Evaluation of COX-2, EGFR, and p53 as biomarkers of non-dysplastic oral leukoplakias.

OBJECTIVE: Identify candidate SEBs (surrogate endpoint biomarkers) for premalignant trends in head and neck mucosa. STUDY DESIGN: Study, by qPCR (quantitative real-time polymerase chain reaction), the expression of COX-2, EGFR and p53 in 24 biopsies of non-dysplastic oral leukoplakia and contra-lateral normal-appearing mucosa. RESULTS: COX-2 was up-regulated in leukoplakia (79.2%); whereas EGFR and p53 were up-regulated (p>0.05) in oral contra-lateral normal-appearing mucosa (60% and 46% respectively). Also, p53 expression was correlated with tobacco smoke habits and Spearman's rank correlation coefficient showed a positive linear correlation between p53 and EGFR mRNA expression levels. CONCLUSIONS: COX-2 would serve as SEB of oral leukoplakia. The results suggest that p53 appears to be one of the molecular targets of tobacco-related carcinogens in leukoplakia and that the co-expression of p53 and EGFR may play a role in this kind of oral pre-cancerous lesion. More detailed studies of EGFR and p53 should be continued in the future.

In silico and in vitro analysis of small breast epithelial mucin as a marker for bone marrow micrometastasis in breast cancer.

Molecular signatures associated with malignant phenotype would be useful for detection of micrometastatic carcinoma cells. The small breast epithelial mucin (SBEM) gene is predicted to code for a low molecular weight glycoprotein. To evaluate its potential role as a marker for bone marrow (BM) micrometastasis in breast cancer (BC) patients, we have studied in silico and in vitro expression profiles of SBEM gene. Digital SBEM expression in libraries obtained from normal and neoplastic tissues and cell-lines (CL) were displayed and counted on the SAGE Anatomic Viewer. Profiles for cytokeratin-19 and mammaglobin (hMAM), commonly targets used for detection of disseminated BC cells were obtained and compared with SBEM data. Human breast and haematopoietic cancer CL and normal BM were examined by RT-PCR for SBEM and hMAM. Bioinformatics tools were used to gain further insights about the biological role of SBEM in normal breast and BC. Genes with expression patterns in breast libraries correlating with SBEM were identified using two-dimensional display. SBEM tag was detected in 40 libraries (21 BC; 8 non-cancerous breast tissues). Intermediate to high expression was found on 15/21 BC libraries and 7/8 non-tumor breast tissue. SBEM tag count was correlated with ERBB2 (0.662), hMAM (0.409), and RRM2 (-0.379). A model system based on RT-PCR for SBEM mRNA was highly sensitive and specific in order to detect isolated tumor cells. Our results demonstrate that SBEM mRNA may be an imp ortant marker for targeting BC micrometastasis.

Enzalutamide: a new prostate cancer targeted therapy against the androgen receptor.

Enzalutamide (MDV3100), an androgen receptor-signalling inhibitor, represents the most recent compound added to the therapeutic armamentarium for the treatment of metastatic castration-resistant prostate cancer (mCRPC) who progressed to docetaxel. The anti-tumour activity and safety of enzalutamide has been demonstrated in a phase III clinical trial, showing a benefit in overall survival, which was the primary endpoint. There are no head-to-head studies comparing the different treatment options in this subset of patients. In this article, most relevant data published in the literature have been reviewed, with special attention to the therapeutic alternatives currently available for postdocexatel mCRPC patients, emphasising the mechanisms of action of the different drugs, efficacy and quality of life-related aspects.

Potential role of sugar transporters in cancer and their relationship with anticancer therapy.

Sugars, primarily glucose and fructose, are the main energy source of cells. Because of their hydrophilic nature, cells use a number of transporter proteins to introduce sugars through their plasma membrane. Cancer cells are well known to display an enhanced sugar uptake and consumption. In fact, sugar transporters are deregulated in cancer cells so they incorporate higher amounts of sugar than normal cells. In this paper, we compile the most significant data available about biochemical and biological properties of sugar transporters in normal tissues and we review the available information about sugar carrier expression in different types of cancer. Moreover, we describe the possible pharmacological interactions between drugs currently used in anticancer therapy and the expression or function of facilitative sugar transporters. Finally, we also go into the insights about the future design of drugs targeted against sugar utilization in cancer cells.