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1.  Impaired uterine artery flow associated with the presence of ovarian endometrioma: preliminary results of a prospective study 
Aim of this prospective, case–control study was to evaluate uterine arteries’ blood flow before and after laparoscopic surgery in patients with ovarian endometriosis and its possible correlation with infertility.
We prospectively enrolled 110 women of reproductive age; 69 with ovarian endometriomas and scheduled for surgery, and 41 controls. At enrolment, a detailed medical, gynecologic and obstetric history was collected. Fertility and pregnancy desire were assessed. All patients underwent complete physical and gynecologic examination. Transvaginal ultrasound with Doppler color flow was performed to evaluate Resistance Index (RI) of uterine arteries during the secretory phase, at enrolment (T0) and 3 months after laparoscopic surgery (T1).
Among cases, 27 patients were excluded because they did not meet the inclusion criteria. At enrolment (T0) unilateral or bilateral flow alterations (RI ≥ 0.8) were found in 38 out of 42 patients with ovarian endometriosis (90%), whereas in the control group only 17 women (41%) had Doppler alterations. The difference in uterine artery RI values between cases and controls was statistically significant (P < 0.0001). A statistically significant improvement in uterine artery flow (P <0.0001) was found 3 months after surgical treatment of endometriosis. Nineteen patients with endometriosis (45%) were infertile before surgery; all of them presented uterine artery Doppler alterations at T0. After surgery the pregnancy rate was significantly higher in patients who presented uterine artery flow normalization than in those with persistent uterine artery flow alterations (p = 0.002).
A strong correlation was found between uterine artery flow abnormalities and ovarian endometriosis. Uterine artery flow improvement following surgery seems to increase the probabilities of achieving pregnancy.
PMCID: PMC3900471  PMID: 24401654
Color doppler; Endometriosis; Infertility; Ultrasounds; Uterine artery flow; Resistance Index (RI)
2.  Investigating Molecular Profiles of Ovarian Cancer: An Update on Cancer Stem Cells 
Journal of Cancer  2014;5(5):301-310.
Currently we are more and more improving our knowledge about the characteristics and the role of cancer stem cells in human cancer. Particularly we have realized that self-renewing ovarian cancer stem cells (CSCs) or ovarian cancer-initiating cells, and mesenchymal stem cells (SCs) too, are probably implicated in the etiopathogenesis of epithelial ovarian cancer (EOC). There is clear evidence that these cells are also involved in its intra- and extra-peritoneal diffusion and in the occurrence of chemo-resistance. In assessing the molecular characteristics of ovarian CSCs, we have to take note that these cellular populations are rare and the absence of specific cell surface markers represents a challenge to isolate and identify pure SC populations. In our review, we focused our attention on the molecular characteristics of epithelial ovarian CSCs and on the methods to detect them starting from their biological features. The study of ovarian CSCs is taking on an increasingly important strategic role, mostly for the potential therapeutic application in the next future.
PMCID: PMC3982176  PMID: 24723972
Epithelial ovarian cancer; Ovarian cancer stem cells; Cancer stem cells markers; Tumor microenvironment; Therapeutic targets.
3.  Is CA72-4 a Useful Biomarker in Differential Diagnosis between Ovarian Endometrioma and Epithelial Ovarian Cancer? 
Disease markers  2013;35(5):331-335.
Background. Surgical excision of ovarian endometriomas in patients desiring pregnancy has recently been criticized because of the risk of damage to healthy ovarian tissue and consequent reduction of ovarian reserve. A correct diagnosis in cases not scheduled for surgery is therefore mandatory in order to avoid unexpected ovarian cancer misdiagnosis. Endometriosis is often associated with high levels of CA125. This marker is therefore not useful for discriminating ovarian endometrioma from ovarian malignancy. The aim of this study was to establish if the serum marker CA72-4 could be helpful in the differential diagnosis between ovarian endometriosis and epithelial ovarian cancer. Methods. Serums CA125 and CA72-4 were measured in 72 patients with ovarian endometriomas and 55 patients with ovarian cancer. Results. High CA125 concentrations were observed in patients with ovarian endometriosis and in those with ovarian cancer. A marked difference in CA72-4 values was observed between women with ovarian cancer (71.0%) and patients with endometriosis (13.8%) (P < 0.0001). Conclusions. This study suggests that CA72-4 determination can be useful to confirm the benign nature of ovarian endometriomas in women with high CA125 levels.
