46 results on '"Girolimetti, Giulia"'
Search Results
2. Characterization of Chemoresistance in Pancreatic Cancer: A Look at MDR-1 Polymorphisms and Expression in Cancer Cells and Patients.
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Girolimetti, Giulia, Balena, Barbara, Cordella, Paola, Verri, Tiziano, Eusebi, Leonardo Henry, Bozzetti, Maria Pia, Bucci, Cecilia, and Guerra, Flora
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DRUG resistance in cancer cells , *GENE expression , *WESTERN immunoblotting , *SINGLE nucleotide polymorphisms , *PANCREATIC cancer - Abstract
Pancreatic malignancy is the fourth cause of cancer-related death in Western countries and is predicted to become the second leading cause of cancer-related mortality by 2030. The standard therapies (FOLFIRINOX and gemcitabine with nab-paclitaxel) are not resolutive because this type of cancer is also characterized by a high chemoresistance, due in part to the activity of the ATP Binding Cassette (ABC) pumps accounting for the reduction in the intracellular concentration of the drugs. In this work, we analyze the occurrence of single-nucleotide polymorphisms (SNPs) in the MDR-1 gene, in different pancreatic cancer cell lines, and in tissues from pancreatic cancer patients by DNA sequencing, as well as the expression levels of MDR-1 mRNA and protein, by qRT-PCR and Western Blot analysis. We found that gemcitabine-resistant cells, in conjunction with homozygosis of analyzed SNPs, showed high MDR-1 basal levels with further increases after gemcitabine treatment. Nevertheless, we did not observe in the human PDAC samples a correlation between the level of MDR-1 mRNA and protein expression and SNPs. Preliminary, we conclude that in our small cohort, these SNPs cannot be used as molecular markers for predicting the levels of MDR-1 mRNA/protein levels and drug responses in patients with PDAC. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Mitochondrial DNA analysis efficiently contributes to the identification of metastatic contralateral breast cancers
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Girolimetti, Giulia, Marchio, Lorena, De Leo, Antonio, Mangiarelli, Miriam, Amato, Laura Benedetta, Zanotti, Simone, Taffurelli, Mario, Santini, Donatella, Gasparre, Giuseppe, and Ceccarelli, Claudio
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- 2021
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4. mtDNA mutations in cancer
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Girolimetti, Giulia, primary, De Luise, Monica, additional, Porcelli, Anna Maria, additional, Gasparre, Giuseppe, additional, and Kurelac, Ivana, additional
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- 2020
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5. List of Contributors
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Achilli, Alessandro, primary, Attimonelli, Marcella, additional, Bacman, Sandra R., additional, Barrientos, Antoni, additional, Berridge, Michael V., additional, Burr, Stephen P., additional, Calabrese, Claudia, additional, Calabrese, Francesco Maria, additional, Chinnery, Patrick F., additional, De Luise, Monica, additional, Diaz, Francisca, additional, Doimo, Mara, additional, Fontanesi, Flavia, additional, Fu, Yi, additional, Gammage, Payam A., additional, Garone, Caterina, additional, Gasparre, Giuseppe, additional, Ghelli, Anna, additional, Girolimetti, Giulia, additional, Glasgow, Ruth I.C., additional, Gomez-Duran, Aurora, additional, Grasso, Carole, additional, Herst, Patries M., additional, Holt, Ian James, additional, Iommarini, Luisa, additional, Kang, Dongchon, additional, Kurelac, Ivana, additional, Lim, Albert Z., additional, Lott, Marie T., additional, Matsuda, Shigeru, additional, McFarland, Robert, additional, Minczuk, Michal, additional, Moraes, Carlos T., additional, Nicholls, Thomas J., additional, Oláhová, Monika, additional, Olivieri, Anna, additional, Pfeiffer, Annika, additional, Pinheiro, Pedro, additional, Pitceathly, Robert D.S., additional, Porcelli, Anna Maria, additional, Preste, Roberto, additional, Procaccio, Vincent, additional, Quadalti, Corinne, additional, Rahman, Shamima, additional, Reyes, Aurelio, additional, Semino, Ornella, additional, Sfeir, Agnel, additional, Shiping, Zhang, additional, Sia, Elaine Ayres, additional, Spinazzola, Antonella, additional, Stein, Alexis, additional, Szczepanowska, Karolina, additional, Tagliabracci, Adriano, additional, Taylor, Robert W., additional, Tigano, Marco, additional, Torroni, Antonio, additional, Trifunovic, Aleksandra, additional, Turchi, Chiara, additional, Vitale, Ornella, additional, Wallace, Douglas C., additional, Wanrooij, Paulina H., additional, Wanrooij, Sjoerd, additional, and Yasukawa, Takehiro, additional
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- 2020
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6. Mitochondrial Mutations in Cancer Progression: Causative, Bystanders, or Modifiers of Tumorigenesis?
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Kurelac, Ivana, Vidone, Michele, Girolimetti, Giulia, Calabrese, Claudia, Gasparre, Giuseppe, Mazurek, Sybille, editor, and Shoshan, Maria, editor
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- 2015
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7. Inducing cancer indolence by targeting mitochondrial Complex I is potentiated by blocking macrophage-mediated adaptive responses
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Kurelac, Ivana, Iommarini, Luisa, Vatrinet, Renaud, Amato, Laura Benedetta, De Luise, Monica, Leone, Giulia, Girolimetti, Giulia, Umesh Ganesh, Nikkitha, Bridgeman, Victoria Louise, Ombrato, Luigi, Columbaro, Marta, Ragazzi, Moira, Gibellini, Lara, Sollazzo, Manuela, Feichtinger, Rene Gunther, Vidali, Silvia, Baldassarre, Maurizio, Foriel, Sarah, Vidone, Michele, Cossarizza, Andrea, Grifoni, Daniela, Kofler, Barbara, Malanchi, Ilaria, Porcelli, Anna Maria, and Gasparre, Giuseppe
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- 2019
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8. Mitochondrial DNA genotyping efficiently reveals clonality of synchronous endometrial and ovarian cancers
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Guerra, Flora, Girolimetti, Giulia, Perrone, Anna Myriam, Procaccini, Martina, Kurelac, Ivana, Ceccarelli, Claudio, De Biase, Dario, Caprara, Giacomo, Zamagni, Claudio, De Iaco, Pierandrea, Santini, Donatella, and Gasparre, Giuseppe
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- 2014
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9. MicroRNA and Metabolic Profiling of a Primary Ovarian Neuroendocrine Carcinoma Pulmonary-Type Reveals a High Degree of Similarity with Small Cell Lung Cancer
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Miglietta, Stefano, primary, Girolimetti, Giulia, additional, Marchio, Lorena, additional, Sollazzo, Manuela, additional, Laprovitera, Noemi, additional, Coluccelli, Sara, additional, De Biase, Dario, additional, De Leo, Antonio, additional, Santini, Donatella, additional, Kurelac, Ivana, additional, Iommarini, Luisa, additional, Ghelli, Anna, additional, Campana, Davide, additional, Ferracin, Manuela, additional, Perrone, Anna Myriam, additional, Gasparre, Giuseppe, additional, and Porcelli, Anna Maria, additional
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- 2022
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10. A multi-parametric workflow for the prioritization of mitochondrial DNA variants of clinical interest
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Santorsola, Mariangela, Calabrese, Claudia, Girolimetti, Giulia, Diroma, Maria Angela, Gasparre, Giuseppe, and Attimonelli, Marcella
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- 2016
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11. Electrochemotherapy in Vulvar Cancer and Cisplatin Combined with Electroporation. Systematic Review and In Vitro Studies
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Perrone, Anna Myriam, primary, Ravegnini, Gloria, additional, Miglietta, Stefano, additional, Argnani, Lisa, additional, Ferioli, Martina, additional, De Crescenzo, Eugenia, additional, Tesei, Marco, additional, Di Stanislao, Marco, additional, Girolimetti, Giulia, additional, Gasparre, Giuseppe, additional, Porcelli, Anna Maria, additional, De Terlizzi, Francesca, additional, Zamagni, Claudio, additional, Morganti, Alessio Giuseppe, additional, and De Iaco, Pierandrea, additional
