Epigenetic mechanisms control gene expression during normal development and their aberrant regulation may lead to human diseases including cancer. Natural phytochemicals can largely modulate mammalian epigenome through regulation of mechanisms and proteins responsible for chromatin remodeling. Phytochemicals are mainly contained in fruits, seeds, and vegetables as well as in foods supplements. These compounds act as powerful cellular antioxidants and anti-carcinogens agents. Several dietary compounds such as catechins, curcumin, genistein, quercetin and resveratrol, among others, exhibit potent anti-tumor activities through the reversion of epigenetic alterations associated to oncogenes activation and inactivation of tumor suppressor genes. In this review, we summarized the actual knowledge about the role of dietary phytochemicals in the restoration of aberrant epigenetic alterations found in cancer cells with a particular focus on DNA methylation and histone modifications. Furthermore, we discussed the mechanisms by which these natural compounds modulate gene expression at epigenetic level and described their molecular targets in diverse types of cancer. Modulation of epigenetic activities by phytochemicals will allow the discovery of novel biomarkers for cancer prevention, and highlights its potential as an alternative therapeutic approach in cancer.

PURPOSE To develop recommendations for duration of adjuvant chemotherapy with a fluoropyrimidine and oxaliplatin for patients with completely resected stage III colon cancer based on the results of trials of 3 months compared with 6 months of treatment. METHODS ASCO convened an Expert Panel and conducted a systematic review of relevant studies. The guideline recommendations were based on the review of evidence by the Expert Panel. RESULTS Pooled data from the six International Duration Evaluation of Adjuvant Chemotherapy (IDEA) Collaboration randomized controlled trials comprise the evidence base for these guideline recommendations. RECOMMENDATIONS The recommendations for therapy duration apply to patients with completely resected stage III colon cancer who are being offered adjuvant chemotherapy with oxaliplatin and a fluoropyrimidine. Recommendations are informed by the findings of a recent pooled analysis of clinical trials that compared 6 months versus 3 months of oxaliplatin-based chemotherapy. For patients at a high risk of recurrence (T4 and/or N2), adjuvant chemotherapy should be offered for a duration of 6 months. For patients at a low risk of recurrence (T1, T2, or T3 and N1), either 6 months of adjuvant chemotherapy or a shorter duration of 3 months may be offered on the basis of a potential reduction in adverse events and no significant difference in disease-free survival with the 3-month regimen. In determining duration of therapy, the Expert Panel recommends a shared decision-making approach, taking into account patient characteristics, values and preferences, and other factors and including a discussion of the potential for benefit and risks of harm associated with treatment duration. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

In last decades, the basic, clinical, and translational research efforts have been directed to the identification of standard biomarkers associated with the degree of malignancy. There is an increasingly public health concern for earlier detection of cancer development at stages in which successful treatments can be achieved. To meet this urgent clinical demand, early stage cancer biomarkers supported by reliable and robust experimental data that can be readily applicable in the clinical practice, are required. In the current standard protocols, when one or two of the canonical proliferating index biomarkers are analyzed, contradictory results are frequently reached leading to incorrect cancer diagnostic and unsuccessful therapies. Therefore, the identification of other cellular characteristics or signatures present in the tumor cells either alone or in combination with the well-established proliferation markers emerge as an alternative strategy in the improvement of cancer diagnosis and treatment. Because it is well known that several pathways and processes are altered in tumor cells, the concept of "single marker" in cancer results incorrect. Therefore, this review aims to analyze and discuss the proposal that the molecular profile of different genes or proteins in different altered tumor pathways must be established to provide a better global clinical pattern for cancer detection and prognosis.

Our data suggest for the first time that abrogation of HDGF by EGCG enhances cisplatin-induced apoptosis and sensitize A549 cells to chemotherapy. Therefore, we propose that decreasing the HDGF levels by using EGCG may represent a novel strategy in lung cancer therapy.

