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Nishi-Tokyo-shi, Japan

Kanai M.,Kyoto University | Yoshimura K.,Kyoto University | Asada M.,Kitano Hospital | Imaizumi A.,Theravalues Corporation | And 11 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2011

Purpose: Curcumin, a plant-derived natural polyphenol, could be a promising anti-cancer drug and shows synergic effects with cytotoxic agents. We evaluated the safety and feasibility of combination therapy using curcumin with gemcitabine-based chemotherapy. Methods: Gemcitabine-resistant patients with pancreatic cancer received 8 g oral curcumin daily in combination with gemcitabine-based chemotherapy. The primary endpoint was safety for phase I and feasibility of oral curcumin for phase II study. Results: Twenty-one patients were enrolled. No dose-limiting toxicities were observed in the phase I study and oral curcumin 8 g/day was selected as the recommended dose for the phase II study. No patients were withdrawn from this study because of the intolerability of curcumin, which met the primary endpoint of the phase II study, and the median compliance rate of oral curcumin was 100% (Range 79-100%). Median survival time after initiation of curcumin was 161 days (95% confidence interval 109-223 days) and 1-year survival rate was 19% (4.4-41.4%). Plasma curcumin levels ranged from 29 to 412 ng/ml in five patients tested. Conclusions: Combination therapy using 8 g oral curcumin daily with gemcitabine-based chemotherapy was safe and feasible in patients with pancreatic cancer and warrants further investigation into its efficacy. © 2010 Springer-Verlag. Source

Theravalues Corporation | Date: 2013-01-29

Dietary and nutritional supplements, health food supplements, vitamin supplements, nutritional drinks used for meal replacement, powdered nutritional supplement drink mix, medicated candy, fodder additives for medical purposes, turmeric supplements; herbal supplements, namely, turmeric.

Tanabe Y.,University of Tsukuba | Maeda S.,University of Tsukuba | Akazawa N.,University of Tsukuba | Zempo-Miyaki A.,University of Tsukuba | And 5 more authors.
European Journal of Applied Physiology | Year: 2015

Purpose: Polyphenolic curcumin is known to have potent anti-inflammatory effects; thus the present study investigated the hypothesis that curcumin ingestion would attenuate muscle damage after eccentric exercise. Methods: Fourteen untrained young men (24 ± 1 years) performed 50 maximal isokinetic (120°/s) eccentric contractions of the elbow flexors of one arm on an isokinetic dynamometer and the same exercise with the other arm 4 weeks later. They took 150 mg of curcumin (theracurmin) or placebo (starch) orally before and 12 h after each eccentric exercise bout in a randomised, crossover design. Maximal voluntary contraction (MVC) torque of the elbow flexors, range of motion of the elbow joint, upper-arm circumference, muscle soreness, serum creatine kinase (CK) activity, and plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentration were measured before, immediately after, and 24, 48, 72 and 96 h after each eccentric exercise. Changes in these variables over time were compared between curcumin and placebo conditions by two-way repeated measures ANOVA. Results: MVC torque decreased smaller and recovered faster (e.g., 4 days post-exercise: −31 ± 13 % vs. −15 ± 15 %), and peak serum CK activity was smaller (peak: 7684 ± 8959 IU/L vs. 3398 ± 3562 IU/L) for curcumin than placebo condition (P < 0.05). However, no significant differences between conditions were evident for other variables, and no significant changes in IL-6 and TNF-α were evident after exercise. Conclusion: It is concluded that theracurmin ingestion attenuates some aspects of muscle damage such as MVC loss and CK activity increase. © 2015, The Author(s). Source

Kawanishi N.,Waseda University | Kato K.,Waseda University | Takahashi M.,Waseda University | Mizokami T.,Waseda University | And 5 more authors.
Biochemical and Biophysical Research Communications | Year: 2013

Downhill running causes muscle damage, and induces oxidative stress and inflammatory reaction. Recently, it is shown that curcumin possesses anti-oxidant and anti-inflammatory potentials. Interestingly, curcumin reduces inflammatory cytokine concentrations in skeletal muscle after downhill running of mice. However, it is not known whether curcumin affects oxidative stress after downhill running-induced muscle damage. Therefore, the purpose of this study was to investigate the effects of curcumin on oxidative stress following downhill running induced-muscle damage. We also investigated whether curcumin affects macrophage infiltration via chemokines such as MCP-1 and CXCL14. Male C57BL/6 mice were divided into four groups; rest, rest plus curcumin, downhill running, or downhill running plus curcumin. Downhill running mice ran at 22. m/min, -15% grade on the treadmill for 150. min. Curcumin (3. mg) was administered in oral administration immediately after downhill running. Hydrogen peroxide concentration and NADPH-oxidase mRNA expression in the downhill running mice were significantly higher than those in the rest mice, but these variables were significantly attenuated by curcumin administration in downhill running mice. In addition, mRNA expression levels of MCP-1, CXCL14 and F4/80 reflecting presence of macrophages in the downhill running mice were significantly higher than those in the rest mice. However, MCP-1 and F4/80 mRNA expression levels were significantly attenuated by curcumin administration in downhill running mice. Curcumin may attenuate oxidative stress following downhill running-induced muscle damage. © 2013 Elsevier Inc. Source

Kanai M.,Kyoto University | Otsuka Y.,Theravalues Corporation | Otsuka K.,Akita University | Sato M.,Hokkaido Information University | And 11 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2013

Background: A growing number of preclinical studies have demonstrated that curcumin could be a promising anticancer drug; however, poor bioavailability has been the major obstacle for its clinical application. To overcome this problem, we developed a new form of curcumin (Theracurmin®) and reported high plasma curcumin levels could be safely achieved after a single administration of Theracurmin® in healthy volunteers. In this study, we aimed to evaluate the safety of repetitive administration of Theracurmin® in cancer patients. Methods: Pancreatic or biliary tract cancer patients who failed standard chemotherapy were eligible for this study. Based on our previous pharmacokinetic study, we selected Theracurmin® containing 200 mg of curcumin (Level 1) as a starting dose, and the dose was safely escalated to Level 2, which contained 400 mg of curcumin. Theracurmin® was orally administered every day with standard gemcitabine-based chemotherapy. In addition to safety and pharmacokinetics data, NF-κB activity, cytokine levels, efficacy, and quality-of-life score were evaluated. Results: Ten patients were assigned to level 1 and six were to level 2. Peak plasma curcumin levels (median) after Theracurmin® administration were 324 ng/mL (range, 47-1,029 ng/mL) at Level 1 and 440 ng/mL (range, 179-1,380 ng/mL) at Level 2. No unexpected adverse events were observed and 3 patients safely continued Theracurmin® administration for >9 months. Conclusions: Repetitive systemic exposure to high concentrations of curcumin achieved by Theracurmin® did not increase the incidence of adverse events in cancer patients receiving gemcitabine-based chemotherapy. © 2013 Springer-Verlag Berlin Heidelberg. Source

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