Vitamin D prevents endothelial progenitor cell dysfunction induced by sera from women with preeclampsia or conditioned media from hypoxic placenta

Context: Placenta-derived circulating factors contribute to the maternal endothelial dysfunction underlying preeclampsia. Endothelial colony forming cells (ECFC), a sub-population of endothelial progenitor cells (EPCs), are thought to be involved in vasculogenesis and endothelial repair. Low vitamin D concentrations are associated with an increased risk for preeclampsia. Objective: We hypothesized that the function of human fetal ECFCs in culture would be suppressed by exposure to preeclampsia-related factors-preeclampsia serum or hypoxic placental conditioned medium- in a fashion reversed by vitamin D. Design, Setting, Patients: ECFCs were isolated from cord blood of uncomplicated pregnancies and expanded in culture. Uncomplicated pregnancy villous placenta in explant culture were exposed to either 2% (hypoxic), 8% (normoxic) or 21% (hyperoxic) O2 for 48 h, after which the conditioned media (CM) was collected. Outcome Measures: ECFC tubule formation (Matrigel assay) and migration were examined in the presence of either maternal serum from preeclampsia cases or uncomplicated pregnancy controls, or pooled CM, in the presence or absence of 1,25(OH)2 vitamin D3. Results: 1,25(OH)2 vitamin D3 reversed the adverse effects of preeclampsia serum or CM from hypoxic placenta on ECFCs capillary-tube formation and migration. Silencing of VDR expression by VDR siRNA, VDR blockade, or VEGF pathway blockade reduced ECFC functional abilities. Effects of VDR or VEGF blockade were partially prevented by vitamin D. Conclusion: Vitamin D promotes the capillary-like tubule formation and migration of ECFCs in culture, minimizing the negative effects of exposure to preeclampsia-related factors. Further evaluation of the role of vitamin D in ECFC regulation and preeclampsia is warranted. © 2014 Brodowski et al

Date Fiber as a Constituent of Broiler Starter Diets

In Oman, efforts are underway to find alternative sources of fwd to support domestic livestock. The date industry thrives in Oman and one of its by-products is date fiber, a by-product of date syrup production. Although the product contains some free sugars, an evaluation of its potential in broiler diets has never been undertaken. Therefore, we conducted an experiment to investigate the value of date fiber in broiler chick diets. The experimental diets consisted of four graded levels of date fiber: 0, 15, 30 and 45 % in a broiler-starter ration replacing corn as an energy source. The diets were isonitrogenous. There were five replicates for each of the four diets and each replicate contained six broiler chicks. As date fiber percent increased in the dietary treatment, there were linear reductions in body weight gain, calculated apparent metabolizable energy (AMEn) content, and apparent protein digestibility (P < 0.05). Poor feed utilization (i .e., reduced feed efficiency) was observed in birds fed date fiber diets compared to the control group (P < 0.05). The poor performance of birds fed date fiber may be attributed to protein and energy limitations. We conclude that date fiber has no value in growing broiler diets. However, it may have utility in diets where a stable body weight is desirable

Date Fiber as a Constituent of Broiler Starter Diets

In Oman, efforts are underway to find alternative sources of fwd to support domestic livestock. The date industry thrives in Oman and one of its by-products is date fiber, a by-product of date syrup production. Although the product contains some free sugars, an evaluation of its potential in broiler diets has never been undertaken. Therefore, we conducted an experiment to investigate the value of date fiber in broiler chick diets. The experimental diets consisted of four graded levels of date fiber: 0, 15, 30 and 45 % in a broiler-starter ration replacing corn as an energy source. The diets were isonitrogenous. There were five replicates for each of the four diets and each replicate contained six broiler chicks. As date fiber percent increased in the dietary treatment, there were linear reductions in body weight gain, calculated apparent metabolizable energy (AMEn) content, and apparent protein digestibility (P < 0.05). Poor feed utilization (i .e., reduced feed efficiency) was observed in birds fed date fiber diets compared to the control group (P < 0.05). The poor performance of birds fed date fiber may be attributed to protein and energy limitations. We conclude that date fiber has no value in growing broiler diets. However, it may have utility in diets where a stable body weight is desirable

Abstract P6-04-29: Vitamin D induces expression of estrogen receptor and restores endocrine therapy response in estrogen receptor-negative breast cancer

