Detection of methylation in the CpG islands of the p16INK4A, RASSF 1A and methylguanine methyltransferase gene promoters in pancreatic adenocarcinoma.

Pancreatic cancer consists of an accumulation of genetic and epigenetic alterations. Recently, aberrant methylation of CpG islands of cancer-related genes has emerged as an important epigenetic mechanism of their transcriptional dysregulation during tumour development [1]. Therefore, new diagnostic methods, for early detection based on a better understanding of the molecular biology of pancreatic cancer, are required.

Preclinical studies of steroid-linked nitrosoureas in murine pancreatic adenocarcinoma PANO2.

Purpose: In earlier studies, this laboratory carried out research on the synthesis and anticancer evaluation of hybrid compounds, which combine two molecules in one such as homo-aza-steroidal esters (HASE) of carboxylic derivatives of N, N-bis (2-chloroethyl) aniline. In this combination, steroidal hormones are employed as carriers for transporting the alkylating agents to specific targeted tissues. Aiming to continue our research, we used alkylating agents, as nitrosoureas, instead of nitrogen mustards.

Cytotoxic effects of a mixed ligand copper(II) chelate complex against a panel of human and murine cancer cells in vitro. Theoretical study of the mechanism of biologic action through molecular modelling.

Purpose: In an effort to discover new compounds with anticancer activity, we have developed a novel copper (II) [Cu(II)] chelate complex with a tridentate ONNSchiff base ligand and the anion of salicylate and we evaluated the in vitro chemosensitivity of various human and murine tumor cell lines by measuring cell growth inhibition. The ultimate goal was to evaluate the existence of a potential antitumor activity of this complex. Beyond the cytotoxic activity assessment of the complex, we aimed at the elucidation of the underlying mechanism of action of this complex and its interactions with biological molecules, carrying out theoretical (quantum-chemical) calculations.

Significant experimental decrease of the hepatocellular carcinoma incidence in C3H/Sy mice after long-term administration of EB1089, a vitamin D analogue.

EB1089, a vitamin D analogue without the acute side effects of 1alpha,25(OH)2D3, the physiologically active form of vitamin D, exerts strong antiproliferative activities in malignant cells, including hepatoma cells in vitro, and in experimental hepatomas in animals as well. It also induces cell cycle arrest and apoptosis in premalignant conditions, suggesting its application in chemopreventive trials. We examined the possible chemopreventive effect of EB1089 on hepatocellular carcinoma (HCC) incidence in C3H/Sy virgin female mice, a strain developing an incidence of 58% spontaneous HCCs.

Histological and ultrastructural study of the effect of chemotherapy with 5-fluorouracil on normal liver of Wistar rats.

Background: In this study, we analysed the histopathological and ultrastructural effects of systemic chemotherapy with 5-fluorouracil (5-FU) on the liver of healthy rats.

Methods: Twenty inbred Wistar rats were used as controls and another 20 rats received a bolus infusion, via the inferior vena cava, of 375 mg/m(2) 5-FU. The animals of each group were sacrificed 16 h, 3 days or 1, 2, 3 and 6 months postoperatively.