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Paola Caria
Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy

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Journal article
Published: 24 June 2021 in International Journal of Molecular Sciences
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Novel psychoactive substances (NPS) are synthetic substances belonging to diverse groups, designed to mimic the effects of scheduled drugs, resulting in altered toxicity and potency. Up to now, information available on the pharmacology and toxicology of these new substances is very limited, posing a considerable challenge for prevention and treatment. The present in vitro study investigated the possible mechanisms of toxicity of two emerging NPS (i) 4′-methyl-alpha-pyrrolidinoexanophenone (3,4-MDPHP), a synthetic cathinone, and (ii) 2-chloro-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA), a phenethylamine. In addition, to apply our model to the class of synthetic opioids, we evaluated the toxicity of fentanyl, as a reference compound for this group of frequently abused substances. To this aim, the in vitro toxic effects of these three compounds were evaluated in dopaminergic-differentiated SH-SY5Y cells. Following 24 h of exposure, all compounds induced a loss of viability, and oxidative stress in a concentration-dependent manner. 2-Cl-4,5-MDMA activates apoptotic processes, while 3,4-MDPHP elicits cell death by necrosis. Fentanyl triggers cell death through both mechanisms. Increased expression levels of pro-apoptotic Bax and caspase 3 activity were observed following 2-Cl-4,5-MDMA and fentanyl, but not 3,4-MDPHP exposure, confirming the different modes of cell death.

ACS Style

Valeria Sogos; Paola Caria; Clara Porcedda; Rafaela Mostallino; Franca Piras; Cristina Miliano; Maria De Luca; M. Castelli. Human Neuronal Cell Lines as An In Vitro Toxicological Tool for the Evaluation of Novel Psychoactive Substances. International Journal of Molecular Sciences 2021, 22, 6785 .

AMA Style

Valeria Sogos, Paola Caria, Clara Porcedda, Rafaela Mostallino, Franca Piras, Cristina Miliano, Maria De Luca, M. Castelli. Human Neuronal Cell Lines as An In Vitro Toxicological Tool for the Evaluation of Novel Psychoactive Substances. International Journal of Molecular Sciences. 2021; 22 (13):6785.

Chicago/Turabian Style

Valeria Sogos; Paola Caria; Clara Porcedda; Rafaela Mostallino; Franca Piras; Cristina Miliano; Maria De Luca; M. Castelli. 2021. "Human Neuronal Cell Lines as An In Vitro Toxicological Tool for the Evaluation of Novel Psychoactive Substances." International Journal of Molecular Sciences 22, no. 13: 6785.

Journal article
Published: 20 May 2021 in Antioxidants
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High-dose of vitamin C (L-ascorbic acid, ascorbate) exhibits anti-tumoral effects, primarily mediated by pro-oxidant mechanisms. This cytotoxic effect is thought to affect the reciprocal crosstalk between redox balance and cell metabolism in different cancer types. Vitamin C also inhibits the growth of papillary thyroid carcinoma (PTC) cells, although the metabolic and redox effects remain to be fully understood. To shed light on these aspects, PTC-derived cell lines harboring the most common genetic alterations characterizing this tumor were used. Cell viability, apoptosis, and the metabolome were explored by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test (MTT), flow cytometry, and UHPLC/MS. Changes were observed in redox homeostasis, with increased reactive oxygen species (ROS) level and perturbation in antioxidants and electron carriers, leading to cell death by both apoptosis and necrosis. The oxidative stress contributed to the metabolic alterations in both glycolysis and TCA cycle. Our results confirm the pro-oxidant effect of vitamin C as relevant in triggering the cytotoxicity in PTC cells and suggest that inhibition of glycolysis and alteration of TCA cycle via NAD+ depletion can play an important role in this mechanism of PTC cancer cell death.

