses on restoring blood flow to the myocardium as quickly as possible. However, reperfusion activates several cellular cascades that contribute to organ dysfunction, resulting in the ischaemia/reperfusion (I/R) injury. The search for treatments against AMI and I/R injury is urgent due to the shortage of effective treatments at present. In this regard, histone deacetylase (HDAC) inhibitors emerge as a promising treatment against myocardial infarction. The objective of this systematic review is to analyse the effects of HDAC inhibitors on ventricular function, cardiac remodelling and infarct size, among other parameters, focusing on the signalling pathways that may mediate these cardiovascular effects and protect against AMI. Methods: Original experimental studies examining the effects of HDAC inhibitors on AMI were included in the review using the PubMed and Scopus databases. Non-experimental papers were excluded. The SYRCLE RoB tool was used to assess risk of bias and the results were summarised in a table and presented in sections according to the type of HDAC inhibitor used. Results: A total of 18 studies were included, 10 of them using trichostatin A (TSA) as an HDAC inhibitor and concluding that the treatment improved ventricular function, reduced infarct size, and inhibited myocardial hypertrophy and remodelling after AMI. Other HDAC inhibitors, such as suberoylanilide hydroxamic acid (SAHA), valproic acid (VPA), mocetinostat, givinostat, entinostat, apicidin, and RGFP966, were also analysed, showing antioxidant and anti-inflammatory effects, an improvement in cardiac function and remodelling, and a decrease in apoptosis, among other effects. Conclusions: HDAC inhibitors constitute a significant promise for the treatment of AMI due to their diverse cardioprotective effects. However, high risk of selection, performance, and detection bias in the in vivo studies means that their application in the clinical setting is still a long way off and more research is needed to better understand their benefits and possible side effects. Full article
(This article belongs to the Section Cardiovascular Medicine)
Show Figures

Graphical abstract

16 pages, 1111 KB  
Perspective
Histone Deacetylase (HDAC) Inhibitors as a Novel Therapeutic Option Against Fibrotic and Inflammatory Diseases
by Maria A. Theodoropoulou, Christiana Mantzourani and George Kokotos
Biomolecules 2024, 14(12), 1605; https://doi.org/10.3390/biom14121605 - 15 Dec 2024
Cited by 4 | Viewed by 2894
Abstract
Histone deacetylases (HDACs) are enzymes that play an essential role in the onset and progression of cancer. As a consequence, a variety of HDAC inhibitors (HDACis) have been developed as potent anticancer agents, several of which have been approved by the FDA for [...] Read more.
Histone deacetylases (HDACs) are enzymes that play an essential role in the onset and progression of cancer. As a consequence, a variety of HDAC inhibitors (HDACis) have been developed as potent anticancer agents, several of which have been approved by the FDA for cancer treatment. However, recent accumulated research results have suggested that HDACs are also involved in several other pathophysiological conditions, such as fibrotic, inflammatory, neurodegenerative, and autoimmune diseases. Very recently, the HDAC inhibitor givinostat has been approved by the FDA for an indication beyond cancer: the treatment of Duchenne muscular dystrophy. In recent years, more and more HDACis have been developed as tools to understand the role that HDACs play in various disorders and as a novel therapeutic approach to fight various diseases other than cancer. In the present perspective article, we discuss the development and study of HDACis as anti-fibrotic and anti-inflammatory agents, covering the period from 2020–2024. We envision that the discovery of selective inhibitors targeting specific HDAC isozymes will allow the elucidation of the role of HDACs in various pathological processes and will lead to the development of promising treatments for such diseases. Full article
(This article belongs to the Section Molecular Medicine)
Show Figures

