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Article ; Online: Bromodomain Inhibitor JQ1 Provides Novel Insights and Perspectives in Rhabdomyosarcoma Treatment.

Marchesi, Irene / Fais, Milena / Fiorentino, Francesco Paolo / Bordoni, Valentina / Sanna, Luca / Zoroddu, Stefano / Bagella, Luigi

International journal of molecular sciences

2022 Volume 23, Issue 7

Abstract: Rhabdomyosarcoma (RMS) is the most common type of pediatric soft tissue sarcoma. It is classified into two main subtypes: embryonal (eRMS) and alveolar (aRMS). MYC family proteins are frequently highly expressed in RMS tumors, with the highest levels ... ...

Abstract	Rhabdomyosarcoma (RMS) is the most common type of pediatric soft tissue sarcoma. It is classified into two main subtypes: embryonal (eRMS) and alveolar (aRMS). MYC family proteins are frequently highly expressed in RMS tumors, with the highest levels correlated with poor prognosis. A pharmacological approach to inhibit MYC in cancer cells is represented by Bromodomain and Extra-Terminal motif (BET) protein inhibitors. In this paper, we evaluated the effects of BET inhibitor (+)-JQ1 (JQ1) on the viability of aRMS and eRMS cells. Interestingly, we found that the drug sensitivity of RMS cell lines to JQ1 was directly proportional to the expression of MYC. JQ1 induces G1 arrest in cells with the highest steady-state levels of MYC, whereas apoptosis is associated with MYC downregulation. These findings suggest BET inhibition as an effective strategy for the treatment of RMS alone or in combination with other drugs.
MeSH term(s)	Apoptosis ; Azepines/pharmacology ; Cell Line, Tumor ; Cell Proliferation ; Child ; Humans ; Proto-Oncogene Proteins c-myc/metabolism ; Rhabdomyosarcoma/drug therapy ; Transcription Factors/metabolism ; Triazoles/pharmacology
Chemical Substances	Azepines ; Proto-Oncogene Proteins c-myc ; Transcription Factors ; Triazoles
Language	English
Publishing date	2022-03-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23073581
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Article ; Online: A Micro-Immunotherapy Sequential Medicine MIM-seq Displays Immunomodulatory Effects on Human Macrophages and Anti-Tumor Properties towards In Vitro 2D and 3D Models of Colon Carcinoma and in an In Vivo Subcutaneous Xenograft Colon Carcinoma Model.

Jacques, Camille / Marchesi, Irene / Fiorentino, Francesco Paolo / Chatelais, Mathias / Lilli, Nicoletta Libera / Appel, Kurt / Lejeune, Beatrice / Floris, Ilaria

International journal of molecular sciences

2022 Volume 23, Issue 11

Abstract: In this study, the immunomodulatory effects of a sequential micro-immunotherapy medicine, referred as MIM-seq, were appraised in human primary M1 and M2 macrophages, in which the secretion of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, ...

Abstract	In this study, the immunomodulatory effects of a sequential micro-immunotherapy medicine, referred as MIM-seq, were appraised in human primary M1 and M2 macrophages, in which the secretion of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-12, IL-23, and tumor necrosis factor (TNF)-alpha, was inhibited. In addition, the potential anti-proliferative effects of MIM-seq on tumor cells was assessed in three models of colorectal cancer (CRC): an in vitro two-dimensions (2D) model of HCT-116 cells, an in vitro tri-dimensional (3D) model of spheroids, and an in vivo model of subcutaneous xenografted mice. In these models, MIM-seq displayed anti-proliferative effects when compared with the vehicle. In vivo, the tumor growth was slightly reduced in MIM-seq-treated animals. Moreover, MIM-seq could slightly reduce the growth of our spheroid models, especially under serum-deprivation. When MIM-seq was combined with two well-known anti-cancerogenic agents, either resveratrol or etoposide, MIM-seq could even further reduce the spheroid's volume, pointing up the need to further assess whether MIM-seq could be beneficial for CRC patients as an adjuvant therapy. Altogether, these data suggest that MIM-seq could have anti-tumor properties against CRC and an immunomodulatory effect towards the mediators of inflammation, whose systemic dysregulation is considered to be a poor prognosis for patients.
MeSH term(s)	Animals ; Carcinoma ; Colonic Neoplasms/drug therapy ; Disease Models, Animal ; Heterografts ; Humans ; Immunologic Factors/pharmacology ; Immunotherapy ; Macrophages ; Mice ; Tumor Necrosis Factor-alpha/pharmacology
Chemical Substances	Immunologic Factors ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2022-05-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23116059
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Article ; Online: BET-Inhibitor I-BET762 and PARP-Inhibitor Talazoparib Synergy in Small Cell Lung Cancer Cells.

