7 results on '"Congiusta N"'
Search Results
2. A Comparative Study of Methyl-BEAMing and Droplet Digital PCR for MGMT Gene Promoter Hypermethylation Detection.
- Author
-
Macagno M, Pessei V, Congiusta N, Lazzari L, Bellomo SE, Idrees F, Cavaliere A, Pietrantonio F, Raimondi A, Gusmaroli E, Zampino MG, Gervaso L, Ciardiello D, Mondello G, Santoro A, Personeni N, Bonoldi E, Aquilano MC, Valtorta E, Siena S, Sartore-Bianchi A, Amatu A, Bonazzina EF, Bencardino KB, Serini G, Marsoni S, Barault L, Di Nicolantonio F, and Maione F
- Abstract
Background: O-6-methylguanine-DNA methyltransferase is responsible for the direct repair of O6-methylguanine lesions induced by alkylating agents, including temozolomide. O-6-methylguanine-DNA methyltransferase promoter hypermethylation is a well-established biomarker for temozolomide response in glioblastoma patients, also correlated with therapeutic response in colorectal cancer. Objectives: The ARETHUSA clinical trial aims to stratify colorectal cancer patients based on their mismatch repair status. Mismatch repair-deficient patients are eligible for treatment with immune checkpoint inhibitors (anti-PDL-1), whereas mismatch repair-proficient samples are screened for O-6-methylguanine-DNA methyltransferase promoter methylation to identify those suitable for temozolomide treatment. Methods: In this context, a subset of ARETHUSA metastatic colorectal cancer samples was used to compare two different techniques for assessing O-6-methylguanine-DNA methyltransferase hypermethylation: Methyl-BEAMing, a highly sensitive digital PCR approach that combines emulsion PCR and flow cytometry, and droplet digital PCR, a more automated procedure that enables the rapid, operator-independent analysis of a large number of samples. Results: Our study clearly demonstrates that the results obtained using Methyl-BEAMing and droplet digital PCR are comparable, with both techniques showing similar accuracy, sensitivity, and reproducibility. Conclusions: Digital droplet PCR proved to be an efficient method for detecting gene promoter methylation. However, the Methyl-BEAMing method has proved more sensitive for detecting low quantities of DNA.
- Published
- 2024
- Full Text
- View/download PDF
3. DNA demethylation triggers cell free DNA release in colorectal cancer cells.
- Author
-
Pessei V, Macagno M, Mariella E, Congiusta N, Battaglieri V, Battuello P, Viviani M, Gionfriddo G, Lamba S, Lorenzato A, Oddo D, Idrees F, Cavaliere A, Bartolini A, Guarrera S, Linnebacher M, Monteonofrio L, Cardone L, Milella M, Bertotti A, Soddu S, Grassi E, Crisafulli G, Bardelli A, Barault L, and Di Nicolantonio F
- Subjects
- Humans, Cell Line, Tumor, DNA Methylation, Cell Proliferation, CpG Islands, Biomarkers, Tumor genetics, Colorectal Neoplasms genetics, Colorectal Neoplasms metabolism, Colorectal Neoplasms pathology, Cell-Free Nucleic Acids genetics, DNA Demethylation
- Abstract
Background: Liquid biopsy based on cell-free DNA (cfDNA) analysis holds significant promise as a minimally invasive approach for the diagnosis, genotyping, and monitoring of solid malignancies. Human tumors release cfDNA in the bloodstream through a combination of events, including cell death, active and passive release. However, the precise mechanisms leading to cfDNA shedding remain to be characterized. Addressing this question in patients is confounded by several factors, such as tumor burden extent, anatomical and vasculature barriers, and release of nucleic acids from normal cells. In this work, we exploited cancer models to dissect basic mechanisms of DNA release., Methods: We measured cell loss ratio, doubling time, and cfDNA release in the supernatant of a colorectal cancer (CRC) cell line collection (N = 76) representative of the molecular subtypes previously identified in cancer patients. Association analyses between quantitative parameters of cfDNA release, cell proliferation, and molecular features were evaluated. Functional experiments were performed to test the impact of modulating DNA methylation on cfDNA release., Results: Higher levels of supernatant cfDNA were significantly associated with slower cell cycling and increased cell death. In addition, a higher cfDNA shedding was found in non-CpG Island Methylator Phenotype (CIMP) models. These results indicate a positive correlation between lower methylation and increased cfDNA levels. To explore this further, we exploited methylation microarrays to identify a subset of probes significantly associated with cfDNA shedding and derive a methylation signature capable of discriminating high from low cfDNA releasers. We applied this signature to an independent set of 176 CRC cell lines and patient derived organoids to select 14 models predicted to be low or high releasers. The methylation profile successfully predicted the amount of cfDNA released in the supernatant. At the functional level, genetic ablation of DNA methyl-transferases increased chromatin accessibility and DNA fragmentation, leading to increased cfDNA release in isogenic CRC cell lines. Furthermore, in vitro treatment of five low releaser CRC cells with a demethylating agent was able to induce a significant increase in cfDNA shedding., Conclusions: Methylation status of cancer cell lines contributes to the variability of cfDNA shedding in vitro. Changes in methylation pattern are associated with cfDNA release levels and might be exploited to increase sensitivity of liquid biopsy assays., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
4. Antagonists of Growth Hormone-Releasing Hormone Inhibit the Growth of Pituitary Adenoma Cells by Hampering Oncogenic Pathways and Promoting Apoptotic Signaling.
