BACKGROUND. There is currently a lack of objective methods to assess scars. OBJECTIVES. The objectives of this study were to (1) determine the pattern of scar formation up to 24 months after a burn, compare clinical and photographic scar assessment, and determine what percentage of scars became hypertrophic after a major trauma and (2) replace each clinical parameter of a clinical scar scale by objective measurements. METHODS. Scars from 62 patients were evaluated from the acute phase up to 24 months after the burn, using photographs and clinical assessment during visits. Photographic planimetry helped estimate the percentage of scars that became hypertrophic. Thereafter, 69 patients had scars evaluated using clinical assessment and several instruments to evaluate pigmentation, erythema, pliability, thickness, and perfusion. The sensitivity and specificity of each instrument were determined regarding their ability to correlate with the parameters of hypertrophic and nonhypertrophic scars. Analysis of variance and Tukey's test were used in statistical analysis, with po.05 indicating significance. RESULTS. Increased scar hypertrophy occurred between 6 and 12 months after the burn, and less than 30% of scars were hypertrophic at 18 to 24 months. Objective assessment of pliability and erythema, but not pigmentation, correlated significantly with clinical evaluation of hypertrophy. Hypertrophic scars had significantly higher perfusion than nonhypertrophic scars. A new scar rating system is proposed, based on the sensitivity and specificity of each instrument, to correlate with hypertrophic and nonhypertrophic scars. CONCLUSIONS. Objective rating systems using reliable instruments can be used to replace subjective scar assessment. Larger multicenter prospective studies should test this new scale in scars due to other mechanisms of injury.

BackgroundFatty acid synthase (FASN) is overexpressed and hyperactivated in several human carcinomas, including lung cancer. We characterize and compare the anti-cancer effects of the FASN inhibitors C75 and (−)-epigallocatechin-3-gallate (EGCG) in a lung cancer model.MethodsWe evaluated in vitro the effects of C75 and EGCG on fatty acid metabolism (FASN and CPT enzymes), cellular proliferation, apoptosis and cell signaling (EGFR, ERK1/2, AKT and mTOR) in human A549 lung carcinoma cells. In vivo, we evaluated their anti-tumour activity and their effect on body weight in a mice model of human adenocarcinoma xenograft.ResultsC75 and EGCG had comparable effects in blocking FASN activity (96,9% and 89,3% of inhibition, respectively). In contrast, EGCG had either no significant effect in CPT activity, the rate-limiting enzyme of fatty acid β-oxidation, while C75 stimulated CPT up to 130%. Treating lung cancer cells with EGCG or C75 induced apoptosis and affected EGFR-signaling. While EGCG abolished p-EGFR, p-AKT, p-ERK1/2 and p-mTOR, C75 was less active in decreasing the levels of EGFR and p-AKT. In vivo, EGCG and C75 blocked the growth of lung cancer xenografts but C75 treatment, not EGCG, caused a marked animal weight loss.ConclusionsIn lung cancer, inhibition of FASN using EGCG can be achieved without parallel stimulation of fatty acid oxidation and this effect is related mainly to EGFR signaling pathway. EGCG reduce the growth of adenocarcinoma human lung cancer xenografts without inducing body weight loss. Taken together, EGCG may be a candidate for future pre-clinical development.

Fatty acid synthase (FASN) is a lipogenic enzyme that is highly expressed in different human cancers. Here we report the development of a new series of polyphenolic compounds 5-30 that have been evaluated for their cytotoxic capacity in SK-Br3 cells, a human breast cancer cell line with high FASN expression. The compounds with an IC(50) < 50 μM have been tested for their ability to inhibit FASN activity. Among them, derivative 30 blocks the 90% of FASN activity at low concentration (4 μM), is highly cytotoxic in a broad panel of tumor cells, induces apoptosis, and blocks the activation of HER2, AKT, and ERK pathways. Remarkably, 30 does not activate carnitine palmitoyltransferase-1 (CPT-1) nor induces in mice weight loss, which are the main drawbacks of other previously described FASN inhibitors. Thus, FASN inhibitor 30 may aid the validation of this enzyme as a therapeutic target for the treatment of cancer.