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  1. Article: Editorial: Hallmark of cancer: sustained proliferative signalling.

    Ciccarone, Fabio / Ciriolo, Maria Rosa

    Frontiers in oncology

    2023  Volume 13, Page(s) 1328827

    Language English
    Publishing date 2023-11-23
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2023.1328827
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Use of oral GnRH antagonists combined therapy in the management of symptomatic uterine fibroids.

    Di Spiezio Sardo, A / Ciccarone, F / Muzii, L / Scambia, G / Vignali, M

    Facts, views & vision in ObGyn

    2023  Volume 15, Issue 1, Page(s) 29–33

    Abstract: Uterine fibroids have an impact on women's lives due to their high prevalence, physical symptoms, their consequences on patients' emotional and psychological well-being and loss of work productivity. The choice of therapeutical approaches varies ... ...

    Abstract Uterine fibroids have an impact on women's lives due to their high prevalence, physical symptoms, their consequences on patients' emotional and psychological well-being and loss of work productivity. The choice of therapeutical approaches varies depending on several factors, and therefore should be applied individually. Currently, there is an unmet need for good, reliable, uterine-sparing options. The oral GnRH antagonists (Elagolix, Relugolix, Linzagolix) represent a new alternative for the medical management of hormone-dependent gynaecological diseases such as uterine fibroids or endometriosis. They rapidly bind to the GnRH receptor, block endogenous GnRH activity and directly suppress LH and FSH production, avoiding unwanted flare-up effects. Some GnRH antagonists are marketed in combination with hormone replacement therapy add-back to counteract hypo-oestrogenic side effects. According to the registration trials, once-daily GhRH antagonist combination therapy results in a significant reduction in menstrual bleeding, as compared with placebo, and preserves bone mineral density, for up to 104 weeks. Further studies in the long term are needed to evaluate the whole impact of medical treatment of uterine fibroids on the management of this common women's disease.
    Language English
    Publishing date 2023-04-03
    Publishing country Belgium
    Document type Journal Article
    ZDB-ID 2701574-9
    ISSN 2032-0418 ; 2684-4230
    ISSN 2032-0418 ; 2684-4230
    DOI 10.52054/FVVO.15.1.059
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A cost-effectiveness analysis of an integrated clinical-radiogenomic screening program for the identification of BRCA 1/2 carriers (e-PROBE study).

    Di Pilla, A / Nero, C / Specchia, M L / Ciccarone, F / Boldrini, L / Lenkowicz, J / Alberghetti, B / Fagotti, A / Testa, A C / Valentini, V / Sala, E / Scambia, G

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 928

    Abstract: Current approach to identify BRCA 1/2 carriers in the general population is ineffective as most of the carriers remain undiagnosed. Radiomics is an emerging tool for large scale quantitative analysis of features from standard diagnostic imaging and has ... ...

    Abstract Current approach to identify BRCA 1/2 carriers in the general population is ineffective as most of the carriers remain undiagnosed. Radiomics is an emerging tool for large scale quantitative analysis of features from standard diagnostic imaging and has been applied also to identify gene mutational status. The objective of this study was to evaluate the clinical and economic impact of integrating a radiogenomics model with clinical and family history data in identifying BRCA mutation carriers in the general population. This cost-effective analysis compares three different approaches to women selection for BRCA testing: established clinical criteria/family history (model 1); established clinical criteria/family history and the currently available radiogenomic model (49% sensitivity and 87% specificity) based on ultrasound images (model 2); same approach used in model 2 but simulating an improvement of the performances of the radiogenomic model (80% sensitivity and 95% specificity) (model 3). All models were trained with literature data. Direct costs were calculated according to the rates currently used in Italy. The analysis was performed simulating different scenarios on the generation of 18-year-old girls in Italy (274,000 people). The main outcome was to identify the most effective model comparing the number of years of BRCA-cancer healthy life expectancy (HLYs). An incremental cost-effectiveness ratio (ICER) was also derived to determine the cost in order to increase BRCA carriers-healthy life span by 1 year. Compared to model 1, model 2 increases the detection rate of BRCA carriers by 41.8%, reduces the rate of BRCA-related cancers by 23.7%, generating over a 62-year observation period a cost increase by 2.51 €/Year/Person. Moreover, model 3 further increases BRCA carriers detection (+ 68.3%) and decrease in BRCA-related cancers (- 38.4%) is observed compared to model 1. Model 3 increases costs by 0.7 €/Year/Person. After one generation, the estimated ICER in the general population amounts to about 3800€ and 653€ in model 2 and model 3 respectively. Model 2 has a massive effect after only one generation in detecting carriers in the general population with only a small cost increment. The clinical impact is limited mainly due to the current low acceptance rate of risk-reducing surgeries. Further multicentric studies are required before implementing the integrated clinical-radiogenomic model in clinical practice.
    MeSH term(s) Humans ; Female ; Adolescent ; Cost-Effectiveness Analysis ; Genetic Carrier Screening ; Health Status ; Healthy Life Expectancy ; Neoplasms
    Language English
    Publishing date 2024-01-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-51031-1
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  4. Article ; Online: Imaging in gynecological disease (27): clinical and ultrasound characteristics of recurrent ovarian stromal cell tumors.

