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Background: Cancer cells require nutrients to survive in the unfavorable microenvironment of primary solid tumors or metastases before angiogenesis development. Fatty acid synthase (FASN) is a multi-enzyme protein that catalyzes fatty acid synthesis. Expression levels of FASN are low or undetectable in normal human tissues except for the liver and the adipose tissue. In contrast, high levels of FASN expression have been detected in breast cancer tumors and other human carcinomas. Several reports highlight that FASN overexpression in tumor samples correlates with progression, aggressiveness and metastatic potential of the disease. In addition, some studies have suggested the same correlation with serum levels of FASN. Our aim was to analyze the association between the expression of tumor and serum levels of FASN with clinical and pathological prognostic factors in early-stage breast cancer patients. Methods: Fifty-five patients with early-stage breast cancer treated with surgery and postoperative chemotherapy were included in the study. We prospectively measured the levels of FASN in tumor and serum samples. Clinical data included demographic characteristics, menarche, pregnancy, breast feeding, menopausal status and body mass index (BMI). Pathological and molecular data included: pathological state, histological grade, estrogen and progesterone receptors, HER2 status, p53 mutation and Ki 67 levels. FASN tissue expression levels were determined by IHC and circulating FASN levels were determined by ELISA. FASN expression was graded from 0 to 3+, meaning 0--1+ normal amounts of FASN protein compared to non-tumor breast tissue, 2+ moderate amounts and 3+ the highest levels of FASN expression. Baseline characteristics were summarized descriptively. Categorical variables were compared by c² or Fisher's exact. For continuous variables, if the data are approximately normal, the two groups were compared using ANOVA. If the normality assumption is not warranted, then the Kruskall-Wallis test has been used. Results: Median age was 49 (rage 33-77). 51% of the patients were menopausal and median BMI was 24,75. Thirty-four percent of the patients had stage I, 51% stage II and 15% stage III. We observed a statistically significant association between FASN over expression and the lack of progesterone receptors (p = 0.027) in tumor samples. In contrast, we found no relation between FASN and estrogen receptor nor between FASN and HER2 tumor expression in this setting. Menopause and age were strongly related to higher levels of FASN tumor expression (p < 0.001). Patients with higher BMI had higher levels of FASN in tumor tissue although this association was not statistically significant (p = 0.07). Finally, we observed a positive relation between breast cancer stage and the levels of FASN tumor (p = 0.05). In contrast, circulating FASN levels were not associated with any pathological or clinical prognostic factor. Conclusions: Our study suggests that FASN overexpression is significantly related to age, menopausal status, more advanced stages and lack of progesterone receptor expression in early-stage breast cancer patients. However, no relation between serum levels of FASN and the clinical or molecular prognostic factors have been observed. [ABSTRACT FROM AUTHOR]

Background/aims: Obesity is characterized by the immune activation that eventually dampens insulin sensitivity and changes metabolism. This study explores the impact of different inflammatory/ anti-inflammatory paradigms on the expression of toll-like receptors (TLR) found in adipocyte cultures, adipose tissue, and blood., Methods: We evaluated by real time PCR the impact of acute surgery stress in vivo (adipose tissue) and macrophages (MCM) in vitro (adipocytes). Weight loss was chosen as an anti-inflammatory model, so TLR were analyzed in fat samples collected before and after bariatric surgery-induced weight loss. Associations with inflammatory and metabolic parameters were analyzed in non-obese and obese subjects, in parallel with gene expression measures taken in blood and isolated adipocytes/ stromal-vascular cells (SVC). Treatments with an agonist of TLR3 were conducted in human adipocyte cultures under normal conditions and upon conditions that simulated the chronic low-grade inflammatory state of obesity., Results: Surgery stress raised TLR1 and TLR8 in subcutaneous (SAT), and TLR2 in SAT and visceral (VAT) adipose tissue, while decreasing VAT TLR3 and TLR4. MCM led to increased TLR2 and diminished TLR3, TLR4, and TLR5 expressions in human adipocytes. The anti-inflammatory impact of weight loss was concomitant with decreased TLR1, TLR3, and TLR8 in SAT. Cross-sectional associations confirmed increased V/ SAT TLR1 and TLR8, and decreased TLR3 in obese patients, as compared with non-obese subjects. As expected, TLR were predominant in SVC and adipocyte precursor cells, even though expression of all of them but TLR8 (very low levels) was also found in ex vivo isolated and in vitro differentiated adipocytes. Among SVC, CD14+ macrophages showed increased TLR1, TLR2, and TLR7, but decreased TLR3 mRNA. The opposite patterns shown for TLR2 and TLR3 in V/ SAT, SVC, and inflamed adipocytes were observed in blood as well, being TLR3 more likely linked to lymphocyte instead of neutrophil counts. On the other hand, decreased TLR3 in adipocytes challenged with MCM dampened lipogenesis and the inflammatory response to Poly(I:C)., Conclusion: Functional variations in the expression of TLR found in blood and hypertrophied fat depots, namely decreased TLR3 in lymphocytes and inflamed adipocytes, are linked to metabolic inflammation., (© 2018 The Author(s). Published by S. Karger AG, Basel.)