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- 2021
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12. Mitochondrial DNA analysis efficiently contributes to the identification of metastatic contralateral breast cancers
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Girolimetti, Giulia, primary, Marchio, Lorena, additional, De Leo, Antonio, additional, Mangiarelli, Miriam, additional, Amato, Laura Benedetta, additional, Zanotti, Simone, additional, Taffurelli, Mario, additional, Santini, Donatella, additional, Gasparre, Giuseppe, additional, and Ceccarelli, Claudio, additional
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- 2020
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13. Plasma-activated Ringer’s Lactate Solution Displays a Selective Cytotoxic Effect on Ovarian Cancer Cells
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Bisag, Alina, primary, Bucci, Cristiana, additional, Coluccelli, Sara, additional, Girolimetti, Giulia, additional, Laurita, Romolo, additional, De Iaco, Pierandrea, additional, Perrone, Anna Myriam, additional, Gherardi, Matteo, additional, Marchio, Lorena, additional, Porcelli, Anna Maria, additional, Colombo, Vittorio, additional, and Gasparre, Giuseppe, additional
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- 2020
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14. Synergistic Effect of Mitochondrial and Lysosomal Dysfunction in Parkinson’s Disease
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Guerra, Flora, primary, Girolimetti, Giulia, additional, Beli, Raffaella, additional, Mitruccio, Marco, additional, Pacelli, Consiglia, additional, Ferretta, Anna, additional, Gasparre, Giuseppe, additional, Cocco, Tiziana, additional, and Bucci, Cecilia, additional
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- 2019
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15. Modulation of RAB7A Protein Expression Determines Resistance to Cisplatin through Late Endocytic Pathway Impairment and Extracellular Vesicular Secretion
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Guerra, Flora, primary, Paiano, Aurora, additional, Migoni, Danilo, additional, Girolimetti, Giulia, additional, Perrone, Anna Myriam, additional, De Iaco, Pierandrea, additional, Fanizzi, Francesco Paolo, additional, Gasparre, Giuseppe, additional, and Bucci, Cecilia, additional
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- 2019
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16. Additional file 1: of Mitochondrial DNA sequencing demonstrates clonality of peritoneal implants of borderline ovarian tumors
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Girolimetti, Giulia, Iaco, Pierandrea De, Procaccini, Martina, Panzacchi, Riccardo, Kurelac, Ivana, Amato, Laura, Dondi, Giulia, Caprara, Giacomo, Ceccarelli, Claudio, Santini, Donatella, Porcelli, Anna, Perrone, Anna, and Gasparre, Giuseppe
- Abstract
Supplementary materials and methods. Detailed Materials and Methods are reported. (DOCX 32 kb)
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- 2017
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17. Potential for Mitochondrial DNA Sequencing in the Differential Diagnosis of Gynaecological Malignancies
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Perrone, Anna, primary, Girolimetti, Giulia, additional, Procaccini, Martina, additional, Marchio, Lorena, additional, Livi, Alessandra, additional, Borghese, Giulia, additional, Porcelli, Anna, additional, De Iaco, Pierandrea, additional, and Gasparre, Giuseppe, additional
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- 2018
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18. PGC1α: Friend or Foe in Cancer?
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Mastropasqua, Francesca, primary, Girolimetti, Giulia, additional, and Shoshan, Maria, additional
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- 2018
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19. Pathological and molecular diagnosis of bilateral inguinal lymph nodes metastases from low-grade endometrial adenocarcinoma: a case report with review of the literature
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Perrone, Anna Myriam, primary, Girolimetti, Giulia, additional, Cima, Simona, additional, Kurelac, Ivana, additional, Livi, Alessandra, additional, Caprara, Giacomo, additional, Santini, Donatella, additional, Castellucci, Paolo, additional, Morganti, Alessio Giuseppe, additional, Gasparre, Giuseppe, additional, and De Iaco, Pierandrea, additional
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- 2018
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20. Molecular and metabolic features of oncocytomas: Seeking the blueprints of indolent cancers
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De Luise, Monica, primary, Girolimetti, Giulia, additional, Okere, Bernard, additional, Porcelli, Anna Maria, additional, Kurelac, Ivana, additional, and Gasparre, Giuseppe, additional
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- 2017
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21. Platinum-induced mitochondrial DNA mutations confer lower sensitivity to paclitaxel by impairing tubulin cytoskeletal organization
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Girolimetti, Giulia, primary, Guerra, Flora, additional, Iommarini, Luisa, additional, Kurelac, Ivana, additional, Vergara, Daniele, additional, Maffia, Michele, additional, Vidone, Michele, additional, Amato, Laura Benedetta, additional, Leone, Giulia, additional, Dusi, Sabrina, additional, Tiranti, Valeria, additional, Perrone, Anna Myriam, additional, Bucci, Cecilia, additional, Porcelli, Anna Maria, additional, and Gasparre, Giuseppe, additional
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- 2017
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22. Mitochondrial DNA sequencing demonstrates clonality of peritoneal implants of borderline ovarian tumors
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Girolimetti, Giulia, primary, De Iaco, Pierandrea, additional, Procaccini, Martina, additional, Panzacchi, Riccardo, additional, Kurelac, Ivana, additional, Amato, Laura Benedetta, additional, Dondi, Giulia, additional, Caprara, Giacomo, additional, Ceccarelli, Claudio, additional, Santini, Donatella, additional, Porcelli, Anna Maria, additional, Perrone, Anna Myriam, additional, and Gasparre, Giuseppe, additional
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- 2017
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23. The α-ketoglutarate dehydrogenase complex in cancer metabolic plasticity
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Vatrinet, Renaud, primary, Leone, Giulia, additional, De Luise, Monica, additional, Girolimetti, Giulia, additional, Vidone, Michele, additional, Gasparre, Giuseppe, additional, and Porcelli, Anna Maria, additional
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- 2017
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24. BRCA-Associated Ovarian Cancer: From Molecular Genetics to Risk Management
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Girolimetti, Giulia, Perrone, Anna Myriam, Santini, Donatella, Barbieri, Elena, Guerra, Flora, Ferrari, Simona, Zamagni, Claudio, De Iaco, Pierandrea, Gasparre, Giuseppe, and Turchetti, Daniela
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endocrine system diseases ,Article Subject ,skin and connective tissue diseases ,female genital diseases and pregnancy complications - Abstract
Ovarian cancer (OC) mostly arises sporadically, but a fraction of cases are associated with mutations in BRCA1 and BRCA2 genes. The presence of a BRCA mutation in OC patients has been suggested as a prognostic and predictive factor. In addition, the identification of asymptomatic carriers of such mutations offers an unprecedented opportunity for OC prevention. This review is aimed at exploring the current knowledge on epidemiological and molecular aspects of BRCA-associated OC predisposition, on pathology and clinical behavior of OC occurring in BRCA mutation carriers, and on the available options for managing asymptomatic carriers.
