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60 It was also demonstrated that a GAG-binding deficient MCP-1/CCL2 mutant retains chemotactic activity in vitro but was unable to recruit cells when administrated intraperitoneally.61 Here, hepatoma cell invasion and migration were drastically reduced by the pre-incubation of the chemokine with heparin or when cellular GAG synthesis is reduced by ��DX cell treatment, suggesting that HS chains play major roles in MCP-1/CCL2-mediated biological activities, as described for others chemokines.11, 12 Interestingly, the inhibition of MCP-1/CCL2's chemotactic activities by anti-SDC-1 and anti-SDC-4 Abs suggested that those heparan sulfate proteoglycans could be membrane coreceptors of the chemokine. Given the role of GAGs in modulating MCP-1/CCL2's activities, our data suggest that targeting the specific GAG-chemokine binding could lead to the development of new therapeutic Y27632 strategy of HCC. In summary, our data show that human liver myofibroblasts act on HCC cells to increase their invasiveness and suggest that myofibroblast-derived MCP-1/CCL2 could be involved in the pathogenesis of HCC. ""The aim of this study was to determine the proportion of human papilloma virus (HPV)-positive cases in tonsillar carcinomas and investigate its development over the last decade. Further aim was to show the oncologic results in accord to HPV status and various treatment modalities. A retrospective study was conducted between 2000 and 2012 and included 275 patients treated for tonsillar carcinoma. P16 immunohistochemistry was used as a surrogate marker for HPV-associated carcinogenesis. A total of 101 (36.7%) patients proved to be p16 positive and 174 p16 negative. 80.2% of the p16-positive cases presented with T1-2 tumor. Of the early-stage patients, 79% of the p16-positive and 52.3% of the p16-negative presented with lymph node metastases. The percentage of p16-positive patients increased from 23.2% in the period 2005�C2007 to 58.6% in the period 2010�C2012 in the whole population and from 30.9% to 76.9% in T1-2 carcinomas. Early T-category p16-positive carcinomas had significantly better disease-specific survival (92.4% vs. 75.5%, P?=?0.007) and overall survival (OS, 79.6% vs. 54.3%, P?<?0.001) compared to p16-negative tumors. This study showed an increase in the percentage of p16-positive patients in tonsillar carcinoma from 23.2% in the years between 2005 and 2007 to 58.6% between 2010 and 2012. The majority (80.2%) of p16-positive patients presented with early T-category tumor but most of these (79.0%) had also lymph node metastases. Nevertheless, p16-positive patients had excellent oncologic results after surgery and adjuvant radiotherapy and could be considered for de-escalation of treatment. ""Childhood cancer represents a relevant economic burden on families.</p>