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31 results on '"Pompili, Luca"'

1. Correction to: Focal adhesion kinase inhibitor TAE226 combined with Sorafenib slows down hepatocellular carcinoma by multiple epigenetic effects

Author

Romito, Ilaria, Porru, Manuela, Braghini, Maria Rita, Pompili, Luca, Panera, Nadia, Crudele, Annalisa, Gnani, Daniela, De Stefanis, Cristiano, Scarsella, Marco, Pomella, Silvia, Mortera, Stefano Levi, de Billy, Emmanuel, Conti, Adrian Libenzio, Marzano, Valeria, Putignani, Lorenza, Vinciguerra, Manlio, Balsano, Clara, Pastore, Anna, Rota, Rossella, Tartaglia, Marco, Leonetti, Carlo, and Alisi, Anna

Published
2022
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2. Targeting the KRAS oncogene: Synthesis, physicochemical and biological evaluation of novel G-Quadruplex DNA binders

Author

D'Aria, Federica, D'Amore, Vincenzo Maria, Di Leva, Francesco Saverio, Amato, Jussara, Caterino, Marco, Russomanno, Pasquale, Salerno, Silvia, Barresi, Elisabetta, De Leo, Marinella, Marini, Anna Maria, Taliani, Sabrina, Da Settimo, Federico, Salgado, Gilmar F., Pompili, Luca, Zizza, Pasquale, Shirasawa, Senji, Novellino, Ettore, Biroccio, Annamaria, Marinelli, Luciana, and Giancola, Concetta

Published
2020
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3. Focal adhesion kinase inhibitor TAE226 combined with Sorafenib slows down hepatocellular carcinoma by multiple epigenetic effects

Author

Romito, Ilaria, Porru, Manuela, Braghini, Maria Rita, Pompili, Luca, Panera, Nadia, Crudele, Annalisa, Gnani, Daniela, De Stefanis, Cristiano, Scarsella, Marco, Pomella, Silvia, Levi Mortera, Stefano, de Billy, Emmanuel, Conti, Adrian Libenzio, Marzano, Valeria, Putignani, Lorenza, Vinciguerra, Manlio, Balsano, Clara, Pastore, Anna, Rota, Rossella, Tartaglia, Marco, Leonetti, Carlo, and Alisi, Anna

Published
2021
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4. MiR ‐182‐3p targets TRF2 and impairs tumor growth of triple‐negative breast cancer

Author

Dinami, Roberto, primary, Pompili, Luca, additional, Petti, Eleonora, additional, Porru, Manuela, additional, D'Angelo, Carmen, additional, Di Vito, Serena, additional, Rizzo, Angela, additional, Campani, Virginia, additional, De Rosa, Giuseppe, additional, Bruna, Alejandra, additional, Serra, Violeta, additional, Mano, Miguel, additional, Giacca, Mauro, additional, Leonetti, Carlo, additional, Ciliberto, Gennaro, additional, Tarsounas, Madalena, additional, Stoppacciaro, Antonella, additional, Schoeftner, Stefan, additional, and Biroccio, Annamaria, additional

Published
2022
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7. Additional file 3 of Correction to: Focal adhesion kinase inhibitor TAE226 combined with Sorafenib slows down hepatocellular carcinoma by multiple epigenetic effects

Author

Romito, Ilaria, Porru, Manuela, Braghini, Maria Rita, Pompili, Luca, Panera, Nadia, Crudele, Annalisa, Gnani, Daniela, De Stefanis, Cristiano, Scarsella, Marco, Pomella, Silvia, Mortera, Stefano Levi, de Billy, Emmanuel, Conti, Adrian Libenzio, Marzano, Valeria, Putignani, Lorenza, Vinciguerra, Manlio, Balsano, Clara, Pastore, Anna, Rota, Rossella, Tartaglia, Marco, Leonetti, Carlo, and Alisi, Anna

Subjects
Data_FILES
Abstract

Additional file 8.

