Various Terpenoids Derived from Herbal and Dietary Plants Function as PPAR Modulators and Regulate Carbohydrate and Lipid Metabolism

Several herbal plants improve medical conditions. Such plants contain many bioactive phytochemicals. Terpenoids (also called “isoprenoids”) constitute one of the largest families of natural products accounting for more than 40,000 individual compounds of both primary and secondary metabolisms. In particular, terpenoids are contained in many herbal plants, and several terpenoids have been shown to be available for pharmaceutical applications, for example, artemisinin and taxol as malaria and cancer medicines, respectively. Various terpenoids are contained in many plants for not only herbal use but also dietary use. In this paper, we describe several bioactive terpenoids contained in herbal or dietary plants, which can modulate the activities of ligand-dependent transcription factors, namely, peroxisome proliferator-activated receptors (PPARs). Because PPARs are dietary lipid sensors that control energy homeostasis, daily eating of these terpenoids might be useful for the management for obesity-induced metabolic disorders, such as type 2 diabetes, hyperlipidemia, insulin resistance, and cardiovascular diseases

Potential Interest in Circulating miR-BART17-5p As a Post-Treatment Biomarker for Prediction of Recurrence in Epstein-Barr Virus-Related Nasopharyngeal Carcinoma

13301甲第4516号博士（医学）金沢大学博士論文本文Full 以下に掲載：PLOS ONE 11(9) pp.e0163609 2016. PLOS ONE. 共著者：Nobuyuki Hirai, Naohiro Wakisaka, Satoru Kondo, Mitsuharu Aga, Makiko Moriyama-Kita, Takayoshi Ueno, Yosuke Nakanishi, Kazuhira Endo, Hisashi Sugimoto, Shigeyuki Murono, Hiroshi Sato, Tomokazu Yoshizak

Functional Food Targeting the Regulation of Obesity-Induced Inflammatory Responses and Pathologies

Obesity is associated with a low-grade systemic chronic inflammatory state, characterized by the abnormal production of pro- and anti-inflammatory adipocytokines. It has been found that immune cells such as macrophages can infiltrate adipose tissue and are responsible for the majority of inflammatory cytokine production. Obesity-induced inflammation is considered a potential mechanism linking obesity to its related pathologies, such as insulin resistance, cardiovascular diseases, type-2 diabetes, and some immune disorders. Therefore, targeting obesity-related inflammatory components may be a useful strategy to prevent or ameliorate the development of such obesity-related diseases. It has been shown that several food components can modulate inflammatory responses in adipose tissue via various mechanisms, some of which are dependent on peroxisome proliferator-activated receptor γ (PPARγ), whereas others are independent on PPARγ, by attenuating signals of nuclear factor-κB (NF-κB) and/or c-Jun amino-terminal kinase (JNK). In this review, we introduce the beneficial effects of anti-inflammatory phytochemicals that can help prevent obesity-induced inflammatory responses and pathologies

Potent PPARα Activator Derived from Tomato Juice, 13-oxo-9,11-Octadecadienoic Acid, Decreases Plasma and Hepatic Triglyceride in Obese Diabetic Mice

Dyslipidemia is a major risk factor for development of several obesity-related diseases. The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that regulates energy metabolism. Previously, we reported that 9-oxo-10,12-octadecadienoic acid (9-oxo-ODA) is presented in fresh tomato fruits and acts as a PPARα agonist. In addition to 9-oxo-ODA, we developed that 13-oxo-9,11-octadecadienoic acid (13-oxo-ODA), which is an isomer of 9-oxo-ODA, is present only in tomato juice. In this study, we explored the possibility that 13-oxo-ODA acts as a PPARα agonist in vitro and whether its effect ameliorates dyslipidemia and hepatic steatosis in vivo. In vitro luciferase assay experiments revealed that 13-oxo-ODA significantly induced PPARα activation; moreover, the luciferase activity of 13-oxo-ODA was stronger than that of 9-oxo-ODA and conjugated linoleic acid (CLA), which is a precursor of 13-oxo-ODA and is well-known as a potent PPARα activator. In addition to in vitro experiment, treatment with 13-oxo-ODA decreased the levels of plasma and hepatic triglycerides in obese KK-Ay mice fed a high-fat diet. In conclusion, our findings indicate that 13-oxo-ODA act as a potent PPARα agonist, suggesting a possibility to improve obesity-induced dyslipidemia and hepatic steatosis

