32 results on '"Raffaele Sessa"'
Search Results
2. Chemical Profile and Promising Applications of Cucurbita pepo L. Flowers
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Ritamaria Di Lorenzo, Luigi Castaldo, Raffaele Sessa, Lucia Ricci, Eleonora Vardaro, Luana Izzo, Michela Grosso, Alberto Ritieni, and Sonia Laneri
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Cucurbita pepo ,polyphenols ,carotenoids ,photo protection ,sustainability ,Q-Exactive ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Although edible flowers have been historically principally used due to their visual appeal and smell, the world is discovering their value as innovative and natural sources of bioactive compounds. Cucurbita pepo L. (CpL), a plant from the Cucurbitaceae family, is widely cultivated for its edible fruits and flowers, which are rich in polyphenols and carotenoids—compounds known for their potent antioxidant and anti-inflammatory properties. Despite their potential, the use of CpL flowers for skin-related applications remains underexplored. This study aimed to comprehensively analyze CpL flower extract (CpLfe), focusing on its polyphenolic and carotenoid content using, for the first time, advanced UHPLC-Q-Orbitrap HRMS and HPLC-DAD analysis. CpLfe highlighted remarkable antioxidant activity according to the DPPH, ABTS, and FRAP tests. CpLfe showed significantly reduced intracellular ROS in HaCaT (23%, p < 0.05) and protected against UVB-induced damage by lowering MMP-1 expression. CpLfe also upregulated genes crucial for skin hydration (AQP3) and barrier function (CerS2, CerS4, and CerS6). A placebo-controlled, randomized clinical trial further validated CpLfe efficacy, demonstrating marked improvements in moisture retention, wrinkle reduction, and collagen production in women aged 35–55. These findings suggested that CpL flowers could be a source of bioactive compounds recovered from edible flowers able to improve the major skin aging and photoaging features.
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- 2024
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3. miR-1202 acts as anti-oncomiR in myeloid leukaemia by down-modulating GATA-1S expression
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Raffaele Sessa, Silvia Trombetti, Alessandra Lo Bianco, Giovanni Amendola, Rosa Catapano, Elena Cesaro, Fara Petruzziello, Maria D'Armiento, Giuseppe Maria Maruotti, Giuseppe Menna, Paola Izzo, and Michela Grosso
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alternative splicing ,Down syndrome ,GATA-1 ,miR-1202 ,myeloid leukaemia ,Biology (General) ,QH301-705.5 - Abstract
Transient abnormal myelopoiesis (TAM) is a Down syndrome-related pre-leukaemic condition characterized by somatic mutations in the haematopoietic transcription factor GATA-1 that result in exclusive production of its shorter isoform (GATA-1S). Given the common hallmark of altered miRNA expression profiles in haematological malignancies and the pro-leukaemic role of GATA-1S, we aimed to search for miRNAs potentially able to modulate the expression of GATA-1 isoforms. Starting from an in silico prediction of miRNA binding sites in the GATA-1 transcript, miR-1202 came into our sight as potential regulator of GATA-1 expression. Expression studies in K562 cells revealed that miR-1202 directly targets GATA-1, negatively regulates its expression, impairs GATA-1S production, reduces cell proliferation, and increases apoptosis sensitivity. Furthermore, data from TAM and myeloid leukaemia patients provided substantial support to our study by showing that miR-1202 down-modulation is accompanied by increased GATA-1 levels, with more marked effects on GATA-1S. These findings indicate that miR-1202 acts as an anti-oncomiR in myeloid cells and may impact leukaemogenesis at least in part by down-modulating GATA-1S levels.
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- 2024
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4. Identification and Functional Analysis of Known and New Mutations in the Transcription Factor KLF1 Linked with β-Thalassemia-like Phenotypes
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Rosa Catapano, Raffaele Sessa, Silvia Trombetti, Elena Cesaro, Filippo Russo, Paola Izzo, Alexandros Makis, and Michela Grosso
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KLF1 ,thalassemia ,globin gene switching ,gene expression ,HbF ,HbA2 ,Biology (General) ,QH301-705.5 - Abstract
The erythroid transcriptional factor Krüppel-like factor 1 (KLF1) is a master regulator of erythropoiesis. Mutations that cause KLF1 haploinsufficiency have been linked to increased fetal hemoglobin (HbF) and hemoglobin A2 (HbA2) levels with ameliorative effects on the severity of β-thalassemia. With the aim of determining if KLF1 gene variations might play a role in the modulation of β-thalassemia, in this study we screened 17 subjects showing a β-thalassemia-like phenotype with a slight or marked increase in HbA2 and HbF levels. Overall, seven KLF1 gene variants were identified, of which two were novel. Functional studies were performed in K562 cells to clarify the pathogenic significance of these mutations. Our study confirmed the ameliorative effect on the thalassemia phenotype for some of these variants but also raised the notion that certain mutations may have deteriorating effects by increasing KLF1 expression levels or enhancing its transcriptional activity. Our results indicate that functional studies are required to evaluate the possible effects of KLF1 mutations, particularly in the case of the co-existence of two or more mutations that could differently contribute to KLF1 expression or transcriptional activity and consequently to the thalassemia phenotype.
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- 2023
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5. Over-Expressed GATA-1S, the Short Isoform of the Hematopoietic Transcriptional Factor GATA-1, Inhibits Ferroptosis in K562 Myeloid Leukemia Cells by Preventing Lipid Peroxidation
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Silvia Trombetti, Nunzia Iaccarino, Patrizia Riccio, Raffaele Sessa, Rosa Catapano, Marcella Salvatore, Stelina Luka, Sergio de Nicola, Paola Izzo, Sante Roperto, Pasqualino Maddalena, Antonio Randazzo, and Michela Grosso
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ferroptosis ,GATA-1 isoforms ,glutathione peroxidase 4 ,myeloid leukemia ,cell death ,lipid peroxidation ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Ferroptosis is a recently recognized form of regulated cell death involving lipid peroxidation. Glutathione peroxidase 4 (GPX4) plays a central role in the regulation of ferroptosis through the suppression of lipid peroxidation generation. Connections have been reported between ferroptosis, lipid metabolism, cancer onset, and drug resistance. Recently, interest has grown in ferroptosis induction as a potential strategy to overcome drug resistance in hematological malignancies. GATA-1 is a key transcriptional factor controlling hematopoiesis-related gene expression. Two GATA-1 isoforms, the full-length protein (GATA-1FL) and a shorter isoform (GATA-1S), are described. A balanced GATA-1FL/GATA-1S ratio helps to control hematopoiesis, with GATA-1S overexpression being associated with hematological malignancies by promoting proliferation and survival pathways in hematopoietic precursors. Recently, optical techniques allowed us to highlight different lipid profiles associated with the expression of GATA-1 isoforms, thus raising the hypothesis that ferroptosis-regulated processes could be involved. Lipidomic and functional analysis were conducted to elucidate these mechanisms. Studies on lipid peroxidation production, cell viability, cell death, and gene expression were used to evaluate the impact of GPX4 inhibition. Here, we provide the first evidence that over-expressed GATA-1S prevents K562 myeloid leukemia cells from lipid peroxidation-induced ferroptosis. Targeting ferroptosis is a promising strategy to overcome chemoresistance. Therefore, our results could provide novel potential therapeutic approaches and targets to overcome drug resistance in hematological malignancies.
