Our results suggest that codon 12 K-ras mutations may have a role in the mucinous differentiation pathway, while codon 13 mutations have biological relevance in terms of colorectal cancer clinical outcome.

Colorectal cancer remains one of the most common and lethal malignancies worldwide despite the use of various therapeutic strategies. A better understanding of the mechanisms responsible for tumor initiation and progression is essential for the development of novel, more powerful therapies. The traditional, so-called "stochastic model" of tumor development, which assumes that each cancer cell is tumorigenic, has been deeply challenged during the past decade by the identification of cancer stem cells (CSCs), a biologically distinct subset of cells within the bulk of tumor mass. This discovery led to the development of the hierarchical model of tumorigenesis which assumes that only CSCs have the ability to initiate tumor growth, both at primary and metastatic sites. This model implies that the elimination of all CSCs is fundamental to eradicate tumors and that failure to do so might be responsible for the occurrence of relapses and/or metastases frequently observed in the clinical management of colorectal cancer patients. Identification and isolation of CSCs is essential for a better understanding of their role in the tumorigenetic process and for the development of CSC-specific therapies. Several methods have been used for this purpose and many efforts have been focused on the identification of specific CSC-surface markers. This review provides an overview of the proposed roles of CSC in human colorectal tumorigenesis focusing on the most important molecules identified as CSC-specific markers in colorectal cancer and on the potential strategies for the development of CSC-targeted therapy.

BackgroundThe process of malignant transformation, progression and metastasis of melanoma is not completely understood. Recently, the microarray technology has been used to survey transcriptional differences that might provide insight into the metastatic process, but the validation of changing gene expression during metastatic transition period is poorly investigated. A large body of literature has been produced on the role of the HOX genes network in tumour evolution, suggesting the involvement of HOX genes in several types of human cancers. Deregulated paralogous group 13 HOX genes expression has been detected in melanoma, cervical cancer and odonthogenic tumors. Among these, Hox C13 is also involved in the expression control of the human keratin genes hHa5 and hHa2, and recently it was identified as a member of human DNA replication complexes.MethodsIn this study, to investigate HOX C13 expression in melanoma progression, we have compared its expression pattern between naevi, primary melanoma and metastasis. In addition HOXC13 profile pattern of expression has been evaluated in melanoma cell lines.ResultsOur results show the strong and progressive HOX C13 overexpression in metastatic melanoma tissues and cytological samples compared to nevi and primary melanoma tissues and cells.ConclusionsThe data presentated in the paper suggest a possible role of HOX C13 in metastatic melanoma switch.

Our study supports the role of TNF-alpha polymorphisms in predicting the response to anti-TNF-alpha agents. In particular, we found that the presence of -238G>A and -308G>A polymorphisms is associated with poor response to a 3-month therapy with etanercept. However, our data have yet to be validated in larger cohorts.

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