Fiorentino, Francesco Paolo / Marchesi, Irene / Schröder, Christoph / Schmidt, Ronny / Yokota, Jun / Bagella, Luigi

International journal of molecular sciences

2020 Volume 21, Issue 24

Abstract: Small cell lung cancer (SCLC) is an aggressive type of lung cancer with high mortality that is caused by frequent relapses and acquired resistance. Despite that several target-based approaches with potential therapeutic impact on SCLC have been ... ...

Abstract	Small cell lung cancer (SCLC) is an aggressive type of lung cancer with high mortality that is caused by frequent relapses and acquired resistance. Despite that several target-based approaches with potential therapeutic impact on SCLC have been identified, numerous targeted drugs have not been successful in providing improvements in cancer patients when used as single agents. A combination of targeted therapies could be a strategy to induce maximum lethal effects on cancer cells. As a starting point in the development of new drug combination strategies for the treatment of SCLC, we performed a mid-throughput screening assay by treating a panel of SCLC cell lines with BETi or AKi in combination with PARPi or EZH2i. We observed drug synergy between I-BET762 and Talazoparib, BETi and PARPi, respectively, in SCLC cells. Combinatorial efficacy was observed in
MeSH term(s)	Antineoplastic Agents/pharmacology ; Benzodiazepines/pharmacology ; Carcinoma, Non-Small-Cell Lung/metabolism ; Cell Line, Tumor ; Cells, Cultured ; DNA Damage/drug effects ; Drug Synergism ; Humans ; Lung Neoplasms/metabolism ; Phthalazines/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology
Chemical Substances	Antineoplastic Agents ; Phthalazines ; Poly(ADP-ribose) Polymerase Inhibitors ; Benzodiazepines (12794-10-4) ; molibresib (5QIO6SRZ2R) ; talazoparib (9QHX048FRV)
Language	English
Publishing date	2020-12-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21249595
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Article ; Online: The tumor suppressor role of CTCF.

Fiorentino, Francesco Paolo / Giordano, Antonio

Journal of cellular physiology

2012 Volume 227, Issue 2, Page(s) 479–492

Abstract: CTCF is an evolutionary conserved and ubiquitously expressed protein that binds thousands of sites in the human genome. Ectopic expression of CTCF in various normal and tumoral human cell lines inhibits cell division and clonogenicity, with the ... ...

Abstract	CTCF is an evolutionary conserved and ubiquitously expressed protein that binds thousands of sites in the human genome. Ectopic expression of CTCF in various normal and tumoral human cell lines inhibits cell division and clonogenicity, with the consequence to consider CTCF a potential tumor-suppressor factor. In this review article, we focused on the molecular mechanisms engaged by CTCF to modulate the expression of several key-regulators of differentiation, cellular senescence, cell cycle control and progression, whose expression is frequently altered in tumors. Moreover, we discussed common features of CTCF at each tumor-related DNA-binding sequence, such as protein-partners, post-translational modifications, and distinctive epigenetic marks establishment. The investigation of the molecular mechanisms engaged by CTCF to modulate tumor-related genes emphasizes the cell-type dependency of its tumor suppressor role. Indeed, the ability of CTCF to bind their promoters strictly depends by cell-type features as DNA methylation, BORIS-binding and post-translational modifications as PARYlation.
MeSH term(s)	CCCTC-Binding Factor ; DNA ; Gene Expression Regulation/physiology ; Humans ; Protein Binding ; Repressor Proteins/genetics ; Repressor Proteins/metabolism ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism
Chemical Substances	CCCTC-Binding Factor ; CTCF protein, human ; Repressor Proteins ; Tumor Suppressor Proteins ; DNA (9007-49-2)
Language	English
Publishing date	2012-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	3116-1
ISSN	1097-4652 ; 0021-9541
ISSN (online)	1097-4652
ISSN	0021-9541
DOI	10.1002/jcp.22780
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Article ; Online: Design of a Lentiviral Vector for the Inducible Expression of MYC: A New Strategy for Construction Approach.