ACS Style

Laura Tronci; Gabriele Serreli; Cristina Piras; Daniela Frau; Tinuccia Dettori; Monica Deiana; Federica Murgia; Maria Santoru; Martina Spada; Vera Leoni; Julian Griffin; Roberta Vanni; Luigi Atzori; Paola Caria. Vitamin C Cytotoxicity and Its Effects in Redox Homeostasis and Energetic Metabolism in Papillary Thyroid Carcinoma Cell Lines. Antioxidants 2021, 10, 809 .

AMA Style

Laura Tronci, Gabriele Serreli, Cristina Piras, Daniela Frau, Tinuccia Dettori, Monica Deiana, Federica Murgia, Maria Santoru, Martina Spada, Vera Leoni, Julian Griffin, Roberta Vanni, Luigi Atzori, Paola Caria. Vitamin C Cytotoxicity and Its Effects in Redox Homeostasis and Energetic Metabolism in Papillary Thyroid Carcinoma Cell Lines. Antioxidants. 2021; 10 (5):809.

Chicago/Turabian Style

Laura Tronci; Gabriele Serreli; Cristina Piras; Daniela Frau; Tinuccia Dettori; Monica Deiana; Federica Murgia; Maria Santoru; Martina Spada; Vera Leoni; Julian Griffin; Roberta Vanni; Luigi Atzori; Paola Caria. 2021. "Vitamin C Cytotoxicity and Its Effects in Redox Homeostasis and Energetic Metabolism in Papillary Thyroid Carcinoma Cell Lines." Antioxidants 10, no. 5: 809.

Journal article
Published: 04 January 2021 in Viruses
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Enterovirus A71 (EV-A71) infection has emerged as a significant public health concern atthe global level. Epidemic events of EV-A71 have been reported worldwide, and this succession of outbreaks has heightened concern that EV-A71 may become a public health threat. In recent years, widespread A71 enterovirus also occurred in European countries. EV-A71 infection causes hand-foot-mouth disease (HFMD), herpangina, and fever. However, it can sometimes induce a variety of neurological complications, including encephalitis, aseptic meningitis, pulmonary edema, and acute flaccid paralysis. We identified new benzimidazole derivatives and described their in vitro cytotoxicity and broad-spectrum anti-enterovirus activity. Among them, derivative 2b resulted in interesting activity against EV-A71, and therefore it was selected for further investigations. Compound 2b proved to be able to protect cell monolayers from EV-A71-induced cytopathogenicity, with an EC50 of 3 µM. Moreover, Vero-76 cells resulted in being significantly protected from necrosis and apoptosis when treated with 2b at 20 and 80 µM. Compound 2b reduced viral adsorption to Vero-76 cells, and when evaluated in a time-of-addition assay, the derivative had the highest effect when added during the infection period. Moreover, derivative 2b reduced viral penetration into host cells. Besides, 2b did not affect intestinal monolayers permeability, showing no toxic effects. A detailed insight into the efficacy of compound 2b against EV-A71 showed a dose-dependent reduction in the viral titer, also at low concentrations. Mechanism of action investigations suggested that our derivative can inhibit viral endocytosis by reducing viral attachment to and penetration into host cells. Pharmacokinetic and toxicity predictions validated compound 2b as a good candidate for further in vivo assays.

ACS Style

Roberta Ibba; Antonio Carta; Silvia Madeddu; Paola Caria; Gabriele Serreli; Sandra Piras; Simona Sestito; Roberta Loddo; Giuseppina Sanna. Inhibition of Enterovirus A71 by a Novel 2-Phenyl-Benzimidazole Derivative. Viruses 2021, 13, 58 .

AMA Style

Roberta Ibba, Antonio Carta, Silvia Madeddu, Paola Caria, Gabriele Serreli, Sandra Piras, Simona Sestito, Roberta Loddo, Giuseppina Sanna. Inhibition of Enterovirus A71 by a Novel 2-Phenyl-Benzimidazole Derivative. Viruses. 2021; 13 (1):58.