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- 2023
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6. Effect of Different Coffee Brews on Tryptophan Metabolite-Induced Cytotoxicity in HT-29 Human Colon Cancer Cells
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Luigi Castaldo, Marianna Toriello, Luana Izzo, Raffaele Sessa, Sonia Lombardi, Silvia Trombetti, Yelko Rodríguez-Carrasco, Alberto Ritieni, and Michela Grosso
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coffee ,anti-inflammatory activity ,ROS ,skatole ,chlorogenic acids ,polyphenols ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Coffee consumption positively influences colon health. Conversely, high levels of tryptophan metabolites such as skatole released from intestinal putrefactive fermentation in the presence of excessive dietary animal protein intake, and gut microbiota alterations, may have several adverse effects, including the development of colorectal cancer. Therefore, this study aimed to elucidate the potential protective effects of coffee in the presence of different skatole levels. The results showed that skatole exposure induced reduced cell viability and oxidative stress in the HT-29 human colon cancer cell line. However, co-treatment of cells with skatole and coffee samples was able to reduce ROS production (up to 45% for espresso) compared to cells not treated with coffee. Real-time PCR analysis highlighted that treating HT-29 cells with skatole increased the levels of inflammatory cytokines and chemokines TNF-α, IL-1β, IL-8, and IL12, whereas exposure to coffee extracts in cells that were pretreated with skatole showed anti-inflammatory effects with decreased levels of these cytokines. These findings demonstrate that coffee may counteract the adverse effects of putrefactive compounds by modulating oxidative stress and exerting anti-inflammatory activity in colonocytes, thus suggesting that coffee intake could improve health conditions in the presence of altered intestinal microbiota metabolism.
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- 2022
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7. Exploring the Leukemogenic Potential of GATA-1S, the Shorter Isoform of GATA-1: Novel Insights into Mechanisms Hampering Respiratory Chain Complex II Activity and Limiting Oxidative Phosphorylation Efficiency
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Silvia Trombetti, Raffaele Sessa, Rosa Catapano, Laura Rinaldi, Alessandra Lo Bianco, Antonio Feliciello, Paola Izzo, and Michela Grosso
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myeloid leukemia ,SDHC ,respiratory chain complex II ,GATA-1 isoforms ,leukemogenesis ,oxidative phosphorylation ,Therapeutics. Pharmacology ,RM1-950 - Abstract
GATA-1 is a key regulator of hematopoiesis. A balanced ratio of its two isoforms, GATA-1FL and GATA-1S, contributes to normal hematopoiesis, whereas aberrant expression of GATA-1S alters the differentiation/proliferation potential of hematopoietic precursors and represents a poor prognostic factor in myeloid leukemia. We previously reported that GATA-1S over-expression correlates with high levels of the succinate dehydrogenase subunit C (SDHC). Alternative splicing variants of the SDHC transcript are over-expressed in several tumors and act as potent dominant negative inhibitors of SDH activity. With this in mind, we investigated the levels of SDHC variants and the oxidative mitochondrial metabolism in myeloid leukemia K562 cells over-expressing GATA-1 isoforms. Over-expression of SDHC variants accompanied by decreased SDH complex II activity and oxidative phosphorylation (OXPHOS) efficiency was found associated only with GATA-1S. Given the tumor suppressor role of SDH and the effects of OXPHOS limitations in leukemogenesis, identification of a link between GATA-1S and impaired complex II activity unveils novel pro-leukemic mechanisms triggered by GATA-1S. Abnormal levels of GATA-1S and SDHC variants were also found in an acute myeloid leukemia patient, thus supporting in vitro results. A better understanding of these mechanisms can contribute to identify novel promising therapeutic targets in myeloid leukemia.
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- 2021
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8. Defective mRNA levels are responsible for a β-thalassemia phenotype associated with Hb Federico II, a novel hemoglobin variant [β-106 (G8) Leu→Val]
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Michela Grosso, Ilaria Palumbo, Emanuela Morelli, Stella Puzone, Raffaele Sessa, and Paola Izzo
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2008
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9. A multidisciplinary approach disclosing unexplored Aflatoxin B1 roles in severe impairment of vitamin D mechanisms of action
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Marco Persico, Raffaele Sessa, Elena Cesaro, Irene Dini, Paola Costanzo, Alberto Ritieni, Caterina Fattorusso, Michela Grosso, Persico, Marco, Sessa, Raffaele, Cesaro, Elena, Dini, Irene, Costanzo, Paola, Ritieni, Alberto, Fattorusso, Caterina, and Grosso, Michela
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Aflatoxin B1 ,Transcriptional regulation ,Vitamin D receptor ,Docking studie ,Health, Toxicology and Mutagenesis ,Retinoid receptor ,Gene expression ,Cell Biology ,Toxicology - Abstract
Aflatoxin B1 (AFB1), produced by fungi of the genus Aspergillus, is the most toxic and carcinogenic mycotoxin among the classes of aflatoxins. Previous research showed that AFB1 affects vitamin D receptor (VDR) expression. In the present study, integrated computational and experimental studies were carried out to investigate how AFB1 can interfere with Vitamin D signalling. A competitive antagonism of AFB1 toward RXRα and VDR was hypothesized by comparing the docked complex of AFB1/RXRα and AFB1/VDR ligand-binding domain (LBD) with the X-ray structures of RXRα and VDR bound to known ligands. Accordingly, we demonstrated that AFB1 can affect vitamin D-mediated transcriptional activation of VDR by impairing the formation of protein complexes containing both VDR-RXRα and RXRα/RAR and affecting the subcellular localization of VDR and RXRα. As a whole, our data indicate that AFB1 can interfere with different molecular pathways triggered by vitamin D with an antagonistic mechanism of action.
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- 2022
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10. Antioxidant and Anti-Inflammatory Activity of Coffee Brew Evaluated after Simulated Gastrointestinal Digestion
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Raffaele Sessa, MARIANNA TORIELLO, ALFONSO NARVAEZ, Michela Grosso, Sonia Lombardi, Luigi Castaldo, Luana Izzo, Alberto Ritieni, Castaldo, L., Toriello, M., Sessa, R., Izzo, L., Lombardi, S., Narvaez, A., Ritieni, A., and Grosso, M.
