Abnormal cannabidiol relaxes human pulmonary arteries in an endothelium-independent and endothelium-dependent manner. The latter component is probably mediated via the putative endothelial cannabinoid receptor, activation of which may release endothelium-derived hyperpolarizing factor, which in turn acts via calcium-activated potassium channels. Abnormal cannabidiol is behaviourally inactive; it may have a therapeutic implication in vascular diseases, especially in the treatment of pulmonary hypertension.
Virodhamine relaxes the human pulmonary artery through the putative endothelial cannabinoid receptor and indirectly through a COX-derived vasorelaxant prostanoid formed from the virodhamine metabolite, arachidonic acid. One or both of these mechanisms may stimulate vasorelaxant Ca(2+)-activated K(+) channels.
It has been suggested that interleukin 6 (IL-6) plays a potential role in the growth and progression of tumors, including esophageal cancer (EC). The aim of the study was to compare clinical significance of serum IL-6 with classic tumor markers - carcinoembryonic antigen (CEA) and squamous cell cancer antigen (SCC-Ag) - in EC patients in relation to its histological types - squamous cell carcinoma of esophagus (ESCC) and adenocarcinoma (AD) of esophagus. The study included 53 EC patients and 90 healthy subjects. Serum IL-6 and CEA levels were determined using immunoenzyme assays, while SCC-Ag - chemiluminescent assay. The diagnostic criteria and prognostic values for markers were defined. The levels of all proteins tested in EC, ESCC, and AD were higher than in healthy subjects. The percentage of elevated results was substantially higher for IL-6 (86%) than for CEA (30%) and SCC-Ag (24%) in EC, similarly as in ESCC (87%, 23%, and 33%) and AD (87%, 39%, and 13%, respectively) patients. Concentrations of IL-6 depended on distant metastases and patients' survival in EC and were significantly higher in ESCC patients with more advanced tumor stage and nodal metastases. The IL-6 area under receiver operating characteristic curve (0.92) was larger than for CEA (0.84) and SCC-Ag (0.62) in EC, likewise in ESCC (0.92, 0.87, 0.77) and AD (0.91, 0.79, 0.57, respectively). Our findings indicate better usefulness of IL-6 than classic tumor markers in the diagnosis of EC, especially in patients with ESCC.
The association of p53 abnormalities and bcl-2 protein expression with clinical data and prognosis in 102 patients with resected nonsmall cell lung cancer (NSCLC) was investigated.Deoxyribonucleic acid analysis of exons 5±8 of the p53 gene showed mutations (p53-M) in 47% of resected NSCLC, serum p53 antibodies (p53-Abs) were detected in 25%, p53 protein overexpression (p53-PE) in 54% and bcl-2 protein overexpression (bcl-2-PE) in 48%. A statistically signi®cant association was found between p53-PE, serum p53-Abs and the presence of a p53 gene alteration. No signi®cant associations were found between results of the p53-M, p53-Abs, bcl-2-PE tests and clinicopathological parameters. In the case of the p53-PE test there were signi®cantly fewer positive results for adenocarcinoma than for squamous cell carcinoma and large cell carcinoma.Survival analysis showed that both p53 abnormalities and negative staining for bcl-2, when analysed separately, were associated with poor overall survival. In a multivariate analysis, only the positive result of the p53-M test remained an independent, statistically signi®cant, unfavourable prognostic factor for survival. When the p53 mutation test was removed from the model, positive results of the p53-PE test and the p53-Abs test became statistically signi®cant, unfavourable prognostic factors.To conclude, among p53 and bcl-2 abnormalities, only p53 gene mutations seem to have a strong and independent effect on prognosis. When deoxyribonucleic acid sequence information is not available, p53 protein expression and the presence of p53 antibodies in serum may be used to obtain important prognostic information. Eur Respir J 2001; 17: 660±666.
Our findings suggest the potential usefulness of serum M-CSF concentrations as a tumor marker for EC, especially in combination with SCC-Ag. However, the diagnostic value of this cytokine may be limited because of its non-specific nature.
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