- Author
-
Gesmundo I, Granato G, Fuentes-Fayos AC, Alvarez CV, Dieguez C, Zatelli MC, Congiusta N, Banfi D, Prencipe N, Leone S, Brunetti L, Castaño JP, Luque RM, Cai R, Sha W, Ghigo E, Schally AV, and Granata R
- Abstract
Pituitary adenomas (PAs) are intracranial tumors, often associated with excessive hormonal secretion and severe comorbidities. Some patients are resistant to medical therapies; therefore, novel treatment options are needed. Antagonists of growth hormone-releasing hormone (GHRH) exert potent anticancer effects, and early GHRH antagonists were found to inhibit GHRH-induced secretion of pituitary GH in vitro and in vivo. However, the antitumor role of GHRH antagonists in PAs is largely unknown. Here, we show that the GHRH antagonists of MIAMI class, MIA-602 and MIA-690, inhibited cell viability and growth and promoted apoptosis in GH/prolactin-secreting GH3 PA cells transfected with human GHRH receptor (GH3-GHRHR), and in adrenocorticotropic hormone ACTH-secreting AtT20 PA cells. GHRH antagonists also reduced the expression of proteins involved in tumorigenesis and cancer progression, upregulated proapoptotic molecules, and lowered GHRH receptor levels. The combination of MIA-690 with temozolomide synergistically blunted the viability of GH3-GHRHR and AtT20 cells. Moreover, MIA-690 reduced both basal and GHRH-induced secretion of GH and intracellular cAMP levels. Finally, GHRH antagonists inhibited cell viability in human primary GH- and ACTH-PA cell cultures. Overall, our results suggest that GHRH antagonists, either alone or in combination with pharmacological treatments, may be considered for further development as therapy for PAs.
- Published
- 2021
- Full Text
- View/download PDF
5. Adipocyte-derived extracellular vesicles regulate survival and function of pancreatic β cells.
- Author
-
Gesmundo I, Pardini B, Gargantini E, Gamba G, Birolo G, Fanciulli A, Banfi D, Congiusta N, Favaro E, Deregibus MC, Togliatto G, Zocaro G, Brizzi MF, Luque RM, Castaño JP, Bocchiotti MA, Arolfo S, Bruno S, Nano R, Morino M, Piemonti L, Ong H, Matullo G, Falcón-Pérez JM, Ghigo E, Camussi G, and Granata R
- Subjects
- 3T3-L1 Cells, Adult, Animals, Female, Humans, Male, Mice, Adipocytes cytology, Adipocytes metabolism, Adipose Tissue metabolism, Adipose Tissue pathology, Extracellular Vesicles metabolism, Islets of Langerhans cytology, Islets of Langerhans metabolism, Obesity metabolism
- Abstract
Extracellular vesicles (EVs) are implicated in the crosstalk between adipocytes and other metabolic organs, and an altered biological cargo has been observed in EVs from human obese adipose tissue (AT). Yet, the role of adipocyte-derived EVs in pancreatic β cells remains to be determined. Here, we explored the effects of EVs released from adipocytes isolated from both rodents and humans and human AT explants on survival and function of pancreatic β cells and human pancreatic islets. EVs from healthy 3T3-L1 adipocytes increased survival and proliferation and promoted insulin secretion in INS-1E β cells and human pancreatic islets, both those untreated or exposed to cytokines or glucolipotoxicity, whereas EVs from inflamed adipocytes caused β cell death and dysfunction. Human lean adipocyte-derived EVs produced similar beneficial effects, whereas EVs from obese AT explants were harmful for human EndoC-βH3 β cells. We observed differential expression of miRNAs in EVs from healthy and inflamed adipocytes, as well as alteration in signaling pathways and expression of β cell genes, adipokines, and cytokines in recipient β cells. These in vitro results suggest that, depending on the physiopathological state of AT, adipocyte-derived EVs may influence β cell fate and function.
