Managing Cancer Drug Resistance from the Perspective of Inflammation.

The development of multidrug resistance in cancer chemotherapy is a major obstacle to the effective treatment of human malignant tumors. Several epidemiological studies have demonstrated that inflammation is closely related to cancer and plays a key role in the development of both solid and liquid tumors. Therefore, targeting inflammation and the molecules involved in the inflammatory process may be a good strategy for treating drug-resistant tumors. In this review, we discuss the molecular mechanisms underlying inflammation in regulating anticancer drug resistance by modulating drug action and drug-mediated cell death pathways. Inflammation alters the effectiveness of drugs through modulation of the expression of multidrug efflux transporters (e.g., ABCG2, ABCB1, and ABCC1) and drug-metabolizing enzymes (e.g., CYP1A2 and CYP3A4). In addition, inflammation can protect cancer cells from drug-mediated cell death by regulating DNA damage repair, downstream adaptive response (e.g., apoptosis, autophagy, and oncogenic bypass signaling), and tumor microenvironment. Intriguingly, manipulating inflammation may affect drug resistance through various molecular mechanisms validated by in vitro/in vivo models. In this review, we aim to summarize the underlying molecular mechanisms that inflammation participates in cancer drug resistance and discuss the potential clinical strategies targeting inflammation to overcome drug resistance.

Effectiveness of gonadotrophin-releasing hormone agonist therapy to improve the outcomes of intrauterine insemination in patients suffering from stage I-II endometriosis.

OBJECTIVE: To explore the role of postoperative gonadotrophin releasing hormone agonist (GnRH-a) therapy before treatment with intrauterine insemination (IUI) for infertile females with stage I-II endometriosis. MATERIAL AND METHODS: Ninety-seven patients diagnosed with stage I-II endometriosis before IUI were enrolled in this study. The clinical pregnancy rate, cumulative pregnancy rate, live birth rate and newborn conditions were compared between the two groups with and without GnRH-a therapy. RESULTS: The clinical pregnancy rate of IUI in the GnRH-a group was higher than that in the control group (15.29% vs. 11.82%, p = .035). By logistic regression analysis, patients treated with GnRH-a had a higher clinical pregnancy rate than those without (adjusted odds ratio (AOR) 23.190, 95% confidence interval (CI) 1.238-434.312). The live birth rate per IUI cycle in the GnRH-a group was also higher than in the controls (12.94% vs. 10%). However, the difference was not statistically significant (p = .311, AOR 4.844, 95% CI 0.229-102.320). The patients with GnRH-a therapy had a similar incidence of multiple pregnancy rate (0% vs. 0%), miscarriage rate (2.35% vs. 0.91%) and ectopic pregnancy rate (0% vs. 0.91%) as compared to the control group. The cumulative pregnancy rates were all higher in patients administered with GnRH-a than those without GnRH-a treatment in different cycles (one cycle: 17.07% vs 12.50%; two cycles: 29.27% vs 19.64%; three cycles: 31.71% vs 23.21%; ≥four cycles: 31.71% vs 23.21%), but the difference was not statistically significant. Notably, there was no more pregnancy after the third IUI cycle. The gestation weeks of delivery in the two groups were 39.09 ± 1.04 and 38.60 ± 1.17, respectively (p = .323). Nor was there difference in birth weight between the two groups (3236 ± 537 g vs 3435 ± 418 g, p = .360). CONCLUSIONS: The administration of GnRH-a in patients with stage I-II endometriosis could be beneficial to the outcomes of IUI. It is recommended that IUI should be discontinued after three failed attempts. KEY MESSAGESEndometriosis is a common cause of infertility, but the exact mechanism remains unclear.The administration of GnRH-a before IUI treatment is beneficial for patients suffering from stage I-II endometriosis.After three failed attempts, IUI should be stopped in patients with stage I-II endometriosis.

Autoantibodies in association with subchorionic haematoma in early pregnancy.