Abstract Background: Approximately 30% of all breast tumors do not express estrogen receptor (ER) and patients with these tumors present poor prognosis and respond poorly to hormone therapy. Calcitriol through its vitamin D receptor (VDR) exerts antiproliferative, apoptotic and pro-differentiating effects in cancer. Calcitriols effects upon ER expression in breast cancer cells is controversial. Therefore, in order to clarify this issue, the aim of the present study was to determine if calcitriol induces ERα expression in ERα-negative breast cancer cells and could restore antiestrogen responses. The evaluation of calcitriol effects was performed in terms of proliferation and regulation of the following genes: Cyclin D1, involved in cell cycle, and Ether-à-go-go 1 (Eag1), related to cell proliferation and tumor progression. Methods: Cultured cells derived from ERα-negative breast tumors and an established ERα-negative breast cancer cell line (SUM 229) were used in this study. These cells were treated with calcitriol and reverse transcription-PCR or western blotting analyses were performed to assess ERα expression. Growth assays with XTT were used to evaluate the antiproliferative response to the antiestrogens fulvestran and tamoxifen. Gene expression analysis for Cyclin D1 and Eag1 was evaluated by real time PCR in cells treated simultaneously with calcitriol plus estradiol or fulvestran. Results: The treatment with calcitriol in ER-negative breast cancer cells resulted in the induction of ERα. This effect was specifically mediated through the vitamin D3 receptor (VDR), since the VDR antagonist TEI-9647 effectively inhibited the ability of calcitriol to stimulate ERα gene expression. Consequently, the induction of ERα by calcitriol restores the response to antiestrogens in breast cancer cells by inhibiting cell proliferation. Co-treatment of calcitriol and antiestrogens down-regulated Cyclin D1 and Eag1 gene expression. Conclusion: Calcitriol induced the expression of ERα and restored antiestrogenic responses in ERα-negative breast cancer cells. Moreover, fulvestran down regulated mRNA expression of Cyclin D1 and Eag1 when ERα-negative cells were pre-treated with calcitriol. These results suggest that the combined treatment with calcitriol and antiestrogens could be a new therapeutic strategy for ERα-negative breast cancer patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-04-29.</jats:p

Abstract P4-06-19: Astemizole and calcitriol: A novel targeted therapeutic strategy for breast cancer

Abstract Calcitriol antiproliferative effects include inhibition of the oncogenic ether-à-go-go-1 potassium channel (Eag1), which expression and activity are necessary for cell cycle progression and tumorigenesis. Astemizole, a new promising antineoplastic drug, targets Eag1 by blocking ion currents. In vitro, we showed that astemizole synergized calcitriol antiproliferative effects by downregulating CYP24A1, the enzyme that degrades calcitriol, and upregulating the vitamin D receptor (VDR), which mediates calcitriol actions. In this study we investigated the antineoplastic effect of astemizole and calcitriol in a murine model xenografted with T-47D and invasive ductal carcinoma-derived breast cancer cells (IDC). Tumor-bearing nude mice were treated with oral astemizole (50 mg/kg/day) and/or i.p. calcitriol (30 μg/kg/twice a week) during 3 weeks. Astemizole and calcitriol significantly inhibited, while the coadministration of both drugs further reduced, tumor growth compared to untreated controls. These results were supported by immunohistochemistry studies of Ki-67, a proliferation marker, which revealed less staining in tumors from mice with the co-treatment compared to controls and calcitriol or astemizole alone. In a similar manner as reported in vitro, we observed that the concomitant administration of astemizole and calcitriol upregulated VDR tumor expression (P &amp;lt; 0.05). Conclusion: Coadministration of calcitriol and astemizole increased the antineoplastic effects of both drugs. Our results indicate that astemizole may improve calcitriol bioactivity by upregulating tumoral VDR. In addition, the findings in this study suggest that VDR-negative tumors could be sensitized to calcitriol antineoplastic effects by concomitant administration with astemizole, which would also allow for less calcitriol dosing without sacrificing overall therapeutic efficacy. Herein we suggest a novel combined adjuvant therapy for the management of breast cancer tumors. These results provide scientific bases for further studies designed to test both compounds simultaneously in patients bearing solid or metastatic tumors. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-06-19.</jats:p