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- 2014
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25. Targeting respiratory Complex I: A metabolic strategy to prevent tumor progression
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Vatrinet, Renaud, primary, Kurelac, Ivana, additional, Iommarini, Luisa, additional, Amato, Laura, additional, Leone, Giulia, additional, Girolimetti, Giulia, additional, Vidone, Michele, additional, De Luise, Monica, additional, Vidali, Silvia, additional, Columbaro, Marta, additional, Calabrese, Claudia, additional, Tullo, Apollonia, additional, Kofler, Barbara, additional, Gasparre, Giuseppe, additional, and Porcelli, Anna Maria, additional
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- 2016
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26. A multi-parametric workflow for the prioritization of mitochondrial DNA variants of clinical interest
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Santorsola, Mariangela, primary, Calabrese, Claudia, additional, Girolimetti, Giulia, additional, Diroma, Maria Angela, additional, Gasparre, Giuseppe, additional, and Attimonelli, Marcella, additional
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- 2015
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27. A comprehensive characterization of mitochondrial DNA mutations in glioblastoma multiforme
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Vidone, Michele, primary, Clima, Rosanna, additional, Santorsola, Mariangela, additional, Calabrese, Claudia, additional, Girolimetti, Giulia, additional, Kurelac, Ivana, additional, Amato, Laura Benedetta, additional, Iommarini, Luisa, additional, Trevisan, Elisa, additional, Leone, Marco, additional, Soffietti, Riccardo, additional, Morra, Isabella, additional, Faccani, Giuliano, additional, Attimonelli, Marcella, additional, Porcelli, Anna Maria, additional, and Gasparre, Giuseppe, additional
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- 2015
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28. Mitochondrial DNA genotyping reveals synchronous nature of endometrial and ovarian cancers
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Guerra, Flora, primary, Girolimetti, Giulia, additional, Kurelac, Ivana, additional, Perrone, Anna Myriam, additional, Procaccini, Martina, additional, De Biase, Dario, additional, Ceccarelli, Claudio, additional, Caprara, Giacomo, additional, De Iaco, Pierandrea, additional, Santini, Donatella, additional, and Gasparre, Giuseppe, additional
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- 2014
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29. Ovarian Neuroendocrine Tumors: Pathological and Immunohistochemical Features of a Single-Center Case Series
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Di Nanni, Doriana Donatella, Domeniconi, Lucia, Ambrosi, Francesca, Girolimetti, Giulia, Santandrea, Giacomo, Santini, Donatella, Giovanni Tallini, and Leo, Antonio
30. Inducing cancer indolence by targeting mitochondrial Complex I is potentiated by blocking macrophage-mediated adaptive responses
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Kurelac, Ivana, Iommarini, Luisa, Vatrinet, Renaud, Amato, Laura Benedetta, Luise, Monica De, Leone, Giulia, Girolimetti, Giulia, Nikkitha Umesh Ganesh, Bridgeman, Victoria Louise, Ombrato, Luigi, Columbaro, Marta, Ragazzi, Moira, Gibellini, Lara, Sollazzo, Manuela, Feichtinger, Rene Gunther, Vidali, Silvia, Baldassarre, Maurizio, Foriel, Sarah, Vidone, Michele, Cossarizza, Andrea, Grifoni, Daniela, Kofler, Barbara, Malanchi, Ilaria, Porcelli, Anna Maria, and Gasparre, Giuseppe
- Subjects
Model organisms ,Stem Cells ,Tumour Biology ,Genetics & Genomics ,3. Good health - Abstract
Converting carcinomas in benign oncocytomas has been suggested as a potential anti-cancer strategy. One of the oncocytoma hallmarks is the lack of respiratory complex I (CI). Here we use genetic ablation of this enzyme to induce indolence in two cancer types, and show this is reversed by allowing the stabilization of Hypoxia Inducible Factor-1 alpha (HIF-1α). We further show that on the long run CI-deficient tumors re-adapt to their inability to respond to hypoxia, concordantly with the persistence of human oncocytomas. We demonstrate that CI-deficient tumors survive and carry out angiogenesis, despite their inability to stabilize HIF-1α. Such adaptive response is mediated by tumor associated macrophages, whose blockage improves the effect of CI ablation. Additionally, the simultaneous pharmacological inhibition of CI function through metformin and macrophage infiltration through PLX-3397 impairs tumor growth in vivo in a synergistic manner, setting the basis for an efficient combinatorial adjuvant therapy in clinical trials.
31. Inducing cancer indolence by targeting mitochondrial Complex I is potentiated by blocking macrophage-mediated adaptive responses
- Author
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Kurelac, Ivana, Iommarini, Luisa, Vatrinet, Renaud, Amato, Laura Benedetta, Luise, Monica De, Leone, Giulia, Girolimetti, Giulia, Nikkitha Umesh Ganesh, Bridgeman, Victoria Louise, Ombrato, Luigi, Columbaro, Marta, Ragazzi, Moira, Gibellini, Lara, Sollazzo, Manuela, Feichtinger, Rene Gunther, Vidali, Silvia, Baldassarre, Maurizio, Foriel, Sarah, Vidone, Michele, Cossarizza, Andrea, Grifoni, Daniela, Kofler, Barbara, Malanchi, Ilaria, Porcelli, Anna Maria, and Gasparre, Giuseppe
- Subjects
Model organisms ,Stem Cells ,Tumour Biology ,Genetics & Genomics ,3. Good health - Abstract
Converting carcinomas in benign oncocytomas has been suggested as a potential anti-cancer strategy. One of the oncocytoma hallmarks is the lack of respiratory complex I (CI). Here we use genetic ablation of this enzyme to induce indolence in two cancer types, and show this is reversed by allowing the stabilization of Hypoxia Inducible Factor-1 alpha (HIF-1α). We further show that on the long run CI-deficient tumors re-adapt to their inability to respond to hypoxia, concordantly with the persistence of human oncocytomas. We demonstrate that CI-deficient tumors survive and carry out angiogenesis, despite their inability to stabilize HIF-1α. Such adaptive response is mediated by tumor associated macrophages, whose blockage improves the effect of CI ablation. Additionally, the simultaneous pharmacological inhibition of CI function through metformin and macrophage infiltration through PLX-3397 impairs tumor growth in vivo in a synergistic manner, setting the basis for an efficient combinatorial adjuvant therapy in clinical trials.
