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Article ; Online: NMR Metabolomics of Primary Ovarian Cancer Cells in Comparison to Established Cisplatin-Resistant and -Sensitive Cell Lines.

Ghini, Veronica / Sorbi, Flavia / Fambrini, Massimiliano / Magherini, Francesca

2024 Volume 13, Issue 8

Abstract: Cancer cell lines are frequently used in metabolomics, such as in vitro tumor models. In particular, A2780 cells are commonly used as a model for ovarian cancer to evaluate the effects of drug treatment. Here, we compare the NMR metabolomics profiles of ... ...

Abstract	Cancer cell lines are frequently used in metabolomics, such as in vitro tumor models. In particular, A2780 cells are commonly used as a model for ovarian cancer to evaluate the effects of drug treatment. Here, we compare the NMR metabolomics profiles of A2780 and cisplatin-resistant A2780 cells with those of cells derived from 10 patients with high-grade serous ovarian carcinoma (collected during primary cytoreduction before any chemotherapeutic treatment). Our analysis reveals a substantial similarity among all primary cells but significant differences between them and both A2780 and cisplatin-resistant A2780 cells. Notably, the patient-derived cells are closer to the resistant A2780 cells when considering the exo-metabolome, whereas they are essentially equidistant from A2780 and A2780-resistant cells in terms of the endo-metabolome. This behavior results from dissimilarities in the levels of several metabolites attributable to the differential modulation of underlying biochemical pathways. The patient-derived cells are those with the most pronounced glycolytic phenotype, whereas A2780-resistant cells mainly diverge from the others due to alterations in a few specific metabolites already known as markers of resistance.
MeSH term(s)	Humans ; Female ; Cisplatin/pharmacology ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Ovarian Neoplasms/drug therapy ; Metabolomics/methods ; Drug Resistance, Neoplasm ; Cell Line, Tumor ; Magnetic Resonance Spectroscopy/methods ; Metabolome/drug effects ; Antineoplastic Agents/pharmacology
Chemical Substances	Cisplatin (Q20Q21Q62J) ; Antineoplastic Agents
Language	English
Publishing date	2024-04-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comparative Study
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells13080661
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Article ; Online: Bleeding and bowel obstruction in giant ovarian serous carcinoma - a video vignette.

Coratti, F / Ghezzi, N / Mongelli, C / Capezzuoli, T / Sorbi, F / Cianchi, F / Petraglia, F

Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland

2020 Volume 22, Issue 6, Page(s) 729

Language	English
Publishing date	2020-02-06
Publishing country	England
Document type	Letter
ZDB-ID	1440017-0
ISSN	1463-1318 ; 1462-8910
ISSN (online)	1463-1318
ISSN	1462-8910
DOI	10.1111/codi.14978
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Article ; Online: Ovarian cancer stem cells: ready for prime time?

Sabini, Carlotta / Sorbi, Flavia / Cunnea, Paula / Fotopoulou, Christina

Archives of gynecology and obstetrics

2020 Volume 301, Issue 4, Page(s) 895–899

Abstract: Introduction: The role of cancer stem cells (CSC) remains controversial and increasingly subject of investigation as a potential oncogenetic platform with promising therapeutic implications. Understanding the role of CSCs in a highly heterogeneous ... ...

Abstract	Introduction: The role of cancer stem cells (CSC) remains controversial and increasingly subject of investigation as a potential oncogenetic platform with promising therapeutic implications. Understanding the role of CSCs in a highly heterogeneous disease like epithelial ovarian cancer (EOC) may potentially lead to the better understanding of the oncogenetic and metastatic pathways of the disease, but also to develop novel strategies against its progression and platinum resistance. Methods: We have performed a review of all relevant literature that addresses the oncogenetic potential of stem cells in EOC, their mechanisms, and the associated therapeutic targets. Results: Cancer stem cells (CSCs) have been reported to be implicated not only in the development and pathways of intratumoral heterogeneity (ITH), but also potentially modulating the tumor microenvironment, leading to the selection of sub-clones resistant to chemotherapy. Furthermore, it appears that the enhanced DNA repair abilities of CSCs are connected with their endurance and resistance maintaining their genomic integrity during novel targeted treatments such as PARP inhibitors, allowing them to survive and causing disease relapse functioning as a tumor seeds. Conclusions: It appears that CSCs play a major role in the underlying mechanisms of oncogenesis and development of relapse in EOC. Part of promising future plans would be to not only use them as therapeutic targets, but also extent their value on a preventative level through engineering mechanisms and prevention of EOC in its origin.
MeSH term(s)	Female ; Humans ; Neoplastic Stem Cells/metabolism ; Ovarian Neoplasms/physiopathology
Language	English
Publishing date	2020-03-21
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	896455-5
ISSN	1432-0711 ; 0932-0067
ISSN (online)	1432-0711
ISSN	0932-0067
DOI	10.1007/s00404-020-05510-9
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Article ; Online: Recurrence of Uterine Fibroids After Conservative Surgery or Radiological Procedures: a Narrative Review.