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Polyphenol ,polyphenols ,food-derived bioactive compounds ,chlorogenic acids ,inflammation ,Anti-Inflammatory Agents ,Coffee ,Antioxidants ,Article ,Plant Extract ,Humans ,TX341-641 ,Colonic Neoplasm ,Nutrition and Dietetics ,Nutrition. Foods and food supply ,Interleukin-6 ,Plant Extracts ,Polyphenols ,Chlorogenic acid ,Gastrointestinal Tract ,Anti-Inflammatory Agent ,HT29 Cell ,Colonic Neoplasms ,Food-derived bioactive compound ,Digestion ,Reactive Oxygen Specie ,Reactive Oxygen Species ,HT29 Cells ,Human ,Food Science - Abstract
Coffee contains human health-related molecules, namely polyphenols that possess a wide range of pharmacological functions, and their intake is associated with reduced colon cancer risk. This study aimed to assess the changes in the anti-inflammatory and antioxidant activity of coffee after simulated gastrointestinal digestion. The evaluation of intracellular reactive oxygen species (ROS) levels in the HT-29 human colon cancer cell line and three in vitro spectrophotometric assays were performed to determine the antioxidant activity of the samples. Characterization of coffee composition was also assessed through a Q-Orbitrap high-resolution mass spectrometry analysis. The results highlighted that the levels of polyphenols in the digested coffee brews were higher than those of the non-digested ones. All assayed samples decreased the levels of intracellular ROS when compared to untreated cells, while digested coffee samples exhibited higher antioxidant capacity and total phenolic content than not-digested coffee samples. Digested coffee samples showed a higher reduction in interleukin-6 levels than the not-digested samples in lipopolysaccharide-stimulated HT-29 cells treated for 48 h and fewer cytotoxic effects in the MTT assay. Overall, our findings suggest that coffee may exert antioxidant and anti-inflammatory properties, and the digestion process may be able to release compounds with higher bioactivity.
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- 2021
11. MiR-137 Targets the 3' Untranslated Region of
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Raffaella, Liccardo, Raffaele, Sessa, Silvia, Trombetti, Marina, De Rosa, Paola, Izzo, Michela, Grosso, and Francesca, Duraturo
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congenital, hereditary, and neonatal diseases and abnormalities ,Lynch Syndrome ,regulation MSH2 mRNA ,nutritional and metabolic diseases ,3′UTR MSH2 ,neoplasms ,miR137 ,digestive system diseases ,Article ,MSH2 ,MMR genes - Abstract
Simple Summary In a previous study, we identified a patient carrying the variant c.*226A>G in the MSH2 3′ untranslated region that showed overexpression of MSH2 protein. In this study, we hypothesized that the MSH2 3′UTR contained a seed region for miR-137, indicating MSH2 was indeed targeted by miR-137. Our in vitro studies showed an inverse correlation between miR-137 and MSH2; this functional interaction was also confirmed in normal and tumoral tissue samples from the patient carrying the c.*226A>G variant in the MSH2 3′UTR. Abstract Mismatch Repair (MMR) gene dysregulation plays a fundamental role in Lynch Syndrome (LS) pathogenesis, a form of hereditary colorectal cancer. Loss or overexpression of key MMR genes leads to genome instability and tumorigenesis; however, the mechanisms controlling MMR gene expression are unknown. One such gene, MSH2, exerts an important role, not only in MMR, but also in cell proliferation, apoptosis, and cell cycle control. In this study, we explored the functions and underlying molecular mechanisms of increased MSH2 expression related to a c.*226A>G variant in the 3′untranslated (UTR) region of MSH2 that had been previously identified in a subject clinically suspected of LS. Bioinformatics identified a putative binding site for miR-137 in this region. To verify miRNA targeting specificity, we performed luciferase gene reporter assays using a MSH2 3′UTR psiCHECK-2 vector in human SW480 cells over-expressing miR-137, which showed a drastic reduction in luciferase activity (p > 0.0001). This effect was abolished by site-directed mutagenesis of the putative miR-137 seed site. Moreover, in these cells we observed that miR-137 levels were inversely correlated with MSH2 expression levels. These results were confirmed by results in normal and tumoral tissues from the patient carrying the 3′UTR c.*226A>G variant in MSH2. Finally, miR-137 overexpression in SW480 cells significantly suppressed cell proliferation in a time- and dose-dependent manner (p < 0.0001), supporting a role for MSH2 in apoptosis and cell proliferation processes. Our findings suggest miR-137 helps control MSH2 expression via its 3′UTR and that dysregulation of this mechanism appears to promote tumorigenesis in colon cells.
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- 2021
12. Oxidative Stress and ROS-Mediated Signaling in Leukemia: Novel Promising Perspectives to Eradicate Chemoresistant Cells in Myeloid Leukemia
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Silvia Trombetti, Elena Cesaro, Raffaele Sessa, Alessandra Lo Bianco, Paola Izzo, Michela Grosso, Rosa Catapano, Trombetti, S., Cesaro, E., Catapano, R., Sessa, R., Bianco, A. L., Izzo, P., and Grosso, M.
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Myeloid ,Apoptosis ,Review ,medicine.disease_cause ,Antineoplastic Agent ,lcsh:Chemistry ,Homeostasis ,oxidative stress ,lcsh:QH301-705.5 ,Spectroscopy ,Antioxidant system ,chemistry.chemical_classification ,chemoreistance ,Myeloid leukemia ,ROS ,General Medicine ,Computer Science Applications ,Leukemia ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Signal transduction ,Reactive Oxygen Specie ,Human ,Signal Transduction ,Antineoplastic Agents ,Biology ,Catalysis ,Leukemogenic ,Inorganic Chemistry ,acute myeloid leukemia (AML) ,Homeostasi ,medicine ,Animals ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,Reactive oxygen species ,Animal ,Organic Chemistry ,ROS-based therapy ,Apoptosi ,antioxidant systems ,medicine.disease ,chemistry ,lcsh:Biology (General) ,lcsh:QD1-999 ,Drug Resistance, Neoplasm ,Cancer research ,Oxidative stre ,Reactive Oxygen Species ,Oxidative stress - Abstract
Myeloid leukemic cells are intrinsically under oxidative stress due to impaired reactive oxygen species (ROS) homeostasis, a common signature of several hematological malignancies. The present review focuses on the molecular mechanisms of aberrant ROS production in myeloid leukemia cells as well as on the redox-dependent signaling pathways involved in the leukemogenic process. Finally, the relevance of new chemotherapy options that specifically exert their pharmacological activity by altering the cellular redox imbalance will be discussed as an effective strategy to eradicate chemoresistant cells.
