Kinin-B1 receptors in ischaemia-induced pancreatitis: Functional importance and cellular localisation

In this study we compare the role of kininB1 and B2 receptors during ischaemia/reperfusion of rat pancreas. Our investigations were prompted by the observation that infusion of a kininB2 receptor antagonist produced significant improvement in acute experimental pancreatitis. In an acute model with two hours of ischaemia/two hours of reperfusion, application of the kininB1 receptor antagonist (CP-0298) alone, or in combination with kininB2 receptor antagonist (CP-0597), significantly reduced the number of adherent leukocytes in postcapillary venules. In a chronic model with five days of reperfusion, the continuous application of kininB1 receptor antagonist or a combination of kininB1 and B2 receptor antagonists markedly reduced the survival rate. In kininreceptor binding studies kininB1 receptor showed a 22-fold increase in expression during the time of ischaemia/ reperfusion. Carboxypeptidase M activity was upregulated 10-fold following two hours of ischaemia and two hours of reperfusion, provided the appropriate specific ligand, desArg10-kallidin and/or desArg9-bradykinin, was used. The occurrence of kininB1 receptor binding sites on acinar cell membranes was demonstrated by microautoradiography. With a specific antibody, the localisation of kininB1 receptor protein was confirmed at the same sites. In conclusion, we have demonstrated the upregulation of the pancreatic acinar cell kininB1 receptors during ischaemia/reperfusion. The novel functional finding was that antagonism of the kininB1 receptors decreased the survival rate in an experimental model of pancreatitis

Prolactin receptor is a negative prognostic factor in patients with squamous cell carcinoma of the head and neck

Background: The influence of human prolactin (hPRL) on the development of breast and other types of cancer is well established. Little information, however, exists on the effects of hPRL on squamous cell carcinomas of the head and neck (SCCHNs). Methods: In this study, we evaluated prolactin receptor (PRLR) expression in SCCHN cell lines and assessed by immunohistochemistry the expression in 89 patients with SCCHNs. The PRLR expression was correlated with clinicopathological characteristics as well as clinical outcome. The effect of hPRL treatment on tumour cell growth was evaluated in vitro. Results: Immunoreactivity for PRLR was observed in 85 out of 89 (95%) tumours. Multivariate COX regression analysis confirmed high levels of PRLR expression (>25% of tumour cells) to be an independent prognostic factor with respect to overall survival (HR=3.70, 95% CI: 1.14–12.01; P=0.029) and disease-free survival (P=0.017). Growth of PRLR-positive cancer cells increased in response to hPRL treatment. Conclusion: Our data indicate that hPRL is an important growth factor for SCCHN. Because of PRLR expression in a vast majority of tumour specimens and its negative impact on overall survival, the receptor represents a novel prognosticator and a promising drug target for patients with SCCHNs