T-status and an oral fluoropyrimidine, S-1, adjuvant chemotherapy are prognostic factors in reduced-RADPLAT for resectable hypopharyngeal cancer

Conclusion: Reduced-RADPLAT for HPC achieved comparative survival and locoregional control rates with lower toxicities compared with concurrent chemoradiotherapies including original RADPLAT. S-1 adjuvant chemotherapy showed a survival benefit. Objectives: To evaluate the efficacy and toxicities of targeted intra-arterial (IA) infusion of cisplatin with concurrent radiotherapy with a reduced dose (reduced-RADPLAT) for resectable hypopharyngeal cancer (HPC). Methods: Between 1999–2012, 50 patients with stage II–IVA HPC primarily treated by reduced-RADPLAT were analyzed. They were treated by 2–5 courses of IA cisplatin infusion (100 mg per body) with simultaneous systemic infusion of sodium thiosulfate concurrent with conventional radiotherapy (66–70 Gy). After 2003, S-1, an oral fluoropyrimidine, adjuvant chemotherapy was administered to all eligible patients. Results: During a median follow-up of 48.6 months, the estimated 3- and 5-year overall survival (OS), progression-free survival (PFS), locoregional control, and laryngoesophageal dysfunction-free survival (LEDFS) rates were 76.0% and 62.0%, 58.0% and 50.0%, 66.0% and 62.0%, and 56.0% and 54.0%, respectively. Grade 3 toxicities were observed in 30.0%. No patient had grade 4 or higher toxicities. No patient required tube feeding or tracheotomy at 3 months after treatment. T4-lesions and S-1 administration were significant factors predicting poor and good OS, PFS, and LEDFS, respectively. © 2016 Informa UK Limited, trading as Taylor & Francis GroupEmbargo Period 12 month

慢性肝内胆汁うっ滞の肝胆道シンチグラフィ-原発性硬化性胆管炎の診断を主体に-

金沢大学大学院医学系研究

Expression of secreted protein acidic and rich in cysteine is an independent prognostic indicator of a poor clinical outcome in oropharyngeal carcinoma patients

Conclusion: SPARC-expression is an indicator of the prognosis in terms of OS, independent of HPV-infection. HPV-negative patients with SPARC-Low show survival as favorable as HPV-positive patients, probably because of their higher salvage rate after relapse than SPARC-High patients. Objective: The objectives of the study were to clarify the correlation between the expression of secreted protein acidic and rich in cysteine (SPARC) and HPV-status, and to determine the prognostic value of SPARC-expression in oropharyngeal squamous cell carcinoma (OPSCC) patients. Methods: Fifty-three formalin-fixed and paraffin-embedded tissues were obtained from patients with OPSCC who underwent curative treatment. The SPARC protein was detected by immunohistochemistry. SPARC-expression level was divided into two categories, SPARC-High and SPARC-Low, according to the staining index. Results: Twenty-two out of the 53 OPSCC patients were HPV-positive. There was no significant correlation between the HPV-status and SPARC-expression level. Multivariate Cox proportional hazards regression analysis revealed that the HPV-status and SPARC-expression are independent prognostic indicators of favorable and unfavorable overall survival (OS) (p = 0.021 and p = 0.012), respectively. For disease-free survival, the HPV-status was the only predictive factor (p = 0.022). After stratification by the HPV-status, high SPARC-expression was a significant predictor of poor OS in HPV-negative OPSCC patients using Kaplan-Meier analysis and the log-rank test (p = 0.014). Ten out of 28 SPARC-Low patients relapsed, among which six patients (60%) were salvaged. However, 14 out of 25 SPARC-High patients relapsed, and only three patients (21.4%) were salvaged. © 2015 Taylor & Francis.Embargo Period 12 month