PMCID: PMC3793285  PMID: 24191126
4.  Vulvar Malignancy in Neurofibromatosis Syndrome 
Type 1 neurofibromatosis (NF1) is a dominantly inherited neurologic disorder that affects primarily the skin, bones, and peripheral nervous system. It may be associated with a variety of clinical manifestations including cafe-au-lait spots, skinfold freckling, Lisch nodules, and visceral neurofibromas. Individuals affected by NF1 harbor an increased risk for both benign and malignant tumors. Malignant transformation is usually observed in the form of neurosarcoma. Rarely, NF1 affects the genital tract, and isolated vulvar localization is extremely rare. Here is reported a rare case of a solitary neurosarcoma of the vulva in a 43-year-old woman affected by NF1 syndrome treated with surgical excision. The purpose of this case is to underline the possibility of association between NF1 and genital tract sarcoma and to suggest an accurate evaluation of rapid growth vulvar mass in this setting.
PMCID: PMC3792537  PMID: 24167749
5.  First case of isolated vaginal metastasis from breast cancer treated by surgery 
BMC Cancer  2012;12:479.
Breast cancer is a leading cause of death in developed countries. This neoplasm frequently relapses at distant sites such as bone, lung, pleura, brain and liver but rarely in the lower female genital tract.
Case presentation
We present the first case of isolated vaginal breast cancer metastasis and its surgical treatment.
This case report focuses on the importance of an accurate genital tract examination as part of regular follow up in breast cancer survivors. Indeed, after this experience we feel that surgery could be considered a valid option for the treatment of an isolated vaginal metastasis.
PMCID: PMC3495020  PMID: 23075305
Breast cancer; Radical surgery; Vaginal metastasis
6.  Monoclonal Antibodies in Gynecological Cancer: A Critical Point of View 
During the last decades, several improvements in treating gynecological malignancies have been achieved. In particular, target therapies, mostly monoclonal antibodies, have emerged as an attractive option for the treatment of these malignancies. In fact, various molecular-targeted agents have been developed for a variety of malignancies with the objective to interfere with a precise tumor associated receptor, essential for cancer cell survival or proliferation, blocking its function, of the cancer cells. Alternatively, monoclonal antibodies have been developed to block immune suppression or enhance functions of immune effector cells. So far, several monoclonal antibodies have been tested for clinical efficacy for the treatment of gynecological cancers. Antibodies against Vascular Endothelial Growth Factor (VEGF) and Epidermal Growth Factor Receptor (EGFR) have been used in different neoplasms such as ovarian and cervical cancer. Catumazumab, a bivalent antibody against CD3 and EpCAM, is effective in the treatment of neoplastic ascites. Other antibodies are peculiar for specific cancer-associated antigen such as Oregovomab against CA125 or Farletuzumab against the folate receptor. Here we describe the preclinical and clinical experience gained up to now with monoclonal antibodies in tumors of the female genital tract and trace future therapeutic and research venues.
PMCID: PMC3253445  PMID: 22235224
7.  HER2-based recombinant immunogen to target DCs through FcγRs for cancer immunotherapy 
Dendritic cell (DC)-based immunotherapy is an attractive approach to induce long lasting antitumor effector cells aiming to control cancer progression. DC targeting is a critical step in the design of DC vaccines in order to optimize delivery and processing of the antigen, and several receptors have been characterized for this purpose. In this study, we employed the FcγRs to target DCs both in vitro and in vivo. We designed a recombinant molecule (HER2-Fc) composed of the immunogenic sequence of the human tumor-associated antigen HER2 (aa 364–391) and the Fc domain of a human IgG1. In a mouse model, HER2-Fc cDNA vaccination activated significant T cell-mediated immune responses towards HER2 peptide epitopes as detected by IFN-γ ELIspot and induced longer tumor latency as compared to Ctrl-Fc-vaccinated control mice. Human in vitro studies indicated that the recombinant HER2-Fc immunogen efficiently targeted human DCs through the FcγRs resulting in protein cross-processing and in the activation of autologous HER2-specific CD8+ T cells from breast cancer patients.