Capezzuoli, Tommaso / Aslan, Batuhan / Vannuccini, Silvia / Orlandi, Gretha / La Torre, Francesco / Sorbi, Flavia / Fambrini, Massimiliano / Petraglia, Felice

Reproductive sciences (Thousand Oaks, Calif.)

2023

Abstract: The present narrative review aims to discuss the available data on the incidence and the risk factors of uterine fibroids (UFs) recurrence after different types of conservative surgical or radiologic procedures in women wishing to preserve their uterus. ... ...

Abstract	The present narrative review aims to discuss the available data on the incidence and the risk factors of uterine fibroids (UFs) recurrence after different types of conservative surgical or radiologic procedures in women wishing to preserve their uterus. UFs are the most common benign tumors in women all over the world. Clinical presentation, including abnormal uterine bleeding (AUB), pelvic pain, bulky symptoms, and infertility affect patients' quality of life, and a large variety of conservative treatments are available especially for those with desire of pregnancy. Fertility sparing surgery, by either laparoscopy, hysteroscopy or laparotomy, or radiological interventions (uterine artery embolization, high-intensity focused ultrasound or magnetic resonance-guided focused ultrasound), are the most common therapeutic approaches. However, the genetic or acquired predisposition to UFs remain despite the treatments, and the recurrences are frequently described in a large percentage of patients. The most relevant risk factors for recurrence of UFs are young age at the first surgery, incomplete fibroid resection, the presence of multiple lesions, an enlarged uterus, and the coexistence with other pelvic diseases. The discussion on the possible medical strategy to reduce the recurrence is an open field of clinical investigation, in particular by using hormonal drugs.
Language	English
Publishing date	2023-12-18
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2276411-2
ISSN	1933-7205 ; 1933-7191
ISSN (online)	1933-7205
ISSN	1933-7191
DOI	10.1007/s43032-023-01418-2
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Article ; Online: Upgrade of an old drug: Auranofin in innovative cancer therapies to overcome drug resistance and to increase drug effectiveness.

Gamberi, Tania / Chiappetta, Giovanni / Fiaschi, Tania / Modesti, Alessandra / Sorbi, Flavia / Magherini, Francesca

Medicinal research reviews

2021 Volume 42, Issue 3, Page(s) 1111–1146

Abstract: Auranofin is an oral gold(I) compound, initially developed for the treatment of rheumatoid arthritis. Currently, Auranofin is under investigation for oncological application within a drug repurposing plan due to the relevant antineoplastic activity ... ...

Abstract	Auranofin is an oral gold(I) compound, initially developed for the treatment of rheumatoid arthritis. Currently, Auranofin is under investigation for oncological application within a drug repurposing plan due to the relevant antineoplastic activity observed both in vitro and in vivo tumor models. In this review, we analysed studies in which Auranofin was used as a single drug or in combination with other molecules to enhance their anticancer activity or to overcome chemoresistance. The analysis of different targets/pathways affected by this drug in different cancer types has allowed us to highlight several interesting targets and effects of Auranofin besides the already well-known inhibition of thioredoxin reductase. Among these targets, inhibitory-κB kinase, deubiquitinates, protein kinase C iota have been frequently suggested. To rationalize the effects of Auranofin by a system biology-like approach, we exploited transcriptomic data obtained from a wide range of cell models, extrapolating the data deposited in the Connectivity Maps website and we attempted to provide a general conclusion and discussed the major points that need further investigation.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Auranofin/pharmacology ; Auranofin/therapeutic use ; Drug Resistance ; Humans ; Neoplasms/drug therapy ; Neoplasms/pathology ; Thioredoxin-Disulfide Reductase
Chemical Substances	Antineoplastic Agents ; Auranofin (3H04W2810V) ; Thioredoxin-Disulfide Reductase (EC 1.8.1.9)
Language	English
Publishing date	2021-12-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	603210-2
ISSN	1098-1128 ; 0198-6325
ISSN (online)	1098-1128
ISSN	0198-6325
DOI	10.1002/med.21872
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Article ; Online: The relation between endometrioma and ovarian cancer.