32. MicroRNA and Metabolic Profiling of a Primary Ovarian Neuroendocrine Carcinoma Pulmonary-Type Reveals a High Degree of Similarity with Small Cell Lung Cancer
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Stefano Miglietta, Giulia Girolimetti, Lorena Marchio, Manuela Sollazzo, Noemi Laprovitera, Sara Coluccelli, Dario De Biase, Antonio De Leo, Donatella Santini, Ivana Kurelac, Luisa Iommarini, Anna Ghelli, Davide Campana, Manuela Ferracin, Anna Myriam Perrone, Giuseppe Gasparre, Anna Maria Porcelli, Miglietta, Stefano, Girolimetti, Giulia, Marchio, Lorena, Sollazzo, Manuela, Laprovitera, Noemi, Coluccelli, Sara, De Biase, Dario, De Leo, Antonio, Santini, Donatella, Kurelac, Ivana, Iommarini, Luisa, Ghelli, Anna, Campana, Davide, Ferracin, Manuela, Perrone, Anna Myriam, Gasparre, Giuseppe, and Porcelli, Anna Maria
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ovarian carcinoma ,microRNA ,small cell neuroendocrine carcinoma ,gynecological cancers ,mTOR ,cancer metabolism ,Genetics ,gynecological cancer ,Molecular Biology ,Biochemistry - Abstract
Small cell neuroendocrine carcinoma is most frequently found in the lung (SCLC), but it has been also reported, albeit with a very low incidence, in the ovary. Here, we analyze a case of primary small cell carcinoma of the ovary of pulmonary type (SCCOPT), a rare and aggressive tumor with poor prognosis, whose biology and molecular features have not yet been thoroughly investigated. The patient affected by SCCOPT had a residual tumor following chemotherapy which displayed pronounced similarity with neuroendocrine tumors and lung cancer in terms of its microRNA expression profile and mTOR-downstream activation. By analyzing the metabolic markers of the neoplastic lesion, we established a likely glycolytic signature. In conclusion, this in-depth characterization of SCCOPT could be useful for future diagnoses, possibly aided by microRNA profiling, allowing clinicians to adopt the most appropriate therapeutic strategy.
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- 2022
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33. Mitochondrial DNA analysis efficiently contributes to the identification of metastatic contralateral breast cancers
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Laura Benedetta Amato, Simone Zanotti, Lorena Marchio, Antonio De Leo, Donatella Santini, Giulia Girolimetti, Claudio Ceccarelli, Giuseppe Gasparre, Miriam Mangiarelli, Mario Taffurelli, Girolimetti, Giulia, Marchio, Lorena, De Leo, Antonio, Mangiarelli, Miriam, Amato, Laura Benedetta, Zanotti, Simone, Taffurelli, Mario, Santini, Donatella, Gasparre, Giuseppe, and Ceccarelli, Claudio
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0301 basic medicine ,Oncology ,Adult ,Cancer Research ,medicine.medical_specialty ,Mitochondrial DNA ,Contralateral breast cancers ,Somatic cell ,Context (language use) ,Breast Neoplasms ,DNA, Mitochondrial ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,Mitochondrial DNA mutations ,Humans ,Contralateral breast ,Neoplasm Metastasis ,Aged ,Aged, 80 and over ,Hematology ,Breast cancer metastasis ,business.industry ,Neoplasms, Second Primary ,General Medicine ,Sequence Analysis, DNA ,Middle Aged ,medicine.disease ,Primary tumor ,030104 developmental biology ,030220 oncology & carcinogenesis ,Mutation ,Mitochondrial DNA mutations · Contralateral breast cancers · Breast cancer metastasis ,Identification (biology) ,Histopathology ,Female ,business ,Original Article – Cancer Research - Abstract
Purpose In daily practice, a contralateral breast cancer (CBC) is usually considered as a new independent tumor despite the indications of several studies showing that the second neoplasia may be a metastatic spread of the primary tumor. Recognition of clonal masses in the context of multiple synchronous or metachronous tumors is crucial for correct prognosis, therapeutic choice, and patient management. Mitochondrial DNA (mtDNA) sequencing shows high informative potential in the diagnosis of synchronous neoplasms, based on the fact that somatic mtDNA mutations are non-recurrent events, whereas tumors sharing them have a common origin. We here applied this technique to reveal clonality of the CBC with respect to the first tumor. Methods We analyzed 30 sample pairs of primary breast cancers and synchronous or metachronous CBCs with detailed clinical information available and compared standard clinico-pathological criteria with mtDNA sequencing to reveal the metastatic nature of CBCs. Results MtDNA analysis was informative in 23% of the cases, for which it confirmed a clonal origin of the second tumor. In addition, it allowed to solve two ambiguous cases where histopathological criteria had failed to be conclusive and to suggest a clonal origin for two additional cases that had been classified as independent by pathologists. Conclusion Overall, the mtDNA-based classification showed a more accurate predictive power than standard histopathology in identifying cases of metastatic rather than bilateral breast cancers in our cohort, suggesting that mtDNA sequencing may be a more precise and easy-to-use method to be introduced in daily routine to support and improve histopathological diagnoses.
- Published
- 2020
34. Electrochemotherapy in Vulvar Cancer and Cisplatin Combined with Electroporation. Systematic Review and In Vitro Studies
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Lisa Argnani, Alessio G. Morganti, Marco Tesei, Claudio Zamagni, Stefano Miglietta, Pierandrea De Iaco, Marco Di Stanislao, Martina Ferioli, Giulia Girolimetti, Eugenia De Crescenzo, Francesca De Terlizzi, Anna Myriam Perrone, Gloria Ravegnini, Giuseppe Gasparre, Anna Maria Porcelli, Perrone, Anna Myriam, Ravegnini, Gloria, Miglietta, Stefano, Argnani, Lisa, Ferioli, Martina, De Crescenzo, Eugenia, Tesei, Marco, Di Stanislao, Marco, Girolimetti, Giulia, Gasparre, Giuseppe, Porcelli, Anna Maria, De Terlizzi, Francesca, Zamagni, Claudio, Morganti, Alessio Giuseppe, and De Iaco, Pierandrea
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Electrochemotherapy ,cisplatin ,Bleomycin ,behavioral disciplines and activities ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,mental disorders ,medicine ,RC254-282 ,Cisplatin ,vulvar cancer ,bleomycin ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Vulvar cancer ,medicine.disease ,electrochemotherapy ,030104 developmental biology ,Systematic review ,chemistry ,Tumor progression ,030220 oncology & carcinogenesis ,Cancer cell ,Vulvar Carcinoma ,Systematic Review ,business ,medicine.drug - Abstract
Simple Summary Electrochemotherapy (ECT) is an emerging treatment for solid tumors and an attracting research field due to its clinical results. ECT in association with bleomycin is an effective and safe treatment option in the vulvar cancer palliative setting. With regard to cisplatin (CSP)-based ECT, considering the clear evidence on its efficacy in gynecological tumors, the possibility to improve local control with CSP-based ECT is intriguing and a well-designed randomized clinical trial should be addressed to this issue. Abstract Electrochemotherapy (ECT) is an emerging treatment for solid tumors and an attractive research field due to its clinical results. This therapy represents an alternative local treatment to the standard ones and is based on the tumor-directed delivery of non-ablative electrical pulses to maximize the action of specific cytotoxic drugs such as cisplatin (CSP) and bleomycin (BLM) and to promote cancer cell death. Nowadays, ECT is mainly recommended as palliative treatment. However, it can be applied to a wide range of superficial cancers, having an impact in preventing or delaying tumor progression and therefore in improving quality of life. In addition, during the natural history of the tumor, early ECT may improve patient outcomes. Our group has extensive clinical and research experience on ECT in vulvar tumors in the palliative setting, with 70% overall response rate. So far, in most studies, ECT was based on BLM. However, the potential of CSP in this setting seems interesting due to some theoretical advantages. The purpose of this report is to: (i) compare the efficacy of CSP and BLM-based ECT through a systematic literature review; (ii) report the results of our studies on CSP-resistant squamous cell tumors cell lines and the possibility to overcome chemoresistance using ECT; (iii) discuss the future ECT role in gynecological tumors and in particular in vulvar carcinoma.
