Synergistic Anti-tumor Effect of Dichloroacetate and Ivermectin.

We formerly reported that the combination of dichloroacetate, omeprazole, and tamoxifen blocked cancer progression by reducing lactic acid production and inducing superoxide production. Recently, ivermectin, a well-known anti-parasite drug, was reported to share the same mechanisms with them and have anti-tumor activity. Here, we present three patients in whom the combination of dichloroacetate, omeprazole (plus tamoxifen), and ivermectin dramatically relieved the symptoms accompanying cancer and sarcoma progression.

Dietary intake and dinner timing among shift workers in Japan.

OBJECTIVES: Shift workers are at an increased risk of diet-related chronic conditions. We aimed to investigate dietary intake and dinner timing among shift workers. METHODS: A questionnaire survey was administered to the employees of 43 companies in Japan between December 2013 and February 2014. The dietary intake of workers was assessed through a validated food frequency questionnaire (FFQ). Nutrient intake was evaluated by adjusting the total energy intake using a nutrient residual model. Analysis of covariance was used to obtain the means of total energy and nutrient intake by the work schedule (shift or daytime), and the means of total energy and nutrient intake by dinner timing (regular or irregular). RESULTS: Valid responses were obtained from 2,062 daytime and 302 shift workers. A valid response rate to the FFQ was slightly but significantly lower among shift workers than among daytime workers (87.1% and 91.8 %). When compared to daytime workers, shift workers were more likely to eat dinner at irregular times (46.7% vs. 3.6%). Shift work was associated with a higher mean body mass index (23.4 kg/m2 vs. 22.3 kg/m2), a higher proportion of being overweight (27.7% and 18.8%), higher total energy intake, and lower intakes of dietary fiber, vitamin B2, folic acid, vitamin C, potassium, calcium, magnesium and iron. Moreover, irregular dinner timing was associated with lower intakes of protein, folic acid, and zinc in daytime workers, and lower intakes of carbohydrate and copper in shift workers. CONCLUSIONS: These findings indicate a need to improve the diet of shift workers.

ATM is the predominant kinase involved in the phosphorylation of histone H2AX after heating.

Heating induces histone H2AX phosphorylation at serine 139 (gammaH2AX). Phosphorylated H2AX subsequently forms foci in numerous mammalian cell lines. The aim of this study was to clarify details in the mechanisms involved in the phosphorylation of H2AX after heating. The cell lines used were DNA-PKcs knockout cells, ATM knockout cells, and their parental cell lines. To elucidate mechanisms of induction of phosphorylation of H2AX after heating, ATM/ATR inhibitor (CGK733) and DNA-PK inhibitor (NU7026) were used. The intensity of gammaH2AX signals was assayed with flow cytometry. The thermal dose-response curve for the fluorescence intensity of gammaH2AX appearance in DNA-PKcs-/- cells during the heating period was similar to that observed in DNA-PKcs+/+ cells. On the other hand, the slope of thermal dose-response curve for them in ATM-/- cells was lower than that in ATM+/+ cells. Phosphorylation of H2AX after heating was suppressed by a combination of CGK733 and NU7026 in the culture medium in DNA-PKcs-/- cells, ATM-/- cells and in their parental cells. Although the phosphorylation of H2AX after heating was not suppressed by NU7026 in their parental cells, such phosphorylation was suppressed by CGK733 in their parental cells. These results indicate that ATM is the predominant protein which is active in the phosphorylation of histone H2AX after heating.