Published
2022
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8. Additional file 2 of Correction to: Focal adhesion kinase inhibitor TAE226 combined with Sorafenib slows down hepatocellular carcinoma by multiple epigenetic effects

Author

Romito, Ilaria, Porru, Manuela, Braghini, Maria Rita, Pompili, Luca, Panera, Nadia, Crudele, Annalisa, Gnani, Daniela, De Stefanis, Cristiano, Scarsella, Marco, Pomella, Silvia, Mortera, Stefano Levi, de Billy, Emmanuel, Conti, Adrian Libenzio, Marzano, Valeria, Putignani, Lorenza, Vinciguerra, Manlio, Balsano, Clara, Pastore, Anna, Rota, Rossella, Tartaglia, Marco, Leonetti, Carlo, and Alisi, Anna

Subjects
Data_FILES
Abstract

Additional file 7.

Published
2022
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9. Additional file 1 of Correction to: Focal adhesion kinase inhibitor TAE226 combined with Sorafenib slows down hepatocellular carcinoma by multiple epigenetic effects

Author

Romito, Ilaria, Porru, Manuela, Braghini, Maria Rita, Pompili, Luca, Panera, Nadia, Crudele, Annalisa, Gnani, Daniela, De Stefanis, Cristiano, Scarsella, Marco, Pomella, Silvia, Mortera, Stefano Levi, de Billy, Emmanuel, Conti, Adrian Libenzio, Marzano, Valeria, Putignani, Lorenza, Vinciguerra, Manlio, Balsano, Clara, Pastore, Anna, Rota, Rossella, Tartaglia, Marco, Leonetti, Carlo, and Alisi, Anna

Subjects
Data_FILES
Abstract

Additional file 6.

Published
2022
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10. MiR‐182‐3p targets TRF2 and impairs tumor growth of triple‐negative breast cancer.

Author

Dinami, Roberto, Pompili, Luca, Petti, Eleonora, Porru, Manuela, D'Angelo, Carmen, Di Vito, Serena, Rizzo, Angela, Campani, Virginia, De Rosa, Giuseppe, Bruna, Alejandra, Serra, Violeta, Mano, Miguel, Giacca, Mauro, Leonetti, Carlo, Ciliberto, Gennaro, Tarsounas, Madalena, Stoppacciaro, Antonella, Schoeftner, Stefan, and Biroccio, Annamaria

Abstract

The telomeric repeat‐binding factor 2 (TRF2) is a telomere‐capping protein that plays a key role in the maintenance of telomere structure and function. It is highly expressed in different cancer types, and it contributes to cancer progression. To date, anti‐cancer strategies to target TRF2 remain a challenge. Here, we developed a miRNA‐based approach to reduce TRF2 expression. By performing a high‐throughput luciferase screening of 54 candidate miRNAs, we identified miR‐182‐3p as a specific and efficient post‐transcriptional regulator of TRF2. Ectopic expression of miR‐182‐3p drastically reduced TRF2 protein levels in a panel of telomerase‐ or alternative lengthening of telomeres (ALT)‐positive cancer cell lines. Moreover, miR‐182‐3p induced DNA damage at telomeric and pericentromeric sites, eventually leading to strong apoptosis activation. We also observed that treatment with lipid nanoparticles (LNPs) containing miR‐182‐3p impaired tumor growth in triple‐negative breast cancer (TNBC) models, including patient‐derived tumor xenografts (PDTXs), without affecting mouse survival or tissue function. Finally, LNPs‐miR‐182‐3p were able to cross the blood–brain barrier and reduce intracranial tumors representing a possible therapeutic option for metastatic brain lesions. Synopsis: A miRNA‐based strategy to inhibit the telomeric protein TRF2 was developed, which led to efficient decrease of triple negative breast cancer growth. miR‐182‐3p was identified as an efficient regulator of TRF2 expression in human cancer through high‐throughput miRNA luciferase screening.TRF2 inhibition by miR‐182‐3p induced DNA damage at telomeric and pericentromeric sites and consequent genomic instability.miR‐182‐3p limited the growth of Triple Negative Breast Cancer (TNBC) models by activating apoptosis.Lipid nanoparticles (LNPs) containing miR‐182‐3p reduced tumor volume in vivo in various TNBC models, including Olaparib‐resistant patient‐derived tumor xenografts.LNPs‐miR‐182‐3p crossed the blood brain barrier, showing therapeutic potential against brain metastasis. [ABSTRACT FROM AUTHOR]