Chicago/Turabian Style

Roberta Ibba; Antonio Carta; Silvia Madeddu; Paola Caria; Gabriele Serreli; Sandra Piras; Simona Sestito; Roberta Loddo; Giuseppina Sanna. 2021. "Inhibition of Enterovirus A71 by a Novel 2-Phenyl-Benzimidazole Derivative." Viruses 13, no. 1: 58.

Review
Published: 27 October 2020 in Cancers
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Thyroid cancer is a rare malignancy in the pediatric population that is highly associated with disease aggressiveness and advanced disease stages when compared to adult population. The biological and molecular features underlying pediatric and adult thyroid cancer pathogenesis could be responsible for differences in the clinical presentation and prognosis. Despite this, the clinical assessment and treatments used in pediatric thyroid cancer are the same as those implemented for adults and specific personalized target treatments are not used in clinical practice. In this review, we focus on papillary thyroid carcinoma (PTC), which represents 80–90% of all differentiated thyroid carcinomas. PTC has a high rate of gene fusions and mutations, which can influence the histologic subtypes in both children and adults. This review also highlights telomere-related genomic instability and changes in nuclear organization as novel biomarkers for thyroid cancers.

ACS Style

Aline Rangel-Pozzo; Luiza Sisdelli; Maria Cordioli; Fernanda Vaisman; Paola Caria; Sabine Mai; Janete Cerutti. Genetic Landscape of Papillary Thyroid Carcinoma and Nuclear Architecture: An Overview Comparing Pediatric and Adult Populations. Cancers 2020, 12, 3146 .

AMA Style

Aline Rangel-Pozzo, Luiza Sisdelli, Maria Cordioli, Fernanda Vaisman, Paola Caria, Sabine Mai, Janete Cerutti. Genetic Landscape of Papillary Thyroid Carcinoma and Nuclear Architecture: An Overview Comparing Pediatric and Adult Populations. Cancers. 2020; 12 (11):3146.

Chicago/Turabian Style

Aline Rangel-Pozzo; Luiza Sisdelli; Maria Cordioli; Fernanda Vaisman; Paola Caria; Sabine Mai; Janete Cerutti. 2020. "Genetic Landscape of Papillary Thyroid Carcinoma and Nuclear Architecture: An Overview Comparing Pediatric and Adult Populations." Cancers 12, no. 11: 3146.

Journal article
Published: 01 February 2019 in Metabolites
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Background: Thyroid cancer is the most common endocrine malignancy, with papillary thyroid carcinoma (PTC) being the most common (85–90%) among all the different types of thyroid carcinomas. Cancer cells show metabolic alterations and, due to their rapid proliferation, an accumulation of reactive oxygen species, playing a fundamental role in cancer development and progression. Currently, the crosstalk among thyrocytes metabolism, redox balance and oncogenic mutations remain poorly characterized. The aim of this study was to investigate the interplay among metabolic alterations, redox homeostasis and oncogenic mutations in PTC-derived cells. Methods: Metabolic and redox profile, glutamate-cysteine ligase, glutaminase-1 and metabolic transporters were evaluated in PTC-derived cell lines with distinguished genetic background (TPC-1, K1 and B-CPAP), as well as in an immortalized thyroid cell line (Nthy-ori3-1) selected as control. Results: PTC-derived cells, particularly B-CPAP cells, harboring BRAF, TP53 and human telomerase reverse transcriptase (hTERT) mutation, displayed an increase of metabolites and transporters involved in energetic pathways. Furthermore, all PTC-derived cells showed altered redox homeostasis, as reported by the decreased antioxidant ratios, as well as the increased levels of intracellular oxidant species. Conclusion: Our findings confirmed the pivotal role of the metabolism and redox state regulation in the PTC biology. Particularly, the most perturbed metabolic phenotypes were found in B-CPAP cells, which are characterized by the most aggressive genetic background.

