BackgroundColorectal cancer is the third most common cancer worldwide; and in 40% of all cases, KRAS4b-activating mutations occur. KRAS4b is transported by phosphodiesterase-6δ (PDEδ) to the plasma membrane, where it gets activated. PDEδ downregulation prevents redistribution and activation of KRAS4b. Thus, targeting the KRAS4b-PDEδ complex is a treatment strategy for colorectal cancer.MethodsUsing docking and molecular dynamics simulations coupled to molecular mechanics, the generalized born model and solvent accessibility (MMGBSA) approach to explore protein-ligand stability, we found that the compound ((2S)-N-(2,5-diclorofenil)-2-[(3,4-dimetoxifenil)metilamino]-propanamida), termed C19, bound and stabilized the KRAS4b-PDEδ complex. We investigated whether C19 decreases the viability and proliferation of colorectal cancer cells, in addition to knowing the type of cell death that it causes and if C19 decreases the activation of KRAS4b and their effectors.ResultsC19 showed high cytotoxicity in the colorectal cancer cell lines HCT116 and LoVo, with a stronger effect in KRAS-dependent LoVo cells. Importantly, C19 significantly decreased tumor size in a xenograft mouse model and showed lower side effects than 5-fluorouracil that is currently used as colorectal cancer treatment.ConclusionsMechanistically, the cytotoxic effect was due to increased apoptosis of tumor cells and decreased phosphorylation of Erk and Akt. Therefore, our results suggest that C19 may serve as a promising new treatment for colorectal cancer.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4968-3) contains supplementary material, which is available to authorized users.
Triple negative breast cancer (TnBc) is a breast cancer subtype associated with high rates of metastasis, heterogeneity, drug resistance and a poor prognosis. extracellular vesicles (eVs) are vesicles of endosomal and plasma membrane origin, and are secreted by healthy and cancer cells. in cancer, eVs contribute to tumor progression by mediating escape from the immune system surveillance, and are involved in extracellular matrix degradation, invasion, angiogenesis, migration and metastasis. Furthermore, eVs have been identified in several human fluids. However, the role of EVs from patients with breast cancer in the migration and invasion of human breast cancer cells is not fully understood. The present study investigated whether eVs isolated from Mexican patients with breast cancer can induce cellular processes related to invasion in breast cancer. Moreover, plasma fractions enriched in eVs and deprived of platelet-derived eVs obtained from blood samples of 32 Mexican patients with biopsy-diagnosed breast cancer at different clinical stages who had not received treatment were analyzed. Furthermore, one control group was included, which consisted of 20 Mexican healthy females. The present results demonstrated that eVs from women with breast cancer promote migration and invasion, and increase matrix metalloproteinase (MMP)-2 and MMP-9 secretion in TnBc Mda-MB-231 cells. in addition, it was found that eVs from patients with breast cancer induced Src and focal adhesion kinase activation, and focal adhesions assembly with an increase in focal adhesions number, while the migration and invasion was dependent on Src activity. collectively, eVs from Mexican patients with breast cancer induce migration and invasion via a Src-dependent pathway in TnBc Mda-MB-231 cells.
Introduction:According to developed countries’ studies, in breast cancer survivors there is a high prevalence of metabolic syndrome; however, in Mexico data is lacking about this issue.Goal:To explore if metabolic syndrome occurs in Mexican women survivors of breast cancer.Material and methods:At a second-level general hospital, women with breast cancer with a surviving >2 years were studied. The analysis involved their demographic and anthropometric features, blood pressure measurement, time of surviving, besides fasting blood levels of lipids and glucose.Results:The sample consisted of 100 women; 42% were obese (body mass index ≥30 kg/m2). The sample´s mean age was 60 years with a mean surviving time of 6.5 years. Their mean glucose level was 122 mg/dL and triglycerides 202 mg/dL. There were 33% with blood pressure ≥130/85mm Hg or diagnosis of hypertension. Fifty-seven percent had glucose >99 mg/dL or diagnosis of diabetes mellitus, and 58% had triglycerides >149 mg/dL. Metabolic syndrome occurred in 57% of obese women.Conclusion:Our results suggest that metabolic syndrome occurs in more than 50% of obese Mexican women survivors of breast cancer.
Introduction: Breast cancer in Mexico is a major health concern. Since there is no precise information about mammography use in regular population of women insured by the Instituto de Seguridad y Servicios Sociales para los Trabajadores del Estado (ISSSTE), we carried out this study. Materials and methods: This was a cross-sectional study, where women insured by the ISSSTE who attended the Hospital General Tacuba at Mexico City were assessed. The study evaluated the regularity of mammography use, and whether this was accordingly to their demographic features. Results: Our sample was of 327 women between 40 and 69 years. There were 146 users (44.7%) of mammography during the past two years. Mammography using during the two previous years, by age group was: 40-49 years, 24.6%; 50-59 years, 59.5%, and 60-69 years, 50.49%. Conclusions: Our results suggest that in women insured by the ISSSTE of an urban city there are still challenges for the extensive use of mammography.
Background: According to an Anglo-Saxon study, in breast cancer survivors, there is a high prevalence of impaired fasting glucose. Our aim was to assess the impaired fasting glucose occurring in Mexican woman survivors of breast cancer. Materials and Methods: At a general hospital in Mexico City, women with breast cancer with a surviving ≥2 years, without type 2 diabetes mellitus, were studied. The analysis included demographic and anthropometric features, time of surviving, and blood levels of lipids and glucose. Results: The sample was 119 women. Impaired fasting glucose happened in 53 (44.5%). In those with normal weight ( n = 28), impaired fasting glucose occurred in 9 (32.1%); however, in overweight participants ( n = 48), it developed in 22 (45.8%) and in obese participants ( n = 43) in 22 (51.1%). Conclusion: Impaired fasting glucose is usual in Mexican breast cancer survivors. It is more in obese and overweight women compared to normal weight.
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