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- 2021
13. Mir-137 targets the 3′ untranslated region of msh2: Potential implications in lynch syndrome-related colorectal cancer
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Paola Izzo, Francesca Duraturo, Michela Grosso, Marina De Rosa, Silvia Trombetti, Raffaele Sessa, Raffaella Liccardo, Liccardo, Raffaella, Sessa, Raffaele, Trombetti, Silvia, DE ROSA, Marina, Izzo, Paola, Grosso, Michela, and Duraturo, Francesca
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Genome instability ,Cancer Research ,congenital, hereditary, and neonatal diseases and abnormalities ,Three prime untranslated region ,Cell growth ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Biology ,medicine.disease_cause ,complex mixtures ,miR137 ,digestive system diseases ,regulation MSH2 mRNA ,mir-137 ,Oncology ,MSH2 ,Lynch Syndrome ,Gene expression ,microRNA ,Cancer research ,medicine ,3′UTR MSH2 ,Carcinogenesis ,RC254-282 ,MMR genes - Abstract
Mismatch Repair (MMR) gene dysregulation plays a fundamental role in Lynch Syndrome (LS) pathogenesis, a form of hereditary colorectal cancer. Loss or overexpression of key MMR genes leads to genome instability and tumorigenesis, however, the mechanisms controlling MMR gene expression are unknown. One such gene, MSH2, exerts an important role, not only in MMR, but also in cell proliferation, apoptosis, and cell cycle control. In this study, we explored the functions and underlying molecular mechanisms of increased MSH2 expression related to a c.*226A>, G variant in the 3′untranslated (UTR) region of MSH2 that had been previously identified in a subject clinically suspected of LS. Bioinformatics identified a putative binding site for miR-137 in this region. To verify miRNA targeting specificity, we performed luciferase gene reporter assays using a MSH2 3′UTR psiCHECK-2 vector in human SW480 cells over-expressing miR-137, which showed a drastic reduction in luciferase activity (p >, 0.0001). This effect was abolished by site-directed mutagenesis of the putative miR-137 seed site. Moreover, in these cells we observed that miR-137 levels were inversely correlated with MSH2 expression levels. These results were confirmed by results in normal and tumoral tissues from the patient carrying the 3′UTR c.*226A>, G variant in MSH2. Finally, miR-137 overexpression in SW480 cells significantly suppressed cell proliferation in a time- and dose-dependent manner (p <, 0.0001), supporting a role for MSH2 in apoptosis and cell proliferation processes. Our findings suggest miR-137 helps control MSH2 expression via its 3′UTR and that dysregulation of this mechanism appears to promote tumorigenesis in colon cells.
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- 2021
14. Transcriptional Repressors of Fetal Globin Genes as Novel Therapeutic Targets in Beta-Thalassemia
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Paola Izzo, Raffaele Sessa, Maria Rosaria Storino, Alessandra Lo Bianco, Michela Grosso, Mariarosaria Giuliano, Rosa Catapano, Silvia Trombetti, and Marianna De Martino
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Genetics ,Globin genes ,Fetus ,InformationSystems_INFORMATIONSTORAGEANDRETRIEVAL ,medicine ,Repressor ,Beta thalassemia ,Biology ,medicine.disease ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) - Published
- 2020
15. Cover Image, Volume 234, Number 11, November 2019
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Patrizia Riccio, Raffaele Sessa, Sergio de Nicola, Fara Petruzziello, Silvia Trombetti, Giuseppe Menna, Giampiero Pepe, Pasquale Maddalena, Paola Izzo, and Michela Grosso
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Physiology ,Clinical Biochemistry ,Cell Biology - Published
- 2019
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16. GATA-1 isoforms differently contribute to the production and compartmentation of reactive oxygen species in the myeloid leukemia cell line K562
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Giampiero Pepe, Patrizia Riccio, Silvia Trombetti, Paola Izzo, Sergio De Nicola, Fara Petruzziello, Pasquale Maddalena, Giuseppe Menna, Michela Grosso, Raffaele Sessa, Riccio, Patrizia, Sessa, R., de Nicola, S., Petruzziello, Fara, Trombetti, S., Menna, G., Pepe Giovanni, Piero., Maddalena, P., Izzo, P., and Grosso, M.
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0301 basic medicine ,Gene isoform ,Myeloid ,Physiology ,Cell Survival ,Clinical Biochemistry ,Apoptosis ,DNA, Mitochondrial ,GATA-1 ,Antioxidants ,GATA‐1 ,myeloid leukemia ,03 medical and health sciences ,0302 clinical medicine ,Original Research Articles ,medicine ,Humans ,Protein Isoforms ,GATA1 Transcription Factor ,Original Research Article ,Transcription factor ,oxidative stre ,mitochondria remodeling ,Chemistry ,Cell growth ,Electron Transport Complex II ,Myeloid leukemia ,Cell Biology ,Cytochrome b Group ,Cell biology ,Cell Compartmentation ,Succinate Dehydrogenase ,Haematopoiesis ,Oxidative Stress ,Protein Subunits ,030104 developmental biology ,medicine.anatomical_structure ,Leukemia, Myeloid ,030220 oncology & carcinogenesis ,succinate dehydrogenase subunit C (SDHC) ,Quercetin ,K562 Cells ,Reactive Oxygen Species ,Oxidation-Reduction ,Intracellular ,K562 cells - Abstract
Maintenance of a balanced expression of the two isoforms of the transcription factor GATA‐1, the full‐length protein (GATA‐1FL) and a shorter isoform (GATA‐1 S), contributes to control hematopoiesis, whereas their dysregulation can alter the differentiation/proliferation potential of hematopoietic precursors thereby eventually leading to a variety of hematopoietic disorders. Although it is well established that these isoforms play opposite roles in these remarkable processes, most of the molecular pathways involved remain unknown. Here, we demonstrate that GATA‐1FL and GATA‐1S are able to differently influence intracellular redox states and reactive oxygen species (ROS) compartmentation in the erythroleukemic K562 cell line, thus shedding novel mechanistic insights into the processes of cell proliferation and apoptosis resistance in myeloid precursors. Furthermore, given the role played by ROS signaling as a strategy to escape apoptosis and evade cell‐mediated immunity in myeloid cells, this study highlights a mechanism through which aberrant expression of GATA‐1 isoforms could play a role in the leukemogenic process.
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- 2018
17. PS1013 IS QUERCETIN ABLE TO REVERT THE APOPTOTIC RESISTANCE TRIGGERED BY THE SHORT ISOFORM OF GATA-1 IN MYELOID LEUKEMIA CELLS?
