Genome-wide expression patterns of invasion front, inner tumor mass and surrounding normal epithelium of colorectal tumors

Background

The normal human prostate glandular epithelium has the unique function of accumulating high levels of zinc. In prostate cancer this capability is lost as an early event in the development of the malignant cells. The mechanism and factors responsible for the ability of the normal epithelial cells to accumulate zinc and the loss of this capability in the malignant cells need to be identified. We previously reported that Zip1 is an important zinc uptake transporter in prostate cells and is down regulated in the malignant cells in situ along with the depletion of zinc levels. In this report we investigated the expression of two other Zip family zinc transporters, Zip2 and Zip3 in malignant versus nonmalignant (normal and BPH) glands. Zip2 and Zip3 relative protein levels were determined by immunohistochemistry analysis of human prostate tissue sections.

Results

Normal and BPH glandular epithelium consistently exhibited the strong presence of both Zip 2 and Zip3; whereas both transporters consistently were essentially non-detectable in the malignant glands. This represents the first report of the expression of Zip3 in human prostate tissue; and more importantly, reveals that ZiP2 and Zip3 are down regulated in malignant cells in situ as we also had demonstrated for Zip1. Zip2 and Zip3 transporter proteins were localized predominantly at the apical cell membrane, which is in contrast to the Zip1 localization at the basolateral membrane. Zip2 and Zip3 seemingly are associated with the re-uptake of zinc from prostatic fluid.

Conclusion

These results coupled with previous reports implicate Zip2 and Zip3 along with Zip1 as important zinc uptake transporters involved in the unique ability of prostate cells to accumulate high cellular zinc levels. Zip1 is important for the extraction of zinc from circulation as the primary source of cellular zinc. Zip 2 and Zip3 appear to be important for retention of the zinc in the cellular compartment. The down regulation of all three transporters in the malignant cells is consistent with the loss of zinc accumulation in these cells. Since zinc imposes tumor suppressor effects, the silencing of the gene expression for these transporters is a required event for the manifestation of the malignant activities of the neoplastic cells. This now provides new insights into the genetic/molecular events associated with the development of prostate cancer; and supports our concept of Zip1, and now Zip2 and Zip3, as tumor suppressor genes and zinc as a tumor suppressor agent.     

Performance comparison between the mycobacteria growth indicator tube system and L?wenstein-Jensen medium in the routine detection of Mycobacterium tuberculosis at public health care facilities in Rio de Janeiro, Brazil: preliminary results of a pragmatic clinical trial

In view of the fact that the World Health Organization has recommended the use of the mycobacteria growth indicator tube (MGIT) 960 system for the diagnosis of tuberculosis and that there is as yet no evidence regarding the clinical impact of its use in health care systems, we conducted a pragmatic clinical trial to evaluate the clinical performance and cost-effectiveness of the use of MGIT 960 at two health care facilities in the city of Rio de Janeiro, Brazil, where the incidence of tuberculosis is high. Here, we summarize the methodology and preliminary results of the trial. (ISRCTN.org Identifier: ISRCTN79888843 [http://isrctn.org/])     

Corneal endothelial permeability and aqueous humor dynamics in normal pressure glaucoma

Corneal endothelial permeability and aqueous humor dynamics were studied in 17 non-treated normal pressure glaucoma patients in order to analyse the relevance of these parameters in the pathophysiology of this disease. Corneal endothelial permeability and aqueous humor flow were measured by fluorophotometry and aqueous outflow facility was determined by tonography. The results were compared with those of 17 healthy controls of similar age. The mean corneal endothelial permeability values and the aqueous flow and outflow facility values of the patients did not differ significantly from those of the healthy controls (P=0.8, P=0.2 and P=0.5, respectively). Normal pressure glaucoma does not affect the corneal endothelial permeability. The aqueous humor dynamics are not primarily involved in the pathophysiology of normal pressure glaucoma.Abbreviations IOP intraocular pressure - NPG normal pressure glaucoma - POAG primary open-angle glaucoma Part of this study was presented at the Annual Meeting of the Association for Eye Research on September 16, 1993 in Granada, Spain     

Development of a lipoprotein based molecular imaging MR contrast agent for the noninvasive detection of early atherosclerotic disease

Introduction: Currently there are no clinically available means of noninvasively detecting early atherosclerotic disease because these lesions are characterized by an accumulation of extracellular lipid and foam cells, but a lack of significant wall thickening or architectural distortion. Objective: We hypothesize that a paramagnetically labeled low density lipoprotein (LDL) could serve as a functional probe to detect sites of abnormal lipid metabolism in the vessel wall that represent sites of early disease. Methods: Isolated LDL was first incubated with manganese–mesoporphyrin, a hydrophobic MR contrast agent (MnMeso). Size exclusion chromatography and absorption mass spectroscopy were performed on the resulting samples to prove that an association between the two occurred. Subsequently, foam cell cultures (n=7) were incubated (10–30g/ml for 48h) with these labeled lipoproteins and the T1 relaxivity of centrifuged pellets of these cells was determined by using an inversion recovery sequence on a 1.5T scanner. These results were compared to control measurements made from foam cell cultures fed unlabeled lipoproteins (n=7). Results: Measured T1 relaxation times of the cells fed the MnMeso–LDL (443.3±51.8ms) was significantly different from the T1 relaxivity obtained from cells fed unlabeled lipoproteins (661.3±60.9ms). These findings indicate that the amount of contrast bound to the constructed lipoproteins is sufficient to produce measurable MR signal changes noninvasively. Conclusions: The study results support the feasibility of future in vivo MR experiments with labeled lipoproteins to assess lipoprotein kinetics in the vessel wall, which will hopefully provide a means of detecting early atherosclerotic disease.