Sorbi, Flavia / Capezzuoli, Tommaso / Saso, Srdjan / Fambrini, Massimiliano / Corda, Martina / Fantappiè, Giulia / Petraglia, Felice

Minerva obstetrics and gynecology

2021 Volume 73, Issue 3, Page(s) 347–353

Abstract: Introduction: The relationship between endometrioma and ovarian cancer is a topic of discussion in the field of endometriosis and to date it is still debated whether ovarian endometriosis may represent a risk factor for ovarian cancers.: Evidence ... ...

Abstract	Introduction: The relationship between endometrioma and ovarian cancer is a topic of discussion in the field of endometriosis and to date it is still debated whether ovarian endometriosis may represent a risk factor for ovarian cancers. Evidence acquisition: A literature search was carried out using Cochrane Library, EMBASE, Medline and Google Scholar up to October 2020. Primary outcome of interest was ovarian cancer incidence in patients with endometriosis. Secondary outcome was ovarian cancer prognosis in patients with endometriosis compared to patient without endometriosis. Evidence synthesis: Patients with ovarian endometriosis has a slight increase risk of developing ovarian cancer (merely 1.8%), being the general population risk for ovarian cancer 1.31%. In patient at postmenopausal age, long-lasting endometriosis, early-age diagnosis, infertility and/or infertility treatment the risk of developing ovarian cancer is higher. Endometriosis-related ovarian cancers are generally clear cell and endometrioid and are diagnosed at early stage compared to non-endometriosis related ovarian cancer. Conclusions: The lifetime risk for ovarian cancer is low in endometriosis patients in general and higher in subgroups of patients allowing a tailored management based on patient characteristics. Endometriosis is a chronic disease negatively affecting the quality of life, nonetheless, concerns on ovarian cancer should be avoided in order to reduce the burden of the disease on women's health.
MeSH term(s)	Carcinoma, Ovarian Epithelial ; Endometriosis/complications ; Endometrium ; Female ; Humans ; Ovarian Neoplasms/epidemiology ; Quality of Life
Language	English
Publishing date	2021-05-18
Publishing country	Italy
Document type	Journal Article
ZDB-ID	3062815-5
ISSN	2724-6450
ISSN (online)	2724-6450
DOI	10.23736/S2724-606X.21.04757-2
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Article ; Online: Risk factors for development of isthmocele following cesarean section.

Sisti, G / Nasioudis, D / Kanninen, T / Sorbi, F / Fambrini, M

Minerva ginecologica

2015 Volume 67, Issue 4, Page(s) 301–306

Abstract: Aim: The aim of this paper was to analyze the risk factors contributing to the development of isthmocele following cesarean section (CS).: Methods: We retrospectively analyzed a cohort of patients presenting to our outpatient clinic for hysteroscopy. ...

Abstract	Aim: The aim of this paper was to analyze the risk factors contributing to the development of isthmocele following cesarean section (CS). Methods: We retrospectively analyzed a cohort of patients presenting to our outpatient clinic for hysteroscopy. Only premenopausal patients with a history of CS were included. The risk factors investigated were: occurrence of previous vaginal delivery antecedent to CS, patient's age at CS, weeks of gestation at CS, phase of labor, type of suture (single/double layer) employed, and uterine flexion (anteversion/retroversion). Results: The association between the identified risk factors and the occurrence of isthmocele was found statistical significant concerning indication for hysteroscopy (c2), stage of labor (c2), age at CS (Mann-Withney U test), according to the univariate analysis. This association was then confirmed in the multivariate logistic regression model pooling all the variables together. Conclusion: The significance of stage of labor to the development of isthmocele confirms previous observations and may be part of the information needed to the clinical decision of the CS time setting decision for the clinicians. Nevertheless, further prospective studies employing larger cohorts are warranted to further clarify the aforementioned risk factors before suggesting any modifications of clinical practice.
MeSH term(s)	Adult ; Cesarean Section/adverse effects ; Cesarean Section/methods ; Cicatrix/epidemiology ; Cicatrix/etiology ; Cicatrix/pathology ; Female ; Humans ; Hysteroscopy/methods ; Logistic Models ; Pregnancy ; Retrospective Studies ; Risk Factors
Language	English
Publishing date	2015-08
Publishing country	Italy
Document type	Journal Article
ZDB-ID	80159-8
ISSN	1827-1650 ; 0026-4784 ; 0325-8793
ISSN (online)	1827-1650
ISSN	0026-4784 ; 0325-8793
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Article ; Online: Cardiometabolic risk is unraveled by color Doppler ultrasound of the clitoral and uterine arteries in women consulting for sexual symptoms.