Tokgun, Onur / Fiorentino, Francesco Paolo / Tokgun, Pervin Elvan / Yokota, Jun / Akca, Hakan

Molecular biotechnology

2017 Volume 59, Issue 6, Page(s) 200–206

Abstract: Lentiviral vectors are powerful tools for gene expression studies. Here we report the construction of pTIJ, a vector for inducible gene expression. pTIJ was generated from pTRIPZ backbone, which is designed for the inducible expression of shRNA sequences, ...

Abstract	Lentiviral vectors are powerful tools for gene expression studies. Here we report the construction of pTIJ, a vector for inducible gene expression. pTIJ was generated from pTRIPZ backbone, which is designed for the inducible expression of shRNA sequences, by the introducing of a multiple cloning site upstream of the Tet promoter and the removal of miR30 flanking sequences. To evaluate pTIJ as a tool for the inducible expression of genes of interest, we introduced MYC cDNA into pTIJ and infected two small cell lung cancer cell lines, H209 and H345. Induction of MYC expression by doxycycline was detectable in both cell lines by real-time PCR and western blot analysis. This study highlights the relevance of pTIJ vector to allow the inducible expression of any gene of interest. In our belief, pTIJ will be an extremely useful tool to simplify the generation of genetically engineered cell lines for the inducible expression of cDNA sequences in biological studies. Furthermore, we report the generation of a pTIJ-MYC vector for the inducible expression of the oncogene MYC.
Language	English
Publishing date	2017-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	1193057-3
ISSN	1559-0305 ; 1073-6085
ISSN (online)	1559-0305
ISSN	1073-6085
DOI	10.1007/s12033-017-0006-y
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Article ; Online: Erratum to: Design of a Lentiviral Vector for the Inducible Expression of MYC: A New Strategy for Construction Approach.

Tokgun, Onur / Fiorentino, Francesco Paolo / Tokgun, Pervin Elvan / Yokota, Jun / Akca, Hakan

Molecular biotechnology

2017 Volume 59, Issue 7, Page(s) 305

Language	English
Publishing date	2017-05-09
Publishing country	United States
Document type	Published Erratum
ZDB-ID	1193057-3
ISSN	1559-0305 ; 1073-6085
ISSN (online)	1559-0305
ISSN	1073-6085
DOI	10.1007/s12033-017-0011-1
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Article ; Online: Clarifying the molecular mechanism of tomentosin‑induced antiproliferative and proapoptotic effects in human multiple myeloma via gene expression profile and genetic interaction network analysis.

Virdis, Patrizia / Migheli, Rossana / Bordoni, Valentina / Fiorentino, Francesco Paolo / Sanna, Luca / Marchesi, Irene / Pintore, Giorgio / Galleri, Grazia / Muroni, Maria Rosaria / Bagella, Luigi / Fozza, Claudio / De Miglio, Maria Rosaria / Podda, Luigi

International journal of molecular medicine

2021 Volume 48, Issue 6

Abstract: Multiple myeloma (MM) is an aggressive B cell malignancy. Substantial progress has been made in the therapeutic context for patients with MM, however it still represents an incurable disease due to drug resistance and recurrence. Development of more ... ...