Figure 1

17 pages, 3697 KB  
Article
Chemokine/ITGA4 Interaction Directs iPSC-Derived Myogenic Progenitor Migration to Injury Sites in Aging Muscle for Regeneration
by Muhammad Ashraf, Srinivas M. Tipparaju, Joung Woul Kim and Wanling Xuan
Cells 2023, 12(14), 1837; https://doi.org/10.3390/cells12141837 - 12 Jul 2023
Cited by 2 | Viewed by 2515
Abstract
The failure of muscle to repair after injury during aging may be a major contributor to muscle mass loss. We recently generated muscle progenitor cells (MPCs) from human-induced pluripotent stem-cell (iPSC) cell lines using small molecules, CHIR99021 and Givinostat (Givi-MPCs) sequentially. Here, we [...] Read more.
The failure of muscle to repair after injury during aging may be a major contributor to muscle mass loss. We recently generated muscle progenitor cells (MPCs) from human-induced pluripotent stem-cell (iPSC) cell lines using small molecules, CHIR99021 and Givinostat (Givi-MPCs) sequentially. Here, we test whether the chemokines overexpressed in injured endothelial cells direct MPC migration to the site by binding to their receptor, ITGA4. ITGA4 was heavily expressed in Givi-MPCs. To study the effects on the mobilization of Givi-MPCs, ITGA4 was knocked down by an ITGA4 shRNA lentiviral vector. With and without ITGA4 knocked down, cell migration in vitro and cell mobilization in vivo using aged NOD scid gamma (NSG) mice and mdx/scid mice were analyzed. The migration of shITGA4-Givi-MPCs was significantly impaired, as shown in a wound-healing assay. The knockdown of ITGA4 impaired the migration of Givi-MPCs towards human aortic endothelial cells (HAECs), in which CX3CL1 and VCAM-1 were up-regulated by the treatment of TNF-α compared with scramble ones using a transwell system. MPCs expressing ITGA4 sensed chemokines secreted by endothelial cells at the injury site as a chemoattracting signal to migrate to the injured muscle. The mobilization of Givi-MPCs was mediated by the ligand–receptor interaction, which facilitated their engraftment for repairing the sarcopenic muscle with injury. Full article
Show Figures

Figure 1

16 pages, 6712 KB  
Article
Oncogenic BRAF and p53 Interplay in Melanoma Cells and the Effects of the HDAC Inhibitor ITF2357 (Givinostat)
by Adriana Celesia, Marzia Franzò, Diana Di Liberto, Marianna Lauricella, Daniela Carlisi, Antonella D’Anneo, Antonietta Notaro, Mario Allegra, Michela Giuliano and Sonia Emanuele
Int. J. Mol. Sci. 2023, 24(11), 9148; https://doi.org/10.3390/ijms24119148 - 23 May 2023
Cited by 10 | Viewed by 2556
Abstract
Oncogenic BRAF mutations have been widely described in melanomas and promote tumour progression and chemoresistance. We previously provided evidence that the HDAC inhibitor ITF2357 (Givinostat) targets oncogenic BRAF in SK-MEL-28 and A375 melanoma cells. Here, we show that oncogenic BRAF localises to the [...] Read more.
Oncogenic BRAF mutations have been widely described in melanomas and promote tumour progression and chemoresistance. We previously provided evidence that the HDAC inhibitor ITF2357 (Givinostat) targets oncogenic BRAF in SK-MEL-28 and A375 melanoma cells. Here, we show that oncogenic BRAF localises to the nucleus of these cells, and the compound decreases BRAF levels in both the nuclear and cytosolic compartments. Although mutations in the tumour suppressor p53 gene are not equally frequent in melanomas compared to BRAF, the functional impairment of the p53 pathway may also contribute to melanoma development and aggressiveness. To understand whether oncogenic BRAF and p53 may cooperate, a possible interplay was considered in the two cell lines displaying a different p53 status, being p53 mutated into an oncogenic form in SK-MEL-28 and wild-type in A375 cells. Immunoprecipitation revealed that BRAF seems to preferentially interact with oncogenic p53. Interestingly, ITF2357 not only reduced BRAF levels but also oncogenic p53 levels in SK-MEL-28 cells. ITF2357 also targeted BRAF in A375 cells but not wild-type p53, which increased, most likely favouring apoptosis. Silencing experiments confirmed that the response to ITF2357 in BRAF-mutated cells depends on p53 status, thus providing a rationale for melanoma-targeted therapy. Full article
(This article belongs to the Special Issue Dual Function Molecules and Processes in Cell Fate Decision 2.0)
Show Figures

