Cachexia or wasting syndrome is loss of weight, muscle atrophy, fatigue, weakness, and significant loss of appetite in someone who is not actively trying to lose weight. The formal definition of cachexia is decrease of body mass, less fatty tissue accumulation that cannot be reversed nutritionally.
A milder form is the unwanted weight loss associated with many medical conditions (see more..)
The disease definition according to a specific consensus conference or to The Diseases Database based on the Unified Medical Language System (NLM)
Also the link to the corresponding Mesh term has to be created
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age, sex, seasonality, etc
- increased TNF alpha production
- increased TNF alpha Receptors sensitivity
PATIENT RISK FACTORS
TISSUE SPECIFIC RISK FACTORS
anatomical (due its structure)
vascular (due to the local circulation)
physiopathological (due to tissue function and activity)
Targeting IL-6 and RANKL signaling inhibits prostate cancer growth in bone.2014
- In prostate cancer metastases to bone, cancer cell-derived cytokines stimulate RANKL expression by cells of the osteoblast lineage, which in turn activates osteoclastic bone resorption. However, it is unclear whether cells of the osteoblast lineage signal back to prostate cancer cells, and if so, whether such direct cross-talk can be targeted therapeutically. Using the human prostate cancer cell line, PC3, we identified two novel signalling pathways acting between cells of the osteoblast lineage and cancer cells. First, exposure to RANKL stimulated the expression and release of IL-6 by PC3 cells in vitro (which is known to promote RANKL expression by osteoblasts). Second, treatment of PC3 cells with IL-6 increased the expression of RANK, the cognate receptor of RANKL, and enhanced the RANKL-induced release of IL-6 by PC3 cells. Third, targeted disruption of IL-6 signaling with tocilizumab, a clinically available antibody against the human IL-6 receptor, inhibited skeletal tumor growth in vivo and reduced serum RANKL levels as well as RANK expression by PC3-derived bone tumors. Similar effects were achieved when RANK expression was knocked down in PC3 cells. In contrast, disruption of IL-6 or RANK/RANKL signalling had no effect on PC3 tumor growth in soft tissues, indicating that these signalling pathways act specifically within the bone microenvironment. In conclusion, prostate cancer cells and cells of the osteoblast lineage communicate via two inter-dependent signaling pathways, which through auto-amplification strongly enhance metastatic prostate cancer growth in bone. Both pathways may be targeted for effective therapeutic intervention.
Histamine enhances interleukin (IL)-1-induced IL-6 gene expression and protein synthesis via H2 receptors in peripheral blood mononuclear cells. 1994
- The regulation of interleukin (IL)-6 synthesis by cAMP-increasing agents remains an unresolved issue. Since an increase in cAMP levels via activation of histamine H2 receptors does not induce IL-1 beta synthesis but enhances self-induction of IL-1 (Vannier, E., and Dinarello, C. A. (1993) J. Clin. Invest. 92, 281-287), we investigated whether histamine regulates IL-6 synthesis. Human peripheral blood mononuclear cells were stimulated with IL-1 alpha in the absence or presence of histamine (1 nM to 100 microM). IL-6 was measured using a specific radioimmunoassay. Histamine alone did not induce protein synthesis or mRNA accumulation for IL-6. Histamine (1-100 microM) enhanced IL-1 alpha-induced synthesis of IL-6 (p < 0.001). Cimetidine and ranitidine, H2 receptor antagonists structurally unrelated to each other, completely reversed the histamine-mediated increase in IL-1 alpha-induced IL-6 synthesis. However, diphenhydramine, an H1 receptor antagonist, did not reverse this effect. Prostaglandin E2, an activator of adenylate cyclase, also enhanced IL-1 alpha-induced synthesis of IL-6. Histamine increased and sustained steady-state levels of IL-6 mRNA in IL-1 alpha-stimulated cells, but reduced IL-6 mRNA half-life (3.5 h versus 1.8 h). Our results indicate that cAMP-increasing agents, such as histamine or prostaglandin E2, fail to induce IL-6 synthesis but rather enhance IL-1-induced IL-6 synthesis.