SN38[BSA]

Human trophoblast cell-surface marker (Trop-2) is a surface glycoprotein originally identified in human placental tissue and subsequently found to be highly expressed by various types of human epithelial solid tumors. We investigated the efficacy of sacituzumab govitecan, an antibody-drug conjugate (ADC) comprised of a humanized anti- Trop-2 antibody, conjugated with active metabolite of irinotecan (SN-38), on Trop-2 positive cervical cancer cell lines and a xenograft model. Trop-2 expression was evaluated in 147 primary cervical tumors by immunohistochemistry, real-time polymerase chain reaction, and flow cytometry. For in vitro experiments, two Trop-2 positive (CVX-8, ADX-3), and one Trop-2 negative (ADX-2) cell lines were used. A cell line with a strong Trop-2 expression (CVX-8) was used to test in vivo antitumor activity in xenografts models. Out of 147 primary cervical cancers, 113 were squamous cell carcinomas (SCCs), and 34 were adenocarcinoma/adenosquamous carcinomas. Moderate to strong diffuse staining was seen in 95% (108/113) of SCCs, and 81% (29/34) of adenocarcinoma/adenosquamous cancers on immunohistochemistry. Trop-2 positive cell lines were highly sensitive to sacituzumab govitecan in vitro, with IC50 values in the range of 0.18 to 0.26nM (p=0.02, and p=0.04 for CVX-8, and ADX-3, respectively). In xenografts, a significant tumor growth inhibition was seen after twice-weekly intravenous administration of the drug for three weeks (p<0.0001, and p=0.001 for sacituzumab govitecan vs naked antibody, and sacituzumab govitecan vs control-ADC, respectively). Overall survival at 90 days was significantly improved in the sacituzumab govitecan group (p=0.014). In conclusion, sacituzumab govitecan may represent a novel targeted therapy option in cervical cancer patients overexpressing Trop-2.

Double network hydrogels (DN gels) are one of most extensively investigated high strength hydrogels. However, conventional DN gels are fully chemically cross-linked, which often suffer from severe softening phenomenon and are lack of self-healing properties. In the present work, fully physically cross-linked Agar/PAAm DN gels, consisting of physical agar gel as the first network and physical polyacrylamide (PAAm) gel as the second network, were prepared by the "one-pot" method, in which both of the networks are cross-linked by hydrogen bonds. It was found hydrogen-bonds cross-linked and highly mechanical PAAm physical single network (SN) gel as well as Agar/PAAm physical DN gel were only achieved at a high AAm concentration (i.e. 50 wt%). At optimal condition, Agar/PAAm physical DN gel achieved E of 498 kPa, sigma(f) of 0.48 MPa, epsilon(f) of 24.11 mm/mm and W of 10.24 MJ/m(3), which was much better than those of PAAm physical SN gel (E of 355 kPa, sigma(f) of 0.24 MPa, epsilon(f) of 23.3 mm/mm and W of 5.82 MJ/m(3)). Both of Agar/PAAm physical DN gel and PAAm physical SN gel exhibited large hysteresis loops. Agar/PAAm physical DN gels also demonstrated rapid self-recovery (similar to 83% toughness recovery for 2 min resting) at room temperature without external stimuli. Different from Agar/PAAm hybrid DN gels with negligible self-healing property, Agar/PAAm physical DN gels exhibited obvious self-healing property, and the healed gel could achieve tensile strength of 0.38 MPa (healing efficiency similar to 75%) and tensile strain of 420%. Combination with high strength, rapid self-recovery, and self-healing performances, fully physical Agar/PAAm DN gels hold promising for potential bio-applications under physiological conditions.