    Moro, F / Giudice, M T / Bolomini, G / Moruzzi, M C / Mascilini, F / Quagliozzi, L / Ciccarone, F / Scambia, G / Fagotti, A / Valentin, L / Testa, A C

    Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology

    2024  Volume 63, Issue 3, Page(s) 399–407

    Abstract: Objective: To describe the clinical and ultrasound characteristics of recurrent granulosa cell and Sertoli-Leydig cell tumors.: Methods: This was a retrospective observational study performed at Fondazione Policlinico Universitario A. Gemelli, ... ...

    Abstract Objective: To describe the clinical and ultrasound characteristics of recurrent granulosa cell and Sertoli-Leydig cell tumors.
    Methods: This was a retrospective observational study performed at Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico, IRCCS, Rome (Gemelli center), Italy. Patients with a histological diagnosis of recurrent granulosa cell tumor or Sertoli-Leydig cell tumor were identified from the database of the Department of Gynecological Oncology. Those who had undergone a preoperative ultrasound examination at the Gemelli center between 2012 and 2020 were included, and the data retrieved from the original ultrasound reports. In all of these reports, the recurrent tumors were described using International Ovarian Tumor Analysis (IOTA) terminology. If a patient had more than one episode of relapse, information from all episodes was collected. If there was more than one recurrent tumor at the same ultrasound examination, all tumors were included. One expert sonographer also reviewed all available ultrasound images to identify typical ultrasound patterns using pattern recognition.
    Results: We identified 30 patients with a histological diagnosis of recurrent granulosa cell tumor (25 patients, 55 tumors) or Sertoli-Leydig cell tumor (five patients, seven tumors). All 30 had undergone at least one preoperative ultrasound examination at the Gemelli center and were included. These women had a total of 66 episodes of relapse, of which a preoperative ultrasound examination had been performed at the Gemelli center in 34, revealing 62 recurrent lesions: one in 22/34 (64.7%) episodes of relapse, two in 4/34 (11.8%) episodes and three or more in 8/34 (23.5%) episodes. Most recurrent granulosa cell tumors (38/55, 69.1%) and recurrent Sertoli-Leydig tumors (6/7, 85.7%) were classified as solid or multilocular-solid tumors, while 8/55 (14.5%) recurrent granulosa cell tumors and 1/7 (14.3%) recurrent Sertoli-Leydig cell tumors were unilocular cysts and 9/55 (16.4%) recurrent granulosa cell tumors were multilocular cysts. The nine unilocular cysts had contents that were anechoic (n = 2) or had low-level echogenicity (n = 7), had either smooth (n = 4) or irregular (n = 5) internal cyst walls, and ranged in largest diameter from 8 to 38 mm, with three being < 20 mm and five being 20-30 mm. On retrospective review of the images, two typical ultrasound patterns were described: small solid tumor measuring < 2 cm (15/62, 24.2%) and tumor with vascularized echogenic ground-glass-like content (12/62, 19.4%).
    Conclusions: Some granulosa cell and Sertoli-Leydig cell recurrences manifest one of two typical ultrasound patterns, while some appear as unilocular cysts. These are usually classified as benign, but in patients being followed up for a granulosa cell tumor or Sertoli-Leydig cell tumor, a unilocular cyst should be considered suspicious of recurrence. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
    MeSH term(s) Pregnancy ; Male ; Humans ; Female ; Sertoli-Leydig Cell Tumor/diagnostic imaging ; Granulosa Cell Tumor/diagnostic imaging ; Neoplasm Recurrence, Local/diagnostic imaging ; Ultrasonography ; Ovarian Neoplasms/diagnostic imaging ; Sex Cord-Gonadal Stromal Tumors/diagnostic imaging ; Genital Diseases, Female ; Cysts ; Recurrence ; Stromal Cells
    Language English
    Publishing date 2024-02-06
    Publishing country England
    Document type Observational Study ; Journal Article
    ZDB-ID 1073183-0
    ISSN 1469-0705 ; 0960-7692
    ISSN (online) 1469-0705
    ISSN 0960-7692
    DOI 10.1002/uog.27504
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Adaptive antioxidant response to mitochondrial fatty acid oxidation determines the proliferative outcome of cancer cells.