- Published
- 2021
35. Plasma-activated Ringer's Lactate Solution Displays a Selective Cytotoxic Effect on Ovarian Cancer Cells
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Vittorio Colombo, Giuseppe Gasparre, Lorena Marchio, Alina Bisag, Sara Coluccelli, Matteo Gherardi, Pierandrea De Iaco, Anna Myriam Perrone, Anna Maria Porcelli, Romolo Laurita, Cristiana Bucci, Giulia Girolimetti, Bisag, Alina, Bucci, Cristiana, Coluccelli, Sara, Girolimetti, Giulia, Laurita, Romolo, De Iaco, Pierandrea, Perrone, Anna Myriam, Gherardi, Matteo, Marchio, Lorena, Porcelli, Anna Maria, Colombo, Vittorio, and Gasparre, Giuseppe
- Subjects
0301 basic medicine ,Cancer Research ,endocrine system diseases ,Ovary ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Cytotoxic T cell ,cold atmospheric pressure plasma ,Fibroblast ,Cytotoxicity ,Chemistry ,selectivity ,Cancer ,plasma medicine ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,medicine.anatomical_structure ,ovarian cancer ,Oncology ,Cell culture ,030220 oncology & carcinogenesis ,Cancer research ,cytotoxicity ,Plasma medicine ,Ovarian cancer ,plasma-activated Ringer’s lactate solution - Abstract
Epithelial Ovarian Cancer (EOC) is one of the leading causes of cancer-related deaths among women and is characterized by the diffusion of nodules or plaques from the ovary to the peritoneal surfaces. Conventional therapeutic options cannot eradicate the disease and show low efficacy against resistant tumor subclones. The treatment of liquids via cold atmospheric pressure plasma enables the production of plasma-activated liquids (PALs) containing reactive oxygen and nitrogen species (RONS) with selective anticancer activity. Thus, the delivery of RONS to cancer tissues by intraperitoneal washing with PALs might be an innovative strategy for the treatment of EOC. In this work, plasma-activated Ringer&rsquo, s Lactate solution (PA-RL) was produced by exposing a liquid substrate to a multiwire plasma source. Subsequently, PA-RL dilutions are used for the treatment of EOC, non-cancer and fibroblast cell lines, revealing a selectivity of PA-RL, which induces a significantly higher cytotoxic effect in EOC with respect to non-cancer cells.
- Published
- 2020
36. Molecular and metabolic features of oncocytomas: Seeking the blueprints of indolent cancers
- Author
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Giulia Girolimetti, Anna Maria Porcelli, Monica De Luise, Giuseppe Gasparre, Bernard Okere, Ivana Kurelac, De Luise, Monica, Girolimetti, Giulia, Okere, Bernard, Porcelli, Anna Maria, Kurelac, Ivana, and Gasparre, Giuseppe
- Subjects
0301 basic medicine ,Biophysics ,Mitochondrial DNA mutation ,Translational research ,Respiratory complex I ,Biology ,DNA, Mitochondrial ,Models, Biological ,Biochemistry ,Mitochondrial Proteins ,03 medical and health sciences ,0302 clinical medicine ,Oncocytic tumor ,Respiratory Complex I ,Mitophagy ,Autophagy ,Adenoma, Oxyphilic ,Humans ,Molecular Targeted Therapy ,Benign neoplasms ,Mitochondrial protein ,Respiratory capacity ,Genetics ,Electron Transport Complex I ,Organelle Biogenesis ,Disease progression ,Neoplasms, Second Primary ,Cell Biology ,Mitochondrial biogenesi ,Mitochondria ,Neoplasm Proteins ,3. Good health ,Phenotype ,030104 developmental biology ,030220 oncology & carcinogenesis ,Mutation ,Disease Progression ,Energy Metabolism ,Neuroscience ,METABOLIC FEATURES ,Genes, Neoplasm - Abstract
Oncocytic tumors are a peculiar subset of human neoplasms in which mitochondria have been proven to have a prominent role. A number of paradoxes render these clinical entities interesting from the translational research point of view. Most oncocytic tumors are generally metabolically constrained due to the impaired respiratory capacity and lack of the ability to respond to hypoxia, yet they maintain features that allow them to strive and persist in an indolent form. Their unique molecular and metabolic characteristics are an object of investigation that may reveal novel ways for therapeutic strategies based on metabolic targeting. With this aim in mind, we here examine the current knowledge on oncocytomas and delve into the molecular causes and consequences that revolve around the oncocytic phenotype, to understand whether we can learn to design therapies from the dissection of benign neoplasms. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux.
- Published
- 2017
37. Synergistic Effect of Mitochondrial and Lysosomal Dysfunction in Parkinson's Disease
- Author
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Cecilia Bucci, Anna Ferretta, Tiziana Cocco, Raffaella Beli, Consiglia Pacelli, Marco Mitruccio, Giuseppe Gasparre, Flora Guerra, Giulia Girolimetti, Guerra, Flora, Girolimetti, Giulia, Beli, Raffaella, Mitruccio, Marco, Pacelli, Consiglia, Ferretta, Anna, Gasparre, Giuseppe, Cocco, Tiziana, Bucci, Cecilia, and Flora Guerra, Giulia Girolimetti, Raffaella Beli, Marco Mitruccio, Consiglia Pacelli, Anna Ferretta, Giuseppe Gasparre, Tiziana Cocco, Cecilia Bucci
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Senescence ,Adult ,Mitochondrial DNA ,autophagy ,Mitochondrial Turnover ,Endocytic cycle ,Mitochondrion ,Biology ,DNA, Mitochondrial ,Article ,Cell Line ,Lysosome ,medicine ,Animals ,Humans ,endocytosis ,lcsh:QH301-705.5 ,Animal ,Dopaminergic Neurons ,Autophagy ,Parkinson Disease ,General Medicine ,Fibroblasts ,Middle Aged ,nervous system diseases ,Cell biology ,Mitochondria ,endocytosi ,medicine.anatomical_structure ,lcsh:Biology (General) ,Mitochondrial biogenesis ,Mutation ,lysosome ,Parkinson’s disease ,Fibroblast ,Lysosomes ,Dopaminergic Neuron ,Human - Abstract
Crosstalk between lysosomes and mitochondria plays a central role in Parkinson&rsquo, s Disease (PD). Lysosomal function may be influenced by mitochondrial quality control, dynamics and/or respiration, but whether dysfunction of endocytic or autophagic pathway is associated with mitochondrial impairment determining accumulation of defective mitochondria, is not yet understood. Here, we performed live imaging, western blotting analysis, sequencing of mitochondrial DNA (mtDNA) and senescence-associated beta-galactosidase activity assay on primary fibroblasts from a young patient affected by PD, her mother and a healthy control to analyze the occurrence of mtDNA mutations, lysosomal abundance, acidification and function, mitochondrial biogenesis activation and senescence. We showed synergistic alterations in lysosomal functions and mitochondrial biogenesis, likely associated with a mitochondrial genetic defect, with a consequent block of mitochondrial turnover and occurrence of premature cellular senescence in PARK2-PD fibroblasts, suggesting that these alterations represent potential mechanisms contributing to the loss of dopaminergic neurons.