Scavello, I / Maseroli, E / Cipriani, S / Di Stasi, V / Verde, N / Menafra, D / Scannerini, S / Marchiani, S / Rastrelli, G / Ricca, V / Sorbi, F / Fambrini, M / Petraglia, F / Maggi, M / Vignozzi, Linda

Scientific reports

2021 Volume 11, Issue 1, Page(s) 18899

Abstract: Female sexual dysfunction (FSD) may be a mirror of a poor cardiometabolic state. In a small pilot study enrolling 71 women with FSD, we previously demonstrated that clitoral Pulsatility Index (PI) evaluated by using color Doppler ultrasound (CDU), ... ...

Abstract	Female sexual dysfunction (FSD) may be a mirror of a poor cardiometabolic state. In a small pilot study enrolling 71 women with FSD, we previously demonstrated that clitoral Pulsatility Index (PI) evaluated by using color Doppler ultrasound (CDU), reflecting vascular resistance, was associated with cardiometabolic risk factors. Data on uterine CDU in this context are lacking. First, to confirm previously reported data on the direct association between clitoral PI and cardiometabolic risk factors on a larger study population of women consulting for sexual symptoms; second, to investigate eventual similar correlations between cardiometabolic risk factors and CDU parameters of the uterine artery. We also ascertained whether uterine artery PI, similarly to what had previously been observed for clitoral artery PI, was directly related to body image uneasiness and psychopathological symptoms, assessed by validated questionnaires. N = 230 women consulting our clinic for sexual symptoms were examined with clitoral CDU and blood sampling and were asked to fill out the Female Sexual Function Index, the Middlesex Hospital Questionnaire (MHQ) and the Body Uneasiness Test (BUT). In a subgroup of women (n = 164), we also performed transvaginal CDU with measurement of uterine artery parameters. At multivariate analysis, we found a direct association between clitoral PI and body mass index (BMI) (p = 0.004), waist circumference (WC) (p = 0.004), triglycerides (p = 0.006), insulin (p = 0.029) and HOMA-IR (p = 0.009). Furthermore, a correlation between obesity and Metabolic Syndrome (MetS) and a higher clitoral PI was observed (p = 0.003 and p = 0.012, respectively). Clitoral PI was also correlated with MHQ-S (p = 0.010), a scale exploring somatized anxiety symptoms, and BUT-B Positive Symptom Distress Index (p = 0.010), a measure of body image concerns. Similarly, when investigating the uterine artery, we were able to demonstrate an association between its PI and BMI (p < 0.0001), WC (p = 0.001), insulin (p = 0.006), glycated haemoglobin (p = < 0.0001), and HOMA-IR (p = 0.009). Women diagnosed with obesity and MetS showed significantly higher uterine PI values vs. those without obesity or MetS (p = 0.001 and p = 0.004, respectively). Finally, uterine PI was associated with BUT-A Global Severity Index (p < 0.0001) and with several other BUT-A subdomains. Vascular resistance of clitoral and uterine arteries is associated with cardiometabolic risk factors and body image concerns in women consulting for sexual symptoms. If further confirmed in different populations, our data could suggest CDU, a common examination method, as a useful tool for an identification-and possible correction-of cardiometabolic risk factors.
MeSH term(s)	Adult ; Body Image/psychology ; Body Mass Index ; Cardiometabolic Risk Factors ; Clitoris/blood supply ; Clitoris/diagnostic imaging ; Female ; Humans ; Metabolic Syndrome ; Middle Aged ; Sexual Dysfunctions, Psychological/physiopathology ; Surveys and Questionnaires ; Ultrasonography, Doppler, Color ; Uterine Artery/diagnostic imaging ; Vascular Resistance
Language	English
Publishing date	2021-09-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-98336-7
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Article ; Online: Effects of testosterone treatment on clitoral haemodynamics in women with sexual dysfunction.

Cipriani, S / Maseroli, E / Di Stasi, V / Scavello, I / Todisco, T / Rastrelli, G / Fambrini, M / Sorbi, F / Petraglia, F / Jannini, E A / Maggi, M / Vignozzi, L

Journal of endocrinological investigation

2021 Volume 44, Issue 12, Page(s) 2765–2776

Abstract: Purpose: To explore the effects of 6-month systemic testosterone (T) administration on clitoral color Doppler ultrasound (CDU) parameters in women with female sexual dysfunction (FSD).: Methods: 81 women with FSD were retrospectively recruited. Data ... ...

