Poly(3-caprolactone)s of controlled molecular weight and low molecular weight distribution were prepared via anionic ring-opening polymerization using a tetra-functional initiator. The prerequisite for crosslinking was achieved by end-capping of the arms with acrylate groups. Novel biodegradable polyester resins were prepared by crosslinking of the functional polyesters via Michael addition using amino-telechelic poly(tetrahydrofuran). Three-dimensional microstructuring via replica molding shows the potential of this material as substrate for biomedical devices. Thermal and mechanical properties were investigated to characterize the polyester resins, accelerated in vitro degradation studies were carried out in a Sørensen buffer at pH 7.4 and 60 C for up to 77 days. At different time intervals, the mass loss of the resins and the pH values of the buffer were determined, degradation products were investigated by means of NMR, SEC and ESI-MS and morphology of the degraded resins was checked via scanning electron microscopy. Compared to linear poly(3-caprolactone) the degradation rate of all resins is higher, showing a mass loss of 50% within 77 days.

Selective estrogen receptor modulators (SERMs) demonstrate differential endometrial cancer (EC) risk. While tamoxifen (TAM) use increases the risk of endometrial hyperplasia and malignancy, raloxifene (RAL) has neutral effects on the uterus. How TAM increases the risk of EC and why TAM and RAL differentially modulate the risk for EC, however, remain elusive. Here, we tested the hypothesis that TAM increases the risk for EC, at least in part, by enhancing the local estrogen biosynthesis and directing estrogen metabolism towards the formation of genotoxic and hormonally active estrogen metabolites. In addition, the differential effects of TAM and RAL in EC risk are attributed to their differential effect on estrogen metabolism/metabolites. The endometrial cancer cell line (Ishikawa cells) and the non-malignant immortalized human endometrial glandular cell line (EM1) were used for the study. The profile of estrogen/estrogen metabolites (EM), depurinating estrogen-DNA adducts, and the expression of estrogen-metabolizing enzymes in cells treated with 17β-estradiol (E2) alone or in combination with TAM or RAL were investigated using high performance liquid chromatography–electrospray ionization-tandem mass spectrometry (HPLC–ESI-MS2), ultraperformance liquid chromatography/tandem mass spectrometry (UPLC–MS/MS), and Western blot analysis, respectively. TAM significantly increased the total EM and enhanced the formation of hormonally active and carcinogenic estrogen metabolites, 4-hydroxestrone (4-OHE1) and 16α-hydroxyestrone, with concomitant reduction in the formation of antiestrogenic and anticarcinogenic 2-hydroxyestradiol and 2-methoxyestradiol. Furthermore, TAM increased the formation of depurinating estrogen-DNA adducts 4-OHE1 [2]-1-N7Guanine and 4-OHE1 [2]-1-N3 Adenine. TAM-induced alteration in EM and depurinating DNA adduct formation is associated with altered expression of estrogen metabolizing enzymes CYP1A1, CYP1B1, COMT, NQO1, and SF-1 as revealed by Western blot analysis. In contrast to TAM, RAL has minimal effect on EM, estrogen-DNA adduct formation, or estrogen-metabolizing enzymes expression. These data show that TAM perturbs the balance of estrogen-metabolizing enzymes and alters the disposition of estrogen metabolites, which can explain, at least in part, the mechanism for TAM-induced EC. These results also implicate the differential effect of TAM and RAL on estrogen metabolism/metabolites as a potential mechanism for their disparate effects on the endometrium.

Arsenic crosses the placenta and may have adverse consequences in utero and later in life. At present, little is known about arsenic concentrations in placenta and their relation to maternal and infant exposures particularly at common levels of exposure. We measured placenta arsenic in a US cohort potentially exposed via drinking water from private wells, and evaluated the relationships between placenta and maternal and infant biomarker arsenic concentrations. We measured total arsenic concentrations in placental samples from women enrolled in the New Hampshire Birth Cohort Study (N=766). We compared these data to maternal urinary arsenic (total arsenic and individual species) collected at approximately 24–28 week gestation, along with maternal post-partum toenails and infant toenails using non-parametric multivariate analysis of log10-transformed data. We also examined the association between placental arsenic and household drinking water arsenic. Placenta arsenic concentrations were related to arsenic concentrations in maternal urine (β 0.55, P value <0.0001), maternal (β 0.30, P value 0.0196) and infant toenails (β 0.40, P value 0.0293) and household drinking water (β 0.09, P value <0.0001). Thus, our data suggest that placenta arsenic concentrations reflect both maternal and infant exposures.

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We show for the first time that E2-induced hESC proliferation is associated with a shift in glucose metabolism toward aerobic glycolysis, and the molecular basis for this metabolic shift is linked to the effects of E2 on PKM2. In addition, PKM2 acts as a transcriptional coactivator for ERα and small-molecule PKM2 activators inhibit ERα transcriptional activity and reduce E2-induced cell proliferation.

Starting from THF and protected glycidols, linear multifunctional polyethers were prepared. Random copolymers were synthesized via cationic ROP while block copolymers were obtained via anionic ROP. Kinetic studies were carried out for the random copolymers. Poly(THF‐co‐glycidol) was converted in polymer‐analogous reactions first to phenoxy‐carbonyloxy‐methyl‐substituted polyethers and then to amphiphilic polyethers by conversion of the former substituted polyethers with different functional amines. The resulting amphiphilic polyesters were tested for their bacteriostatic effect.

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