Nicotinamide in Combination with EGFR-TKIs for the Treatment of Stage IV Lung Adenocarcinoma with EGFR Mutations: A Randomized Double-Blind (Phase IIb) Trial.

PURPOSE: RUNX3 is a tumor suppressor gene, which is inactivated in approximately 70% of lung adenocarcinomas. Nicotinamide, a sirtuin inhibitor, has demonstrated potential in re-activating epigenetically silenced RUNX3 in cancer cells. This study assessed the therapeutic benefits of combining nicotinamide with first-generation EGFR-tyrosine kinase inhibitors (TKI) for patients with stage IV lung cancer carrying EGFR mutations. PATIENTS AND METHODS: We assessed the impact of nicotinamide on carcinogen-induced lung adenocarcinomas in mice and observed that nicotinamide increased RUNX3 levels and inhibited lung cancer growth. Subsequently, 110 consecutive patients with stage IV lung cancer who had EGFR mutations were recruited: 70 females (63.6%) and 84 never-smokers (76.4%). The patients were randomly assigned to receive either nicotinamide (1 g/day, n = 55) or placebo (n = 55). The primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively. RESULTS: After a median follow-up of 54.3 months, the nicotinamide group exhibited a median PFS of 12.7 months [95% confidence interval (CI), 10.4-18.3], while the placebo group had a PFS of 10.9 months (9.0-13.2; P = 0.2). The median OS was similar in the two groups (31.0 months with nicotinamide vs. 29.4 months with placebo; P = 0.2). Notably, subgroup analyses revealed a significant reduction in mortality risk for females (P = 0.01) and never-smokers (P = 0.03) treated with nicotinamide. CONCLUSIONS: The addition of nicotinamide with EGFR-TKIs demonstrated potential improvements in PFS and OS, with notable survival benefits for female patients and those who had never smoked (ClinicalTrials.gov Identifier: NCT02416739).

Verification of efficacy as an ergogenic aid and safety in doping of sibjeondaebo-tang.

PURPOSE: Various kinds of food substances from all over the world have been proposed to use as ergogenic aids for the additional improvement of exercise performance especially in athletes. Herb medicine which usually being applied for the cure of disease is used as a performance booster in several far eastern countries including Korea. Many scientists and coaches have asked very objective verifications on the reality of herb medicines practically used but never been scientifically elucidated well enough. In addition to the possibility as an ergogenic aid, the safety in doping is the critical factor to be examined thoroughly. In this study, Sibjeondaebo-Tang, a leading popular prescribed herb medicine in Korea, was examined. METHODS: After the intake of Sibjeondaebo-Tang, its effects on VO2max, recovery from fatigue, and doping safety through the official process as WADA suggested. Six volunteered male Taekwondo Pumsae players were subjected in a repeatedly examined protocol. RESULTS: First of all, every subjects showed 'negative' in doping test, and the treatment did not show any significant improvement on VO2max even though there was a significant decrease in blood lactate level on a step test. CONCLUSION: In conclusion, Sibjeondaebo-Tang may have some limited effects as a fatigue delayer and the use of it showed safe to doping test with the strict limitation as the way in this study. So we should abstain from the over-interpreted application of the results so far.

Effects of vitamin D supplementation and circuit training on indices of obesity and insulin resistance in T2D and vitamin D deficient elderly women.

PURPOSE: The purpose of this study was to investigate the effects of vitamin D supplementation and circuit training on body composition, abdominal fat, blood lipids, and insulin resistance in T2D and vitamin D deficient elderly women. METHODS: Fifty-two elderly women were randomly assigned to either the vitamin D supplementation with circuit training group (D+T: n = 15), the circuit training group (T: n = 13), the vitamin D supplementation group (D: n = 11), or the control group (CON: n = 13). The subjects in D took vitamin D supplements at 1,200 IU per day for 12 weeks; the subjects in T exercised 3 to 4 times per week, 25 to 40 minutes per session for 12 weeks; and the subjects in D+T participated in both treatments. Subjects in CON were asked to maintain normal daily life pattern for the duration of the study. Body composition, abdominal fat, blood lipids, and surrogate indices for insulin resistance were measured at pre- and post-test and the data were compared among the four groups and between two tests by utilizing two-way ANOVA with repeated measures. The main results of the present study were as follows: RESULTS: 1) Body weight, fat mass, percent body fat, and BMI decreased significantly in T, whereas there were no significant changes in the variables in D and CON. Lean body mass showed no significant changes in all groups. 2) TFA and SFA decreased significantly in T, whereas there were no significant changes in the variables in D and CON. The other abdominal fat related variables showed no significant changes in all groups. 3) TC, TG, HDL-C, and LDL-C showed improvements in T, whereas there were no significant changes in the variables in D and CON. 4) Fasting glucose, fasting insulin, and HOMA-IR tended to be lower in D+T. CONCLUSION: It was concluded that the 12 weeks of vitamin D supplementation and circuit training would have positive effects on abdominal fat and blood lipid profiles in T2D and vitamin D deficient elderly women. Vitamin D supplementation was especially effective when it was complemented with exercise training.

Crystal structure of tuguaconitine, a diterpene alkaloid from Aconitum sibiricum.

The three-dimensional structure of a natural product, tuguaconitine (C23H35NO7) from Aconitumrn sibiricum was determined by single crystal X-ray diffraction analysis. The compound was recrystallized from a methanol solution into orthorhombic crystal system, with a = 18.093(4), b = 12.075(11), c = 9.824(4) A, Dm = 1.35, Dx= 1.354 g/cm3, space group P2(1)2(1)2(1), and Z=4. The structure was solved by direct method and refined by least-squares procedure to the final R value of 0.046 for 1495 observed reflections with I > or = 2sigma(I). Aconitines are diterpene alkaloid composed of six rings. In the molecule, two 6-membered rings have stable chair conformation, but other two 6-membered rings have unstable boat conformation because of their bonding strain and hydrogen bonds. Based on the three-dimensional structure of tuguaconitine, we suggest another 2D-diagram for the compound which is far better in imagination of the spatial shape of the molecule than the ordinary one.