Short-term outcomes of fetoscopic laser surgery for severe twin–twin transfusion syndrome from Taiwan single center experience: Demonstration of learning curve effect on the fetal outcomes

AbstractObjectiveTo evaluate the learning curve effect on fetal outcomes while using fetoscopic laser photocoagulation (FLP) for twin–twin transfusion syndrome (TTTS) as managed by a newly established single center in Taiwan.Materials and MethodsBetween October 2005 and October 2010, women diagnosed to have TTTS before 26 weeks of gestation were offered FLP surgery. Cases were divided into first-half and second-half groups to evaluate the learning effect on fetal outcomes including at least one survival rate, two survival rate, and gestational age of delivery.ResultsA total of 44 cases with a median gestational age of 20.1 weeks (range 16–25) at operation were included in the study. Overall, both twins survived in 22 (50.0%) cases, whereas only one twin was born alive in 13 (29.5%), and neither was born alive in the remaining nine cases (20.5%). The total survival rate was 64.8%. When comparing the first-half 22 cases and the second-half 22 cases, there were significant improvements in total survival rate (54.7% vs. 75.0%, p = 0.045), a prolonged interval between operation and delivery (62.1 vs. 89.1 days, p = 0.042), and more advanced gestational age of delivery (28.3 vs. 33.0 weeks, p = 0.008) in the second-half 22 cases.ConclusionsWith increasing experience in using fetoscopic guide laser therapy for TTTS, the fetal survival rate could be improved with advanced gestational age at delivery

Zinc-Chelation Contributes to the Anti-Angiogenic Effect of Ellagic Acid on Inhibiting MMP-2 Activity, Cell Migration and Tube Formation

Ellagic acid (EA), a dietary polyphenolic compound, has been demonstrated to exert anti-angiogenic effect but the detailed mechanism is not yet fully understood. The aim of this study was to investigate whether the zinc chelating activity of EA contributed to its anti-angiogenic effect.The matrix metalloproteinases-2 (MMP-2) activity, a zinc-required reaction, was directly inhibited by EA as examined by gelatin zymography, which was reversed dose-dependently by adding zinc chloride. In addition, EA was demonstrated to inhibit the secretion of MMP-2 from human umbilical vein endothelial cells (HUVECs) as analyzed by Western blot method, which was also reversed by the addition of zinc chloride. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), known to down-regulate the MMP-2 activity, was induced by EA at both the mRNA and protein levels which was correlated well with the inhibition of MMP-2 activity. Interestingly, zinc chloride could also abolish the increase of EA-induced RECK expression. The anti-angiogenic effect of EA was further confirmed to inhibit matrix-induced tube formation of endothelial cells. The migration of endothelial cells as analyzed by transwell filter assay was suppressed markedly by EA dose-dependently as well. Zinc chloride could reverse these two effects of EA also in a dose-dependent manner. Since magnesium chloride or calcium chloride could not reverse the inhibitory effect of EA, zinc was found to be involved in tube formation and migration of vascular endothelial cells.Together these results demonstrated that the zinc chelation of EA is involved in its anti-angiogenic effects by inhibiting MMP-2 activity, tube formation and cell migration of vascular endothelial cells. The role of zinc was confirmed to be important in the process of angiogenesis

Immunotherapy for advanced or relapsed cervical cancer

Cervical cancer is the third most commonly diagnosed cancer and the fourth leading cause of cancer deaths worldwide. Conventional approaches by surgery, radiotherapy, and/or chemotherapy cannot provide satisfied therapeutic outcomes for advanced or relapsed cervical cancer. Thus, immunotherapy or biotherapy for these patients has been the mode of treatment. A number of studies on immunotherapy for cervical cancer in animals has been published. This time, we summarized our experiences and concepts with regard to the therapeutic approach for advanced cervical cancer in humans

Zinc chloride reversed the inhibition of MMP-2 secretion by ellagic acid.

<p>Cells treated without or with EA in the presence or absence of ZnCl₂ for 24 hours were processed for Western blot method to analyze the protein levels of MMP-2 in conditioned media and in cytosol.</p

Zinc reversed the matrix-induced tube formation of HUVECs inhibited by EA.

<p>A. and B. Cells were treated with 5 µM ellagic acid in the presence of ZnCl₂ ranged from 0–100 µM for 24 hours. C. Cells were treated with or without 100 µM ZnCl₂ for 24 hours and processed for tube formation analysis. D. Cells were treated with 5 µM EA in the presence of 100 µM Zn(C₂H₃O₂)2, Ca Cl2 or MgCl2 for 24 hours and processed for tube formation analysis. The number of completely formed tubes in each group was determined and compared. Values are mean (n = 3) ± SEM. An asterisk demonstrated the significant difference (p<0.05) between none-treated and EA-treated groups.</p

Zinc chloride reversed the direct inhibition of MMP-2 activity by ellagic acid.

<p>A. EA directly inhibited the MMP-2 activity in cell-free conditioned medium dose-dependently. B. Co-incubation with ZnCl₂ reversed the direct inhibition of MMP-2 activity in cell-free conditioned medium by EA. Conditioned medium containing the MMP-2 activity was taken from cultures of HUVECs. C. The activity of purified MMP-2 in the presence of EA was inhibited which could also be reversed by ZnCl₂ dose-dependently.</p