- Published
- 2019
38. Modulation of RAB7A Protein Expression Determines Resistance to Cisplatin through Late Endocytic Pathway Impairment and Extracellular Vesicular Secretion
- Author
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Giulia Girolimetti, Danilo Migoni, Pierandrea De Iaco, Flora Guerra, Cecilia Bucci, Anna Myriam Perrone, Aurora Paiano, Giuseppe Gasparre, Francesco Paolo Fanizzi, Guerra, Flora, Paiano, Aurora, Migoni, Danilo, Girolimetti, Giulia, Perrone, Anna Myriam, De Iaco, Pierandrea, Fanizzi, Francesco Paolo, Gasparre, Giuseppe, Bucci, Cecilia, Perrone, Anna, and Fanizzi, Francesco
- Subjects
0301 basic medicine ,inorganic chemicals ,Cancer Research ,Endocytic cycle ,cisplatin ,Endocytosis ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,Lysosome ,medicine ,Extracellular ,endocytosis ,Secretion ,neoplasms ,Endocytosi ,Chemistry ,RAB7A ,chemoresistance ,Transfection ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,lysosome ,Cisplatin ,Intracellular ,Chemoresistance - Abstract
Background: Cisplatin (CDDP) is widely used in treatment of cancer, yet patients often develop resistance with consequent therapeutical failure. In CDDP-resistant cells alterations of endocytosis and lysosomal functionality have been revealed, although their causes and contribution to therapy response are unclear. Methods: We investigated the role of RAB7A, a key regulator of late endocytic trafficking, in CDDP-resistance by comparing resistant and sensitive cells using western blotting, confocal microscopy and real time PCR. Modulation of RAB7A expression was performed by transfection and RNA interference, while CDDP sensitivity and intracellular accumulation were evaluated by viability assays and chemical approaches, respectively. Also extracellular vesicles were purified and analyzed. Finally, correlations between RAB7A and chemotherapy response was investigated in human patient samples. Results: We demonstrated that down-regulation of RAB7A characterizes the chemoresistant phenotype, and that RAB7A depletion increases CDDP-resistance while RAB7A overexpression decreases it. In addition, increased production of extracellular vesicles is modulated by RAB7A expression levels and correlates with reduction of CDDP intracellular accumulation. Conclusions: We demonstrated, for the first time, that RAB7A regulates CDDP resistance determining alterations in late endocytic trafficking and drug efflux through extracellular vesicles.
- Published
- 2019
39. Inducing cancer indolence by targeting mitochondrial Complex I is potentiated by blocking macrophage-mediated adaptive responses
- Author
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Laura Benedetta Amato, Ilaria Malanchi, Giulia Girolimetti, Nikkitha Umesh Ganesh, Anna Maria Porcelli, Silvia Vidali, Michele Vidone, Marta Columbaro, Andrea Cossarizza, Giulia Leone, Moira Ragazzi, Renaud Vatrinet, Luigi Ombrato, Giuseppe Gasparre, Manuela Sollazzo, Luisa Iommarini, Victoria L. Bridgeman, Monica De Luise, Lara Gibellini, Ivana Kurelac, Maurizio Baldassarre, René G. Feichtinger, Barbara Kofler, Sarah Foriel, Daniela Grifoni, Kurelac, Ivana, Iommarini, Luisa, Vatrinet, Renaud, Amato, Laura Benedetta, De Luise, Monica, Leone, Giulia, Girolimetti, Giulia, Umesh Ganesh, Nikkitha, Bridgeman, Victoria Louise, Ombrato, Luigi, Columbaro, Marta, Ragazzi, Moira, Gibellini, Lara, Sollazzo, Manuela, Feichtinger, Rene Gunther, Vidali, Silvia, Baldassarre, Maurizio, Foriel, Sarah, Vidone, Michele, Cossarizza, Andrea, Grifoni, Daniela, Kofler, Barbara, Malanchi, Ilaria, Porcelli, Anna Maria, and Gasparre, Giuseppe
- Subjects
0301 basic medicine ,Angiogenesis ,Adenoma, Oxyphilic ,Aminopyridines ,Animals ,Antineoplastic Agents ,Cell Line, Tumor ,Cell Proliferation ,Drosophila ,Electron Transport Complex I ,Female ,Gene Knockout Techniques ,HCT116 Cells ,Humans ,Hypoxia-Inducible Factor 1, alpha Subunit ,Macrophages ,Metformin ,Mice ,Mice, Knockout ,Mice, Nude ,NADH Dehydrogenase ,Neovascularization, Pathologic ,Pyrroles ,Xenograft Model Antitumor Assays ,Nude ,General Physics and Astronomy ,02 engineering and technology ,urologic and male genital diseases ,Neovascularization ,Medicine ,Oncocytoma ,lcsh:Science ,Multidisciplinary ,Tumor ,021001 nanoscience & nanotechnology ,3. Good health ,macrophages ,Hypoxia-Inducible Factor 1 ,medicine.symptom ,0210 nano-technology ,Mitochondrial Complex I ,Adenoma ,combinatorial therapy ,Science ,Knockout ,alpha Subunit ,General Biochemistry, Genetics and Molecular Biology ,Article ,Cell Line ,03 medical and health sciences ,In vivo ,Adjuvant therapy ,cancer ,Pathologic ,business.industry ,Cell growth ,Oxyphilic ,General Chemistry ,Hypoxia (medical) ,medicine.disease ,030104 developmental biology ,Cell culture ,Cancer research ,lcsh:Q ,business - Abstract
Converting carcinomas in benign oncocytomas has been suggested as a potential anti-cancer strategy. One of the oncocytoma hallmarks is the lack of respiratory complex I (CI). Here we use genetic ablation of this enzyme to induce indolence in two cancer types, and show this is reversed by allowing the stabilization of Hypoxia Inducible Factor-1 alpha (HIF-1α). We further show that on the long run CI-deficient tumors re-adapt to their inability to respond to hypoxia, concordantly with the persistence of human oncocytomas. We demonstrate that CI-deficient tumors survive and carry out angiogenesis, despite their inability to stabilize HIF-1α. Such adaptive response is mediated by tumor associated macrophages, whose blockage improves the effect of CI ablation. Additionally, the simultaneous pharmacological inhibition of CI function through metformin and macrophage infiltration through PLX-3397 impairs tumor growth in vivo in a synergistic manner, setting the basis for an efficient combinatorial adjuvant therapy in clinical trials., Lack of respiratory complex I is a hallmark of oncocytomas. Here the authors show that inactivation of this complex via knockout of the NDUFS3 subunit or using metformin, converts tumors from an aggressive phenotype into low-proliferative oncocytomas, which can be further inhibited by targeting pro-tumorigenic macrophages.