Abstract	Multiple myeloma (MM) is an aggressive B cell malignancy. Substantial progress has been made in the therapeutic context for patients with MM, however it still represents an incurable disease due to drug resistance and recurrence. Development of more effective or synergistic therapeutic approaches undoubtedly represents an unmet clinical need. Tomentosin is a bioactive natural sesquiterpene lactone extracted by various plants with therapeutic properties, including anti‑neoplastic effects. In the present study, the potential antitumor activity of tomentosin was evaluated on the human RPMI‑8226 cell line, treated with increasing tomentosin concentration for cytotoxicity screening. The data suggested that both cell cycle arrest and cell apoptosis could explain the antiproliferative effects of tomentosin and may result in the inhibition of RPMI‑8226 cell viability. To assess differentially expressed genes contributing to tomentosin activity and identify its mechanism of action, a microarray gene expression profile was performed, identifying 126 genes deregulated by tomentosin. To address the systems biology and identify how tomentosin deregulates gene expression in MM from a systems perspective, all deregulated genes were submitted to enrichment and molecular network analysis. The Protein‑Protein Interaction (PPI) network analysis showed that tomentosin in human MM induced the downregulation of genes involved in several pathways known to lead immune‑system processes, such as cytokine‑cytokine receptor interaction, chemokine or NF‑κB signaling pathway, as well as genes involved in pathways playing a central role in cellular neoplastic processes, such as growth, proliferation, migration, invasion and apoptosis. Tomentosin also induced endoplasmic reticulum stress via upregulation of cyclic AMP‑dependent transcription factor ATF‑4 and DNA damage‑inducible transcript 3 protein genes, suggesting that in the presence of tomentosin the protective unfolded protein response signaling may induce cell apoptosis. The functional connections analysis executed using the Connectivity Map tool, suggested that the effects of tomentosin on RPMI‑8226 cells might be similar to those exerted by heat shock proteins inhibitors. Taken together, these data suggested that tomentosin may be a potential drug candidate for the treatment of MM.
MeSH term(s)	Antineoplastic Agents, Phytogenic/pharmacology ; Apoptosis/drug effects ; Apoptosis/genetics ; Cell Cycle/drug effects ; Cell Line, Tumor ; Drug Screening Assays, Antitumor ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Lactones/pharmacology ; Multiple Myeloma/drug therapy ; Multiple Myeloma/genetics ; Multiple Myeloma/pathology ; Protein Interaction Maps/drug effects ; Protein Interaction Maps/genetics ; Sesquiterpenes/chemistry ; Sesquiterpenes/pharmacology
Chemical Substances	Antineoplastic Agents, Phytogenic ; Lactones ; Sesquiterpenes ; tomentosin
Language	English
Publishing date	2021-10-13
Publishing country	Greece
Document type	Journal Article
ZDB-ID	1444428-8
ISSN	1791-244X ; 1107-3756
ISSN (online)	1791-244X
ISSN	1107-3756
DOI	10.3892/ijmm.2021.5046
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Article: Tomentosin a Sesquiterpene Lactone Induces Antiproliferative and Proapoptotic Effects in Human Burkitt Lymphoma by Deregulation of Anti- and Pro-Apoptotic Genes.

Virdis, Patrizia / Marchesi, Irene / Fiorentino, Francesco Paolo / Migheli, Rossana / Sanna, Luca / Bordoni, Valentina / Pintore, Giorgio / Galleri, Grazia / Muroni, Maria Rosaria / Bagella, Luigi / Fozza, Claudio / De Miglio, Maria Rosaria / Podda, Luigi

Life (Basel, Switzerland)

2021 Volume 11, Issue 11

Abstract: 1) Tomentosin is the most representative sesquiterpene lactone extracted ... ...

Abstract	(1) Tomentosin is the most representative sesquiterpene lactone extracted by
Language	English
Publishing date	2021-10-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life11111128
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Article ; Online: On the role of retinoblastoma family proteins in the establishment and maintenance of the epigenetic landscape.