    Castelli, Serena / Ciccarone, Fabio / De Falco, Pamela / Ciriolo, Maria Rosa

    Cancer letters

    2022  Volume 554, Page(s) 216010

    Abstract: Alterations in lipid catabolism have been broadly described in cancer cells and show tumor-type specific effects on proliferation and cell survival. The factor(s) responsible for this heterogeneity is currently unknown and represents the main limitation ... ...

    Abstract Alterations in lipid catabolism have been broadly described in cancer cells and show tumor-type specific effects on proliferation and cell survival. The factor(s) responsible for this heterogeneity is currently unknown and represents the main limitation in the development of therapeutic interventions that impair lipid metabolism. In this study, we focused on hexanoic acid, a medium-chain fatty acid, that can quickly boost oxidative metabolism by passively crossing mitochondrial membranes. We demonstrated that the antioxidant adaptation of cancer cells to increased fatty acid oxidation is predictive of the proliferative outcome. By interfering with SOD1 expression and glutathione homeostasis, we verified that mitochondrial fatty acid oxidation has antitumor effects in cancer cells that efficiently buffer ROS. In contrast, increased ROS levels promote proliferation in cells with an imbalanced antioxidant response. In addition, an increase in mitochondrial mass and mitophagy activation were observed, respectively. Overall, these data demonstrate that the capacity to manage ROS from mitochondrial oxidative metabolism determines whether lipid catabolism is advantageous or detrimental for cancer cells.
    MeSH term(s) Humans ; Antioxidants/pharmacology ; Antioxidants/metabolism ; Reactive Oxygen Species/metabolism ; Lipid Metabolism ; Fatty Acids/metabolism ; Lipids ; Oxidation-Reduction ; Oxidative Stress ; Neoplasms/drug therapy
    Chemical Substances Antioxidants ; Reactive Oxygen Species ; Fatty Acids ; Lipids
    Language English
    Publishing date 2022-11-17
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 195674-7
    ISSN 1872-7980 ; 0304-3835
    ISSN (online) 1872-7980
    ISSN 0304-3835
    DOI 10.1016/j.canlet.2022.216010
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  6. Article ; Online: Ultrasound, macroscopic and histological features of malignant ovarian tumors. Metastatic tumors to the ovary: ovarian metastases from biliary tract and ovarian metastases from colon cancer.

    Ciccarone, Francesca / Codecà, Claudia / Versace, Valeria / Moro, Francesca

    International journal of gynecological cancer : official journal of the International Gynecological Cancer Society

    2021  Volume 31, Issue 10, Page(s) 1388–1390

    MeSH term(s) Adenocarcinoma/pathology ; Aged ; Biliary Tract Neoplasms/pathology ; Colonic Neoplasms/pathology ; Diagnosis, Differential ; Female ; Humans ; Ovarian Neoplasms/diagnostic imaging ; Ovarian Neoplasms/secondary ; Tomography, X-Ray Computed ; Ultrasonography
    Language English
    Publishing date 2021-09-20
    Publishing country England
    Document type Case Reports ; Journal Article ; Video-Audio Media
    ZDB-ID 1070385-8
    ISSN 1525-1438 ; 1048-891X
    ISSN (online) 1525-1438
    ISSN 1048-891X
    DOI 10.1136/ijgc-2020-002250
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Applicazioni cliniche di bevacizumab nel trattamento del tumore del colon-retto e dell’ovaio.