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A. Lo Bianco, Silvia Trombetti, M. Caballero Cavallè, M. Miranda, Michela Grosso, Raffaele Sessa, Rosa Catapano, and Paola Izzo
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Gene isoform ,chemistry.chemical_compound ,chemistry ,Apoptosis ,Cancer research ,Myeloid leukemia ,Hematology ,Quercetin - Published
- 2019
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18. Prenatal diagnosis of haemoglobinopathies: our experience of 523 cases
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Raffaele Sessa, Paola Izzo, Michela Grosso, Maria Rosaria Storino, Stella Puzone, Grosso, Michela, Puzone, Stella, Storino, MARIA ROSARIA, Sessa, Raffaele, and Izzo, Paola
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amniocyte ,thalassemia ,medicine.medical_specialty ,Genetic counseling ,Clinical Biochemistry ,Prenatal diagnosis ,Abortion ,Molecular heterogeneity ,Pregnancy ,Prenatal Diagnosis ,medicine ,Humans ,Maternal contamination ,hemoglobinopathie ,Gynecology ,prenatal diagnosi ,Fetus ,business.industry ,Biochemistry (medical) ,Reproducibility of Results ,General Medicine ,chorionic villi ,medicine.disease ,Hemoglobinopathies ,medicine.anatomical_structure ,Chorionic villi ,Female ,business ,genetic counselling - Abstract
Background: We performed counselling for prenatal diagnosis (PD) of haemoglobinopathies in 372 couples. Thirty-four out of 372 (9.1%) did not undergo PD: six due to spontaneous abortion; nine because it was too difficult to make a decision if PD was positive; 18 because counselling excluded the carrier status of one or both parents; and one because parental mutations were mild. Methods: Eleven out of 338 (3.3%) couples underwent PD because they had a thalassaemic child; 106 (31.4%) were found to be at high risk during pre-conceptional screening; 221 (65.4%) because of familiarity. Of 523 PDs in 486 (92.9%), including six dichorionic twin pregnancies, PD was performed on DNA from chorionic villi (CV), and in 37 from amniocytes (7.1%). In 1/523 cases, PD was not completed because DNA from CV was not sufficient; in two cases single tandem repeat analysis revealed maternal contamination of foetal DNA; in 7/522 (1.3%) cases PD revealed non-paternity. In 435/522 (83.3%) cases, PD was performed using reverse dot-blot and ARMS; 34/522 (6.5%) required sequencing. In 53/522 (10.2%) cases it was necessary to test globin loci for large rearrangements. Results: One hundred and twenty out of 522 (23.0%) PDs revealed an affected foetus. In all but two cases the couple interrupted pregnancy. In the six twin pregnancies PD revealed a normal and a carrier foetus (two cases), carrier status in both foetuses (two cases) and a carrier and an affected foetus (two cases). In these latter cases the couple planned selective interruption. Conclusions: Our PD procedure is successful and reliable, and is useful in high-risk areas characterised by molecular heterogeneity.
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- 2013
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19. research paper: Role of the cold shock domain protein A in the transcriptional regulation of HBG expression
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Michela Grosso, Giovanna D’Urzo, Giovanni Amendola, Maria Amendolara, Raffaella Petruzzelli, Stella Puzone, Sara Gaudino, Paola Izzo, Raffaele Sessa, and Rosanna Di Concilio
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Regulation of gene expression ,Reporter gene ,HBG1 ,hemic and lymphatic diseases ,Gene expression ,Transcriptional regulation ,Repressor ,Hematology ,Globin ,Biology ,Gene ,Molecular biology - Abstract
Impaired switching from fetal haemoglobin (HbF) to adult globin gene expression leads to hereditary persistence of fetal haemoglobin (HPFH) in adult life. This is of prime interest because elevated HbF levels ameliorate β-thalassaemia and sickle cell anaemia. Fetal haemoglobin levels are regulated by complex mechanisms involving factors linked or not to the β-globin gene (HBB) locus. To search for factors putatively involved in the expression of the γ-globin genes (HBG1, HBG2), we examined the reticulocyte transcriptome of three siblings who had different HbF levels and different degrees of β-thalassaemia severity although they had the same ΗBA- and ΗΒB cluster genotypes. By mRNA differential display we isolated the cDNA coding for the cold shock domain protein A (CSDA), also known as dbpA, previously reported to interact in vitro with the HBG2 promoter. Expression studies performed in K562 and in primary erythroid cells showed an inverse relationship between HBG and CSDA expression levels. Functional studies performed by Chromatin Immunoprecipitation and reporter gene assays in K562 cells demonstrated that CSDA is able to bind the HBG2 promoter and suppress its expression. Therefore, our study demonstrated that CSDA is a trans-acting repressor factor of HBG expression and modulates the HPFH phenotype.
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- 2010
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20. Defective mRNA levels are responsible for a beta-thalassemia phenotype associated with Hb Federico II, a novel haemoglobin variant (beta 106 (G8) Leu->Val)
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Emanuela Morelli, Ilaria Palumbo, Raffaele Sessa, Paola Izzo, Stella Puzone, Michela Grosso, Grosso, Michela, Ilaria, Palumbo, Emanuela, Morelli, Stella, Puzone, Raffaele, Sessa, and Izzo, Paola
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Male ,Heterozygote ,thalassemia ,Hemoglobins, Abnormal ,Thalassemia ,Biology ,Hb variant ,Hemoglobins ,Leucine ,medicine ,Humans ,Codon ,mRNA instability ,Genetics ,Models, Genetic ,beta-Thalassemia ,Hemoglobin variants ,Valine ,Sequence Analysis, DNA ,Hematology ,medicine.disease ,Molecular biology ,Phenotype ,Pedigree ,Hemoglobin disorders ,Mrna level ,Mutation ,Female - Abstract
This study provides the first experimental evidence that a single nucleotide mutation within the coding region of the β-globin gene affects mRNA expression levels and causes a β-thalassemic defect. Furthermore, our data suggest that other regions besides the 3′UTR, whose role in constitutively regulation of this mechanism has been recently identified, may contribute to the stabilization of β-globin mRNA and could, therefore, help to characterize the molecular basis of thalassemic hemoglobinopathies.
- Published
- 2008
21. Giant malignant granular cell tumor (GCT) of the posterior mediastinum
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Giuseppe De Luca, Francesco Petteruti, Raffaele Sessa, Antonella Luciano, and Giulio Benincasa
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Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,business.industry ,Middle Aged ,Mediastinal Neoplasms ,Oncology ,Granular Cell Tumor ,medicine ,Malignant Granular Cell Tumor ,Humans ,Female ,business ,Posterior mediastinum - Published
- 2013
22. Molecular Basis of Thalassemia
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Maria Rosaria Storino, Paola Izzo, Raffaele Sessa, Michela Grosso, Stella Puzone, Dr. Donald Silverberg, Grosso, Michela, Sessa, Raffaele, Puzone, Stella, Storino, MARIA ROSARIA, and Izzo, Paola
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Genetics ,HPFH ,thalassemia ,Genetic counseling ,Thalassemia ,Prenatal diagnosis ,Biology ,medicine.disease ,Sickle cell anemia ,Genotype ,Fetal hemoglobin ,medicine ,Globin ,hemoglobinopathies ,Malaria - Abstract
Hemoglobinopathies are a heterogeneous group of monogenic disorders widespread overall. They are commonly subdivided into three partially overlapping subgroups: structural variants which comprise the sickle cell anemia syndrome; thalassemias, characterized by a reduced rate of synthesis of one or more globin chains of hemoglobin; conditions of high persistence of fetal hemoglobin in adulthood (HPFH) (Weatherall & Clegg, 2001). As a group, they are the commonest monogenic disorders in the world population. It is thought that the high prevalence of these defects could be due to selective advantage of the carrier state to malaria infection. However, in spite of epidemiological evidences supporting this hypothesis as well as of extensive hematological studies, the mechanisms underlying this protection still remain unknown. It is, however, evident that as a consequence of this positive selection, these diseases are mostly common in geographic areas extending from the Mediterranean region through tropical countries including Sub-Saharian Africa, the Middle East, India, Southeast Asia and Indonesia, where malaria was or still is endemic (Weatherall & Clegg, 2001). In many of these areas the estimated frequencies of these disorders range from 3 to 10 percent, even though in some specific areas the carrier frequencies may be higher, reaching 80-90% in some tribal populations in India (Harteveld & Higgs, 2010). Because of their high frequencies, different hemoglobin defects may be co-inherited, giving rise to an extremely complex series of genotypes and clinical phenotypes. In fact, in many regions thalassemic defects coexist with structural Hb variants; it is also quite common for individuals from areas at high frequency of thalassemic defects to inherit genes for more than one type of thalassemia. Furthermore, some Hb variants are synthesized at reduced rate or are highly instable, leading both to functional and structural deficiency of the affected globin chain, thus resulting in a thalassemic condition, generally showing dominant inheritance. These complex interactions contribute to generate a wide range of clinical disorders that, taken together, constitute the thalassemic syndromes (Weatherall, 2001). The complex and heterogeneous spectrum of molecular defects underlying these inherited conditions is regionally specific and in most cases the geographic and ethnic distributions have been determined, providing support for prevention programs based on screening, genetic counselling and prenatal diagnosis in couples at risk.