He leído con gran atención el artículo "Variabilidad de la composición corporal medida por bioimpedanciometría eléctrica según condiciones de realización: influencia del ayuno y el reposo", publicado en la revista Nutrición Hospitalaria por los autores Cáceres y cols. (1) y desearía realizar unas puntualizaciones que creo han podido afectar a los resultados presentados.La bioimpedancia eléctrica (BIA) es un método de evaluación de la composición corporal que está muy extendido en diferentes situaciones, tanto en la hospitalaria como fuera de ella (2). El trabajo presentado por Cáceres y cols. parte de una premisa de trabajo realista que tiene que ver con la disponibilidad de tiempo en los centros hospitalarios, sobrecargados por la actividad asistencial, pero la realización de una BIA requiere el cumplimiento escrupuloso de una serie de requisitos metodológicos de gran importancia en estas evaluaciones que aseguren la fiabilidad y la precisión de las medidas.Por tanto, en este trabajo se parte de una situación de base presuntamente alteradora, como es el mantener a los sujetos de estudio a 60 minutos de decúbito supino, previa a la evaluación inicial (tomando esta medición como medición basal), para posteriormente comparar con las dos situaciones planteadas: de ayuno-no reposo y no ayuno-no reposo. Los análisis de los cambios de la composición corporal presentados en el trabajo son inicialmente congruentes con los producidos por las dos situaciones, pero la valoración inicial probablemente esta distorsionada e invalida las comparaciones estadísticas.Existen múltiples factores bien conocidos que alteran los resultados, como es la posición en decúbito supino. Con la posición de decúbito supino se pueden producir variaciones en la primera hora de hasta 10-15 Ω (3-5), lo cual puede comportar variaciones tanto para la masa libre de grasa como por sustracción a la masa grasa hasta de un 2% (4).Otro asunto es la ligera discrepancia en las variaciones de la resistencia encontradas entre el grupo de hombres y mujeres a través de las diversas mediciones. Las mayores variaciones en las estimaciones de la composición corporal no están en los instrumentos de medida, sino en los factores que pueden distorsionar dichas medidas y que pueden ser acumulables, influyendo en las estimaciones finales por el llamado error de propagación. BIBLIOGRAFÍA 1. Cáceres DI, Messagi-Sartor M, Rodríguez DA, FE, Gea J, Orozco-Levi M. Variabilidad de la composición corporal medida con bioimpedanciometría eléctrica según condiciones de realización: influencia del ayuno y del reposo. Nutr Hosp 2014;30(6):1359-65. 2. Alvero-Cruz JR, Correas-Gómez L, Ronconi MF, Fernandez-Vázquez R, Porta J. Bioelectrical impedance analysis as a method of body composition estimation: a practical approach. Rev Med Deport 2011;4(4):167-74. 3. Slinde F, Bark A, Jansson J, Rossander-Hulthén L. Bioelectrical impedance variation in healthy subjects during 12 h in the supine position. Clin Nutr 2003;22(2):153-7.

Vasculogenic mimicry (VM) is a novel cancer hallmark in which malignant cells develop matrix-associated 3D tubular networks with a lumen under hypoxia to supply nutrients needed for tumor growth. Recent studies showed that microRNAs (miRNAs) may have a role in VM regulation. In this study, we examined the relevance of hypoxia-regulated miRNAs (hypoxamiRs) in the early stages of VM formation. Data showed that after 48 h hypoxia and 12 h incubation on matrigel SKOV3 ovarian cancer cells undergo the formation of matrix-associated intercellular connections referred hereafter as 3D channels-like structures, which arose previous to the apparition of canonical tubular structures representative of VM. Comprehensive profiling of 754 mature miRNAs at the onset of hypoxia-induced 3D channels-like structures showed that 11 hypoxamiRs were modulated (FC>1.5; p < 0.05) in SKOV3 cells (9 downregulated and 2 upregulated). Bioinformatic analysis of the set of regulated miRNAs showed that they might impact cellular pathways related with tumorigenesis. Moreover, overall survival analysis in a cohort of ovarian cancer patients ( n = 485) indicated that low miR-765, miR-193b, miR-148a and high miR-138 levels were associated with worst patients outcome. In particular, miR-765 was severely downregulated after hypoxia (FC < 32.02; p < 0.05), and predicted to target a number of protein-encoding genes involved in angiogenesis and VM. Functional assays showed that ectopic restoration of miR-765 in SKOV3 cells resulted in a significant inhibition of hypoxia-induced 3D channels-like formation that was associated with a reduced number of branch points and patterned tubular-like structures. Mechanistic studies confirmed that miR-765 decreased the levels of VEGFA, AKT1 and SRC-α transducers and exerted a negative regulation of VEGFA by specific binding to its 3‘UTR. Finally, overall survival analysis of a cohort of ovarian cancer patients ( n = 1435) indicates that high levels of VEGFA, AKT1 and SRC-α and low miR-765 expression were associated with worst patients outcome. In conclusion, here we reported a novel hypoxamiRs signature which constitutes a molecular guide for further clinical and functional studies on the early stages of VM. Our data also suggested that miR-765 coordinates the formation of 3D channels-like structures through modulation of VEGFA/AKT1/SRC-α axis in SKOV3 ovarian cancer cells.

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