- Published
- 2021
- Full Text
- View/download PDF
6. Calcitriol Inhibits Viability and Proliferation in Human Malignant Pleural Mesothelioma Cells.
- Author
-
Gesmundo I, Silvagno F, Banfi D, Monica V, Fanciulli A, Gamba G, Congiusta N, Libener R, Riganti C, Ghigo E, and Granata R
- Subjects
- Calcitriol therapeutic use, Cell Cycle Checkpoints drug effects, Cell Cycle Checkpoints physiology, Cell Line, Tumor, Cell Proliferation physiology, Cell Survival physiology, Humans, Mesothelioma, Malignant drug therapy, Tumor Cells, Cultured, Vitamins therapeutic use, Calcitriol pharmacology, Cell Proliferation drug effects, Cell Survival drug effects, Mesothelioma, Malignant pathology, Vitamins pharmacology
- Abstract
Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor, often associated with exposure to asbestos and characterized by poor prognosis and limited treatment options. The biologically active form of vitamin D, calcitriol, exerts anticancer effects in many cell types, both alone and in combination with chemotherapy drugs, through binding to vitamin D receptor (VDR); however, the role of calcitriol in MPM is still unknown. This study aimed to determine the potential antitumor role of calcitriol in MPM. The results showed that calcitriol reduces cell viability and proliferation in human MPM cells lines, which express both cytoplasmic and nuclear VDR; furthermore, calcitriol potentiated the inhibitory activity of the chemotherapy drug PEM. These effects were paralleled by cell cycle arrest and inhibition in expression of c-Myc and cyclins involved in cell cycle progression. Exposure of MPM cells to calcitriol also produced an alteration in mitochondrial function and inhibition in the expression of respiratory chain complex subunits. Finally, the inhibitory effects of calcitriol were also observed on viability of human primary MPM cells. Collectively, these results indicate a novel anticancer role for calcitriol in MPM, suggesting potential for vitamin D derivatives, alone or in combination with chemotherapy, in the treatment of this malignancy., (Copyright © 2020 Gesmundo, Silvagno, Banfi, Monica, Fanciulli, Gamba, Congiusta, Libener, Riganti, Ghigo and Granata.)
- Published
- 2020
- Full Text
- View/download PDF
7. PPARs are mediators of anti-cancer properties of superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with conjugated linoleic acid.
- Author
-
Ricci M, Miola M, Multari C, Borroni E, Canuto RA, Congiusta N, Vernè E, Follenzi A, and Muzio G
- Subjects
- Anilides pharmacology, Animals, Antineoplastic Agents therapeutic use, Apoptosis drug effects, Breast Neoplasms, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival, Female, Interleukin-1beta metabolism, Linoleic Acids, Conjugated therapeutic use, Magnetite Nanoparticles therapeutic use, Mice, Tumor Necrosis Factor-alpha metabolism, Antineoplastic Agents pharmacology, Linoleic Acids, Conjugated chemistry, Magnetite Nanoparticles chemistry, Peroxisome Proliferator-Activated Receptors pharmacology
- Abstract
Breast cancer chemotherapy can cause side effects due to nonspecific drug delivery, low solubility and fast metabolism of drugs used in conventional therapy. Moreover, the therapeutic effect of the drugs is often reduced by the strengthening of chemoresistance, which occurs via a variety of mechanisms. Different strategies have been developed to reduce multidrug resistance (MDR)-associated gene expressions including the use of surfactants and polymers. In this study superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with conjugated linoleic acid (CLA) reduced the number and viability of cells in comparison with both untreated cells or cells treated with SPIONs alone. This cytostatic effect correlated with the increase of peroxisome proliferator-activated receptors γ (PPARγ). The necrotic cell death induced, as a consequence, an inflammatory process, as evidenced by the decrease of the anti-inflammatory PPARα and increase of pro-inflammatory TNFα and IL-1β. PPARs were examined because CLA is one of their natural ligands. The antitumor effect observed was accompanied by a down-regulation of p-glycoprotein (P-gp), which was the first important discovered efflux transporter belonging to MDR, and of ALDH3A1, an enzyme able to metabolize some drugs, reducing their effects. The down-regulation of P-gp correlated with the increase of cytokines. The ALDH3A1 decrease correlated with the increase of PPARγ. Based on these results, PPARs are molecular mediators of anti-cancer effect of SPIONs functionalized with CLA, being changes in these nuclear receptors correlated with induction of cytotoxicity and inflammation, and decreased ability of cancer cells in blocking anti-cancer drug effect., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.