- Published
- 2012
23. Large deletion involving exon 5 of the arylsulfatase B gene caused apparent homozygosity in a mucopolysaccharidosis type VI patient
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Guglielmo R. D. Villani, Michelina Sibilio, Raffaele Sessa, Michela Grosso, Gianfranco Pontarelli, Paola Di Natale, Armando Chierchia, Giancarlo Parenti, Villani, GUGLIELMO ROSARIO DOMENI, Grosso, Michela, Pontarelli, Gianfranco, A., Chierchia, R., Sessa, M., Sibilio, Parenti, Giancarlo, and DI NATALE, Paola
- Subjects
Arylsulfatase B ,Male ,Heterozygote ,DNA, Complementary ,N-Acetylgalactosamine-4-Sulfatase ,Mucopolysaccharidosis type VI ,Molecular Sequence Data ,Biology ,medicine.disease_cause ,Frameshift mutation ,Exon ,Complementary DNA ,medicine ,Humans ,Child ,Frameshift Mutation ,Gene ,molecular diagnosi ,Genetics (clinical) ,DNA Primers ,Sequence Deletion ,Genetics ,Mutation ,Mucopolysaccharidosis VI ,Base Sequence ,apparent homozygosity ,Homozygote ,General Medicine ,Exons ,Molecular biology ,genomic DNA ,Codon, Nonsense ,Female - Abstract
Apparent homozygosity for the mutation p.R315X present on exon 5 of the arylsulfatase B (ARSB) gene in a mucopolysaccharidosis type VI patient was solved in this study by further testing for a second mutation. Patient cDNA analysis revealed that the entire exon 5 of the ARSB gene was lacking; this new mutation was identified as c.899-1142del. As the genomic DNA sequencing excluded the presence of splicing mutations, polymerase chain reaction analysis was performed for polymorphisms listed in the NCBI SNP database for the ARSB gene. This allowed the mutation at the genomic DNA level to be identified as g.99367-102002del; this gross deletion, involving the entire exon 5 of the gene and parts of introns 4 and 5 led to a frameshift starting at amino acid 300 and resulting in a protein with 39% amino acids different from the normal enzyme. We stress that extensive DNA analysis needs to be performed in case of apparent homozygosity to avoid potential errors in genetic counseling.
- Published
- 2010
24. Identification and molecular characterization of the --CAMPANIA deletion, a novel α°-thalassemic defect, in two unrelated Italian families
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Leonilde Pagano, Raffaele Sessa, Paola Izzo, Simona Colucci, Massimiliano Ammirabile, Michela Grosso, Stella Puzone, Carmelo Piscopo, Sessa, R., Puzone, S., Ammirabile, M., Piscopo, C., Pagano, L., Colucci, S., Izzo, Paola, and Grosso, Michela
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Genetics ,Hemolytic anemia ,medicine.medical_specialty ,Hematology ,business.industry ,Nucleic acid sequence ,medicine.disease ,Alu element ,Hemoglobinopathy ,Internal medicine ,medicine ,Alpha thalassemia ,Identification (biology) ,deletion ,business - Abstract
We describe a novel deletion form of alpha-thalassemia which removes a region of 31 kilobase encompassing the entire a-globin gene cluster. In association with the - alpha+ 3.7 deletion this defect gave rise to a typical hemoglobin H (HbH) disease in two unrelated boys of Southern Italian descent. The molecular characterization of the deletion revealed involvement of Alu repeat sequences, indicating that this rearrangement was originated from an event of unequal recombination. Furthermore, sequence analysis of the junctional region and genotyping of polymorphic sites flanking the 5’ and 3’ breakpoints suggest a unique origin for this mutation in these two patients. Our study contributes to define the wide spectrum of mutations that underlie the thalassemia syndromes in the Mediterranean area and provides support to prevention programs of a-thalassemia based on molecular screening and prenatal diagnosis in couples at risk.
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- 2010
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25. P-150 Prognostic significance of GATA-1 and WT1 Levels in pediatric hematological disorders
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E.D. Giovannone, P. Izzo, Raffaele Sessa, Giuseppe Menna, Fara Petruzziello, A. De Matteo, R. Cuccurullo, M. Grosso, Vincenzo Poggi, M. Catania, and Rosanna Parasole
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Oncology ,Hematological disorders ,Cancer Research ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Hematology ,business - Published
- 2013
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26. Cisplatin plus vinorelbine as induction chemotherapy followed by surgery in the treatment of stage IIIB non-small cell lung cancer. Final results of a multicenter phase II study
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Silvio, Cigolari, Carlo, Curcio, Alfonso, Maiorino, Raffaele, Sessa, Angela, Cioffi, and Mario, Massimo
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Adult ,Male ,Lung Neoplasms ,Remission Induction ,Vinorelbine ,Middle Aged ,Vinblastine ,Disease-Free Survival ,Neoadjuvant Therapy ,Carcinoma, Non-Small-Cell Lung ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Patient Compliance ,Female ,Cisplatin ,Aged ,Neoplasm Staging - Abstract
The combination of cisplatin and vinorelbine has been shown to be effective in patients with advanced non-small cell lung cancer (NSCLC). Based on these data, we planned to treat patients with stage IIIB NSCLC without malignant pleural effusion and/or metastatic supraclavicular lymph nodes, in order to study the potential effectiveness of this association as neoadjuvant treatment.Thirty patients entered into the study and were treated preoperatively with cisplatin 120 mg/m2 given on day 1 and vinorelbine 30 mg/m2 given on days 1 and 8, recycled every 3 weeks for a maximum of 3 cycles. The main characteristics of patients were: male/female 23/7, median age 61 years, performance status 0/1/2, 8/17/5. Only patients who achieved an objective response underwent surgery.A total of 82 (91.1%) cycles were administered with moderate toxicity: WHO grade (G) 2 and 3 neutropenia occurred in 20 (66.6%) patients, G 3 anaemia occurred in 4 (13.3%), G 3 nausea/vomiting in 20 (66.6%) and G 1-2 renal toxicity in 2 (6.6%). Eighteen (60%; exact 95% confidence limits, 40.6% to 77.3%) patients achieved a partial response and 14 (46.6%) underwent surgery. Complete resection (R0) was achieved in 11 (36.6% of all patients) and pathological complete resection in 5 (16.6%). No postoperative pulmonary complications were reported. The median survival for all patients was 25.5 (exact 95% confidence limits, 13 to 39) months. The median progression-free survival in responsive patients was 27 (exact 95% confidence limits, 13 to 33) months.The combination of cisplatin and vinorelbine is effective and safe as a neoadjuvant therapy in stage IIIB NSCLC, showing a high response rate (60%) and amenability to surgery.