Published
2023
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11. Identification of effective anticancer G-quadruplex-targeting chemotypes through the exploration of a high diversity library of natural compounds

Author

Mori, Mattia, primary, Platella, Chiara, additional, Ghirga, Francesca, additional, Zizza, Pasquale, additional, Pompili, Luca, additional, Marzano, Simona, additional, Pagano, Bruno, additional, Quaglio, Deborah, additional, Vergine, Valeria, additional, Cammarone, Silvia, additional, Botta, Bruno, additional, Biroccio, Annamaria, additional, and Montesarchio, Daniela, additional

Published
2021
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12. TRF1 poly(ADP-ribosyl)ation by PARP1 allows proper telomere replication through helicase recruitment in non-ALT cells

Author

Dello Stritto, Angela, primary, Maresca, Carmen, additional, D'Angelo, Carmen, additional, Petti, Eleonora, additional, Vertecchi, Eleonora, additional, Pompili, Luca, additional, Berardinelli, Francesco, additional, Sgura, Antonella, additional, Antoccia, Antonio, additional, Graziani, Grazia, additional, Biroccio, Annamaria, additional, and Salvati, Erica, additional

Published
2021
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13. Identification of Effective Anticancer G-Quadruplex-Targeting Chemotypes through the Exploration of a High Diversity Library of Natural Compounds

Author

Platella, Chiara, primary, Ghirga, Francesca, additional, Zizza, Pasquale, additional, Pompili, Luca, additional, Marzano, Simona, additional, Pagano, Bruno, additional, Quaglio, Deborah, additional, Vergine, Valeria, additional, Cammarone, Silvia, additional, Botta, Bruno, additional, Biroccio, Annamaria, additional, Mori, Mattia, additional, and Montesarchio, Daniela, additional

Published
2021
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14. Focal adhesion kinase inhibitor TAE226 combined with Sorafenib slows down hepatocellular carcinoma by multiple epigenetics effects

Author

Romito, Ilaria, primary, Porru, Manuela, additional, Braghini, Maria Rita, additional, Pompili, Luca, additional, Panera, Nadia, additional, Crudele, Annalisa, additional, Gnani, Daniela, additional, De Stefanis, Cristiano, additional, Scarsella, Marco, additional, Pomella, Silvia, additional, Mortera, Stefano Levi, additional, de Billy, Emmanuel, additional, Conti, Libenzio Adrian, additional, Marzano, Valeria, additional, Putignani, Lorenza, additional, Vinciguerra, Manlio, additional, Balsano, Clara, additional, Pastore, Anna, additional, Rota, Rossella, additional, Tartaglia, Marco, additional, Leonetti, Carlo, additional, and Alisi, Anna, additional

Published
2021
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15. Additional file 7 of Focal adhesion kinase inhibitor TAE226 combined with Sorafenib slows down hepatocellular carcinoma by multiple epigenetic effects

Author

Romito, Ilaria, Porru, Manuela, Braghini, Maria Rita, Pompili, Luca, Panera, Nadia, Crudele, Annalisa, Gnani, Daniela, De Stefanis, Cristiano, Scarsella, Marco, Pomella, Silvia, Levi Mortera, Stefano, de Billy, Emmanuel, Conti, Adrian Libenzio, Marzano, Valeria, Putignani, Lorenza, Vinciguerra, Manlio, Balsano, Clara, Pastore, Anna, Rota, Rossella, Tartaglia, Marco, Leonetti, Carlo, and Alisi, Anna

Subjects
digestive system diseases
Abstract

Additional file 7: Figure S2. Evaluation of the IC50 values of TAE226 and SOR on HCC cell viability after 2 and 5 days. Cell viability, measured by XTT assay, after 2 and 5 days from treatment with TAE226 or SOR, in HepG2 and Huh7 cells. Values are the mean OD �� SD of three independent experiments repeated at least in duplicate. Data were analysed by ANOVA. ***p