ACS Style

Laura Tronci; Paola Caria; Daniela Virginia Frau; Sonia Liggi; Cristina Piras; Federica Murgia; Maria Laura Santoru; Monica Pibiri; Monica Deiana; Julian Leether Griffin; Roberta Vanni; Luigi Atzori. Crosstalk between Metabolic Alterations and Altered Redox Balance in PTC-Derived Cell Lines. Metabolites 2019, 9, 23 .

AMA Style

Laura Tronci, Paola Caria, Daniela Virginia Frau, Sonia Liggi, Cristina Piras, Federica Murgia, Maria Laura Santoru, Monica Pibiri, Monica Deiana, Julian Leether Griffin, Roberta Vanni, Luigi Atzori. Crosstalk between Metabolic Alterations and Altered Redox Balance in PTC-Derived Cell Lines. Metabolites. 2019; 9 (2):23.

Chicago/Turabian Style

Laura Tronci; Paola Caria; Daniela Virginia Frau; Sonia Liggi; Cristina Piras; Federica Murgia; Maria Laura Santoru; Monica Pibiri; Monica Deiana; Julian Leether Griffin; Roberta Vanni; Luigi Atzori. 2019. "Crosstalk between Metabolic Alterations and Altered Redox Balance in PTC-Derived Cell Lines." Metabolites 9, no. 2: 23.

Journal article
Published: 31 January 2019 in Metabolites
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Background: Thyroid cancer is the most common endocrine malignancy, with papillary thyroid carcinoma (PTC) being the most common (85–90%) among all the different types of thyroid carcinomas. Cancer cells show metabolic alterations and, due to their rapid proliferation, an accumulation of reactive oxygen species, playing a fundamental role in cancer development and progression. Currently, the crosstalk among thyrocytes metabolism, redox balance and oncogenic mutations remain poorly characterized. The aim of this study was to investigate the interplay among metabolic alterations, redox homeostasis and oncogenic mutations in PTC-derived cells. Methods: Metabolic and redox profile, glutamate-cysteine ligase, glutaminase-1 and metabolic transporters were evaluated in PTC-derived cell lines with distinguished genetic background (TPC-1, K1 and B-CPAP), as well as in an immortalized thyroid cell line (Nthy-ori3-1) selected as control. Results: PTC-derived cells, particularly B-CPAP cells, harboring BRAF, TP53 and human telomerase reverse transcriptase (hTERT) mutation, displayed an increase of metabolites and transporters involved in energetic pathways. Furthermore, all PTC-derived cells showed altered redox homeostasis, as reported by the decreased antioxidant ratios, as well as the increased levels of intracellular oxidant species. Conclusion: Our findings confirmed the pivotal role of the metabolism and redox state regulation in the PTC biology. Particularly, the most perturbed metabolic phenotypes were found in B-CPAP cells, which are characterized by the most aggressive genetic background.

ACS Style

Laura Tronci; Paola Caria; Daniela Virginia Frau; Sonia Liggi; Cristina Piras; Federica Murgia; Maria Laura Santoru; Monica Pibiri; Monica Deiana; Julian Leether Griffin; Roberta Vanni; Luigi Atzori. Crosstalk between Metabolic Alterations and Altered Redox Balance in PTC-Derived Cell Lines. Metabolites 2019, 9, 1 .

AMA Style

Laura Tronci, Paola Caria, Daniela Virginia Frau, Sonia Liggi, Cristina Piras, Federica Murgia, Maria Laura Santoru, Monica Pibiri, Monica Deiana, Julian Leether Griffin, Roberta Vanni, Luigi Atzori. Crosstalk between Metabolic Alterations and Altered Redox Balance in PTC-Derived Cell Lines. Metabolites. 2019; 9 (2):1.

Chicago/Turabian Style

Laura Tronci; Paola Caria; Daniela Virginia Frau; Sonia Liggi; Cristina Piras; Federica Murgia; Maria Laura Santoru; Monica Pibiri; Monica Deiana; Julian Leether Griffin; Roberta Vanni; Luigi Atzori. 2019. "Crosstalk between Metabolic Alterations and Altered Redox Balance in PTC-Derived Cell Lines." Metabolites 9, no. 2: 1.