Figure 1

29 pages, 2073 KB  
Review
Histone Deacetylases: Molecular Mechanisms and Therapeutic Implications for Muscular Dystrophies
by Martina Sandonà, Giorgia Cavioli, Alessandra Renzini, Alessia Cedola, Giuseppe Gigli, Dario Coletti, Timothy A. McKinsey, Viviana Moresi and Valentina Saccone
Int. J. Mol. Sci. 2023, 24(5), 4306; https://doi.org/10.3390/ijms24054306 - 21 Feb 2023
Cited by 40 | Viewed by 7349
Abstract
Histone deacetylases (HDACs) are enzymes that regulate the deacetylation of numerous histone and non-histone proteins, thereby affecting a wide range of cellular processes. Deregulation of HDAC expression or activity is often associated with several pathologies, suggesting potential for targeting these enzymes for therapeutic [...] Read more.
Histone deacetylases (HDACs) are enzymes that regulate the deacetylation of numerous histone and non-histone proteins, thereby affecting a wide range of cellular processes. Deregulation of HDAC expression or activity is often associated with several pathologies, suggesting potential for targeting these enzymes for therapeutic purposes. For example, HDAC expression and activity are higher in dystrophic skeletal muscles. General pharmacological blockade of HDACs, by means of pan-HDAC inhibitors (HDACi), ameliorates both muscle histological abnormalities and function in preclinical studies. A phase II clinical trial of the pan-HDACi givinostat revealed partial histological improvement and functional recovery of Duchenne Muscular Dystrophy (DMD) muscles; results of an ongoing phase III clinical trial that is assessing the long-term safety and efficacy of givinostat in DMD patients are pending. Here we review the current knowledge about the HDAC functions in distinct cell types in skeletal muscle, identified by genetic and -omic approaches. We describe the signaling events that are affected by HDACs and contribute to muscular dystrophy pathogenesis by altering muscle regeneration and/or repair processes. Reviewing recent insights into HDAC cellular functions in dystrophic muscles provides new perspectives for the development of more effective therapeutic approaches based on drugs that target these critical enzymes. Full article
(This article belongs to the Special Issue Molecular Advances of Muscular Dystrophy)
Show Figures

Figure 1

17 pages, 3284 KB  
Article
The Histone Deacetylase Inhibitor ITF2357 (Givinostat) Targets Oncogenic BRAF in Melanoma Cells and Promotes a Switch from Pro-Survival Autophagy to Apoptosis
by Adriana Celesia, Antonietta Notaro, Marzia Franzò, Marianna Lauricella, Antonella D’Anneo, Daniela Carlisi, Michela Giuliano and Sonia Emanuele
Biomedicines 2022, 10(8), 1994; https://doi.org/10.3390/biomedicines10081994 - 17 Aug 2022
Cited by 7 | Viewed by 2487
Abstract
Histone deacetylase inhibitors (HDACI) are epigenetic compounds that have been widely considered very promising antitumor agents. Here, we focus on the effects of the pan-HDAC inhibitor ITF2357 (Givinostat) in comparison with SAHA (Vorinostat) in melanoma cells bearing BRAF V600E oncogenic mutation. Our results [...] Read more.
Histone deacetylase inhibitors (HDACI) are epigenetic compounds that have been widely considered very promising antitumor agents. Here, we focus on the effects of the pan-HDAC inhibitor ITF2357 (Givinostat) in comparison with SAHA (Vorinostat) in melanoma cells bearing BRAF V600E oncogenic mutation. Our results indicate both ITF2357 and SAHA dose-dependently reduce the viability of BRAF-mutated SK-MEL-28 and A375 melanoma cells. The comparison of IC50 values revealed that ITF2357 was much more effective than SAHA. Interestingly, both inhibitors markedly decreased oncogenic BRAF protein expression levels, ITF2357 being the most effective compound. Moreover, the BRAF decrease induced by ITF2357 was accompanied by a decrease in the level of phospho-ERK1/2. The inhibitor of upstream MEK activity, U0126, reduced ERK1/2 phosphorylation and dramatically potentiated the antitumor effect of ITF2357, exacerbating the reduction in the BRAF level. ITF2357 stimulated an early pro-survival autophagic response, which was followed by apoptosis, as indicated by apoptotic markers evaluation and the protective effects exerted by the pan-caspase inhibitor z-VADfmk. Overall, our data indicate for the first time that ITF2357 targets oncogenic BRAF in melanoma cells and induces a switch from autophagy to classic apoptosis, thus representing a possible candidate in melanoma targeted therapy. Full article
(This article belongs to the Special Issue Epigenetics in Cancer and the Therapeutic Potential of Epi-Drugs)
Show Figures

