RESUMEN
BACKGROUND: The interrelationship between cellular metabolism and the epithelial-to-mesenchymal transition (EMT) process has made it an interesting topic to investigate the adjuvant effect of therapeutic diets in the treatment of cancers. However, the findings are controversial. In this study, the effects of glucose limitation along and with the addition of beta-hydroxybutyrate (bHB) were examined on the expression of specific genes and proteins of EMT, Wnt, Hedgehog, and Hippo signaling pathways, and also on cellular behavior of gastric cancer stem-like (MKN-45) and non-stem-like (KATO III) cells. METHODS AND RESULTS: The expression levels of chosen genes and proteins studied in cancer cells gradually adopted a low-glucose condition of one-fourth, along and with the addition of bHB, and compared to the unconditioned control cells. The long-term switching of the metabolic fuels successfully altered the expression profiles and behaviors of both gastric cancer cells. However, the results for some changes were the opposite. Glucose limitation along and with the addition of bHB reduced the CD44+ population in MKN-45 cells. In KATO III cells, glucose restriction increased the CD44+ population. Glucose deprivation alleviated EMT-related signaling pathways in MKN-45 cells but stimulated EMT in KATO III cells. Interestingly, bHB enrichment reduced the beneficial effect of glucose starvation in MKN-45 cells, but also alleviated the adverse effects of glucose restriction in KATO III cells. CONCLUSIONS: The findings of this research clearly showed that some controversial results in clinical trials for ketogenic diet in cancer patients stemmed from the different signaling responses of various cells to the metabolic changes in a heterogeneous cancer mass.
Asunto(s)
Ácido 3-Hidroxibutírico , Transición Epitelial-Mesenquimal , Glucosa , Transducción de Señal , Neoplasias Gástricas , Transición Epitelial-Mesenquimal/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Humanos , Línea Celular Tumoral , Ácido 3-Hidroxibutírico/farmacología , Ácido 3-Hidroxibutírico/metabolismo , Glucosa/metabolismo , Cetosis/metabolismo , Regulación Neoplásica de la Expresión Génica , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Receptores de Hialuranos/metabolismo , Receptores de Hialuranos/genéticaRESUMEN
INTRODUCTION: Tuberculosis (TB) is a major global health problem, and anti-tuberculosis drugs can cause severe adverse reactions. The aim of this study was to determine hematological and biochemical changes and associated risk factors in smear positive pulmonary tuberculosis patients undergoing treatment with standard protocols. METHODS: In a descriptive study, a total of 40 tuberculosis patients aged between 15-60 years were collected from hospitals in Khuzestan Province (Iran) from March 2013 to March 2014. The patients were treated with drugs (isoniazid, rifampicin, ethambutol, and pyrazinamide) during the initial two months, followed by isoniazid and rifampicin for the next four to six months. Activities of liver enzymes (ALT, AST, and ALP) and hematological parameters were recorded before and after treatment. Data were analyzed using paired samples t-test and Wilcoxon test by SPSS 16. RESULTS: After using drug treatments, hematological parameters (RBC, Hb, HCT, MCV, MCH, and MCHC), except platelet count, were changed significantly (p ≤ 0.001). Liver enzyme activities (ALT, AST, and ALP) were decreased significantly (p ≤ 0.001) after treatment. CONCLUSION: In this study, changes of hematological and biochemical parameters have been observed in patients with pulmonary tuberculosis. It can be concluded that the anti-tuberculosis treatment is associated with changes of hematological parameters and liver enzymes.