Tumor-derived exosomes are emerging as local and systemic cell-to-cell mediators of oncogenic information through the horizontal transfer of mRNAs, microRNAs and proteins during tumorigenesis. The exosomal content has been described as biologically active when taken up by the recipient cell. Identifying the specific molecular cargo of exosomes will help to determine their function in specific steps of the tumorigenic process. Here we evaluate whether ΔNp73 is selectively packaged in tumor-derived exosomes, its function in the acceptor cells in vitro and in vivo and its prognosis potential in cancer. ΔNp73 messenger is enriched in tumor-derived exosomes, suggesting its active sorting in these microvesicles. We observed the transmission of this exosome cargo to different cell types and how it confers proliferation potential and chemoresistance to the acceptor cells in vitro and in animal models. Finally, our data support the potential prognostic value of exosomal ΔNp73 in colon cancer patients.

Background: The acquired resistance to chemotherapy represents the major limitation in the treatment of cancer. New strategies to solve this failure and improve patients' outcomes are necessary. The cancer preventive effect of b-cryptoxanthin has been widely described in population studies. Few reports support its putative use as an antitumoral compound. Here we focus on the therapeutic potential of b-cryptoxanthin individually or in combination with oxaliplatin in colon cancer and try to decipher the molecular basis underlying its effect.Methods: Apoptosis, viability and proliferation assays, mouse models, and an intervention study in 20 healthy subjects were performed. A PCR array was carried out to unravel the molecular putative basis of the b-cryptoxanthin effect, and further signaling experiments were conducted. Comet Assay was completed to evaluate the genotoxicity of the treatments.

TP73 is a member of the TP53 family, whose deregulated expression has been reported in a wide variety of cancers and linked to patients' outcome. The fact that TP73 encodes a complex number of isoforms (TAp73 and ΔTAp73) with opposing functions and the cross-talk with other members of the family (TP53 and TP63) make it difficult to determine its clinical relevance. Here, we review the molecular mechanisms driving TAp73 and ΔTAp73 expression and how these variants inhibit or promote carcinogenesis. We also highlight the intricate interplay between TP53 family members. In addition, we comment on current pharmacological approaches targeting the TP73 pathway and those affecting the TAp73/ΔTAp73 ratio. Finally, we discuss the current data available in the literature that provide evidence on the role of TP73 variants in predicting prognosis. To date, most of the studies that evaluate the status levels of TP73 isoforms have been based on limited-size series. Despite this limitation, these publications highlight the correlation between high levels of the oncogenic forms and failure to respond to chemotherapy and/or shorter survival. Finally, we emphasize the need for studies to evaluate the significance of combining the deregulation of various members of the TP53 family in order to define patient outcome or their responsiveness to specific therapies.

Phytosterol (PS) intake may be used for hypercholesterolaemia in some groups although the presence of non-responders is well known. Carotenoids and PS/ cholesterol may compete for the same transporters during absorption. As part of a randomized, double-blind, crossover, multiple-dose supplementation study with b-cryptoxanthin (b-Cx) and PS, single and combined, polymorphisms of ABCG8 (A632V) and NCPL1 (L272L) were determined in 19 post-menopausal women. Subjects carrying CC polymorphism for NCP1L1 (L272L) showed a net increase in total cholesterol and LDL after PS intake but, interestingly, displayed a decrease in both lipid fractions after consuming PS plus b-Cx. For the ABCG8 (A632V) gene, CT/TT carriers consuming PS also displayed an increase in total cholesterol and LDL, but this increment was much lower after the intake of PS plus b-Cx. Additionally, in CC carriers for ABCG8 (A632V), a greater decrease in total cholesterol and LDL was found after the intake of PS plus b-Cx compared to that observed after PS alone. Overall, our results suggest that b-Cx improves the response to PS in individuals carrying specific genetic polymorphisms (i.e. non-responders), opening the possibility to modulate the response to PS by food technology. (ClinicalTrials.gov NCT01074723).