Stable PEG-coated silver nanoparticles - A comprehensive toxicological profile.

The present study was purported to assess the toxicological profile of bare and polyethylene glycol (PEG) coated spherical silver nanoparticles (AgNPs) by means of in vitro (on human keratinocytes - HaCat cells) and in vivo non-invasive tests (after intraperitoneal - i.p. administration to mice). Bare and PEG-coated AgNPs were synthesized by applying Turkevich's method slightly modified. The physico-chemical characterization revealed the formation of stable, spherical AgNPs and PEG-AgNPs, with narrow size distributions and mean hydrodynamic sizes in the range of 19 nm and 50 nm, respectively. Toxicity data revealed a dose-dependent safe profile for low concentrations of test compounds (<10 µM) in terms of cell viability, whereas higher concentrations were associated with a high rate of cell mortality. In vivo acute/subacute toxicity data showed no denotive changes in mice health status after i.p. administration. Histological observations of internal organs and the biochemical parameters analyzed together with the other biological observations showed a low toxicity level with no major differences related to control, albeit at skin level a reduced number of mast cells was detected. All these observations provide strong support for the idea that coated silver nanoparticles could be applied as targeted nanocarriers for skin pathologies and diagnostic.

Histochemical and immunohistochemical evidence of tumor heterogeneity in colorectal cancer.

INTRODUCTION: Intratumoral heterogeneity implies the existence of differences between tumor cells, which can best be shown by histochemical and immunohistochemical techniques. The histological study is a mandatory step in any research aimed at characterizing tumor heterogeneity. Immunohistochemistry (IHC) also plays an important role in the differentiation of tumor types, assessing aggressiveness. MATERIALS AND METHODS: Investigated group consisted of 50 patients with colorectal adenocarcinoma, for each were recorded clinicopathological data and harvested samples intraoperatively, which were included in paraffin blocks. We perform Hematoxylin-Eosin staining for histological grade and other indices. IHC study used Avidin-Biotin-Peroxidase (ABC), with the markers: CK7, CK20, MUC1, MUC2, Ki-67, PCNA, p53, KRAS, BCL2, PTEN, EGFR. The resulting data were analyzed by statistical methods. RESULTS: Most of colorectal adenocarcinoma studied had no special histological features and had G2 grade. IHC detected in most cases the CK20+÷CK7- phenotype (78%) and MUC1 (74%) protein expression. The proliferation markers (Ki-67 and PCNA) were present in all tumor mass with a variable index, which shows high intratumoral heterogeneity, but p53 and KRAS were distributed more uniformly, showing low intratumoral heterogeneity. PTEN was expressed nuclearly in 86% of the cases and EGFR in 42%. CONCLUSIONS: The expression profiles of cytokeratins and mucins in the colorectal adenocarcinomas are useful in defining tumor phenotypes with different prognosis and therapy. We found a significant positive correlation between KRAS protein expression and BCL2 and TP53 expression. The study demonstrated the intratumoral and intertumoral heterogeneity, expressed at phenotypic level.