Genome-wide <i>in vivo</i> screen identifies novel host regulators of metastatic colonisation

Metastasis is the leading cause of death for cancer patients. This multi-stage process requires tumour cells to survive in the circulation, extravasate at distant sites, then proliferate; it involves contributions from both the tumour cell and tumour microenvironment ('host', which includes stromal cells and the immune system). Studies suggest the early steps of the metastatic process are relatively efficient, with the post-extravasation regulation of tumour growth ('colonization') being critical in determining metastatic outcome. Here we show the results of screening 810 mutant mouse lines using an in vivo assay to identify microenvironmental regulators of metastatic colonization. We identify 23 genes that, when disrupted in mouse, modify the ability of tumour cells to establish metastatic foci, with 19 of these genes not previously demonstrated to play a role in host control of metastasis. The largest reduction in pulmonary metastasis was observed in sphingosine-1-phosphate (S1P) transporter spinster homologue 2 (Spns2)-deficient mice. We demonstrate a novel outcome of S1P-mediated regulation of lymphocyte trafficking, whereby deletion of Spns2, either globally or in a lymphatic endothelial-specific manner, creates a circulating lymphopenia and a higher percentage of effector T cells and natural killer (NK) cells present in the lung. This allows for potent tumour cell killing, and an overall decreased metastatic burden.status: publishe

SIAARTI recommendations for chronic noncancer pain

In this paper are summarized italian guidelines for the treatment of chronic non cancer pai

SIAARTI recommendations for chronic noncancer pain.

PMID: 1709598

SIAARTI recommendations for chronic noncancer pain.

The purpose of these reccomendations is to educate anaesthesia and intensive care specialists to consider CNCP as a disease, rather than a symptom. The aim is to individualize the optimal diagnostic and therapeutic approach, according to the actual model of disease management that focuses on patient's outcome, quality of care, and patient's information and involvement. Anaesthesiologists should be supported in: - individualizing the etiopathological mechanisms of "pain as a disease"; - optimizing the management of "pain as a disease"; - improving both subjective and objective patient's quality of life; - minimizing the number of "nonresponder" patients, related to the therapy and possible complications; - rationalizing the cost of care in order to obtain optimal cost-effectiveness, cost efficiency and cost-quality relationships