- Published
- 2019
40. A multi-parametric workflow for the prioritization of mitochondrial DNA variants of clinical interest
- Author
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Giulia Girolimetti, Marcella Attimonelli, Mariangela Santorsola, Maria Angela Diroma, Claudia Calabrese, Giuseppe Gasparre, Santorsola, Mariangela, Calabrese, Claudia, Girolimetti, Giulia, Diroma, Maria Angela, Gasparre, Giuseppe, and Attimonelli, Marcella
- Subjects
0301 basic medicine ,Mitochondrial DNA ,Optic Atrophy, Hereditary, Leber ,Disease ,Adenocarcinoma ,Biology ,DNA, Mitochondrial ,MTDNA mutations ,Haplogroup ,03 medical and health sciences ,Phylogenetics ,Consensus Sequence ,Genetics ,Consensus sequence ,Humans ,Genetics(clinical) ,Chromatography, High Pressure Liquid ,Germ-Line Mutation ,Genetics (clinical) ,Original Investigation ,Ovarian Neoplasms ,Haplotype ,Human genetics ,3. Good health ,030104 developmental biology ,Workflow ,Haplotypes ,Female ,Colorectal Neoplasms - Abstract
Assigning a pathogenic role to mitochondrial DNA (mtDNA) variants and unveiling the potential involvement of the mitochondrial genome in diseases are challenging tasks in human medicine. Assuming that rare variants are more likely to be damaging, we designed a phylogeny-based prioritization workflow to obtain a reliable pool of candidate variants for further investigations. The prioritization workflow relies on an exhaustive functional annotation through the mtDNA extraction pipeline MToolBox and includes Macro Haplogroup Consensus Sequences to filter out fixed evolutionary variants and report rare or private variants, the nucleotide variability as reported in HmtDB and the disease score based on several predictors of pathogenicity for non-synonymous variants. Cutoffs for both the disease score as well as for the nucleotide variability index were established with the aim to discriminate sequence variants contributing to defective phenotypes. The workflow was validated on mitochondrial sequences from Leber’s Hereditary Optic Neuropathy affected individuals, successfully identifying 23 variants including the majority of the known causative ones. The application of the prioritization workflow to cancer datasets allowed to trim down the number of candidate for subsequent functional analyses, unveiling among these a high percentage of somatic variants. Prioritization criteria were implemented in both standalone (http://sourceforge.net/projects/mtoolbox/) and web version (https://mseqdr.org/mtoolbox.php) of MToolBox. Electronic supplementary material The online version of this article (doi:10.1007/s00439-015-1615-9) contains supplementary material, which is available to authorized users.
- Published
- 2015
41. Potential for Mitochondrial DNA Sequencing in the Differential Diagnosis of Gynaecological Malignancies
- Author
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Anna Maria Porcelli, Pierandrea De Iaco, Giulia Borghese, Giuseppe Gasparre, Lorena Marchio, Martina Procaccini, Giulia Girolimetti, Anna Myriam Perrone, Alessandra Livi, Perrone, Anna Myriam, Girolimetti, Giulia, Procaccini, Martina, Marchio, Lorena, Livi, Alessandra, Borghese, Giulia, Porcelli, Anna Maria, De Iaco, Pierandrea, and Gasparre, Giuseppe
- Subjects
0301 basic medicine ,Oncology ,Female circumcision ,Mitochondrial DNA ,medicine.medical_specialty ,Metastatic lesions ,Genital Neoplasms, Female ,Review ,mitochondrial DNA ,DNA, Mitochondrial ,Sensitivity and Specificity ,Catalysis ,lcsh:Chemistry ,Inorganic Chemistry ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,synchronous tumors ,Internal medicine ,medicine ,Humans ,Physical and Theoretical Chemistry ,lcsh:QH301-705.5 ,Molecular Biology ,Spectroscopy ,Ovarian Neoplasms ,DNA genotyping ,Therapeutic regimen ,business.industry ,Endometrial cancer ,Organic Chemistry ,borderline ovarian tumors ,General Medicine ,Sequence Analysis, DNA ,gynecological cancer ,medicine.disease ,Computer Science Applications ,Endometrial Neoplasms ,borderline ovarian tumor ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,030220 oncology & carcinogenesis ,Monoclonal ,Mutation ,Female ,Differential diagnosis ,Ovarian cancer ,business - Abstract
In the event of multiple synchronous gynecological lesions, a fundamental piece of information to determine patient management, prognosis, and therapeutic regimen choice is whether the simultaneous malignancies arise independently or as a result of metastatic dissemination. An example of synchronous primary tumors of the female genital tract most frequently described are ovarian and endometrial cancers. Surgical findings and histopathological examination aimed at resolving this conundrum may be aided by molecular analyses, although they are too often inconclusive. High mitochondrial DNA (mtDNA) variability and its propensity to accumulate mutations has been proposed by our group as a tool to define clonality. We showed mtDNA sequencing to be informative in synchronous primary ovarian and endometrial cancer, detecting tumor-specific mutations in both lesions, ruling out independence of the two neoplasms, and indicating clonality. Furthermore, we tested this method in another frequent simultaneously detected gynecological lesion type, borderline ovarian cancer and their peritoneal implants, which may be monoclonal extra-ovarian metastases or polyclonal independent masses. The purpose of this review is to provide an update on the potential use of mtDNA sequencing in distinguishing independent and metastatic lesions in gynecological cancers, and to compare the efficiency of molecular analyses currently in use with this novel method.
- Published
- 2018
42. PGC1α: Friend or Foe in Cancer?
- Author
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Maria C. Shoshan, Giulia Girolimetti, Francesca Mastropasqua, Mastropasqua, Francesca, Girolimetti, Giulia, and Shoshan, Maria
- Subjects
0301 basic medicine ,lcsh:QH426-470 ,Review ,Biology ,medicine.disease_cause ,Metastasis ,03 medical and health sciences ,Downregulation and upregulation ,PGC1α ,Genetic ,PGC1α ,Genetics ,medicine ,PPARGC1A ,Tumor cell metabolism ,Genetics (clinical) ,Cancer ,medicine.disease ,Phenotype ,Tumor progression ,lcsh:Genetics ,030104 developmental biology ,Mitochondrial biogenesis ,Cancer research ,Carcinogenesis - Abstract
The PGC1 family (Peroxisome proliferator-activated receptor γ (PPAR γ) coactivators) of transcriptional coactivators are considered master regulators of mitochondrial biogenesis and function. The PGC1α isoform is expressed especially in metabolically active tissues, such as the liver, kidneys and brain, and responds to energy-demanding situations. Given the altered and highly adaptable metabolism of tumor cells, it is of interest to investigate PGC1α in cancer. Both high and low levels of PGC1α expression have been reported to be associated with cancer and worse prognosis, and PGC1α has been attributed with oncogenic as well as tumor suppressive features. Early in carcinogenesis PGC1α may be downregulated due to a protective anticancer role, and low levels likely reflect a glycolytic phenotype. We suggest mechanisms of PGC1α downregulation and how these might be connected to the increased cancer risk that obesity is now known to entail. Later in tumor progression PGC1α is often upregulated and is reported to contribute to increased lipid and fatty acid metabolism and/or a tumor cell phenotype with an overall metabolic plasticity that likely supports drug resistance as well as metastasis. We conclude that in cancer PGC1α is neither friend nor foe, but rather the obedient servant reacting to metabolic and environmental cues to benefit the tumor cell.