Journal article
Published: 27 September 2018 in International Journal of Molecular Sciences
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Papillary thyroid carcinoma (PTC), is characterized by a heterogeneous group of cells, including cancer stem cells (CSCs), crucially involved in tumor initiation, progression and recurrence. CSCs appear to have a distinct metabolic phenotype, compared to non-stem cancer cells. How they adapt their metabolism to the cancer process is still unclear, and no data are yet available for PTC. We recently isolated thyrospheres, containing cancer stem-like cells, from B-CPAP and TPC-1 cell lines derived from PTC of the BRAF-like expression profile class, and stem-like cells from Nthy-ori3-1 normal thyreocyte-derived cell line. In the present study, gas chromatography/mass spectrometry metabolomic profiles of cancer thyrospheres were compared to cancer parental adherent cells and to non cancer thyrospheres profiles. A statistically significant decrease of glycolytic pathway metabolites and variations in Krebs cycle metabolites was found in thyrospheres versus parental cells. Moreover, cancer stem-like cells showed statistically significant differences in Krebs cycle intermediates, amino acids, cholesterol, and fatty acids content, compared to non-cancer stem-like cells. For the first time, data are reported on the metabolic profile of PTC cancer stem-like cells and confirm that changes in metabolic pathways can be explored as new biomarkers and targets for therapy in this tumor.

ACS Style

Paola Caria; Laura Tronci; Tinuccia Dettori; Federica Murgia; Maria Laura Santoru; Julian L. Griffin; Roberta Vanni; Luigi Atzori. Metabolomic Alterations in Thyrospheres and Adherent Parental Cells in Papillary Thyroid Carcinoma Cell Lines: A Pilot Study. International Journal of Molecular Sciences 2018, 19, 2948 .

AMA Style

Paola Caria, Laura Tronci, Tinuccia Dettori, Federica Murgia, Maria Laura Santoru, Julian L. Griffin, Roberta Vanni, Luigi Atzori. Metabolomic Alterations in Thyrospheres and Adherent Parental Cells in Papillary Thyroid Carcinoma Cell Lines: A Pilot Study. International Journal of Molecular Sciences. 2018; 19 (10):2948.

Chicago/Turabian Style

Paola Caria; Laura Tronci; Tinuccia Dettori; Federica Murgia; Maria Laura Santoru; Julian L. Griffin; Roberta Vanni; Luigi Atzori. 2018. "Metabolomic Alterations in Thyrospheres and Adherent Parental Cells in Papillary Thyroid Carcinoma Cell Lines: A Pilot Study." International Journal of Molecular Sciences 19, no. 10: 2948.

Journal article
Published: 21 October 2016 in International Journal of Molecular Sciences
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Extensive research is dedicated to understanding if sporadic and familial papillary thyroid carcinoma are distinct biological entities. We have previously demonstrated that familial papillary thyroid cancer (fPTC) cells exhibit short relative telomere length (RTL) in both blood and tissues and that these features may be associated with chromosome instability. Here, we investigated the frequency of HER2 (Human Epidermal Growth Factor Receptor 2) amplification, and other recently reported genetic alterations in sporadic PTC (sPTC) and fPTC, and assessed correlations with RTL and BRAF mutational status. We analyzed HER2 gene amplification and the integrity of ALK, ETV6, RET, and BRAF genes by fluorescence in situ hybridization in isolated nuclei and paraffin-embedded formalin-fixed sections of 13 fPTC and 18 sPTC patients. We analyzed BRAFV600E mutation and RTL by qRT-PCR. Significant HER2 amplification (p = 0.0076), which was restricted to scattered groups of cells, was found in fPTC samples. HER2 amplification in fPTCs was invariably associated with BRAFV600E mutation. RTL was shorter in fPTCs than sPTCs (p < 0.001). No rearrangements of other tested genes were observed. These findings suggest that the association of HER2 amplification with BRAFV600E mutation and telomere shortening may represent a marker of tumor aggressiveness, and, in refractory thyroid cancer, may warrant exploration as a site for targeted therapy.

