Impact of metabolic syndrome on the risk of endometrial cancer and the role of lifestyle in prevention

Endometrial cancer is the second gynecological cancer with the highest global incidence. Among many associated risk factors, metabolic syndrome is an important and preventable one. It comprises a group of conditions that often occur together: central adiposity, hyperglycemia, arterial hypertension, and atherogenic dyslipidemia. This review aimed to describe the epidemiological and biological relationship between metabolic syndrome and endometrial cancer, focusing on the role of lifestyle in prevention. A literature search was carried out in the PubMed database. 4824 publications were screened, and 123 were included for this review. The association between metabolic syndrome and endometrial cancer has been described. Chronic adipose tissue inflammation and insulin resistance are involved in the development of obesity, particularly visceral adiposity. These changes promote the ideal environment for the development of endometrial cancer. Strategies based on lifestyle modifications may be effective for the prevention of metabolic syndrome and consequently endometrial cancer. Some of these modifications include adopting a diet rich in fruits, vegetables, whole grains, and legumes, depending to the accessibility of these foods for each region. Avoiding ultra-processed foods and increasing daily physical activity were also some suggested modifications. We propose that women be screened for metabolic syndrome to establish early treatment and to possibly prevent endometrial cancer. Clinical trials designed to prove the effect of lifestyle modifications on the prevention of endometrial cancer are needed

Dietary Compounds as Epigenetic Modulating Agents in Cancer

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

HypoxamiRs Profiling Identify miR-765 as a Regulator of the Early Stages of Vasculogenic Mimicry in SKOV3 Ovarian Cancer Cells

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

Impact of preemptive hospitalization on health outcomes at the temporary COVID-19 hospital in Mexico City: a prospective observational study.

INTRODUCTION: In response to the evolution of the coronavirus disease 2019 (COVID-19) pandemic, the admission protocol for the temporary COVID-19 hospital in Mexico City has been updated to hospitalize patients preemptively with an oxygen saturation (SpO2) of >90%. METHODS: This prospective, observational, single-center study compared the progression and outcomes of patients who were preemptively hospitalized versus those who were hospitalized based on an SpO2 ⩽90%. We recorded patient demographics, clinical characteristics, COVID-19 symptoms, and oxygen requirement at admission. We calculated the risk of disease progression and the benefit of preemptive hospitalization, stratified by CALL Score: age, lymphocyte count, and lactate dehydrogenase (<8 and ⩾8) at admission. RESULTS: Preemptive hospitalization significantly reduced the requirement for oxygen therapy (odds ratio 0.45, 95% confidence interval 0.31-0.66), admission to the intensive care unit (ICU) (0.37, 0.23-0.60), requirement for invasive mechanical ventilation (IMV) (0.40, 0.25-0.64), and mortality (0.22, 0.10-0.50). Stratification by CALL score at admission showed that the benefit of preemptive hospitalization remained significant for patients requiring oxygen therapy (0.51, 0.31-0.83), admission to the ICU (0.48, 0.27-0.86), and IMV (0.51, 0.28-0.92). Mortality risk remained significantly reduced (0.19, 0.07-0.48). CONCLUSION: Preemptive hospitalization reduced the rate of disease progression and may be beneficial for improving COVID-19 patient outcomes

Effect of ovarian cancer ascites on SKOV-3 cells proteome: new proteins associated with aggressive phenotype in epithelial ovarian cancer

Abstract Background Epithelial ovarian cancer is the second most lethal gynecological cancer worldwide. Ascites can be found in all clinical stages, however in advanced disease stages IIIC and IV it is more frequent and could be massive, associated with worse prognosis. Due to the above, it was our interest to understanding how the ascites of ovarian cancer patients induces the mechanisms by which the cells present in it acquire a more aggressive phenotype and to know new proteins associated to this process. Methods A proteomic analysis of SKOV-3 cells treated with five different EOC ascites was performed by two-dimensional electrophoresis coupled to MALDI-TOF. The level of expression of the proteins of interest was validated by RT-PCR because several of these proteins have only been reported at the messenger level. Results Among the proteins identified that increased their expression in ascites-treated SKOV-3 cells, were Ran GTPase, ZNF268, and Synaptotagmin like-3. On the other hand, proteins that were negatively regulated by ascites were HLA-I, HSPB1, ARF1, Synaptotagmin 1, and hnRNPH1, among others. Furthermore, an interactome for every one of these proteins was done in order to identify biological processes, molecular actions, and cellular components in which they may participate. Conclusions Identified proteins participate in cellular processes highly relevant to the aggressive phenotype such as nuclear transport, regulation of gene expression, vesicular trafficking, evasion of the immune response, invasion, metastasis, and in resistance to chemotherapy. These proteins may represent a source of information which has the potential to be evaluated for the design of therapies directed against these malignant cells that reside on ovarian cancer ascites

Artículo especiAl Epidemiological overview, advances in diagnosis, prevention, treatment and management of epithelial ovarian cancer in Mexico

Abstract The epithelial ovarian cancer (EOC) has been underdiagnosed because it does not have a specific clinical presentation, and the signs and symptoms are similar to the irritable bowel syndrome and pelvic inflammatory disease. EOC is less common than breast and cervical cancer, but it is more lethal. On the whole, EOC has an early dissemination to peritoneal cavity, which delays a timely diagnosis and increases the rate of advanced diagnosed disease. The diagnosis usually surprises the women and the primary care physician. Therefore, it is necessary to count on prevention and early diagnosis programs. EOC has 80% response to surgical treatment, but nearly 70% of the patients may relapse in five years. The objectives of this document are presenting a summary of Resumen El cáncer ovárico epitelial (COE) ha sido subdiagnosticado debido a que no tiene presentación clínica específica y a que los signos y síntomas son similares al síndrome de colon irritable y a la enfermedad inflamatoria pélvica. Es menos común que el cáncer de mama o el cervicouterino, pero es más letal. En general, tiene diseminación temprana a cavidad peritoneal, lo cual retrasa un pronóstico oportuno e incrementa la tasa de diagnóstico de enfermedad avanzada. Usualmente, el diagnóstico sorprende a la mujer y al médi-co de primer contacto. Entonces, es necesario contar con programas de prevención y diagnóstico temprano. El COE tiene 80% de respuesta quirúrgica, pero cerca de 70% de las pacientes puede recaer en cinco años. Los objetivos de est