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1.
EMBO Mol Med ; 3(8): 480-94, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21739604

ABSTRACT

Epithelial ovarian carcinoma (EOC) is an aggressive neoplasm, which mainly disseminates to organs of the peritoneal cavity, an event mediated by molecular mechanisms that remain elusive. Here, we investigated the expression and functional role of neural cell adhesion molecule (NCAM), a cell surface glycoprotein involved in brain development and plasticity, in EOC. NCAM is absent from normal ovarian epithelium but becomes highly expressed in a subset of human EOC, in which NCAM expression is associated with high tumour grade, suggesting a causal role in cancer aggressiveness. We demonstrate that NCAM stimulates EOC cell migration and invasion in vitro and promotes metastatic dissemination in mice. This pro-malignant function of NCAM is mediated by its interaction with fibroblast growth factor receptor (FGFR). Indeed, not only FGFR signalling is required for NCAM-induced EOC cell motility, but targeting the NCAM/FGFR interplay with a monoclonal antibody abolishes the metastatic dissemination of EOC in mice. Our results point to NCAM-mediated stimulation of FGFR as a novel mechanism underlying EOC malignancy and indicate that this interplay may represent a valuable therapeutic target.


Subject(s)
Carcinoma/pathology , Neural Cell Adhesion Molecules/metabolism , Ovarian Neoplasms/pathology , Receptor, Fibroblast Growth Factor, Type 1/metabolism , Signal Transduction , Animals , Carcinoma/secondary , Cell Movement , Disease Models, Animal , Female , Humans , Immunohistochemistry , Mice , Neoplasm Invasiveness , Neoplasm Metastasis/pathology , Ovarian Neoplasms/secondary
2.
Reprod Biomed Online ; 22 Suppl 1: S20-2, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21575845

ABSTRACT

This study assessed the ovarian stimulation characteristics of recombinant follitropin a filled by mass (rFSH-fbm) versus recombinant follitropin a filled by conventional bioassay (rFSH-bio) in the same egg donor patients. Eleven egg donors, who had two ovarian stimulation cycles for oocyte retrieval (total of 23 cycles), one with rFSH-bio (Gonal-f Multidose®) and the second one with rFSH-fbm (Gonal-f® RFF), were evaluated. The protocol of ovarian stimulation was exactly the same in both cycles, consisting of GnRH suppression (luteal phase) followed by exclusive stimulation with rFSH. Despite no differences in the number of days of rFSH treatment and in the total dosage of rFSH administered, the number of follicles >14 mm and the number of oocytes retrieved were significantly higher in the rFSH-fbm group (P = 0.01 and 0.04 respectively). The mean oestradiol peak values showed a trend in favour of rFSH-fbm (3123 versus 2405 pg/ml respectively). These results suggest that the consistency in dosing provided by follitropin a filled by mass as opposed to follitropin a filled by bioassay offers added value for the ovarian stimulation of oocyte donor patients.

3.
Gynecol Oncol ; 119(2): 274-7, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20797775

ABSTRACT

BACKGROUND: Borderline ovarian tumors (BOTs) are a histological category of epithelial ovarian tumors and 70% of them are early diagnosed (stage I). Since early stage is the most important prognostic factor, restaging procedure could be justified. This study aims to evaluate the role of restaging surgery in the management of patients with borderline ovarian tumors referred to our Institution after being incompletely surgically staged in other hospitals. MATERIALS AND METHODS: We retrospectively reviewed the charts of patients with BOT who were referred to our centre to undergo restaging procedure. From December 1995 to May 2008, 186 patients were treated for BOT and 70 patients met the inclusion criteria. Data collected included patients' age, primary and re-staging surgery details, FIGO stage after first and second procedure, pathological findings, and follow-up data. RESULTS: FIGO stage after primary surgery was IA in 46 patients (68.6%), IB in 7 patients (10.4%), IC in 12 patients (17.9%, 6 due to ruptured cyst), IIA in 1 patient (1.4%), IIB in 1 patient (1.4%), III B in 2 patients (2.8%), and IIIC in 1 patient (1.4%). Among stage I patients (representing 97% of all patients), 12.3% (8 patients) were up-staged. The upstaging rate among serous tumors was 16.2%, and 4% among mucinous tumors. The mean follow-up time was 60.4 months from restaging surgery (SD 30.6 months). We observed 8 primary recurrences of the disease and 3 second recurrences. CONCLUSIONS: There were no differences in terms of overall survival between patients who were upstaged and those who were not. Restaging procedure does not seem to have a significant impact on the management of patients diagnosed with borderline ovarian tumors, especially in mucinous subtype and apparent FIGO stage higher than I.