Fiorentino, Francesco Paolo / Marchesi, Irene / Giordano, Antonio

Journal of cellular physiology

2013 Volume 228, Issue 2, Page(s) 276–284

Abstract: RB family members are negative regulators of the cell cycle, involved in numerous biological processes such as cellular senescence, development and differentiation. Disruption of RB family pathways are linked to loss of cell cycle control, cellular ... ...

Abstract	RB family members are negative regulators of the cell cycle, involved in numerous biological processes such as cellular senescence, development and differentiation. Disruption of RB family pathways are linked to loss of cell cycle control, cellular immortalization and cancer. RB family, and in particular the most studied member RB/p105, has been considered a tumor suppressor gene by more than three decades, and numerous efforts have been done to understand his molecular activity. However, the epigenetic mechanisms behind Rb-mediated tumor suppression have been uncovered only in recent years. In this review, the role of RB family members in cancer epigenetics will be discussed. We start with an introduction to epigenomes, chromatin modifications and cancer epigenetics. In order to provide a clear picture of the involvement of RB family in the epigenetic field, we describe the RB family role in the epigenetic landscape dynamics based on the heterochromatin variety involved, facultative or constitutive. We want to stress that, despite dissimilar modulations, RB family is involved in both mammalian varieties of heterochromatin establishment and maintenance and that disruption of RB family pathways drives to alterations of both heterochromatin structures, thus to the global epigenetic landscape.
MeSH term(s)	Animals ; Cell Differentiation/genetics ; Cell Differentiation/physiology ; Chromatin/genetics ; Chromatin/metabolism ; Chromatin Assembly and Disassembly/genetics ; Chromatin Assembly and Disassembly/physiology ; DNA Methylation/genetics ; DNA Methylation/physiology ; Epigenesis, Genetic ; Female ; Histones/metabolism ; Humans ; Mice ; Neoplasms/genetics ; Neoplasms/metabolism ; Protein Processing, Post-Translational/genetics ; Protein Processing, Post-Translational/physiology ; Retinoblastoma Protein/genetics ; Retinoblastoma Protein/metabolism
Chemical Substances	Chromatin ; Histones ; Retinoblastoma Protein
Language	English
Publishing date	2013-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	3116-1
ISSN	1097-4652 ; 0021-9541
ISSN (online)	1097-4652
ISSN	0021-9541
DOI	10.1002/jcp.24141
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Article ; Online: Antiproliferative and proapoptotic effects of

Virdis, Patrizia / Migheli, Rossana / Galleri, Grazia / Fancello, Silvia / Cadoni, Maria Piera L / Pintore, Giorgio / Petretto, Giacomo Luigi / Marchesi, Irene / Fiorentino, Francesco Paolo / di Francesco, Alessandra / Sanges, Francesca / Bagella, Luigi / Muroni, Maria Rosaria / Fozza, Claudio / De Miglio, Maria Rosaria / Podda, Luigi

Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine

2020 Volume 42, Issue 2, Page(s) 1010428319901061

Abstract: Burkitt lymphoma is a very aggressive B-cell non-Hodgkin lymphoma. Although remarkable progress has been made in the therapeutic scenario for patients with Burkitt lymphoma, search and development of new effective anticancer agents to improve patient ... ...

Abstract	Burkitt lymphoma is a very aggressive B-cell non-Hodgkin lymphoma. Although remarkable progress has been made in the therapeutic scenario for patients with Burkitt lymphoma, search and development of new effective anticancer agents to improve patient outcome and minimize toxicity has become an urgent issue. In this study, the antitumoral activity of
MeSH term(s)	Apoptosis/drug effects ; Burkitt Lymphoma/drug therapy ; Burkitt Lymphoma/genetics ; Burkitt Lymphoma/pathology ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Inula/chemistry ; Neoplasm Proteins/genetics ; Plant Extracts/chemistry ; Plant Extracts/pharmacology
Chemical Substances	Neoplasm Proteins ; Plant Extracts
Language	English
Publishing date	2020-02-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	605825-5
ISSN	1423-0380 ; 0289-5447 ; 1010-4283
ISSN (online)	1423-0380
ISSN	0289-5447 ; 1010-4283
DOI	10.1177/1010428319901061
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