Published
2021
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16. Additional file 6 of Focal adhesion kinase inhibitor TAE226 combined with Sorafenib slows down hepatocellular carcinoma by multiple epigenetic effects

Author

Romito, Ilaria, Porru, Manuela, Braghini, Maria Rita, Pompili, Luca, Panera, Nadia, Crudele, Annalisa, Gnani, Daniela, De Stefanis, Cristiano, Scarsella, Marco, Pomella, Silvia, Levi Mortera, Stefano, de Billy, Emmanuel, Conti, Adrian Libenzio, Marzano, Valeria, Putignani, Lorenza, Vinciguerra, Manlio, Balsano, Clara, Pastore, Anna, Rota, Rossella, Tartaglia, Marco, Leonetti, Carlo, and Alisi, Anna

Subjects
digestive system diseases
Abstract

Additional file 6: Figure S1. FAK phosphorylation in HCC cells after IC50 values of treatments. Quantitative analysis of pTyr397FAK expression after 48 h of treatment with the different drugs, in HepG2 and Huh7 cells. Values are the mean arbitrary units �� SD of at least three independent experiments. Data were analysed by 2-tailed Student���s t test. *p

Published
2021
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17. Additional file 10 of Focal adhesion kinase inhibitor TAE226 combined with Sorafenib slows down hepatocellular carcinoma by multiple epigenetic effects

Author

Romito, Ilaria, Porru, Manuela, Braghini, Maria Rita, Pompili, Luca, Panera, Nadia, Crudele, Annalisa, Gnani, Daniela, De Stefanis, Cristiano, Scarsella, Marco, Pomella, Silvia, Levi Mortera, Stefano, de Billy, Emmanuel, Conti, Adrian Libenzio, Marzano, Valeria, Putignani, Lorenza, Vinciguerra, Manlio, Balsano, Clara, Pastore, Anna, Rota, Rossella, Tartaglia, Marco, Leonetti, Carlo, and Alisi, Anna

Abstract

Additional file 10: Figure S5. Analysis of FAK nuclear interaction with specific epigenetics regulators. (A) Coomassie-stained 1D SDS-PAGE gels used for the in-gel digestions of nuclear immunoprecipitates of FAK in HCC cells. The photographs showed gel lanes excision into 10 bands for mass spectrometry characterization of FAK nuclear interactors. (B) Pipeline employed for the analysis of proteomics data.

Published
2021
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18. Additional file 2 of Focal adhesion kinase inhibitor TAE226 combined with Sorafenib slows down hepatocellular carcinoma by multiple epigenetic effects

Author

Romito, Ilaria, Porru, Manuela, Braghini, Maria Rita, Pompili, Luca, Panera, Nadia, Crudele, Annalisa, Gnani, Daniela, De Stefanis, Cristiano, Scarsella, Marco, Pomella, Silvia, Levi Mortera, Stefano, de Billy, Emmanuel, Conti, Adrian Libenzio, Marzano, Valeria, Putignani, Lorenza, Vinciguerra, Manlio, Balsano, Clara, Pastore, Anna, Rota, Rossella, Tartaglia, Marco, Leonetti, Carlo, and Alisi, Anna

Abstract

Additional file 2: Table S2. In vivo antitumor efficacy of TAE226>SOR combination on orthotopic liver tumour.

Published
2021
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19. Additional file 9 of Focal adhesion kinase inhibitor TAE226 combined with Sorafenib slows down hepatocellular carcinoma by multiple epigenetic effects

Author

Romito, Ilaria, Porru, Manuela, Braghini, Maria Rita, Pompili, Luca, Panera, Nadia, Crudele, Annalisa, Gnani, Daniela, De Stefanis, Cristiano, Scarsella, Marco, Pomella, Silvia, Levi Mortera, Stefano, de Billy, Emmanuel, Conti, Adrian Libenzio, Marzano, Valeria, Putignani, Lorenza, Vinciguerra, Manlio, Balsano, Clara, Pastore, Anna, Rota, Rossella, Tartaglia, Marco, Leonetti, Carlo, and Alisi, Anna

