Spatial distribution of mast cells around vessels and glands in human gastric carcinoma

The spatial distribution of mast cells inside the tumor stroma has been little investigated. In this study, we have evaluated tumor mast cells (MCs) distribution in gastric cancer through the analysis of the morphological features of the spatial patterns generated by these cells, including size, shape, and architecture of the cell pattern. The pattern of distribution of tryptase- and chymase-positive MCs around the blood vessels and gastric glands in human gastric adenocarcinoma samples was investigated by immunohistochemical techniques and by introducing a quantitative approach to characterize the spatial distribution of MCs. In human gastric cancer, both chymase-positive MC and vessels exhibited significant deviations from randomness for what it concerns their spatial relationship with gastric parenchyma. As indicated by cell-to-gland distances shorter than expected by chance, in grade II samples a preferential localization of chymase-positive MC near the gastric glands was observed. Interestingly, the same type of spatial association was exhibited by vessels in grade IV samples, where vessel-to-gland distances shorter than expected by chance were observed. These two findings allow to speculate about a sequence of events in which a subpopulation of MC is first recruited around gastric parenchyma to drive the subsequent development of a vascular support to the tissue.     

Liver transplantation for hepatocellular cancer: should the current indication criteria be changed?

Liver transplantation (LTx) is the best treatment for hepatocellular carcinoma (HCC), but should be offered only to selected patients. The usual procedure is to transplant only for small and unilobular tumors. The aim of this paper is to verify whether the actual indication criteria are still justified. The details of 121 patients with HCC who were submitted to LTx from 1985 to 2000 were analyzed. Age, gender, liver disease, Child class, alpha-fetoprotein (AFP) level, presence of tumor capsule, vascular invasion, size and number of nodules, histological grade, and pTNM were considered. The 5- and 10-year actuarial survival rates were 61.7% and 53.1%. Freedom from recurrence was 85.9% and 85.9%, respectively. At univariate analysis, size, presence of capsule, AFP levels, vascular invasion, grade, pTNM, transarterial chemoembolization (TACE), Child class, and age were all significantly related to survival and/or cancer recurrence. Presence of capsule, AFP levels, and viral cirrhosis were independent variables in Cox's analysis for survival, whereas histological grade, AFP levels, and vascular invasion were significant independent variables for recurrence. In conclusion, a strict selection should be made to optimize graft allocation while size and multifocality should probably no longer be considered a contraindication for LTx. Histological grade, AFP levels, and vascular invasion, as indicator of tumor behavior, more likely reflect the risk of recurrence.     

HIV-1 matrix protein p17 binds to the IL-8 receptor CXCR1 and shows IL-8-like chemokine activity on monocytes through Rho/ROCK activation

Exogenous HIV-1 matrix protein p17 was found to deregulate biologic activities of many different immune cells that are directly or indirectly involved in AIDS pathogenesis after binding to unknown cellular receptor(s). In particular, p17 was found to induce a functional program in monocytes related to activation and inflammation. In the present study, we demonstrate that CXCR1 is the receptor molecule responsible for p17 chemokine-like activity on monocytes. After CXCR1 binding, p17 was capable of triggering rapid adhesion and chemotaxis of monocytes through a pathway that involved Rho/ROCK. Moreover, CXCR1-silenced primary monocytes lost responsiveness to p17 chemoattraction, whereas CXCR1-transfected Jurkat cells acquired responsiveness. Surface plasmon resonance studies confirmed the capacity of p17 to bind CXCR1 and showed that the p17/CXCR1 interaction occurred with a low affinity compared with that measured for IL-8, the physiologic CXCR1 ligand. In all of its activities, p17 mimicked IL-8, the natural high-affinity ligand of CXCR1. Recent studies have highlighted the role of IL-8 and CXCR1 in HIV-1 replication and AIDS pathogenesis. Our findings herein call for an exploration of the therapeutic potential of blocking the p17/IL-8/CXCR1 axis in HIV-1 infection.