4 research outputs found
Cachexia-associated adipose tissue morphological rearrangement in gastrointestinal cancer patients
Background and aims: Cachexia is a syndrome characterized by marked involuntary loss of body weight. Recently, adipose tissue (AT) wasting has been shown to occur before the appearance of other classical cachexia markers. We investigated the composition and rearrangement of the extracellular matrix, adipocyte morphology and inflammation in the subcutaneous AT (scAT) pad of gastrointestinal cancer patients. Methods: surgical biopsies for scAT were obtained from gastrointestinal cancer patients, who were signed up into the following groups: cancer cachexia (CC, nâ=â11), weightâstable cancer (WSC, nâ=â9) and weightâstable control (nonâcancer) (control, nâ=â7). The stable weight groups were considered as those with no important weight change during the last year and body mass index <25âkg/m2. Subcutaneous AT fibrosis was quantified and characterized by quantitative PCR, histological analysis and immunohistochemistry. Results: the degree of fibrosis and the distribution and collagen types (I and III) were different in WSC and CC patients. CC patients showed more pronounced fibrosis in comparison with WSC. Infiltrating macrophages surrounding adipocytes and CD3 Ly were found in the fibrotic areas of scAT. Subcutaneous AT fibrotic areas demonstrated increased monocyte chemotactic protein 1 (MCPâ1) and Cluster of Differentiation (CD)68 gene expression in cancer patients. Conclusions: our data indicate architectural modification consisting of fibrosis and inflammatory cell infiltration in scAT as induced by cachexia in gastrointestinal cancer patients. The latter was characterized by the presence of macrophages and lymphocytes, more evident in the fibrotic areas. In addition, increased MCPâ1 and CD68 gene expression in scAT from cancer patients may indicate an important role of these markers in the early phases of cancer
Social Preferences and the Efficiency of Bilateral Exchange
Under what conditions do social preferences, such as altruism or a concern for fair outcomes, generate efficient trade? I analyze theoretically a simple bilateral exchange game: Each player sequentially takes an action that reduces his own material payoff but increases the other playerâs. Each playerâs preferences may depend on both his/her own material payoff and the other playerâs. I identify necessary conditions and sufficient conditions on the playersâ preferences for the outcome of their interaction to be Pareto efficient. The results have implications for interpreting the rotten kid theorem, gift exchange in the laboratory, and gift exchange in the field
Cachexia causes timeâdependent activation of the inflammasome in the liver
Abstract Background Cachexia is a wasting syndrome associated with systemic inflammation and metabolic disruption. Detection of the early signs of the disease may contribute to the effective attenuation of associated symptoms. Despite playing a central role in the control of metabolism and inflammation, the liver has received little attention in cachexia. We previously described relevant disruption of metabolic pathways in the organ in an animal model of cachexia, and herein, we adopt the same model to investigate temporal onset of inflammation in the liver. The aim was thus to study inflammation in rodent liver in the wellâcharacterized cachexia model of Walker 256 carcinosarcoma and, in addition, to describe inflammatory alterations in the liver of one cachectic colon cancer patient, as compared to one control and one weightâstable cancer patient. Methods Colon cancer patients (one weight stable [WSC] and one cachectic [CC]) and one patient undergoing surgery for cholelithiasis (control, n = 1) were enrolled in the study, after obtainment of fully informed consent. Eightâweekâold male rats were subcutaneously inoculated with a Walker 256 carcinosarcoma cell suspension (2 Ă 107 cells in 1.0 mL; tumourâbearing [T]; or phosphateâbuffered salineâcontrols [C]). The liver was excised on Days 0 (n = 5), 7 (n = 5) and 14 (n = 5) after tumour cell injection. Results In rodent cachexia, we found progressively higher numbers of CD68+ myeloid cells in the liver along cancerâcachexia development. Similar findings are described for CC, whose liver showed infiltration of the same cell type, compared with both WSC and control patient organs. In advanced rodent cachexia, hepatic phosphorylated câJun Nâterminal kinase protein content and the inflammasome pathway protein expression were increased in relation to baseline (P < 0.05). These changes were accompanied by augmented expression of the active interleukinâ1β (ILâ1β) form (P < 0.05 for both circulating and hepatic content). Conclusions The results show that cancer cachexia is associated with an increase in the number of myeloid cells in rodent and human liver and with modulation of hepatic inflammasome pathway. The latter contributes to the aggravation of systemic inflammation, through increased release of ILâ1β