Subject(s)
Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Adolescent , Adult , Aged , Female , Humans , Middle Aged , Neoplasm Staging , Retrospective Studies , Young Adult
4.
Gynecol Oncol ; 115(1): 60-64, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19638333

ABSTRACT

OBJECTIVE: To compare the surgical outcome of robotic radical hysterectomy (RRH) versus abdominal radical hysterectomy (ARH) for the treatment of early stage cervical cancer. METHODS: A prospective collection of data of all RRH for stages IA2-IIA cervical cancer was done. The procedures were performed at the European Institute of Oncology, Milan, Italy, between November 1, 2006 and February 1, 2009. RESULTS: A total of 40 RRH were analyzed, and compared with 40 historic ARH cases. The groups did not differ significantly in body mass index, stage, histology, or intraoperative complications, but in age (p=0.035). The mean (SD) operative time was significantly shorter for ARH than RRH, 199.6 (65.6) minutes and 272.27 (42.3) minutes respectively (p=0.0001). The mean (SD) estimated blood loss (EBL) was 78 ml (94.8) in RRH group and 221.8 ml (132.4) in ARH. This difference was statistically significant in favor of RRH group (p<0.0001). Statistically significantly higher number of pelvic lymph nodes was removed by ARH than by RRH, mean (SD) 26.2 (11.7) versus 20.4 (6.9), p<0.05. Mean length of stay was significantly shorter for the RRH group (3.7 versus 5.0 days, p<0.01). There was no significant difference in terms of postoperative complications between groups. CONCLUSION: This study shows that RRH is safe and feasible. However, a comparison of oncologic outcomes and cost-benefit analysis is still needed and it has to be carefully evaluated in the future.


Subject(s)
Hysterectomy/methods , Robotics/methods , Uterine Cervical Neoplasms/surgery , Adult , Case-Control Studies , Cohort Studies , Female , Follow-Up Studies , Humans , Hysterectomy/adverse effects , Laparotomy/adverse effects , Laparotomy/methods , Length of Stay , Middle Aged , Neoplasm Staging , Postoperative Period , Prospective Studies , Uterine Cervical Neoplasms/pathology
5.
J Minim Invasive Gynecol ; 16(4): 427-31, 2009.
Article in English | MEDLINE | ID: mdl-19467930

ABSTRACT

STUDY OBJECTIVE: To study the effect of robotic surgery on the surgical approach to endometrial cancer in a gynecologic oncology center over a short time. DESIGN: Prospective analysis of patients with early-stage endometrial cancer who underwent robotic surgery. SETTING: Teaching hospital. PATIENTS: Eighty patients who underwent robotic surgery. INTERVENTIONS: Between November 2006 and October 2008, 80 consecutive patients with an initial diagnosis of endometrial cancer consented to undergo robotic surgery at the European Institute of Oncology, Milan, Italy. MEASUREMENTS AND MAIN RESULTS: We collected all patient data for demographics, operating time, estimated blood loss, histologic findings, lymph node count, analgesic-free postoperative day, length of stay, and intraoperative and early postoperative complications. Mean (SD) patient age was 58.3 (11.5) years (95% confidence interval [CI], 55.7-60.9). Body mass index was 25.2 (6.1) kg/m(2) (95% CI, 23.6-26.7). In 3 patients (3.7%), conversion to conventional laparotomy was required. Mean operative time was 181.1 (63.1) minutes (95% CI, 166.7-195.5). Mean docking time was 4.5 (1.1) minutes (95% CI, 2.2-2.7). Mean hospital stay was 2.5 (1.1) days (95% CI, 2.2-2.7), and 93% of patients were analgesic-free on postoperative day 2. CONCLUSIONS: Over a relatively short time using the da Vinci surgical system, we observed a substantial change in our surgical activity. For endometrial cancer, open surgical procedures decreased from 78% to 35%. Moreover, our preliminary data confirm that surgical robotic staging for early-stage endometrial cancer is feasible and safe. Age, obesity, and previous surgery do not seem to be contraindications.