Electronic supplementary material
The online version of this article (doi:10.1007/s00109-011-0794-7) contains supplementary material, which is available to authorized users.
PMCID: PMC3218291  PMID: 21845448
Dendritic cells; Cancer immunotherapy; HER2; Antigen processing; FcγR; Dendritic cell targeting
8.  Immune Effects of Trastuzumab 
Journal of Cancer  2011;2:317-323.
Trastuzumab's targeted therapy has become a stronghold for human epidermal growth factor receptor 2 positive breast cancer patients. This humanized monoclonal antibody binds to the extracellular juxta-membrane domain of HER2 and inhibits the proliferation and survival of HER2 dependent cancer cells. The ways by which this molecule exerts its action have been partially elucidated but several new mechanisms are being constantly identified. Several new agents are being introduced that interfere with HER2. Several new immunotherapy strategies are being introduced in order to direct the immune system against cells and tissues that aberrantly overexpressed HER2. We review the strategies currently adopted and those suggested against HER2 expressing tumors.
PMCID: PMC3119394  PMID: 21716848
autologous cells vaccines; Trastuzumab; HER2; Lapatinib; allo-vesicles
9.  Multiple Bulky Lymph Nodal Metastasis in Microinvasive Cervical Cancer: A Case Report and Literature Review 
Case Reports in Oncology  2010;3(2):176-181.
Microinvasive squamous cell cervival carcinoma is characterized by an exceptional incidence of lymph nodal metastasis. We report the case of a 45-year-old woman affected by IA1 squamous cell carcinoma, found to have massive pelvic lymph nodal metastasis. After a systematic pelvic and aortic selective lymphadenectomy, at 16 months of follow-up, she is still disease-free. Patients suitable for conservative therapy should be carefully counselled about the established risks and benefits of nondestructive treatment options.
PMCID: PMC2919996  PMID: 20740193
Cervical cancer; Microinvasive carcinoma; Lymph nodal spread; Bulky
10.  A Small Molecule SMAC Mimic LBW242 Potentiates TRAIL- and Anticancer Drug-Mediated Cell Death of Ovarian Cancer Cells 
PLoS ONE  2012;7(4):e35073.
Ovarian cancer remains a leading cause of death in women and development of new therapies is essential. Second mitochondria derived activator of caspase (SMAC) has been described to sensitize for apoptosis. We have explored the pro-apoptotic activity of LBW242, a mimic of SMAC/DIABLO, on ovarian cancer cell lines (A2780 cells and its chemoresistant derivative A2780/ADR, SKOV3 and HEY cells) and in primary ovarian cancer cells. The effects of LBW242 on ovarian cancer cell lines and primary ovarian cancer cells was determined by cell proliferation, apoptosis and biochemical assays.
Principal Findings
LBW242 added alone elicited only a moderate pro-apoptotic effect; however, it strongly synergizes with tumor necrosis factor-related apoptosis inducing ligand (TRAIL) or anticancer drugs in inducing apoptosis of both ovarian cancer cell lines and primary ovarian cancer cells. Mechanistic studies show that LBW242-induced apoptosis in ovarian cancer cells is associated with activation of caspase-8. In line with this mechanism, c-FLIP overexpression inhibits LBW242-mediated apoptosis.
LBW242 sensitizes ovarian cancer cells to the antitumor effects of TRAIL and anticancer drugs commonly used in clinic. These observations suggest that the SMAC/DIABLO mimic LBW242 could be of value for the development of experimental strategies for treatment of ovarian cancer.
PMCID: PMC3338831  PMID: 22558117

Results 1-10 (10)