The fact that the identity of the cells that initiate metastasis in most human cancers is unknown hampers the development of antimetastatic therapies. Here we describe a subpopulation of CD44 cells in human oral carcinomas that do not overexpress mesenchymal genes, are slow-cycling, express high levels of the fatty acid receptor CD36 and lipid metabolism genes, and are unique in their ability to initiate metastasis. Palmitic acid or a high-fat diet specifically boosts the metastatic potential of CD36 metastasis-initiating cells in a CD36-dependent manner. The use of neutralizing antibodies to block CD36 causes almost complete inhibition of metastasis in immunodeficient or immunocompetent orthotopic mouse models of human oral cancer, with no side effects. Clinically, the presence of CD36 metastasis-initiating cells correlates with a poor prognosis for numerous types of carcinomas, and inhibition of CD36 also impairs metastasis, at least in human melanoma- and breast cancer-derived tumours. Together, our results indicate that metastasis-initiating cells particularly rely on dietary lipids to promote metastasis.

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a b s t r a c tThe use of CO 2 laser has become a routine procedure for the treatment of oral leukoplakia. In this retrospective study, we evaluated 65 patients with oral leukoplakia treated with CO 2 laser vaporization. The main location was the tongue (n ¼ 21/65, 32.3%). The initial biopsy showed mild/moderate dysplasia in almost half the patients (n ¼ 29, 44.6%) and hyperplasia without dysplasia in around a third of the patients (n ¼ 21, 32.3%). The recurrence and malignant transformation rates were 33.8% (n ¼ 22) and 15.4% (n ¼ 10), respectively. The follow-up mean (standard deviation) was 15.0 (10.6) months. The procedure-related complications rate was 7.7% (n ¼ 5). The KaplaneMeier curves for time to recurrence showed differences only for gingiva lesions compared to tongue lesions (log rank, p ¼ 0.032). Malignant leukoplakia transformation is independent of treatment, although it seems advisable to treat leukoplakia with or without dysplasia.

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a b s t r a c tWe conducted a systematic review of the literature to evaluate treatment of oral leukoplakia with the carbon dioxide (CO 2 ) laser.A comprehensive search of studies published between 1981 and 2015 and listed in the PubMed (National Library of Medicine, NCBI) database yielded 378 articles which were screened in detail. Relevant studies were selected according to predetermined inclusion and exclusion criteria. A total of 33 articles met the final inclusion criteria and were analysed in detail in accordance with the PRISMA-P statement. These full-text papers were classified as synopses (n ¼ 7), recurrence and malignant transformation studies (n ¼ 17), comparative studies between CO 2 laser and cold knife surgery (n ¼ 3) and studies evaluating the efficacy of CO 2 , Nd:YAG and KTP lasers.According to the literature the CO 2 laser is the workhorse of oral leukoplakia treatment due to its effectiveness and low associated morbidity. However, randomized clinical trials are needed to compare CO 2 laser with other lasers. The results of our systematic review showed that there is no consensus regarding the factors involved in higher recurrence and malignization rates, so further studies are needed.