Expression of gastrin-releasing peptide receptor in epidermoid carcinoma of the anal canal.

Gastrin-releasing peptide is a neuroendocrine homolog of bombesin that demonstrated important growth-stimulatory effects in various types of cancer. High levels of expression of gastrin-releasing peptide receptors (GRPR) has been found in different malignancies, and the studies exploring the therapeutic use of GRPR antagonists have shown promising results. Our aim was to determine the GRPR expression in epidermoid carcinoma of the anal canal and discuss its potential clinical applications. We performed immunohistochemical analysis for GRPR on formalin-fixed and paraffin-embedded tumor samples obtained from 35 patients with anal cancer. As a control group, we analyzed 24 samples of nonmalignant anal tissues (hemorrhoidectomy specimens). GRPR expression was evaluated using a semiquantitative approach according to the intensity and distribution of staining. All analyzed tissues, except 1 control sample, showed positive GRPR immunoexpression. GRPR was strongly expressed in 54% of cancer specimens as compared with only 12% of the control specimens (P<0.003). In tumors, the receptor showed a diffuse and homogenous pattern of distribution within the specimens. In contrast, control specimens showed a focal pattern of staining restricted to the basal half of the epithelium. In conclusion, we demonstrated that GRPR is highly expressed in epidermoid carcinoma of the anal canal, suggesting this receptor might have a role in anal carcinogenesis. Our results provide a basis for exploiting GRPR as a target for diagnostic and therapeutic purposes in the anal cancer.

Caffeine modulates P50 auditory sensory gating in healthy subjects.

The P50 suppression paradigm is an index of sensory gating assumed to reflect an inhibitory process. Adenosine is a neuromodulator with mostly inhibitory activity that is released by physiological stimuli and can be blocked by non-selective adenosine receptor antagonists such as theophylline and caffeine. A previous study showed that a single dose of theophylline decreased P50 suppression in healthy volunteers. Here we investigated the effect of caffeine (0, 100, 200 and 400 mg p.o.) on P50 sensory gating in 24 healthy volunteers (15 habitual caffeine high-users and 9 low-users). The 200 and 400 mg doses reduced P50 gating, whereas 100 mg produced a non-significant effect. The effect of caffeine was independent of gender and habitual caffeine intake. High caffeine users also showed baseline differences, with lower S(2) amplitudes compared to low-users. These results reinforce the participation of adenosine in the modulation of P50 sensory gating and suggest that caffeine ingestion should be controlled for in the P50 sensory gating paradigm.

Carcinoma da vesícula biliar / Carcinoma of gallbladder

Os autores fazem uma revisão sobre o adenocarcinoma da vesícula biliar abordando aspectos diagnósticos, manifestações clínicas e tratamento.