Biomedical subjects

E Gazi

Publications and source records attributed to E Gazi.

4 recordsLinked to original sources

PubMed2006

Promotion of prostatic metastatic migration towards human bone marrow stoma by Omega 6 and its inhibition by Omega 3 PUFAs.

Epidemiological studies have shown not only a relationship between the intake of dietary lipids and an increased risk of developing metastatic prostate cancer, but also the type of lipid intake that influences the risk of metastatic prostate cancer. The Omega-6 poly-unsaturated fatty acid, Arachidonic acid, has been shown to enhance the proliferation of malignant prostate epithelial cells and increase the risk of advanced prostate cancer. However, its role in potentiating the migration of cancer cells is unknown. Here we show that arachidonic acid at concentrations <or=5 microM is a potent stimulator of malignant epithelial cellular invasion, which is able to restore invasion toward hydrocortisone-deprived adipocyte-free human bone marrow stroma completely. This observed invasion is mediated by the arachidonic acid metabolite prostaglandin E2 and is inhibited by the Omega-3 poly-unsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid at a ratio of 1 : 2 Omega-3 : Omega-6, and by the COX-2 inhibitor NS-398. These results identify a mechanism by which arachidonic acid may potentiate the risk of metastatic migration and secondary implantation in vivo, a risk which can be reduced with the uptake of Omega-3 poly-unsaturated fatty acids.

Arachidonic Acid↗

PubMed2005

Fixation protocols for subcellular imaging by synchrotron-based Fourier transform infrared microspectroscopy.

Synchrotron-based Fourier transform infrared (SR-FTIR) microspectroscopy is a powerful bioanalytical technique for the simultaneous analysis of lipids, proteins, carbohydrates, and a variety of phosphorylated molecules within intact cells. SR-FTIR microspectroscopy can be used in the imaging mode to generate biospectroscopic maps of the distribution and intensity profiles of subcellular biomolecular domains at diffraction-limited spatial resolution. However, the acquisition of highly spatially resolved IR images of cells is not only a function of instrumental parameters (source brightness, sampling aperture size) but also the cell preparation method employed. Additionally, for the IR data to be biochemically relevant the cells must be preserved in a life-like state without introducing artefacts. In the present study we demonstrate, for the first time, the differences in biomolecular localizations observed in SR-FTIR images of cells fixed by formalin, formalin-critical point drying (CPD), and glutaraldehyde-osmium tetroxide-CPD, using the PC-3 prostate cancer cell line. We compare these SR-FTIR images of fixed cells to unfixed cells. The influence of chemical fixatives on the IR spectrum is discussed in addition to the biological significance of the observed localizations. Our experiments reveal that formalin fixation at low concentration preserves lipid, phosphate, and protein components without significantly influencing the IR spectrum of the cell.

Animals↗

PubMed2003

Applications of Fourier transform infrared microspectroscopy in studies of benign prostate and prostate cancer. A pilot study.

Fourier transform infrared (FTIR) microspectroscopy has been applied to a study of prostate cancer cell lines derived from different metastatic sites and to tissue from benign prostate and Gleason-graded malignant prostate tissue. Paraffin-embedded tissue samples were analysed by FTIR, after mounting onto a BaF(2) plate and subsequent removal of wax using Citroclear followed by acetone. Cell lines were analysed as aliquots of cell suspension held between two BaF(2) plates. It was found that the ratio of peak areas at 1030 and 1080 cm(-1), corresponding to the glycogen and phosphate vibrations respectively, suggests a potential method for the differentiation of benign from malignant cells. The use of this ratio in association with FTIR spectral imaging provides a basis for estimating areas of malignant tissue within defined regions of a specimen. Initial chemometric treatment of FTIR spectra, using the linear discriminant algorithm, demonstrates a promising method for the classification of benign and malignant tissue and the separation of Gleason-graded CaP spectra. Using the principle component analysis, this study has achieved for the first time the separation of FTIR spectra of prostate cancer cell lines derived from different metastatic sites.

Adenocarcinoma↗

PubMed1999

Transplacental and lactational transfer of p,p'-DDE in Sprague-Dawley rats.

p,p'-DDE (hereafter DDE), a persistent metabolite of p,p'-DDT, is a widespread environmental contaminant that can induce antiandrogenic developmental effects in rats. Quantitative measurements of the transfer of DDE from pregnant or lactating dams to the fetus or suckling neonate were performed, and physiologically based pharmacokinetic (PBPK) models for the transplacental and lactational transfer of DDE were developed. Pregnant Sprague-Dawley rats were dosed by gavage in corn oil with either 10 or 100 mg DDE per kg body wt per day from Gestation Day (gd) 14 to 18. DDE was analyzed in several maternal tissues as well as in fetal and neonatal tissues from gd 15 to Postnatal Day (pnd) 21. Fetal DDE concentrations were about threefold lower than corresponding placental concentrations. By adopting a cross-fostering design, the contributions of transplacental and lactational transfer were compared. In the pup liver, where DDE was detectable in the 100 mg/kg groups on pnd 10, the lactationally exposed group had DDE concentrations about 50 times higher than those of the in utero only exposure group; the lactation only exposure groups had DDE tissue dose profiles very similar to those of the in utero plus lactation exposure groups, indicating that the lactational route is far more important than the in utero route quantitatively. The PBPK models postulated initial absorption of DDE into both the blood circulation and lymphatic system with the primary storage sites being maternal and neonatal adipose tissues. Mobilization of DDE from its storage sites is postulated to occur via its association with mobilized fatty acids and lipoproteins. The results provide an overall framework for evaluating the tissue dosimetry of DDE and for understanding how maternal exposure to DDE could affect perinatal sexual development in utero or in the early postnatal period.

Adipose Tissue↗