Figure 1

22 pages, 2540 KB  
Article
Histone Deacetylase Inhibitors Restore Cancer Cell Sensitivity towards T Lymphocytes Mediated Cytotoxicity in Pancreatic Cancer
by Chin-King Looi, Li-Lian Gan, Wynne Sim, Ling-Wei Hii, Felicia Fei-Lei Chung, Chee-Onn Leong, Wei-Meng Lim and Chun-Wai Mai
Cancers 2022, 14(15), 3709; https://doi.org/10.3390/cancers14153709 - 29 Jul 2022
Cited by 8 | Viewed by 4434
Abstract
Despite medical advancements, the prognosis of pancreatic ductal adenocarcinoma (PDAC) has not improved significantly over the past 50 years. By utilising the large-scale genomic datasets available from the Australia Pancreatic Cancer Project (PACA-AU) and The Cancer Genomic Atlas Project (TCGA-PAAD), we studied the [...] Read more.
Despite medical advancements, the prognosis of pancreatic ductal adenocarcinoma (PDAC) has not improved significantly over the past 50 years. By utilising the large-scale genomic datasets available from the Australia Pancreatic Cancer Project (PACA-AU) and The Cancer Genomic Atlas Project (TCGA-PAAD), we studied the immunophenotype of PDAC in silico and identified that tumours with high cytotoxic T lymphocytes (CTL) killing activity were associated with favourable clinical outcomes. Using the STRING protein–protein interaction network analysis, the identified differentially expressed genes with low CTL killing activity were associated with TWIST/IL-6R, HDAC5, and EOMES signalling. Following Connectivity Map analysis, we identified 44 small molecules that could restore CTL sensitivity in the PDAC cells. Further high-throughput chemical library screening identified 133 inhibitors that effectively target both parental and CTL-resistant PDAC cells in vitro. Since CTL-resistant PDAC had a higher expression of histone proteins and its acetylated proteins compared to its parental cells, we further investigated the impact of histone deacetylase inhibitors (HDACi) on CTL-mediated cytotoxicity in PDAC cells in vitro, namely SW1990 and BxPC3. Further analyses revealed that givinostat and dacinostat were the two most potent HDAC inhibitors that restored CTL sensitivity in SW1990 and BxPC3 CTL-resistant cells. Through our in silico and in vitro studies, we demonstrate the novel role of HDAC inhibition in restoring CTL resistance and that combinations of HDACi with CTL may represent a promising therapeutic strategy, warranting its further detailed molecular mechanistic studies and animal studies before embarking on the clinical evaluation of these novel combined PDAC treatments. Full article
Show Figures

