Excessive adiposity has long been associated with increased incidence of breast cancer in postmenopausal women, as well as with increased mortality of breast cancer, regardless of menopausal status. While adipose tissue-derived estrogen contributes to obesity-associated risk for estrogen receptor (ER)-positive breast cancer, the estrogen-independent impact of adipose tissue on tumor invasion and progression remains to be elucidated. Here we show that adipose stromal cells (ASCs) significantly stimulate migration and invasion of ER-negative breast cancer cells in vitro and tumor invasion in a co-transplant xenograft mouse model. Our study also identifies cofilin-1, a known regulator of actin dynamics, as a determinant for the tumor-promoting activity of ASCs. The cofilin-1-dependent pathway affects the production of interleukin 6 (IL-6) in ASCs. Depletion of IL-6 from ASC-conditioned medium abrogated the stimulatory effect of ASCs on the migration and invasion of breast tumor cells. Thus, our work uncovers a link between cytoskeleton-based pathway in ASCs and the stromal impact on breast cancer cells.

No abstract

Several nutrition, food and dietary compounds have been suggested to be involved in the onset and maintenance of depressive disorders and in the severity of depressive symptoms. Nutritional compounds might modulate depression associated biomarkers and parallel the development of depression, obesity and diabetes. In this context, recent studies revealed new mediators of both energy homeostasis and mood changes (i.e. IGF-1, NPY, BDNF, ghrelin, leptin, CCK, GLP-1, AGE, glucose metabolism and microbiota) acting in gut brain circuits. In this context several healthy foods such as olive oil, fish, fruits, vegetables, nuts, legumes, poultry, dairy and unprocessed meat have been inversely associated with depression risk and even have been postulated to improve depressive symptoms. In contrast, unhealthy western dietary patterns including the consumption of sweetened beverage, refined food, fried food, processed meat, refined grain, and high fat diary, biscuits, snacking and pastries have been shown to be associated with an increased risk of depression in longitudinal studies. However, it is always difficult to conclude a real prospective causal relationship from these mostly retrospective studies as depressed individuals might also change their eating habits secondarily to their depression. Additionally specific selected nutritional compounds, e.g. calcium, chromium, folate, PUFAs, vitamin D, B12, zinc, magnesium and D-serine have been postulated to be used as ad-on strategies in antidepressant treatment. In this context, dietary and lifestyle interventions may be a desirable, effective, pragmatical and non-stigmatizing prevention and treatment strategy for depression. At last, several medications (pioglitazone, metformin, exenatide, atorvastatin, gram-negative antibiotics), which have traditionally been used to treat metabolic disorders showed a certain potential to treat depression in first randomized controlled clinical trials.

Right lobe living donor liver transplantation (LD-LTx) is currently performed at an increasing number of transplant centers. Donor selection, donor safety, donor recovery, and postdonation psychological impairment are essential criteria to determine whether and under which conditions LD-LTx is justifiable. Before commencing the LD-LTx program, approval was obtained from the local ethics committee. Potential donors underwent a comprehensive multistep evaluation protocol to exclude any conditions that could lead to an increased operative risk. Each donation was approved by the local Living Donation Commission. Follow-up investigations were performed after 6 and 12 months. Liver regeneration was assessed by computed tomography scan and magnetic resonance imaging scan derived volumetries. Quality of life (QOL) was investigated according to the Anamnestic Comparative Self-Assessment Scale (ACSA) before donation, and 6 and 12 months after donation. As of December 2001,43 right lobe living donations have been performed at the Charit& Campus Virchow, Berlin. None of the donors died or has suffered life-threatening or persisting complications. All patients recovered completely. Complications occured in 8 donors (18%). The incidence of perioperative surgical complications was g%, comprising temporary biliary leakages (n = 3; 6.8%) as well as postoperative bleeding (n = 1). Liver volume regeneration approximated 72% 2 15% of predonation volume by 6 months and 85% k 18% (mean 2 SD) by 12 months. There was no evidence of significant psychological impairment after donation. QOL increased after donation compared with the preoperative state (P < .OS). In our experience, LDLTx has proven to be a practicable and safe procedure. However, there is a considerable risk of postoperative complications. The donor selection process plays a pivotal role in preventing complications. The discussion of potential risks, especially potential life-threatening risks, must be an integral part of informed consent. (Liver Transpl2002;8:829-83%)

Consuming a calorically dense diet stimulates microglial reactivity in the mediobasal hypothalamus (MBH) in association with decreased number of appetite-curbing pro-opiomelanocortin (POMC) neurons; whether the reduction in POMC neuronal function is secondary to the microglial activation is unclear. Here we show that in hypercaloric diet-induced obese mice, persistently activated microglia in the MBH hypersecrete TNFα that in turn stimulate mitochondrial ATP production in POMC neurons, promoting mitochondrial fusion in their neurites, and increasing POMC neuronal firing rates and excitability. Specific disruption of the gene expressions of TNFα downstream signals TNFSF11A or NDUFAB1 in the MBH of diet-induced obese mice reverses mitochondrial elongation and reduces obesity. These data imply that in a hypercaloric environment, persistent elevation of microglial reactivity and consequent TNFα secretion induces mitochondrial stress in POMC neurons that contributes to the development of obesity.