ColoLipidGene: signature of lipid metabolism-related genes to predict prognosis in stage-II colon cancer patients ColoLipidGene: signature of lipid metabolism-related genes to predict prognosis in stage-II colon cancer patients

Cancer remains an important cause of mortality nowadays and, therefore, new therapeutic approaches are still needed. Rosemary (Rosmarinus officinalis L.) has been reported to possess antitumor activities both in vitro and in animal studies. Some of these activities were attributed to its major components, such as carnosic acid, carnosol, ursolic acid, and rosmarinic acid. Initially, the antitumor effects of rosemary were attributed to its antioxidant activity. However, in recent years, a lack of correlation between antioxidant and antitumor effects exerted by rosemary was reported, and different molecular mechanisms were related to its tumor inhibitory properties. Moreover, supported by the U.S. Food and Drug Administration and the European Food and Safety Authority, specific compositions of rosemary extract were demonstrated to be safe for human health and used as antioxidant additive in foods, suggesting the potential easy application of this agent as a complementary approach in cancer therapy. In this review, we aim to summarize the reported anticancer effects of rosemary, the demonstrated molecular mechanisms related to these effects and the interactions between rosemary and currently used anticancer agents. The possibility of using rosemary extract as a complementary agent in cancer therapy in comparison with its isolated components is discussed.

Colorectal and pancreatic cancers remain important contributors to cancer mortality burden and, therefore, new therapeutic approaches are urgently needed. Rosemary (Rosmarinus officinalis L.) extracts and its components have been reported as natural potent antiproliferative agents against cancer cells. However, to potentially apply rosemary as a complementary approach for cancer therapy, additional information regarding the most effective composition, its antitumor effect in vivo and its main molecular mediators is still needed. In this work, five carnosic acid-rich supercritical rosemary extracts with different chemical compositions have been assayed for their antitumor activity both in vivo (in nude mice) and in vitro against colon and pancreatic cancer cells. We found that the antitumor effect of carnosic acid together with carnosol was higher than the sum of their effects separately, which supports the use of the rosemary extract as a whole. In addition, gene and microRNA expression analyses have been performed to ascertain its antitumor mechanism, revealing that up-regulation of the metabolic-related gene GCNT3 and down-regulation of its potential epigenetic modulator miR-15b correlate with the antitumor effect of rosemary. Moreover, plasmatic miR-15b down-regulation was detected after in vivo treatment with rosemary. Our results support the use of carnosic acid-rich rosemary extract as a complementary approach in colon and pancreatic cancer and indicate that GCNT3 expression may be involved in its antitumor mechanism and that miR-15b might be used as a non-invasive biomarker to monitor rosemary anticancer effect.

Chimeric antigen receptor (CAR)-T cell therapy is one of the most promising advances in cancer treatment. It is based on genetically modified T cells to express a CAR, which enables the recognition of the specific tumour antigen of interest. To date, CAR-T cell therapies approved for commercialisation are designed to treat haematological malignancies, showing impressive clinical efficacy in patients with relapsed or refractory advanced-stage tumours. However, since they all use the patient´s own T cells as starting material (i.e. autologous use), they have important limitations, including manufacturing delays, high production costs, difficulties in standardising the preparation process, and production failures due to patient T cell dysfunction. Therefore, many efforts are currently being devoted to contribute to the development of safe and effective therapies for allogeneic use, which should be designed to overcome the most important risks they entail: immune rejection and graft-versus-host disease (GvHD). This systematic review brings together the wide range of different approaches that have been studied to achieve the production of allogeneic CAR-T cell therapies and discuss the advantages and disadvantages of every strategy. The methods were classified in two major categories: those involving extra genetic modifications, in addition to CAR integration, and those relying on the selection of alternative cell sources/subpopulations for allogeneic CAR-T cell production (i.e. γδ T cells, induced pluripotent stem cells (iPSCs), umbilical cord blood T cells, memory T cells subpopulations, virus-specific T cells and cytokine-induced killer cells). We have observed that, although genetic modification of T cells is the most widely used approach, new approaches combining both methods have emerged. However, more preclinical and clinical research is needed to determine the most appropriate strategy to bring this promising antitumour therapy to the clinical setting.