Subject(s)
Endometrial Neoplasms/surgery , Minimally Invasive Surgical Procedures/methods , Robotics/methods , Aged , Contraindications , Female , Hospitals, Teaching , Humans , Middle Aged , Prospective Studies , Time Factors
6.
Ann N Y Acad Sci ; 1127: 59-63, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18443330

ABSTRACT

A male factor is implicated in about 50% of couples treated with advanced assisted reproductive techniques (in vitro fertilization [IVF] or intracytoplasmic sperm injection [ICSI]). An important function of spermatozoa is to deliver the paternal genome to the oocyte. However, neither the routine testing of male fertility potential, nor its treatment, addresses the specific mechanisms by which spermatozoal factors may impact reproductive outcome. Recently, a number of screening tests for DNA integrity have been proposed to assess sperm chromatin abnormalities. These include nonspecific DNA strand breaks, numerical abnormalities in spermatozoal chromosome content, and alterations in the epigenetic regulation of the paternal genome. This minireview discusses methods to assess the influence of the paternal genome on reproduction beyond that which can be appreciated by simple quantitative and morphologic evaluation of spermatozoa. Finally, new data on how to select the "best fit" sperm for ICSI will be presented.


Subject(s)
DNA/analysis , Fertilization in Vitro/methods , Genomics , Infertility, Male/therapy , Semen/metabolism , Sperm Injections, Intracytoplasmic/methods , Spermatozoa/pathology , Andrology/methods , Chromatin/pathology , Comet Assay , Female , Humans , In Situ Hybridization, Fluorescence , In Situ Nick-End Labeling , Male
7.
Reprod Biomed Online ; 14(1): 26-8, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17207327

ABSTRACT

This study assessed the ovarian stimulation characteristics of recombinant follitropin alpha filled by mass (rFSH-fbm) versus recombinant follitropin alpha filled by conventional bioassay (rFSH-bio) in the same egg donor patients. Eleven egg donors, who had two ovarian stimulation cycles for oocyte retrieval (total of 23 cycles), one with rFSH-bio (Gonal-f Multidose) and the second one with rFSH-fbm (Gonal-f RFF), were evaluated. The protocol of ovarian stimulation was exactly the same in both cycles, consisting of GnRH suppression (luteal phase) followed by exclusive stimulation with rFSH. Despite no differences in the number of days of rFSH treatment and in the total dosage of rFSH administered, the number of follicles >14 mm and the number of oocytes retrieved were significantly higher in the rFSH-fbm group (P = 0.01 and 0.04 respectively). The mean oestradiol peak values showed a trend in favour of rFSH-fbm (3123 versus 2405 pg/ml respectively). These results suggest that the consistency in dosing provided by follitropin alpha filled by mass as opposed to follitropin alpha filled by bioassay offers added value for the ovarian stimulation of oocyte donor patients.


Subject(s)
Follicle Stimulating Hormone/administration & dosage , Glycoprotein Hormones, alpha Subunit/administration & dosage , Ovulation Induction , Adult , Biological Assay , Chromatography, High Pressure Liquid , Female , Follicle Stimulating Hormone/pharmacology , Follicle Stimulating Hormone/standards , Glycoprotein Hormones, alpha Subunit/pharmacology , Glycoprotein Hormones, alpha Subunit/standards , Humans , Oocyte Donation , Ovarian Follicle/drug effects
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