Abstract

Additional file 9: Figure S4. Pilot study for quantitative setting of TAE226 concentration in a heterotopic HepG2 xenograft model of HCC. (A) Quantitative analysis of tumour weight at various time points in NT animals or after TAE226 treatments. P values were calculated at day 12 using an unpaired two-tailed t-test, between treated and untreated tumours. **** p

Published
2021
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20. Additional file 3 of Focal adhesion kinase inhibitor TAE226 combined with Sorafenib slows down hepatocellular carcinoma by multiple epigenetic effects

Author

Romito, Ilaria, Porru, Manuela, Braghini, Maria Rita, Pompili, Luca, Panera, Nadia, Crudele, Annalisa, Gnani, Daniela, De Stefanis, Cristiano, Scarsella, Marco, Pomella, Silvia, Levi Mortera, Stefano, de Billy, Emmanuel, Conti, Adrian Libenzio, Marzano, Valeria, Putignani, Lorenza, Vinciguerra, Manlio, Balsano, Clara, Pastore, Anna, Rota, Rossella, Tartaglia, Marco, Leonetti, Carlo, and Alisi, Anna

Abstract

Additional file 3: Table S3. Common up- and down-regulated genes.

Published
2021
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21. Additional file 5 of Focal adhesion kinase inhibitor TAE226 combined with Sorafenib slows down hepatocellular carcinoma by multiple epigenetic effects

Author

Romito, Ilaria, Porru, Manuela, Braghini, Maria Rita, Pompili, Luca, Panera, Nadia, Crudele, Annalisa, Gnani, Daniela, De Stefanis, Cristiano, Scarsella, Marco, Pomella, Silvia, Levi Mortera, Stefano, de Billy, Emmanuel, Conti, Adrian Libenzio, Marzano, Valeria, Putignani, Lorenza, Vinciguerra, Manlio, Balsano, Clara, Pastore, Anna, Rota, Rossella, Tartaglia, Marco, Leonetti, Carlo, and Alisi, Anna

Subjects
Data_FILES
Abstract

Additional file 5: Table S5. GO annotations.

Published
2021
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22. Additional file 8 of Focal adhesion kinase inhibitor TAE226 combined with Sorafenib slows down hepatocellular carcinoma by multiple epigenetic effects

Author

Romito, Ilaria, Porru, Manuela, Braghini, Maria Rita, Pompili, Luca, Panera, Nadia, Crudele, Annalisa, Gnani, Daniela, De Stefanis, Cristiano, Scarsella, Marco, Pomella, Silvia, Levi Mortera, Stefano, de Billy, Emmanuel, Conti, Adrian Libenzio, Marzano, Valeria, Putignani, Lorenza, Vinciguerra, Manlio, Balsano, Clara, Pastore, Anna, Rota, Rossella, Tartaglia, Marco, Leonetti, Carlo, and Alisi, Anna

Abstract

Additional file 8: Figure S3. IGF-1R in HCC cells after treatment with TAE226 > SOR compared to single treatments. Representative immunoblot and quantitative analysis of phosphorylated IGF-1R after 48 h from treatment with the different drugs, in HepG2 (A) and Huh7 cells (B). ��Tubulin served as loading control. Values are the mean arbitrary units �� SD of at least three independent experiments. Data were analysed by 2-tailed Student���s t test. **p

Published
2021
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24. Dyads of G‐Quadruplex Ligands Triggering DNA Damage Response and Tumour Cell Growth Inhibition at Subnanomolar Concentration

Author

Doria, Filippo, primary, Salvati, Erica, additional, Pompili, Luca, additional, Pirota, Valentina, additional, D'Angelo, Carmen, additional, Manoli, Francesco, additional, Nadai, Matteo, additional, Richter, Sara N., additional, Biroccio, Annamaria, additional, Manet, Ilse, additional, and Freccero, Mauro, additional

Published
2019
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28. Targeting <italic>KRAS</italic> in metastatic colorectal cancer: current strategies and emerging opportunities.