ACS Style

Paola Caria; Silvia Cantara; Daniela Virginia Frau; Furio Pacini; Roberta Vanni; Tinuccia Dettori. Genetic Heterogeneity of HER2 Amplification and Telomere Shortening in Papillary Thyroid Carcinoma. International Journal of Molecular Sciences 2016, 17, 1759 .

AMA Style

Paola Caria, Silvia Cantara, Daniela Virginia Frau, Furio Pacini, Roberta Vanni, Tinuccia Dettori. Genetic Heterogeneity of HER2 Amplification and Telomere Shortening in Papillary Thyroid Carcinoma. International Journal of Molecular Sciences. 2016; 17 (10):1759.

Chicago/Turabian Style

Paola Caria; Silvia Cantara; Daniela Virginia Frau; Furio Pacini; Roberta Vanni; Tinuccia Dettori. 2016. "Genetic Heterogeneity of HER2 Amplification and Telomere Shortening in Papillary Thyroid Carcinoma." International Journal of Molecular Sciences 17, no. 10: 1759.

Journal article
Published: 22 August 2014 in Molecular Cytogenetics
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Many of the exciting new developments in solid tumor molecular cytogenetics impact classical and molecular pathology. Fluorescence in situ hybridization to identify specific DNA target sequences in nuclei of non-dividing cells in solid neoplasms has contributed to the integration of molecular cytogenetics into cytology in spite of the remarkable promiscuity of cancer genes. Indeed, although it is a low-throughput assay, fluorescence in situ hybridization enables the direct disclosure and localization of genetic markers in single nuclei. Gene fusions are among the most prominent genetic alterations in cancer, providing markers that may be determinant in needle biopsies that are negative or suspicious for malignancy, and may contribute to the correct classification of the tumors. In view of the expanding use of fluorescence in situ hybridization in cytology, future challenges include automated sample evaluation and the specification of common criteria for interpreting and reporting results.

ACS Style

Paola Caria; Roberta Vanni. FISH molecular testing in cytological preparations from solid tumors. Molecular Cytogenetics 2014, 7, 56 -56.

AMA Style

Paola Caria, Roberta Vanni. FISH molecular testing in cytological preparations from solid tumors. Molecular Cytogenetics. 2014; 7 (1):56-56.

Chicago/Turabian Style

Paola Caria; Roberta Vanni. 2014. "FISH molecular testing in cytological preparations from solid tumors." Molecular Cytogenetics 7, no. 1: 56-56.

Journal article
Published: 01 January 2011 in Molecular Cytogenetics
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Differentiated thyroid carcinoma offers a good model to investigate the possible correlation between specific gene mutations and chromosome instability. Papillary thyroid neoplasms are characterized by different mutually exclusive genetic alterations, some of which are associated with aneuploidy and aggressive phenotype.

ACS Style

Irena Marić; Silvia Viaggi; Paola Caria; Daniela V Frau; Paolo Degan; Roberta Vanni. Centrosomal and mitotic abnormalities in cell lines derived from papillary thyroid cancer harboring specific gene alterations. Molecular Cytogenetics 2011, 4, 26 -26.

AMA Style

Irena Marić, Silvia Viaggi, Paola Caria, Daniela V Frau, Paolo Degan, Roberta Vanni. Centrosomal and mitotic abnormalities in cell lines derived from papillary thyroid cancer harboring specific gene alterations. Molecular Cytogenetics. 2011; 4 (1):26-26.

Chicago/Turabian Style

Irena Marić; Silvia Viaggi; Paola Caria; Daniela V Frau; Paolo Degan; Roberta Vanni. 2011. "Centrosomal and mitotic abnormalities in cell lines derived from papillary thyroid cancer harboring specific gene alterations." Molecular Cytogenetics 4, no. 1: 26-26.