Graphical abstract

23 pages, 5802 KB  
Article
Analysis of Givinostat/ITF2357 Treatment in a Rat Model of Neonatal Hypoxic-Ischemic Brain Damage
by Paulina Pawelec, Joanna Sypecka, Teresa Zalewska and Malgorzata Ziemka-Nalecz
Int. J. Mol. Sci. 2022, 23(15), 8287; https://doi.org/10.3390/ijms23158287 - 27 Jul 2022
Cited by 3 | Viewed by 3002
Abstract
The histone deacetylase inhibitor (HDACi) Givinostat/ITF2357 provides neuroprotection in adult models of brain injury; however, its action after neonatal hypoxia-ischemia (HI) is still undefined. The aim of our study was to test the hypothesis that the mechanism of Givinostat is associated with the [...] Read more.
The histone deacetylase inhibitor (HDACi) Givinostat/ITF2357 provides neuroprotection in adult models of brain injury; however, its action after neonatal hypoxia-ischemia (HI) is still undefined. The aim of our study was to test the hypothesis that the mechanism of Givinostat is associated with the alleviation of inflammation. For this purpose, we analyzed the microglial response and the effect on molecular mediators (chemokines/cytokines) that are crucial for inducing cerebral damage after neonatal hypoxia-ischemia. Seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by 60 min of hypoxia (7.6% O2). Givinostat (10 mg/kg b/w) was administered in a 5-day regimen. The effects of Givinostat on HI-induced inflammation (cytokine, chemokine and microglial activation and polarization) were assessed with a Luminex assay, immunohistochemistry and Western blot. Givinostat treatment did not modulate the microglial response specific for HI injury. After Givinostat administration, the investigated chemokines and cytokines remained at the level induced by HI. The only immunosuppressive effect of Givinostat may be associated with the decrease in MIP-1α. Neonatal hypoxia-ischemia produces an inflammatory response by activating the proinflammatory M1 phenotype of microglia, disrupting the microglia–neuron (CX3CL1/CX3CR1) axis and elevating numerous proinflammatory cytokines/chemokines. Givinostat/ITF2357 did not prevent an inflammatory reaction after HI. Full article
Show Figures

Figure 1

20 pages, 3486 KB  
Article
Givinostat-Liposomes: Anti-Tumor Effect on 2D and 3D Glioblastoma Models and Pharmacokinetics
by Lorenzo Taiarol, Chiara Bigogno, Silvia Sesana, Marcelo Kravicz, Francesca Viale, Eleonora Pozzi, Laura Monza, Valentina Alda Carozzi, Cristina Meregalli, Silvia Valtorta, Rosa Maria Moresco, Marcus Koch, Federica Barbugian, Laura Russo, Giulio Dondio, Christian Steinkühler and Francesca Re
Cancers 2022, 14(12), 2978; https://doi.org/10.3390/cancers14122978 - 16 Jun 2022
Cited by 19 | Viewed by 3710
Abstract
Glioblastoma is the most common and aggressive brain tumor, associated with poor prognosis and survival, representing a challenging medical issue for neurooncologists. Dysregulation of histone-modifying enzymes (HDACs) is commonly identified in many tumors and has been linked to cancer proliferation, changes in metabolism, [...] Read more.
Glioblastoma is the most common and aggressive brain tumor, associated with poor prognosis and survival, representing a challenging medical issue for neurooncologists. Dysregulation of histone-modifying enzymes (HDACs) is commonly identified in many tumors and has been linked to cancer proliferation, changes in metabolism, and drug resistance. These findings led to the development of HDAC inhibitors, which are limited by their narrow therapeutic index. In this work, we provide the proof of concept for a delivery system that can improve the in vivo half-life and increase the brain delivery of Givinostat, a pan-HDAC inhibitor. Here, 150-nm-sized liposomes composed of cholesterol and sphingomyelin with or without surface decoration with mApoE peptide, inhibited human glioblastoma cell growth in 2D and 3D models by inducing a time- and dose-dependent reduction in cell viability, reduction in the receptors involved in cholesterol metabolism (from −25% to −75% of protein levels), and reduction in HDAC activity (−25% within 30 min). In addition, liposome-Givinostat formulations showed a 2.5-fold increase in the drug half-life in the bloodstream and a 6-fold increase in the amount of drug entering the brain in healthy mice, without any signs of overt toxicity. These features make liposomes loaded with Givinostat valuable as potential candidates for glioblastoma therapy. Full article
Show Figures