- Published
- 2003
27. Molecular Basis of Thalassemia
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Michela Grosso, Raffaele Sessa, Stella Puzone, Maria Rosaria Storino, Paola Izzo, Michela Grosso, Raffaele Sessa, Stella Puzone, Maria Rosaria Storino, and Paola Izzo
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- 2012
- Full Text
- View/download PDF
28. Huge glomus tumor of the lung
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Giuseppe De Luca, Francesco Petteruti, and Raffaele Sessa
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Adult ,Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Biopsy, Fine-Needle ,CD34 ,Standardized uptake value ,Cytokeratin ,Bronchoscopy ,Biopsy ,Biomarkers, Tumor ,Humans ,Medicine ,Lung ,biology ,medicine.diagnostic_test ,business.industry ,Chromogranin A ,General Medicine ,Glomus Tumor ,medicine.disease ,Immunohistochemistry ,Tumor Burden ,Glomus tumor ,Treatment Outcome ,medicine.anatomical_structure ,Thoracotomy ,Positron-Emission Tomography ,biology.protein ,Female ,Surgery ,Desmin ,Tomography, X-Ray Computed ,Cardiology and Cardiovascular Medicine ,business - Abstract
A 37-year-old female smoker was referred with a persistent siccus cough. Chest radiography revealed an abnormal mass in the parahilar region of the left lung (Figure 1(a)). Chest computed tomography showed a well-defined huge round nodule of 9.7 6 cm in the left upper lobe (Figure 1(b)). Positron-emission tomography demonstrated moderate isotope uptake (maximum standardized uptake value 5.2; Figure 1(c)). Bronchoscopy was negative, and a fine-needle biopsy was inconclusive. The patient underwent a musclesparing left lateral thoracotomy, and a typical lingulectomy was performed. Macroscopically, a well-demarcated, round red soft mass of 9.7 cm in greatest dimension was found. Microscopically, the mass consisted of solid proliferative cells with round nuclei and eosinophilic cytoplasm. The tumor cells frequently showed an ovalto spindle-shaped nuclear appearance. These cells surrounded blood vessels lined with normal endothelial. An immunohistochemical study revealed the tumor cells to be positive for CD34, smooth muscle actin, and vimentin (Figure 1(d)–(f)), but negative for desmin, cytokeratin, chromogranin, synaptophysin, CD56, CD117, TTF1, and CD15. The final pathological diagnosis was intrapulmonary glomus tumor of the proper type. The postoperative course was an uneventful, and the patient was discharged on the 6th day after surgery.
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- 2013
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29. Structural and Functional Characterization of Csda Protein Complexes Involved In Modulation of Fetal Globin Gene Expression
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Michela Grosso, Giovanni Amendola, Stella Puzone, Rosanna Di Concilio, Maria Amendolara, Giovanna D’Urzo, Paola Izzo, Sara Gaudino, Antonio M. Risitano, Maria Rosaria Storino, Annamaria Aurino, Raffaele Sessa, and Raffaella Petruzzelli
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Genetics ,Hereditary persistence of fetal hemoglobin ,Immunology ,Repressor ,Promoter ,Cell Biology ,Hematology ,Biology ,medicine.disease ,Biochemistry ,Gene expression ,Gene cluster ,Fetal hemoglobin ,medicine ,Differential display technique ,Gene - Abstract
Abstract 2071 Impaired switching from fetal hemoglobin (HbF) to adult globin gene expression leads to hereditary persistence of fetal hemoglobin (HPFH) in adult life. This is of prime interest because elevated HbF levels ameliorate beta-thalassemia and sickle cell anemia. Fetal hemoglobin levels are regulated by complex mechanisms involving factors linked or not to the beta-globin gene locus. Recently, we reported an inverse relationship between Ggamma-globin gene (HBG2) and Cold Shock Domain Protein A (CSDA) expression levels. Based on mRNA differential display analysis, RNA interference and over-expression studies in K562 and primary erythroid cells we postulated that CSDA could contribute to regulate HBG2 expression. The putative mechanism by which CSDA modulates HBG2 expression was investigated in K562 cells by gene reporter assays on wild-type and mutant constructs of the HBG2 promoter region suspected to bind CSDA, providing experimental evidence that CSDA acts as repressor of HBG2 expression. Furthermore, chromatin immunoprecipitation (ChIP) analysis on K562 cells showed that CSDA interacts in vivo with this promoter region. In this way we were able to demonstrate that CSDA modulates HBG2 expression at least in part at the transcriptional level (Petruzzelli R et al, Br J Haematol 2010). The CSDA gene is located at position 12p13.1 and comprises 10 exons. The C-terminus (exons 6–9) is involved in protein-protein interactions. Alternative splicing of exon 6 results in two main isoforms, namely CSDA isoform a and isoform b, which show different C-terminal domains, potentially able to take part to specific protein complexes. We found that expression levels of CSDA isoform a were reduced in HPFH patients respect to isoform b. These findings suggested that isoform a could be much more involved in repression of HBG2 expression compared to isoform b. To identify putative CSDA interactors, we over-expressed these two FLAG-tagged CSDA isoforms in K562 cells. Western-blot analysis on proteins immunoprecipitated with a FLAG antibody revealed the presence of NF-kB p50 and p65 subunits and histone deacethylase 2 (HDAC2) only in samples co-immunoprecipitated with CSDA isoform a, but not with isoform b (Fig. 1). By ChIP assays with antibodies against p65, p50 and HDAC2, we demonstrated that both the NF-kB p50-p65 heterodimer and HDAC2 interact with the –200 bp region of the HBG2 promoter containing the CSDA binding site (Fig. 2). To examine the role of NF-kB and histone deacetylases on the transcriptional repression of HBG2 expression, we treated K562 cells with the proteasome inhibitor bortezomib which blocks the nuclear traslocation and transcriptional activity of the NF-kB p65-p50 complex or with the histone deacetylase inhibitor trichostatin A (TSA). Quantitative analysis by Real Time PCR showed that HBG2 expression increased following either bortezomib or TSA treatments. Furthermore, by ChIP analysis we were able to demonstrate that knock-down of CSDA abolished these interactions. To investigate if treatment with bortezomib or TSA affects the histone acetylation levels at the -200 bp region of the HBG2 promoter, we performed ChIP assays in K562 cells using an anti-acetyl-H3 antibody. Results indicated that both these drugs induces a considerable increase in H3 acetylation levels at the -200 bp region of the HBG2 promoter (Fig. 3). Taken altogether these data indicate that NF-kB and HDAC2 interact with CSDA to form a multiprotein complex which take part to the regulation of HBG2 expression by modulating local chromatin conformation. Furthermore, our study contributes to better define the role played by CSDA in fetal globin gene expression and shed novel light on the molecular mechanisms involved in globin gene switching. Disclosures: No relevant conflicts of interest to declare.