Author

Porru, Manuela, Pompili, Luca, Caruso, Carla, Biroccio, Annamaria, and Leonetti, Carlo

Subjects
METASTASIS, COLON cancer, GENE targeting, ONCOGENES, CANCER research
Abstract

Developing drugs that target KRAS, the most frequently mutated oncogene in cancer, has not been successful despite much concerted efforts dedicated towards it in the last thirty years. Considering the key role this driver oncogene plays, the pharmacological drugging of KRAS remains a key challenge for cancer research. In this review, we highlight the emerging experimental strategies for blocking KRAS function and signaling and its direct targeting. We also report on the results in this field of research produced by our group. [ABSTRACT FROM AUTHOR]

Published
2018
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29. MiR-182-3p targets TRF2 and impairs tumor growth of triple-negative breast cancer

Author

Roberto Dinami, Luca Pompili, Eleonora Petti, Manuela Porru, Carmen D'Angelo, Serena Di Vito, Angela Rizzo, Virginia Campani, Giuseppe De Rosa, Alejandra Bruna, Violeta Serra, Miguel Mano, Mauro Giacca, Carlo Leonetti, Gennaro Ciliberto, Madalena Tarsounas, Antonella Stoppacciaro, Stefan Schoeftner, Annamaria Biroccio, Institut Català de la Salut, [Dinami R, Pompili L, Petti E, Porru M, D'Angelo C] Translational Oncology Research Unit, IRCCS—Regina Elena National Cancer Institute, Rome, Italy. [Di Vito S] Translational Oncology Research Unit, IRCCS—Regina Elena National Cancer Institute, Rome, Italy. Department of Ecological and Biological Sciences (DEB), University of Tuscia, Viterbo, Italy. [Serra V] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Dinami, Roberto [0000-0002-3585-3439], Petti, Eleonora [0000-0001-8189-1906], Porru, Manuela [0000-0002-6614-9110], Rizzo, Angela [0000-0001-5421-3085], Serra, Violeta [0000-0001-6620-1065], Mano, Miguel [0000-0003-1922-4824], Giacca, Mauro [0000-0003-2927-7225], Tarsounas, Madalena [0000-0002-4273-2870], Biroccio, Annamaria [0000-0003-3198-3532], Apollo - University of Cambridge Repository, Dinami, Roberto, Pompili, Luca, Petti, Eleonora, Porru, Manuela, D'Angelo, Carmen, Di Vito, Serena, Rizzo, Angela, Campani, Virginia, De Rosa, Giuseppe, Bruna, Alejandra, Serra, Violeta, Mano, Miguel, Giacca, Mauro, Leonetti, Carlo, Ciliberto, Gennaro, Tarsounas, Madalena, Stoppacciaro, Antonella, Schoeftner, Stefan, and Biroccio, Annamaria

Subjects
Apoptosis, Triple Negative Breast Neoplasms, TRF2, miR-182-3p, Cells::Cellular Structures::Intracellular Space::Cell Nucleus::Cell Nucleus Structures::Intranuclear Space::Chromosomes::Chromosome Structures::Telomere [ANATOMY], fenómenos fisiológicos celulares::muerte celular::apoptosis [FENÓMENOS Y PROCESOS], Mice, Cell Line, Tumor, Animals, Humans, telomere, Telòmer, target therapy, Apoptosi, Telomere, telomeres, neoplasias::neoplasias por localización::neoplasias de la mama::neoplasias de mama triple negativos [ENFERMEDADES], Gene Expression Regulation, Neoplastic, MicroRNAs, triple-negative breast cancer, Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms [DISEASES], Molecular Medicine, Mama - Càncer - Aspectes genètics, células::estructuras celulares::espacio intracelular::núcleo celular::estructuras del núcleo celular::espacio intranuclear::cromosomas::estructuras cromosómicas::telómero [ANATOMÍA], Cell Physiological Phenomena::Cell Death::Apoptosis [PHENOMENA AND PROCESSES]
Abstract

