Biomedical subjects

L Rodríguez-Fragoso

Publications and source records attributed to L Rodríguez-Fragoso.

6 recordsLinked to original sources

PubMed2001

Expression of urokinase-type plasminogen activator in an experimental model of hepatocarcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Molecular genetic analyses have clarified that accumulation of genome changes provides important steps in carcinogenesis. Urokinase type plasminogen activator (uPA) forms part of an important enzymatic system that degraded the extracellular matrix in process of invasion and metastasis. In order to study the kinetics of uPA cellular expression during this process, we used specific polyclonal antibodies against uPA in an immunohistochemistry assay in liver sections from a HCC in rats. The neoplastic transformation induced with this model was preceded by the appearance of numerous hyperplastic nodules during early stages, after time lesions progressed to well-differentiated HCC. The morphological changes of premalignant and malignant lesions were associated with a progressive increment of uPA expression, which reached its peak at 5 and 6 months after the administration of the carcinogenic drugs. Of the enzymatic markers analyzed, the gamma glutamyl transpeptidase showed correlationship with the histological findings. Our results suggest that the increase in the uPA expression should not only be considered as the hallmark of metastasis, but may also be related to early events in the neoplastic transformation and with the proliferation of vessels and biliary ducts.

Animals↗

PubMed1999

Acetaldehyde increases the activity and gene expression of urokinase type plasminogen activator in a hepatic stellate cell line.

The aim of this study was to investigate the effect of acetaldehyde on the activity and expression of urokinase type plasminogen activator gene in a clone of hepatic stellate cells. CFSC-2G cells showed typical morphological changes of the stellate cell activation, which were accompanied by an increase in the amount of collagen with all doses of acetaldehyde used. The treatment of the cells with doses of 100 and 175 micromol/l acetaldehyde, produced an increase in the urokinase type plasminogen activator activity not only in the cell extract, but also in conditioned medium. However, the use of higher doses of acetaldehyde (250 and 350 micromol/l) produced an inhibitory effect on the urokinase type plasminogen activator activity. In contrast, the higher urokinase type plasminogen activator gene expression was observed with doses of 175, 250, and 350 micromol/l. Our results shown that acetaldehyde induced changes in synthesis, release, and expression of urokinase type plasminogen activator in CFSC-2G cells. Those findings suggest that the alterations in the synthesis and expression of the urokinase type plasminogen activator might be another event associated to the activation of hepatic stellate cell after exposure to hepatotoxic agents like-acetaldehyde. The role of urokinase type plasminogen activator in fibrogenesis was analyzed.

Acetaldehyde↗

PubMed1995

Interferon-alpha 2b increases fibrolysis in fibrotic livers from bile duct ligated rats: possible participation of the plasminogen activator.

Interferons are known to prevent liver collagen by an antifibrogenic mechanism that involves mRNA procollagen regulation. The aim of the present work was to determine whether interferon could also decrease collagen by increasing its degradation. Fibrosis was induced in male Wistar rats by double ligation and section of the common bile duct. Interferon-alpha 2b (100,000 IU/rat s.c.) was administered to bile duct ligated rats daily after surgery for 4 weeks. Interferon increased the capacity of the liver to degrade type I and III collagens and matrigel. In addition, the plasminogen activator activity also increased. Since plasminogens are thought to be key participants in the balance of proteolytic activities that regulate extracellular matrix degradation, their elevation may also provide another antifibrotic (proteolytic) mechanism of action of interferon.

Animals↗

PubMedDate not supplied

Trimethylcolchicinic acid decreases liver fibrosis and cholestasis induced by prolonged biliary obstruction in the rat.

Colchicine is effective in decreasing hepatic fibrosis. However, several toxic reactions have been reported after colchicine treatment which are attributed to its ability to bind tubulin. The aim of this work is to determine if trimethylcolchicinic acid, which does not bind tubulin, is able to decrease experimental liver fibrosis and cholestasis. In male Wistar rats, the common bile duct was ligated. Administration of trimethylcolchicinic acid (TMCA, 100 micrograms rat-1 day-1, p.o.) began 4 weeks after biliary obstruction and continued for a further 4 weeks. The liver was used for histological and ultrastructural analysis and for collagen quantification (hydroxyproline content). The degradation of Matrigel and collagen (types I and III), as well as plasminogen activator activity, was determined in liver homogenates. Bilirubins and enzyme activities were measured in serum. Trimethylcolchicinic acid was able to improve normal liver histology, ultrastructure, collagen content and biochemical markers of liver damage. It also increased matrigel degradation and plasminogen activator activity. The mechanism of TMCA is probably associated with its ability to increase Matrigel degradation; however, other actions cannot be discarded.

Alkaline Phosphatase↗

PubMedDate not supplied

[Gene therapy].

In the last years there has been much progress in our understanding of molecular mechanisms in the pathogenesis of disease. In this review we provide an overview of gene therapy, its most actualized techniques for gene delivery, and we give specific examples of laboratory and clinical achievements to date. The development of methods for delivering genes to mammalian cells has stimulated great interest in the possibility of treating human disease by gene-based therapies. As a result, concepts and methods that would have been considered purely science fiction 50 years ago are now used in the treatment of diseases. The widespread application of gene therapy technology to many diseases is already breaking down the traditional boundaries of modern medicine. However, despite its progress, several key technical drawbacks need to be overcome before gene therapy can be used safely and effectively in clinical settings. Technological developments, particularly in the areas of gene delivery and cell transplantation, will be critical for the successful practice of gene therapy.

Forecasting↗

PubMedDate not supplied

[Physiologic and physiopathologic role of hepatocyte growth factor].

Hepatocyte growth factor (HGF), originally described as an hepatocyte specific mitogen, has been shown to be a potent stimulator of DNA synthesis in a wide variety of cell types. In addition to its mitogenic effect, HGF has the unique ability to transmit information that determines the spatial organization of epithelial cells in tissues as well as induce cell migration and invasion of extracellular matrix in a variety of epithelial cells. HGF is involved in physiological processes like embryogenesis and development, and also in pathophysiological process as regeneration and carcinogenesis. Although the role that HGF plays in liver cancer is not clear, the findings strongly suggest that it influences the malignant cells. The present paper shows a review on the advances in the knowledge of HGF in physiological processes and in those related to liver diseases.

Extracellular Matrix↗