IntroductionMetastasis remains the major cause for cancer-related death. Hematogenous metastasis comprises multiple steps including tumor cell dissemination through the circulation, arrest in the microvasculature, and ultimately colonization of distant organs. 1,2 The known inefficiency of the metastatic process implies that tumor cells are very limited in ability to colonize and to grow in healthy tissues of distant organs. 3 Thus, tumor cells survive and proliferate at distant sites only within a favorable microenvironment. 3 Cell-cell interactions among tumor cells, platelets, leukocytes, and endothelial cells were shown to contribute to the enhanced tumor cell survival and to the facilitation of hematogenous metastasis. 3,4 Platelet association with intravascular tumor cells enhances hematogenous dissemination and protects tumor cells from immune-mediated clearance. 5,6 Activated platelets release cytokines and present surface molecules, which are able to activate endothelial cells. 7 Several cell adhesion molecules including glycoprotein IIb/IIIa integrin and P-selectin are known to mediate platelet-tumor cell interactions and facilitate metastasis. 8,9 In addition, activated platelets are commonly observed in the circulation of cancer patients. 10 Although the contribution of leukocytes to the formation of primary tumors is well recognized, mechanisms by which leukocytes govern the process of metastasis remains poorly understood. 11,12 Depending on the microenvironmental signals, leukocytes can either exert antitumoral activity or promote cancer progression. 12 Tumor-associated myeloid cells including polymorphonuclear leukocytes (PMNs), monocytes, as well as differentiated macrophages were shown to facilitate immunosuppression, angiogenesis, tumor cell survival, and invasion and thereby contribute to metastatic dissemination. 11,12 Previously, we showed that the absence of L-selectin results in an attenuation of tumor cell survival and metastasis, implicating leukocytes in the colonization process. 13,14 Activation of the endothelium is observed both in advanced cancer patients and within the microenvironment of experimentally metastasizing tumor cells. [15][16][17] Activated microvascular endothelial cells increase the expression of cell adhesion molecules and the production of chemokines, which leads to a recruitment of leukocytes, neutrophils, and monocytes. 18 The activated state of endothelial cells is reflected in increased levels of soluble endothelial cell adhesion molecules, for example, E-selectin and vascular cell adhesion molecule 1 (VCAM-1), as found in the serum of colorectal cancer patients. 17 In a mouse model of liver metastasis, sinusoidal microvascular endothelial cells were activated upon interaction of colorectal tumor cells with resident Kupffer cells. 15 Inhibition of endothelial activation was shown to attenuate metastasis in several mouse models. 4,16,19 By contrast, experimental activation of the endothelium by the administration of cytokines prior to the inoculation of tumor cel...

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Background: Plasma concentrations of B-type natriuretic peptide (BNP) and N-terminal proBNP (NTproBNP) are diagnostic and prognostic biomarkers of heart failure and are also increased in patients with chronic kidney disease (CKD). We examined the relevance of BNP and NT-proBNP as predictors of CKD progression. Methods: Of 227 nondiabetic patients with mild-tomoderate renal insufficiency, 177 patients ages 18 -65 years were followed in a prospective multicenter cohort study for a period of <7 years. CKD progression was assessed by recording renal endpoints, defined as doubling of baseline serum creatinine or end-stage renal disease (ESRD) requiring renal replacement therapy. Results: BNP and NT-proBNP were significantly higher among 65 patients who reached the combined renal endpoint than among the 112 who did not [median

In viral meningitis the inflammatory response involves activated T cells and monocytes which are recruited into the subarachnoid space. To identify the chemotactic signals attracting the cells to the site of infection in the meninges, we measured the levels of two CXC chemokines, interferon-gamma (IFN-gamma) inducible protein (IP)-10 and monokine induced by IFN-gamma, four CC chemokines, monocyte chemotactic protein (MCP)-1, RANTES, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, as well as the cytokines interleukin (IL)-15 and IL-16 in the cerebrospinal fluid (CSF) of patients suffering from viral meningitis. The results point to an involvement of two chemokines, MCP-1 and IP-10, since (1) unlike the other cytokines, MCP-1 and IP-10 were present in 97% and 79% of the CSF, respectively, at concentrations sufficient to induce chemotaxis of mononuclear cells; (2) more than 90% of the CSF of viral meningitis induced chemotaxis of peripheral blood mononuclear cells (PBMC) and all of them induced chemotaxis of activated T cells, and (3) the CSF-mediated chemotaxis of PBMC was inhibited by anti-MCP-1 antibodies and chemotaxis of activated T cells was abolished by the combination of anti-MCP-1 and anti-IP-10 antibodies. Our data provide evidence that MCP-1 and IP-10 lead to accumulation of activated T cells and monocytes in the CSF compartment in viral meningitis.