    Danesi, Romano / Cremolini, Chiara / Ciccarone, Francesca / Lorusso, Domenica

    Recenti progressi in medicina

    2021  Volume 112, Issue 6, Page(s) 444–453

    Abstract: The development of biological drugs, which began in the 1980s, has revolutionized the treatment of numerous oncological diseases and severely disabling autoimmune diseases, with widely demonstrated evidence of benefit. Today, biological drugs represent ... ...

    Title translation Clinical applications of bevacizumab in the treatment of colorectal and ovarian cancer.
    Abstract The development of biological drugs, which began in the 1980s, has revolutionized the treatment of numerous oncological diseases and severely disabling autoimmune diseases, with widely demonstrated evidence of benefit. Today, biological drugs represent an important and continuously developing category and are used both as a support therapy in onco-hematology and as molecules with their own therapeutic activity, such as monoclonal antibodies. Among these, bevacizumab represents a drug of relevant clinical value, used as antiangiogenic therapy in numerous cancers, in particular colorectal and ovarian cancers. The expiry of the patent period of monoclonal antibodies, including bevacizumab, has opened up to the development of biosimilar drugs, represented by structurally similar molecules with pharmacokinetic, pharmacodynamic and clinical characteristics equivalent to a biological drug already present in clinical use (originator biologic). The development process of these drugs is contained in the guidelines of the major regulatory bodies (FDA/EMA) and is faster than that provided for the originator biologic. Since biosimilars have a lower cost than reference drugs, their use represents a possibility of containing health care costs and of satifying the growing demand in terms of efficacy and personalization of pharmacological therapies. Considering the particular severity of the diseases treated, including colorectal and ovarian cancers, biosimilar drugs must be used with full awareness, in terms of efficacy and safety, since their approval is based on a rigorous analytical process, as well as preclinical and clinical evaluation.
    MeSH term(s) Antibodies, Monoclonal ; Antineoplastic Agents, Immunological/therapeutic use ; Bevacizumab ; Biosimilar Pharmaceuticals/pharmacokinetics ; Biosimilar Pharmaceuticals/therapeutic use ; Colorectal Neoplasms/drug therapy ; Drug Approval ; Female ; Humans ; Ovarian Neoplasms/drug therapy
    Chemical Substances Antibodies, Monoclonal ; Antineoplastic Agents, Immunological ; Biosimilar Pharmaceuticals ; Bevacizumab (2S9ZZM9Q9V)
    Language Italian
    Publishing date 2021-06-15
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 138266-4
    ISSN 2038-1840 ; 0034-1193
    ISSN (online) 2038-1840
    ISSN 0034-1193
    DOI 10.1701/3620.36027
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  8. Article ; Online: Dynamic transvaginal ultrasound examination for assessing anatomy of parametrium.

    Moro, F / Zermano, S / Ianieri, M M / De Cicco Nardone, A / Carfagna, P / Ciccarone, F / Ercoli, A / Querleu, D / Scambia, G / Testa, A C

    Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology

    2023  Volume 62, Issue 6, Page(s) 904–906

    MeSH term(s) Humans ; Female ; Pregnancy ; Peritoneum ; Ultrasonography ; Ultrasonography, Prenatal
    Language English
    Publishing date 2023-07-19
    Publishing country England
    Document type Letter
    ZDB-ID 1073183-0
    ISSN 1469-0705 ; 0960-7692
    ISSN (online) 1469-0705
    ISSN 0960-7692
    DOI 10.1002/uog.26313
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Adipose Tissue and FoxO1: Bridging Physiology and Mechanisms.

    Ioannilli, Laura / Ciccarone, Fabio / Ciriolo, Maria Rosa

    Cells

    2020  Volume 9, Issue 4

    Abstract: Forkhead box O class proteins (FoxOs) are expressed nearly in all tissues and are involved in different functions such as energy metabolism, redox homeostasis, differentiation, and cell cycle arrest. The plasticity of FoxOs is demonstrated by post- ... ...