Target therapy; Telomeres; Triple-negative breast cancer Terapia dirigida; Telómeros; Cáncer de mama triple negativo Teràpia dirigida; Telòmers; Càncer de mama triple negatiu The telomeric repeat-binding factor 2 (TRF2) is a telomere-capping protein that plays a key role in the maintenance of telomere structure and function. It is highly expressed in different cancer types, and it contributes to cancer progression. To date, anti-cancer strategies to target TRF2 remain a challenge. Here, we developed a miRNA-based approach to reduce TRF2 expression. By performing a high-throughput luciferase screening of 54 candidate miRNAs, we identified miR-182-3p as a specific and efficient post-transcriptional regulator of TRF2. Ectopic expression of miR-182-3p drastically reduced TRF2 protein levels in a panel of telomerase- or alternative lengthening of telomeres (ALT)-positive cancer cell lines. Moreover, miR-182-3p induced DNA damage at telomeric and pericentromeric sites, eventually leading to strong apoptosis activation. We also observed that treatment with lipid nanoparticles (LNPs) containing miR-182-3p impaired tumor growth in triple-negative breast cancer (TNBC) models, including patient-derived tumor xenografts (PDTXs), without affecting mouse survival or tissue function. Finally, LNPs-miR-182-3p were able to cross the blood–brain barrier and reduce intracranial tumors representing a possible therapeutic option for metastatic brain lesions. The research leading to these results has been funded by Italian Association for Cancer Research (AIRC # 21579) and Ministry of Health (CO-2019-12369662) to AB. This work was financially supported by Ministry of Health Ricerca Corrente 2022 and intramural grant-in-aid to EP. RD, LP and EP were supported by AIRC fellowships.

Published
2023

30. Dyads of G-Quadruplex Ligands Triggering DNA Damage Response and Tumour Cell Growth Inhibition at Subnanomolar Concentration.

Author

Doria F, Salvati E, Pompili L, Pirota V, D'Angelo C, Manoli F, Nadai M, Richter SN, Biroccio A, Manet I, and Freccero M

Subjects
Cell Line, Tumor, Cell Proliferation drug effects, Drug Screening Assays, Antitumor, Humans, Imides chemical synthesis, Imides chemistry, Ligands, Metaphase drug effects, Microscopy, Fluorescence, Naphthalenes chemical synthesis, Naphthalenes chemistry, Proto-Oncogene Proteins c-kit genetics, Proto-Oncogene Proteins c-kit metabolism, Proto-Oncogene Proteins c-myc genetics, Proto-Oncogene Proteins c-myc metabolism, Telomere drug effects, Telomere metabolism, DNA Damage drug effects, DNA Repair drug effects, G-Quadruplexes, Imides pharmacology, Naphthalenes pharmacology
Abstract

Naphthalene diimide (NDI) dyads exhibiting a different substitution pattern and linker length have been synthesised and evaluated as G-quadruplex (G4) ligands, by investigating their cytotoxicity in selected cell lines. The dyads with the long C 7 linker exhibit extremely low IC 50 values, below 10 nm, on different cancer cell lines. Contrary, the dyads with the shorter C 4 linker were much less effective, with IC values increasing up to 1 μm. Among the three dyads with the longest linker, small differences in the IC 50 values emerge, suggesting that the linker length plays a more important role than the substitution pattern. We have further shown that the dyads are able to induce cellular DNA damage response, which is not limited to the telomeric regions and is likely the origin of their cytotoxicity. Both absorption titration and dynamic light scattering of the most cytotoxic dyads in the presence of hTel22 highlight their ability to induce effective G4 aggregation, acting as non-covalent cross-linking agents., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2019
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31. Xenograft as In Vivo Experimental Model.

Author

Porru M, Pompili L, Caruso C, and Leonetti C

Subjects
Animals, Disease Models, Animal, Drug Resistance, Neoplasm physiology, Humans, Mice, Neoplastic Stem Cells metabolism, Neoplastic Stem Cells pathology, Xenograft Model Antitumor Assays, Transplantation, Heterologous methods
Abstract

The identification of experimental models that recapitulate human cancers designed to predict patient clinical response to therapies is a major break in oncology. Cancer stem cells (CSCs) represent a small tumor cell population responsible for drug resistance, where their effective killing may lead to identifying better treatment options. While the CSCs hypothesis highlights the need for a specific tumor target, patient-derived xenografts (PDXs) should also be considered for drug development as they better represent tumor heterogeneity and the environment in which a tumor develops.

Published
2018
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