Metástasis intracanalicular de la vía biliar por carcinoma colorrectal como causa de ictericia obstructiva / Intracanalicular metastasis of biliary tract from colorectal carcinoma as cause of obstructive jaundice

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Role of reactive oxygen species in apoptosis: implications for cancer therapy.

Reactive oxygen species are widely generated in biological systems. Consequently humans have evolved antioxidant defence systems that limit their production. Intracellular production of active oxygen species such as *OH, O2- and H2O2 is associated with the arrest of cell proliferation. Similarly, generation of oxidative stress in response to various external stimuli has been implicated in the activation of transcription factors and to the triggering of apoptosis. Here we review how free radicals induce DNA sequence changes in the form of mutations. deletions, gene amplification and rearrangements. These alterations may result in the initiation of apoptosis signalling leading to cell death, or to the activation of several proto-oncogenes and or the inactivation of some tumour suppressor genes. The regulation of gene expression by means of oxidants, antioxidants and the redox state remains as a promising therapeutic approach. Several anticarcinogenic agents have been shown to inhibit reactive oxygen species production and oxidative DNA damage, inhibiting tumour promotion. In addition, recombinant vectors expressing radical-scavenging enzymes reduce apoptosis. In conclusion, oxidative stress has been implicated in both apoptosis and the pathogenesis of cancer providing contrived support for two notions: free radical reactions may be increased in malignant cells and oxidant scavenging systems may be useful in cancer therapy.

Antioxidant enzymatic activities in human blood cells after an allergic reaction to pollen or house dust mite.

Several diseases have been related to oxidative stress. Recently, antioxidant functions have also been linked to anti-inflammatory properties. Cell defenses against reactive oxygen species include antioxidant enzymes. We studied the enzymatic antioxidant capacity in human blood of both red blood and mononuclear cells from patients suffering from an allergic reaction to pollen or house dust mite. We determined superoxide dismutases (SODs), glutathione peroxidase (GSHPx) and catalase (CAT) activities in each cell type. We also determined the extent of thiobarbituric acid reactive substances (TBARS), in order to study the correlation between the cellular enzymatic activities, the redox status and the disease. In mononuclear cells from allergic patients, SODs and CAT activities were enhanced compared to controls. Conversely, a decrease in GSHPx activity was found. In erythrocytes, higher values for GSHPx and SODs and similar CAT activities were found in allergic patients and controls. Interestingly, CuZnSOD and MnSOD activities were enhanced in the same proportion for both, erythrocytes and mononuclear cells. TBARS were also enhanced in both types of cells. The respective enzymatic imbalances in mononuclear cells and erythrocytes, namely, GSHPx/SOD and CAT/SOD, and their consequences are discussed. To our knowledge, this is the first global study of antioxidant enzymes, including TBARS level determinations, in allergy.

Emergency subtotal colectomy as treatment of choice in obstructing carcinomas of the left colon.

PURPOSE: To assess the morbidity, mortality and function following emergency subtotal colectomy (ESC) with primary anastomosis in obstructing carcinomas of the left colon, to determine whether this technique is warranted as the current treatment of choice for this condition. METHODS: Retrospective review of a series of 70 patients with obstructing carcinomas of the left colon who underwent an ESC with primary anastomosis between September 1989 and December 1996. Morbidity, mortality, hospital stay and functional results were analysed, as well as the percentage of patients submitted to this technique. RESULTS: The use of ESC has steadily increased at our institution over the last few years, from 22% in 1990 to 84% of all the procedures performed for obstructing carcinomas of the left colon in 1995. The mortality rate of the series was 4.2%. Anastomotic leak rate was 10%, with only three major leaks. A prolonged obstructive ileus was a frequent and distressing complication (26%), and the main determinant of hospital stay. Average daily stool frequency on discharge from hospital was of 2 (range 1-6), with many patients having discontinued anti-diarrhoeal medications. CONCLUSION: Emergency SC with primary anastomosis has evolved into the treatment of choice for most patients with acutely obstructing malignancies of the left colon at our institution. It can be performed with low mortality, a reasonable morbidity and good functional results.

Vinca alkaloids enhance the half-life of tumour ornithine decarboxylase.

Naturally occurring vinca alkaloids, vincristine and vinblastine, at micromolar concentrations enhanced the ornithine decarboxylase activity in a dose-response manner in primary cultures of Ehrlich ascites carcinoma cells. After 8 h of culture in the presence or absence of vinblastine, cycloheximide was added to the medium, a 4.5-fold increase in the half-life of the ornithine decarboxylase activity was observed in vinblastine-treated cells. This effect is probably due to the inhibition of the intracellular enzyme degradation by the vinca alkaloids.

Chlorpheniramine inhibits the ornithine decarboxylase induction of Ehrlich carcinoma growing in vivo.

The antihistaminic (+/-)-chlorpheniramine significantly reduced the progression of Ehrlich carcinoma when it was administered at 0.5 mg/mouse/day from the third day on, after tumour inoculation. The ODC activity of tumour cells was diminished by 70% on day 7 after tumour transplantation, when maximum ODC activity is detected in non-treated tumour growing 'in vivo'. Northern blot analyses indicated that the inhibitory effect of this 1,4-diamine takes place at a post-transcriptional level. Results obtained from serum-free cultured cells indicated that chlorpheniramine inhibits the ODC synthesis rate.

Histamine and serotonin inhibit induction of ornithine decarboxylase by ornithine in perifused Ehrlich ascites tumour cells.

Ornithine induced more than 36-fold the ornithine decarboxylase activity in confined Ehrlich ascites tumour cells after 3.5 h of continuous perifusion with 0.5 mM ornithine; arginine and glutamine also induced the activity 3- and 4-fold, respectively. The addition of cycloheximide or actinomycin D antibiotics to the perifusion medium confirmed that the regulation of the enzyme synthesis takes place at the level of translation. Perifusion in the presence of 0.5 mM ornithine and 55, 25, and 10 microM histamine suppressed the induction by 91, 53, and 35% respectively. Similar results were obtained in the presence of serotonin. Histidine also showed inhibitory effect but 5 mM histidine was required to produce 21% inhibition; other basic amino acids were ineffective.

Contribution by host tissues to circulating glutamine in mice inoculated with Ehrlich ascites tumor cells.

Twenty-four h after tumor transplantation increases of free glutamine in plasma, liver, and kidney occurred simultaneously with the exponential phase of tumor growth. Kidney and muscle glutamine synthetase also increased in the first 2 days following tumor transplantation, while kidney and liver glutaminases decreased. The levels of free glutamine in plasma and tissues, and the activities of glutamine synthetase and glutaminase, tended to approach normal values in the last days of life of the tumor-transplanted animals. Eleven days after transplantation, liver glutamine synthetase activity diminished. The results are discussed in terms of a glutamate/glutamine intercellular cycle which could augment the circulating glutamine, the main source of nitrogen for tumor cells.

Variability between and within laboratories in the analysis of structural chromosomal abnormalities.

The frequency of structural chromosomal aberrations in two samples (AM and PM of the same day) from each of nine normal subjects, cultured in two different laboratories, was studied by six observers. The results were analyzed in order to determine the relative importance of inter- and intralaboratory factors in the variability of chromosomal abnormalities. In addition to the difference in the frequency of the abnormalities between the subjects studied, there were differences due to observers from different laboratories (P less than 0.01), as well as between laboratories (P less than 0.01). These results could be explained in part by insufficient agreement between observers from different laboratories and by differences in the quality of the method used.