Figure 1

9 pages, 1753 KB  
Article
Detection of Pathogenic Isoforms of IKZF1 in Leukemic Cell Lines and Acute Lymphoblastic Leukemia Samples: Identification of a Novel Truncated IKZF1 Transcript in SUP-B15
by Weiqiang Zhao, Ying Li, Chenjiao Yao, Guojuan Zhang, Kevin Y. Zhao, Wei Chen, Peng Ru, Xiaokang Pan, Huolin Tu and Daniel Jones
Cancers 2020, 12(11), 3161; https://doi.org/10.3390/cancers12113161 - 28 Oct 2020
Cited by 2 | Viewed by 3192
Abstract
Leukemia-associated alternative splicing of IKZF1 can result in proteins with loss of one to four copies of its N-terminal zinc finger domains (N-ZnF). The best characterized pathogenic splice isoforms, Ik-6 and Ik-8, have been commonly found in BCR-ABL1+ acute lymphoblastic leukemia (ALL) and [...] Read more.
Leukemia-associated alternative splicing of IKZF1 can result in proteins with loss of one to four copies of its N-terminal zinc finger domains (N-ZnF). The best characterized pathogenic splice isoforms, Ik-6 and Ik-8, have been commonly found in BCR-ABL1+ acute lymphoblastic leukemia (ALL) and a subset of BCR-ABL1-like ALL. Infantile and childhood ALL that express these pathogenic IKZF1 isoforms have shown inferior clinical outcomes and can be resistant to tyrosine kinase inhibitors. Using ALL cell lines, we designed and validated a method to detect abnormal IKZF1 transcripts. In the SUP-B15 leukemia cell line, we noted novel IKZF1 transcripts that include both an Ik-6 splice and a transcript with a 14 base pair insertion at the C-terminus. There was also increased IKZF2 protein in SUP-B15 as compared to other ALL lines. Expression of Ik-6 could be suppressed by treatment with the pro-apoptotic type II histone deacetylase inhibitor givinostat. In 17 adult ALL samples, we noted the Ik-6 isoforms in 6 of 15 BCR-ABL1, and 1 of 2 BCR-ABL1+ cases, with Ik-8 also expressed in one case. Cases with Ik-6 expression showed inferior survival as well as older age at presentation, lower expression of CD10 and more commonly a diploid karyotype. Full article
Show Figures

Figure 1

16 pages, 268 KB  
Review
New Perspectives on Polycythemia Vera: From Diagnosis to Therapy
by Alessandra Iurlo, Daniele Cattaneo, Cristina Bucelli and Luca Baldini
Int. J. Mol. Sci. 2020, 21(16), 5805; https://doi.org/10.3390/ijms21165805 - 13 Aug 2020
Cited by 40 | Viewed by 10879
Abstract
Polycythemia vera (PV) is mainly characterized by elevated blood cell counts, thrombotic as well as hemorrhagic predisposition, a variety of symptoms, and cumulative risks of fibrotic progression and/or leukemic evolution over time. Major changes to its diagnostic criteria were made in the 2016 [...] Read more.
Polycythemia vera (PV) is mainly characterized by elevated blood cell counts, thrombotic as well as hemorrhagic predisposition, a variety of symptoms, and cumulative risks of fibrotic progression and/or leukemic evolution over time. Major changes to its diagnostic criteria were made in the 2016 revision of the World Health Organization (WHO) classification, with both hemoglobin and hematocrit diagnostic thresholds lowered to 16.5 g/dL and 49% for men, and 16 g/dL and 48% for women, respectively. The main reason leading to these changes was represented by the recognition of a new entity, namely the so-called “masked PV”, as individuals suffering from this condition have a worse outcome, possibly owing to missed or delayed diagnoses and lower intensity of treatment. Thrombotic risk stratification is of crucial importance to evaluate patients’ prognosis at diagnosis. Currently, patients are stratified into a low-risk group, in the case of younger age (<60 years) and no previous thromboses, and a high-risk group, in the case of patients older than 60 years and/or with a previous thrombotic complication. Furthermore, even though they have not yet been formally included in a scoring system, generic cardiovascular risk factors, particularly hypertension, smoking, and leukocytosis, contribute to the thrombotic overall risk. In the absence of agents proven to modify its natural history and prevent progression, PV management has primarily been focused on minimizing the thrombotic risk, representing the main cause of morbidity and mortality. When cytoreduction is necessary, conventional therapies include hydroxyurea as a first-line treatment and ruxolitinib and interferon in resistant/intolerant cases. Each therapy, however, is burdened by specific drawbacks, underlying the need for improved strategies. Currently, the therapeutic landscape for PV is still expanding, and includes several molecules that are under investigation, like long-acting pegylated interferon alpha-2b, histone deacetylase inhibitors, and murine double minute 2 (MDM2) inhibitors. Full article
(This article belongs to the Special Issue BCR-ABL1 Negative Myeloproliferative Neoplasms)
17 pages, 6154 KB  
Article
Development of Artificial Plasma Membranes Derived Nanovesicles Suitable for Drugs Encapsulation
by Carolina Martinelli, Fabio Gabriele, Elena Dini, Francesca Carriero, Giorgia Bresciani, Bianca Slivinschi, Marco Dei Giudici, Lisa Zanoletti, Federico Manai, Mayra Paolillo, Sergio Schinelli, Alberto Azzalin and Sergio Comincini
Cells 2020, 9(7), 1626; https://doi.org/10.3390/cells9071626 - 6 Jul 2020
Cited by 20 | Viewed by 4746
Abstract
Extracellular vesicles (EVs) are considered as promising nanoparticle theranostic tools in many pathological contexts. The increasing clinical employment of therapeutic nanoparticles is contributing to the development of a new research area related to the design of artificial EVs. To this aim, different approaches [...] Read more.
Extracellular vesicles (EVs) are considered as promising nanoparticle theranostic tools in many pathological contexts. The increasing clinical employment of therapeutic nanoparticles is contributing to the development of a new research area related to the design of artificial EVs. To this aim, different approaches have been described to develop mimetic biologically functional nanovescicles. In this paper, we suggest a simplified procedure to generate plasma membrane-derived nanovesicles with the possibility to efficiently encapsulate different drugs during their spontaneously assembly. After physical and molecular characterization by Tunable Resistive Pulse Sensing (TRPS) technology, transmission electron microscopy, and flow cytometry, as a proof of principle, we have loaded into mimetic EVs the isoquinoline alkaloid Berberine chloride and the chemotherapy compounds Temozolomide or Givinostat. We demonstrated the fully functionality of these nanoparticles in drug encapsulation and cell delivery, showing, in particular, a similar cytotoxic effect of direct cell culture administration of the anticancer drugs. In conclusion, we have documented the possibility to easily generate scalable nanovesicles with specific therapeutic cargo modifications useful in different drug delivery contexts. Full article
Show Figures