OBJECTIVE: To explore the possible aetiology of subchorionic haematoma (SCH), especially its association with autoantibodies. MATERIAL AND METHODS: Early pregnant women who were detected SCH through ultrasonography were identified as the study group and those without SCH at comparable ages who visited the clinic at the same period of time were compared as the control group. Indexes of laboratory immune tests were compared between the two groups, as well as their pregnancy outcomes. RESULTS: A total of 97 SCH patients and 130 control cases were recruited in this study. A higher proportion of women was detected autoantibodies in the SCH group compared with control group (45.36% vs 21.54%, p = .000). Positive rates of ANA (24.74% vs 10.77%, p = .005) and laboratory antiphospholipid antibodies (ACL, anti-ß2 GP1 or LA) (25.77% vs 11.54%, p = .005) showed significant differences between the two groups. The incidence of vaginal bleeding was significantly higher in the SCH group (43.30% vs 20.00%, p = .000). While the miscarriage rates were not significantly different (17.53% vs 15.38%, p = .666). And there were no significant differences in terms of preterm delivery rate, caesarean section rate, birth weight and pregnancy complications. Most SCHs (96.25%) were absorbed before 20th gestational week. In the SCH group, the average birth weight was significantly lower in women with autoantibodies. Clinical features and other pregnancy outcomes showed no significant differences between SCH patients with and without autoantibodies. CONCLUSIONS: The occurrence of SCH may be associated with autoantibodies. The pregnancy outcomes were comparable between women with and without SCH.KEY MESSAGESSubchorionic haematoma (SCH) is increasingly commonly observed in early pregnancy period, but the aetiology is uncertain and the clinical significance of SCH is controversial.The occurrence of SCH may be associated with autoantibodies.The pregnancy outcomes were not significantly different between women with and without SCH.

Effect of 20-hydroxyeicosatetraenoic acid on biological behavior of human villous trophoblasts and uterine vascular smooth muscle cells.

During pregnancy, disorders in uterine spiral artery remodeling (USAR) cause preeclampsia and other diseases. The aim of this study was to investigate the effect of 20-hydroxyeicosatetraenoic acid (20-HETE) on the biological behavior of human villous trophoblasts (HVTs) and human uterine vascular smooth muscle cells (HUVSMCs), and explore the role of 20-HETE in USAR. 20-HETE and its inhibitor HET0016 were used to study migration, invasion and apoptosis in the HVT and HVT-HUVSMC models. 20-HETE inhibited the migration and invasion of HVTs, and inhibited apoptosis in HUVSMCs and HUVSMCs co-cultured with HVTs. 20-HETE had thus obvious effects on the biological behavior of HVTs and HUVSMCs. These effects may cause USAR disorders and vascular dysfunction, leading to preeclampsia.

Thermo-responsive hollow silica microgels with controlled drug release properties.

Thermo-responsive hollow silica microgels (THSMGs) consisting of a hollow core, an intermediate silica supporting layer and a smart polymer gel corona were fabricated via organic-inorganic hybridization. Hollow silica particles and PNIPAAm microgels were successfully combined by utilizing the cross-linking reaction between 3-(trimethoxysilyl) propyl methacrylate (TMSPMA) and silanol groups on the silica surface, and then the copolymerization of TMSPMA and N-isopropylacrylamide (NIPAAm). The morphology and chemical composition were systematically examined by field emission scanning electron microscope (FESEM), transmission electron microscope (TEM), energy dispersive X-ray spectroscopy (EDS) and the Brunauer-Emmett-Teller (BET) measurement. The thermo-responsive phase transition behavior was investigated by the determination of the lower critical solution temperature (LCST), and particle size measurement using dynamic light scattering. THSMGs remain porous even after the coverage of PNIPAAm gels, and also have obvious hydrophilic/hydrophobic transition property and good swelling/collapse capability in spite of the rigid silica layer. The results of in vitro cytotoxicity evaluation and Rhodamine B (RHB) release study demonstrated that THSMGs have good biocompatibility, and achieve a thermo-responsive controlled-release behavior. The prepared THSMGs show considerable potential for applications as targeted and ambient temperature responsive drug delivery system.