- Published
- 2018
43. Pathological and molecular diagnosis of bilateral inguinal lymph nodes metastases from low-grade endometrial adenocarcinoma: a case report with review of the literature
- Author
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Anna Myriam Perrone, Ivana Kurelac, Alessandra Livi, S. Cima, Giuseppe Gasparre, Alessio G. Morganti, Giulia Girolimetti, Pierandrea De Iaco, Donatella Santini, Giacomo Caprara, Paolo Castellucci, Perrone, Anna Myriam, Girolimetti, Giulia, Cima, Simona, Kurelac, Ivana, Livi, Alessandra, Caprara, Giacomo, Santini, Donatella, Castellucci, Paolo, Morganti, Alessio Giuseppe, Gasparre, Giuseppe, and De Iaco, Pierandrea
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Inguinal Canal ,Inguinal lymph nodes metastasis ,Case Report ,Physical examination ,Endometrial carcinoma ,Adenocarcinoma ,DNA, Mitochondrial ,lcsh:RC254-282 ,Mitochondrial DNA sequencing ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Surgical oncology ,Genetics ,Carcinoma ,Humans ,Medicine ,Pathological ,Neoplasm Grading ,medicine.diagnostic_test ,business.industry ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Inguinal canal ,Endometrial Neoplasms ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Female ,Lymph Nodes ,Radiology ,business ,Inguinal lymph nodes metastasi - Abstract
Background Extra-abdominal metastases in low grade endometrial carcinoma are rare events. Inguinal lymphatic spread occurs usually in advanced disease and is associated with abdominal lymph nodes involvement. To our knowledge, isolated inguinal lymph node metastases in patients with early endometrial carcinoma have never been described thus far. Case presentation We present an uncommon case of inguinal lymph node metastasis in a 51-year old patient with early endometrial disease without other metastatic involvement. The metastatic loci were analyzed with the recently validated method of mitochondrial DNA sequencing to demonstrate clonality of the lesions. Conclusions We describe the first case of inguinal metastasis from intramucous endometrial carcinoma; this case confirms the unpredictable spread of endometrial neoplasia and the importance of both patient’s history and physical examination in good clinical practice.
- Published
- 2018
44. The α-ketoglutarate dehydrogenase complex in cancer metabolic plasticity
- Author
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Anna Maria Porcelli, Michele Vidone, Renaud Vatrinet, Monica De Luise, Giuseppe Gasparre, Giulia Girolimetti, Giulia Leone, Vatrinet, Renaud, Leone, Giulia, De Luise, Monica, Girolimetti, Giulia, Vidone, Michele, Gasparre, Giuseppe, and Porcelli, Anna Maria
- Subjects
0301 basic medicine ,Cell signaling ,α-Ketoglutarate dehydrogenase complex ,Dehydrogenase ,Review ,Biology ,03 medical and health sciences ,medicine ,chemistry.chemical_classification ,Cancer plasticity ,α-Ketoglutarate dehydrogenase complex, α-Ketoglutarate, Mitochondrial function, Metabolic stresses, Cancer plasticity, Cell signaling, Oncometabolite, Epigenetics ,Cancer ,Metabolism ,medicine.disease ,Cell biology ,Citric acid cycle ,Psychiatry and Mental health ,Metabolic pathway ,α-Ketoglutarate ,030104 developmental biology ,Enzyme ,Biochemistry ,chemistry ,Oncometabolite ,Cancer cell ,Metabolic stresses ,Epigenetics ,Mitochondrial function ,Flux (metabolism) - Abstract
Deregulated metabolism is a well-established hallmark of cancer. At the hub of various metabolic pathways deeply integrated within mitochondrial functions, the α-ketoglutarate dehydrogenase complex represents a major modulator of electron transport chain activity and tricarboxylic acid cycle (TCA) flux, and is a pivotal enzyme in the metabolic reprogramming following a cancer cell’s change in bioenergetic requirements. By contributing to the control of α-ketoglutarate levels, dynamics, and oxidation state, the α-ketoglutarate dehydrogenase is also essential in modulating the epigenetic landscape of cancer cells. In this review, we will discuss the manifold roles that this TCA enzyme and its substrate play in cancer.
- Published
- 2017
45. Mitochondrial DNA sequencing demonstrates clonality of peritoneal implants of borderline ovarian tumors
- Author
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Laura Benedetta Amato, Pierandrea De Iaco, Ivana Kurelac, Riccardo Panzacchi, Claudio Ceccarelli, Anna Myriam Perrone, Giuseppe Gasparre, Martina Procaccini, Anna Maria Porcelli, Donatella Santini, Giacomo Caprara, Giulia Dondi, Giulia Girolimetti, Girolimetti, Giulia, De Iaco, Pierandrea, Procaccini, Martina, Panzacchi, Riccardo, Kurelac, Ivana, Amato, Laura Benedetta, Dondi, Giulia, Caprara, Giacomo, Ceccarelli, Claudio, Santini, Donatella, Porcelli, Anna Maria, Perrone, Anna Myriam, and Gasparre, Giuseppe
- Subjects
0301 basic medicine ,Adult ,Cancer Research ,Mitochondrial DNA ,Pathology ,medicine.medical_specialty ,Borderline ovarian tumor ,Mitochondrial DNA mutation ,Biology ,Peritoneal implants ,medicine.disease_cause ,Borderline ovarian tumors ,DNA, Mitochondrial ,Stromal Invasion ,Clonal Evolution ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Mitochondrial DNA mutations ,Neoplastic transformation ,Stage (cooking) ,Letter to the Editor ,Peritoneal Neoplasms ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Ovarian Neoplasms ,Mutation ,Cell growth ,Sequence Analysis, DNA ,Middle Aged ,Prognosis ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Gynecological cancer ,Molecular Medicine ,Female ,Implant - Abstract
Borderline ovarian tumors are rare low malignant potential neoplasms characterized by the absence of stromal invasion, whose main prognostic factors are stage and type of peritoneal implants. The latter are defined as invasive when cell proliferation invades the underlying tissue (peritoneal surface, omentum and intestinal wall), or noninvasive. It is still unknown if these implants are metastatic spread from the primary ovarian mass or a neoplastic transformation de novo of the peritoneal surface. Mitochondrial DNA sequencing was performed to assess clonality in eight patients presenting both borderline ovarian tumors and implants. In 37.5% of the cases, the same mitochondrial DNA mutation was present in both borderline ovarian tumors and the peritoneal implant, being this evidence that implants may arise as a consequence of a spread from a single ovarian site. Electronic supplementary material The online version of this article (doi:10.1186/s12943-017-0614-y) contains supplementary material, which is available to authorized users.
- Published
- 2017
46. Mitochondrial DNA genotyping reveals synchronous nature of endometrial and ovarian cancers
- Author
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Ivana Kurelac, Dario de Biase, Anna Myriam Perrone, Donatella Santini, Giacomo Caprara, Giuseppe Gasparre, Giulia Girolimetti, Martina Procaccini, Pierandrea De Iaco, Claudio Ceccarelli, Flora Guerra, Flora Guerra, Giulia Girolimetti, Ivana Kurelac, Anna Myriam Perrone, Martina Procaccini, Dario De Biase, Claudio Ceccarelli, Giacomo Caprara, Pierandrea De Iaco, Donatella Santini, Giuseppe Gasparre, Guerra, Flora, Girolimetti, Giulia, Kurelac, Ivana, Perrone, Anna Myriam, Procaccini, Martina, De Biase, Dario, Ceccarelli, Claudio, Caprara, Giacomo, De Iaco, Pierandrea, Santini, Donatella, and Gasparre, Giuseppe
- Subjects
Genetics ,Mitochondrial DNA ,Bioengineering ,General Medicine ,Biology ,Applied Microbiology and Biotechnology ,Genotyping ,Biotechnology - Published
- 2014
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