Graphical abstract

23 pages, 8765 KB  
Article
Identification of Combinations of Protein Kinase C Activators and Histone Deacetylase Inhibitors that Potently Reactivate Latent HIV
by Francesca Curreli, Shahad Ahmed, Sofia M. Benedict Victor and Asim K. Debnath
Viruses 2020, 12(6), 609; https://doi.org/10.3390/v12060609 - 3 Jun 2020
Cited by 12 | Viewed by 3387
Abstract
Combination antiretroviral therapy (cART) is successful in maintaining undetectable levels of HIV in the blood; however, the persistence of latent HIV reservoirs has become the major barrier for a HIV cure. Substantial efforts are underway in finding the best latency-reversing agents (LRAs) to [...] Read more.
Combination antiretroviral therapy (cART) is successful in maintaining undetectable levels of HIV in the blood; however, the persistence of latent HIV reservoirs has become the major barrier for a HIV cure. Substantial efforts are underway in finding the best latency-reversing agents (LRAs) to purge the latent viruses from the reservoirs. We hypothesize that identifying the right combination of LRAs will be the key to accomplishing that goal. In this study, we evaluated the effect of combinations of three protein kinase C activators (prostratin, (-)-indolactam V, and TPPB) with four histone deacetylase inhibitors (AR-42, PCI-24781, givinostat, and belinostat) on reversing HIV latency in different cell lines including in a primary CD4+ T-cell model. Combinations including indolactam and TPPB with AR-42 and PCI produced a strong synergistic effect in reactivating latent virus as indicated by higher p24 production and envelope gp120 expression. Furthermore, treatment with TPPB and indolactam greatly downregulated the cellular receptor CD4. Indolactam/AR-42 combination emerged from this study as the best combination that showed a strong synergistic effect in reactivating latent virus. Although AR-42 alone did not downregulate CD4 expression, indolactam/AR-42 showed the most efficient downregulation. Our results suggest that indolactam/AR-42 is the most effective combination, showing a strong synergistic effect in reversing HIV latency combined with the most efficient CD4 downregulation. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
Show Figures

Figure 1

Back to TopTop