Abstract	Purpose: To explore the effects of 6-month systemic testosterone (T) administration on clitoral color Doppler ultrasound (CDU) parameters in women with female sexual dysfunction (FSD). Methods: 81 women with FSD were retrospectively recruited. Data on CDU parameters at baseline and after 6 months with four different treatments were available and thus further longitudinally analyzed: local non-hormonal moisturizers (NH group), n = 37; transdermal 2% T gel 300 mcg/day (T group), n = 23; local estrogens (E group), n = 12; combined therapy (T + E group), n = 9. Patients underwent physical, laboratory, and genital CDU examinations at both visits and completed different validated questionnaires, including the Female Sexual Function Index (FSFI). Results: At 6-month visit, T therapy significantly increased clitoral artery peak systolic velocity (PSV) when compared to both NH (p < 0.0001) and E (p < 0.0001) groups. A similar increase was found in the T + E group (p = 0.039 vs. E). In addition, T treatment was associated with significantly higher FSFI desire, pain, arousal, lubrication, orgasm, and total scores at 6-month visit vs. baseline. Similar findings were observed in the T + E group. No significant differences in the variations of total and high-density lipoprotein-cholesterol, triglycerides, fasting glycemia, insulin and glycated hemoglobin levels were found among the four groups. No adverse events were observed. Conclusion: In women complaining for FSD, systemic T administration, either alone or combined with local estrogens, was associated with a positive effect on clitoral blood flow and a clinical improvement in sexual function, showing a good safety profile. Trial registration number: NCT04336891; date of registration: April 7, 2020.
MeSH term(s)	Administration, Cutaneous ; Administration, Topical ; Adult ; Clitoris/blood supply ; Clitoris/diagnostic imaging ; Clitoris/physiopathology ; Estrogens/administration & dosage ; Estrogens/adverse effects ; Female ; Gonadal Hormones/administration & dosage ; Hemodynamics/drug effects ; Humans ; Outcome Assessment, Health Care/methods ; Sexual Dysfunction, Physiological/diagnosis ; Sexual Dysfunction, Physiological/metabolism ; Sexual Dysfunction, Physiological/physiopathology ; Sexual Dysfunction, Physiological/therapy ; Testosterone/administration & dosage ; Testosterone/adverse effects ; Treatment Outcome ; Ultrasonography, Doppler, Color/methods
Chemical Substances	Estrogens ; Gonadal Hormones ; Testosterone (3XMK78S47O)
Language	English
Publishing date	2021-06-12
Publishing country	Italy
Document type	Journal Article ; Observational Study
ZDB-ID	432272-1
ISSN	1720-8386 ; 0391-4097 ; 1121-1369
ISSN (online)	1720-8386
ISSN	0391-4097 ; 1121-1369
DOI	10.1007/s40618-021-01598-1
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Article ; Online: Epidemiology and Risk Factors of Uterine Fibroids.

Pavone, Dora / Clemenza, Sara / Sorbi, Flavia / Fambrini, Massimiliano / Petraglia, Felice

Best practice & research. Clinical obstetrics & gynaecology

2018 Volume 46, Page(s) 3–11

Abstract: Risk factors, both modifiable and non-modifiable, are associated with the development of fibroids. These include age, race, endogenous and exogenous hormonal factors, obesity, uterine infection, and lifestyle (diet, caffeine and alcohol consumption, ... ...

Abstract	Risk factors, both modifiable and non-modifiable, are associated with the development of fibroids. These include age, race, endogenous and exogenous hormonal factors, obesity, uterine infection, and lifestyle (diet, caffeine and alcohol consumption, physical activity, stress, and smoking). Some of the epidemiological data were conflicting; consequently, further studies are needed to better understand the factors that influence fibroid prevalence.
MeSH term(s)	African Continental Ancestry Group/statistics & numerical data ; Age Factors ; European Continental Ancestry Group/statistics & numerical data ; Female ; Humans ; Leiomyoma/epidemiology ; Leiomyoma/etiology ; Leiomyoma/genetics ; Prevalence ; Risk Factors ; Uterine Neoplasms/epidemiology ; Uterine Neoplasms/etiology ; Uterine Neoplasms/genetics
Language	English
Publishing date	2018-01
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2050090-7
ISSN	1532-1932 ; 1521-6934
ISSN (online)	1532-1932
ISSN	1521-6934
DOI	10.1016/j.bpobgyn.2017.09.004
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