    Abstract Forkhead box O class proteins (FoxOs) are expressed nearly in all tissues and are involved in different functions such as energy metabolism, redox homeostasis, differentiation, and cell cycle arrest. The plasticity of FoxOs is demonstrated by post-translational modifications that determine diverse levels of transcriptional regulations also controlled by their subcellular localization. Among the different members of the FoxO family, we will focus on FoxO1 in adipose tissue, where it is abundantly expressed and is involved in differentiation and transdifferentiation processes. The capability of FoxO1 to respond differently in dependence of adipose tissue subtype underlines the specific involvement of the transcription factor in energy metabolism and the "browning" process of adipocytes. FoxO1 can localize to nuclear, cytoplasm, and mitochondrial compartments of adipocytes responding to different availability of nutrients and source of reactive oxygen species (ROS). Specifically, fasted state produced-ROS enhance the nuclear activity of FoxO1, triggering the transcription of lipid catabolism and antioxidant response genes. The enhancement of lipid catabolism, in combination with ROS buffering, allows systemic energetic homeostasis and metabolic adaptation of white/beige adipocytes. On the contrary, a fed state induces FoxO1 to accumulate in the cytoplasm, but also in the mitochondria where it affects mitochondrial DNA gene expression. The importance of ROS-mediated signaling in FoxO1 subcellular localization and retrograde communication will be discussed, highlighting key aspects of FoxO1 multifaceted regulation in adipocytes.
    MeSH term(s) Adipocytes/metabolism ; Adipose Tissue/physiology ; Adipose Tissue, Brown/metabolism ; Animals ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism ; Humans ; Reactive Oxygen Species/metabolism ; Signal Transduction
    Chemical Substances Forkhead Transcription Factors ; Reactive Oxygen Species
    Language English
    Publishing date 2020-03-31
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells9040849
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  10. Article ; Online: Aconitase 2 sensitizes MCF-7 cells to cisplatin eliciting p53-mediated apoptosis in a ROS-dependent manner.

    Ciccarone, Fabio / De Falco, Pamela / Ciriolo, Maria Rosa

    Biochemical pharmacology

    2020  Volume 180, Page(s) 114202

    Abstract: Aconitase 2 (ACO2) belongs to the tricarboxylic acid (TCA) cycle, which represents a key metabolic hub for cellular metabolism that is frequently altered in cancer for satisfying bioenergetic and biosynthetic requirements of proliferating cells. The ... ...

    Abstract Aconitase 2 (ACO2) belongs to the tricarboxylic acid (TCA) cycle, which represents a key metabolic hub for cellular metabolism that is frequently altered in cancer for satisfying bioenergetic and biosynthetic requirements of proliferating cells. The promotion of ACO2 activity in breast cancer cell lines was shown to slow down proliferation imposing a switch from aerobic glycolysis to oxidative metabolism. The alteration of metabolic pathways in cancer also impinges on the sensitivity to chemotherapeutic interventions. In this work, we evidence that the presence of ACO2 sensitizes cells to the treatment with the genotoxic agents cisplatin (CDDP) and doxorubicin activating the apoptotic cell death mechanism. This response was driven by the accumulation of reactive oxygen species (ROS) following both ACO2 overexpression and CDDP exposure that permit the stabilization/activation of p53 in nuclear and mitochondrial compartments. Collectively, our results highlight that in ACO2 overexpressing cells the promotion of mitochondrial metabolism accounts for increased ROS production that was buffered by p53 mitochondrial recruitment and autophagy induction. However, these systems are not able to counteract the CDDP-mediated oxidative stress that becomes the Achilles heel for increasing susceptibility to apoptotic cell death.
    MeSH term(s) Aconitate Hydratase/metabolism ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Apoptosis/physiology ; Cisplatin/pharmacology ; DNA Damage/drug effects ; DNA Damage/physiology ; DNA, Mitochondrial/metabolism ; Humans ; MCF-7 Cells ; Reactive Oxygen Species/metabolism ; Tumor Suppressor Protein p53/metabolism
    Chemical Substances Antineoplastic Agents ; DNA, Mitochondrial ; Reactive Oxygen Species ; Tumor Suppressor Protein p53 ; ACO2 protein, human (EC 4.2.1.3) ; Aconitate Hydratase (EC 4.2.1.3) ; Cisplatin (Q20Q21Q62J)
    Language English
    Publishing date 2020-08-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 208787-x
    ISSN 1873-2968 ; 0006-2952
    ISSN (online) 1873-2968
    ISSN 0006-2952
    DOI 10.1016/j.bcp.2020.114202
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