We recently reported that activation of Trop-2 through its cleavage at R87-T88 by ADAM10 underlies Trop-2–driven progression of colon cancer. However, the mechanism of action and pathological impact of Trop-2 in metastatic diffusion remain unexplored. Through searches for molecular determinants of cancer metastasis, we identified TROP2 as unique in its up-regulation across independent colon cancer metastasis models. Overexpression of wild-type Trop-2 in KM12SM human colon cancer cells increased liver metastasis rates in vivo in immunosuppressed mice. Metastatic growth was further enhanced by a tail-less, activated ΔcytoTrop-2 mutant, indicating the Trop-2 tail as a pivotal inhibitory signaling element. In primary tumors and metastases, transcriptome analysis showed no down-regulation of CDH1 by transcription factors for epithelial-to-mesenchymal transition, thus suggesting that the pro-metastatic activity of Trop-2 is through alternative mechanisms. Trop-2 can tightly interact with ADAM10. Here, Trop-2 bound E-cadherin and stimulated ADAM10-mediated proteolytic cleavage of E-cadherin intracellular domain. This induced detachment of E-cadherin from β-actin, and loss of cell-cell adhesion, acquisition of invasive capability, and membrane-driven activation of β-catenin signaling, which were further enhanced by the ΔcytoTrop-2 mutant. This Trop-2/E-cadherin/β-catenin program led to anti-apoptotic signaling, increased cell migration, and enhanced cancer-cell survival. In patients with colon cancer, activation of this Trop-2–centered program led to significantly reduced relapse-free and overall survival, indicating a major impact on progression to metastatic disease. Recently, the anti-Trop-2 mAb Sacituzumab govitecan-hziy was shown to be active against metastatic breast cancer. Our findings define the key relevance of Trop-2 as a target in metastatic colon cancer.

Women with polycystic ovary syndrome (PCOS) have several cardiovascular disease risk factors. Since hyperhomocysteinemia is associated with early atherosclerosis, it was postulated that the homocysteine levels are higher in PCOS patients than in control subjects which, therefore, may explain the cardiovascular disease risk. Thirty-five women with PCOS and 20 healthy subjects were studied. Endocrine assays, lipid profile, homocysteine and insulin level determinations, and ultrasound evaluation were performed in all subjects. We found significantly higher mean plasma homocysteine concentrations in patients with PCOS as compared with controls (10.4 ± 4.4 vs. 7.2 ± 1.5 ng/dl; p < 0.003). These data show that in PCOS early atherosclerosis is not exclusively dependent on hyperinsulinemia and elevated lipid profile – PCOS patients are exposed to significantly higher homocysteine levels which might increase the cardiovascular disease risk.

The aim of this study was to assess the effect of human immunodeficiency virus (HIV), hepatitis C (HCV) and B (HBV) virus infection on semen parameters. Semen samples were obtained from 27 HCV, 34 HIV, 30 HBV and 41 HCV-HIV-seropositive patients and compared with those of a control population of healthy seronegative subjects. Tests for detection of HIV, HCV and HBV were performed on seminal samples. The sperm concentration was significantly decreased in HCV- and HBV-seropositive males compared to that of controls (P < 0.001). The mean sperm motility (a + b) was significantly decreased in HCV- and HBV-seropositive (P < 0.001) and in HCV-HIV-seropositive subjects (P < 0.05) compared to that of controls. The sperm viability was significantly lower in HCV- and HBV-seropositive men than in controls (P < 0.001). The normal morphology was significantly reduced in HCV-seropositive and HBV-seropositive men (P < 0.05) with respect to that of controls (P < 0.05). The sperm concentration after sperm wash was significantly higher in controls than in HCV-, HIV-, HBV- and HIV-HCV-seropositive men (P < 0.001). We can conclude that HBV- and HCV-infected men have a significantly impaired sperm quality compared with that of controls. The reason for the better sperm quality in our series of HIV- and HCV-HIV-infected men is still under debate. Further investigations in a larger case series are warranted.

Several protocols are actually available for in Vitro Fertilization and Embryo Transfer. The review summarizes the main differences and the clinic characteristics of the protocols in use with GnRH agonists and GnRH antagonists by emphasizing the major outcomes and hormonal changes associated with each protocol. The majority of randomized clinical trials clearly shows that in “in Vitro” Fertilization and Embryo Transfer, the combination of exogenous Gonadotropin plus a Gonadotropin Releasing Hormone (GnRH) agonist, which is able to suppress pituitary FSH and LH secretion, is associated with increased pregnancy rate as compared with the use of gonadotropins without a GnRH agonist. Protocols with GnRH antagonists are effective in preventing a premature rise of LH and induce a shorter and more cost-effective ovarian stimulation compared to the long agonist protocol. However, a different synchronization of follicular recruitment and growth occurs with GnRH agonists than with GnRH antagonists. Future developments have to be focused on timing of the administration of GnRH antagonists, by giving a great attention to new strategies of stimulation in patients in which radio-chemotherapy cycles are needed.