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- 2010
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30. Erratum: 'Identification and molecular characterization of the-CAMPANIAdeletion, a novel α°-thalassemic defect, in two unrelated Italian families' by Sessa et al.,Am J Hematol2010, DOI number 21591
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Raffaele Sessa, Leonilde Pagano, Massimiliano Ammirabile, Paola Izzo, Simona Colucci, Stella Puzone, Carmelo Piscopo, and Michela Grosso
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Genetics ,Identification (biology) ,Hematology ,Biology - Published
- 2010
- Full Text
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31. Identification of a Transcription Factor Potentially Involved in γ-Globin Gene Expression
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Michela Grosso, Giovanni Amendola, Stella Puzone, Rosanna Di Concilio, Giovanna D’Urzo, Paola Izzo, Raffaella Petruzzelli, and Raffaele Sessa
- Subjects
Genetics ,Sequence analysis ,Immunology ,Haplotype ,Cell Biology ,Hematology ,Biology ,Biochemistry ,Molecular biology ,Regulatory sequence ,Fetal hemoglobin ,Gene expression ,Gene cluster ,Globin ,Gene - Abstract
The switch from fetal to adult globin gene expression occurs around birth when fetal hemoglobin (HbF) production gradually declines within a few months. Much effort is underway to clarify the molecular basis of this mechanism, since impaired hemoglobin switching leading to persistent expression of fetal globin genes in adults (HPFH) offers therapeutic potential for hemoglobinopathies (S.L. Thein. Br. J. Haematol2004; 124: 264–74). In order to identify and study regulatory factors putatively involved in γ-globin gene expression, we examined the reticulocyte mRNAs differently expressed in three siblings (one brother, 54 years-old and two sisters 35- and 37-years old, respectively). The eldest brother had been referred to Umberto I Hospital for evaluation of a severe condition of β-thalassemia intermedia on chronic transfusion therapy since 1990. Both of his sisters resulted clinically affected by a milder form of thalassemia intermedia, non-transfusion dependent, showing Hb values around 8.4 g/dL, Hb A2 levels from 6.0 to 7.9% and HbF ranging from 14.5 to 27.6%, values higher than those resulted in their brother (5.9% Hb A2 and 7.2% HbF). Molecular analysis was performed on DNA extracted from peripheral leucocytes and revealed the same β-globin gene cluster genotype for all these subjects who resulted homozygous for the β+ IVSI-6 (C→T) mutation associated to haplotype VI chromosomes. Different levels of HbF were thus presumably responsible of different clinical phenotypes. To investigate the possible causes of the variations in γ-globin gene expression, extensive sequence analysis was performed on putative regulatory regions within the β-globin gene cluster (Zhi-Hong Lu et al., Blood1996; 87: 1604–11). Results showed the same genetic background in all the siblings. It was thus supposed that genetic determinants external to the β-globin gene cluster were responsible of the different γ-globin gene expression. To explore this hypothesis, the reticulocyte transcriptome was analyzed by a differential mRNA display approach. Reticulocytes were isolated from peripheral blood and total RNA extracted for all family members. Our study revealed several bands differentially displayed in the sample from the more severely affected sibling respect to his sisters. Selected bands were cloned in a pGEM T-vector (Promega, WI) and sequenced. Comparative sequence searches were performed using the BLAST algorithm. Preliminary data gave, for two of the clones originated from bands with increased expression in the brother, a complete homology (greater than 95%) with the cDNA sequence of a cold shock domain protein, displaying features of a repressor factor for several hematopoietic genes (Horwitz M. et al. JBC1994; 269: 14130–39; P. Coles et al. Nucleic Acids Res1996; 12: 2311–17).
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- 2005
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32. Motility of cryopreserved spermatozoa for the ecotoxicological evaluation of aquatic environments
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Fabbrocini, D'Adamo, Del Prete, Langellotti, A.L., Barone, C.M.A., Rinna, Sessa, Silvestri, Villani, Vitiello, Sansone, Adele, Fabbrocini, Raffaele, D'Adamo, Francesco Del, Prete, Langellotti, ANTONIO LUCA, Barone, CARMELA MARIA ASSUNTA, Rinna, Francesca, Raffaele, Sessa, Fausto, Silvestri, Giovanni, Villani, Valentina, Vitiello, and Sansone, Giovanni
- Subjects
Serial dilution ,cadmium ,Motility ,Semen ,Biology ,cryopreservation ,Cryopreservation ,sea breams ,Toxicology ,Andrology ,chemistry.chemical_compound ,sperm motility ,Bioassay ,Ecology, Evolution, Behavior and Systematics ,Sperm motility ,General Environmental Science ,Ecology ,dumpsite leachate ,computerised sperm motility analyses ,Sperm ,ecotoxicological test ,chemistry ,sediment elutriate ,General Earth and Planetary Sciences ,sea bream ,Toxicant - Abstract
A new approach to environmental studies was investigated by the authors, who propose the use of cryopreserved biological systems in ecotoxicological bioassays. The feasibility of spermiotoxicity tests using cryopreserved semen of the sea bream Sparus aurata, with sperm motility parameters as the endpoint, was evaluated. Thawed sperm was incubated in environmental samples (sediment elutriate and dumpsite leachate) and in a reference toxicant (cadmium) at scaled concentrations. Motility was then evaluated by video-microscopy using both visual and computer-assisted analyses. Activation time, sperm motility and velocity and motility duration were assessed on thawing and at the end of the incubation time, and the difference with respect to the control was statistically evaluated. All the endpoints of the bioassay proved to have good sensitivity even at the highest dilutions of the tested matrices. Observed differences in the sensitivity thresholds of the endpoints were considered to be representative of different aspects of sperm physiology. Therefore the proposed bioassay is a promising starting point for the development of toxicity tests that are increasingly tailored to the needs of ecotoxicology and environmental quality evaluation strategies for aquatic environments.
- Published
- 2013
- Full Text
- View/download PDF
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