Dual-targeting of tumor cells and subcellular endoplasmic reticulum via AgPPIX-based Janus nanoparticles for photodynamic/immunotherapy against TNBC.

Triple-negative breast cancer (TNBC) is known for its strong invasiveness, high recurrence rates, and poor prognosis. Heme oxygenase-1 (HO-1) is closely related to tumor invasion, metastasis, recurrence and formation of tumor immunosuppression. The expression of HO-1 is high in TNBC and low in normal tissues. In this study, AgPPIX was synthesized as a heme oxygenase-1 (HO-1) inhibitor and a photosensitizer for TNBC therapy. PDA nanoparticles were synthesized and modified with anti-CD24 and p-toluenesulfonamide (PTSC) on their both sides to obtain PTSC@AgPPIX/PDA@anti-CD24 Janus nanoparticles (PAPC) for AgPPIX-targeted delivery. Anti-CD24 is targeted to CD24 on tumor cells and the PTSC moiety is targeted to endoplasmic reticulum (ER), where HO-1 is located. The results indicated that PAPC Janus nanoparticles exhibited higher cytotoxicity in 4T1 cells than that of the mono-modified nanoparticles. PAPC not only inhibited the expression of HO-1 and VEGF but also reduced TrxR activity significantly. Furthermore, PAPC not only promoted intracellular ROS production under laser irradiation for tumor photodynamic therapy (PDT) but also polarized TAMs from M2-type to M1 for tumor immunotherapy. In vivo experiments confirmed that PAPC could remodel the tumor immune microenvironment and almost completely inhibit the tumor growth in mouse models. Therefore, PAPC Janus nanoparticles are a promising nanoplatform with a dual-targeting capacity for TNBC immune/PDT synergistic therapy.

Quantitative risk assessment to guide the treatment of cesarean scar pregnancy.

OBJECTIVE: To develop a risk-factor scoring system for the prediction of bleeding during ultrasound-guided dilation and curettage (D&C) for cesarean scar pregnancy (CSP). METHODS: The retrospective study included patients with a CSP of 31-67 days who underwent transabdominal ultrasonography-guided D&C in 2010-2014. Binary logistic regression analysis was used to identify risk factors for the need of Foley catheter hemostasis. The predictive accuracy of a risk-scoring system based on significant factors was evaluated by receiver operating curve analysis. RESULTS: Among 82 included patients, 66 (80%) were successfully treated without any complications, whereas 16 (20%) required Foley catheter compression hemostasis. Four patients who received the Foley catheter needed further treatment. A longer pregnancy duration (odds ratio 1.171, 95% confidence interval 1.050-1.305; P=0.004) and a rich blood supply on ultrasonography (odds ratio 3.282, 95% confidence interval 1.441-4.742; P=0.005) were significant risk factors for the need of compression hemostasis. A scoring system based on these two risk factors would have identified 93.8% of patients requiring compression hemostasis if the optimum cutoff score was used. CONCLUSION: Heavy bleeding during transabdominal ultrasound-guided D&C for CSP is associated with a longer pregnancy duration and a rich blood supply on ultrasonography. The new risk-scoring system can be used to predict bleeding during surgery.

Decreased peritoneal concentrations of interleukin-15 in women with advanced stage endometriosis.

OBJECTIVE: To assess the concentrations of interleukin-15 (IL-15) in peritoneal fluid from women with endometriosis and fertile disease-free controls. STUDY DESIGN: Peritoneal fluid samples were obtained from 50 women with endometriosis and 29 fertile women having tubal ligation. Concentrations of IL-15 were measured. RESULTS: The mean (S.D.s) concentration of IL-15 in peritoneal fluid was 11.17 pg/mL (3.89) for women with endometriosis, and 12.59 pg/mL (4.11) for fertile disease-free controls. The difference of peritoneal IL-15 concentrations between endometriosis and control women was not statistically significant. However, peritoneal IL-15 concentrations were significantly lower in women with moderate/severe endometriosis when compared with those in women with minimal/mild endometriosis, and in controls (P<0.05). In addition, peritoneal IL-15 concentrations did not correlate with the phase of menstrual cycle in endometriosis or control women. CONCLUSIONS: Our results suggest that the decreased peritoneal IL-15 concentrations in women with moderate/severe endometriosis imply a role of IL-15 in the pathogenesis of advanced endometriosis as compared to those with minimal/mild endometriosis and fertile disease-free controls.