• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.993-1001
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• 2016

Type 2 diabetes mellitus patients are at increased risk of many forms of malignancies, especially of the pancreas, colon and hepatocellular cancer. Unfortunately, little is known of the possible interaction between antidiabetic drugs and anticancer agents. The present study investigates the influence of metformin (MET) and sitagliptin (SITA) on the in vitro anticancer activity of the microtubule depolymerization inhibitor agent epothilone A (EpoA). Hepatocellular liver carcinoma cell line (HepG2) viability and apoptosis were determined by the MTT test and by double staining with PO-PRO-1 and 7-aminoactinomycin D, respectively, after treatment with EpoA, metformin or sitagliptin. The levels of nuclear factor NF-${\kappa}B$ and p53 were evaluated in the presence and absence of inhibitors. While EpoA and MET inhibited HepG2 cell proliferation, SITA did not. EpoA and SITA induced higher p53 levels than MET. All tested drugs increased the level of NF-${\kappa}B$. Only MET enhanced the proapoptotic effect of EpoA. The EpoA+MET combination evoked the highest cytotoxic effect on HepG2 cells and led to apoptosis independent of p53, decreasing the level of NF-${\kappa}B$. These findings support the link between NF-${\kappa}B$ and p53 in the modulation of apoptotic effects in HepG2 cells treated by EpoA. Our studies indicate that the combination of EpoA and MET applied in subtoxic doses has a stronger cytotoxic effect on liver cancer cells than each of the compounds alone. The therapeutic advantages of the combination of EpoA with MET may be valuable in the treatment of patients with diabetes mellitus type 2 (T2DM) and liver cancer.

• Bulletin of the Korean Chemical Society
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• 제34권11호
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• pp.3284-3288
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• 2013

This paper describes first development and validation of pentafluorophenylprophyl ligand-based liquid chromatography coupled to tandem mass spectrometry (PFPLC-MS/MS) method to determine metformin, a highly polar compound, in human plasma. Metformin and Phenformin (internal standard) were extracted from human plasma 50 ${\mu}L$ with a single-step protein precipitation. The chromatographic separation was performed using a linear gradient elution of mobile phase involving 5.0 mM ammonium formate solution with 0.1% formic acid (A) and acetonitrile (B) over 3.0 min of run time on a Phenomenex Luna PFP column. The detection was performed using a triple-quadrupole tandem mass spectrometer (Waters Quattro micro) with electrospray ionization in the mode of positive ionization and multiple-reaction monitoring (MRM). The developed method was validated with 5.0 ng/mL of lower limit of quantification (LLOQ). The calibration curve was linear over 5-3000 ng/mL of the concentration range ($R^2$ > 0.99). The specificity, selectivity, carry-over effect, precision, accuracy and stability of the method met the acceptance criteria. The method developed in this study had had rapidness, simplicity and ruggedness. The reliable method was successfully applied to high throughput analysis of real samples for a practical purpose of a pharmacokinetic study.

• 한방비만학회지
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• 제15권1호
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• pp.24-32
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• 2015

Objectives: This study was to investigate the antioxiative capacity, antiobesity effects of Atractylodes Rhizoma Alba, Houttuyniae Herba, Lonicerae Flos, Scutellariae Radix, and Coptidis Rhizoma on Raw 264.7 and 3T3-L1 cell lines. Methods: Three different types of herb extracts (A. Rhizoma Alba, H. Herba, L. Flos, S. Radix, and C. Rhizoma; water 100%, ethanol 30%, ethanol 100%) were used in this study. Total polyphenol compound, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, reactive oxygen species (ROS) activity, NO production and cell proliferation were measured. Results: Total polyphenol compound measurement of L. Flos, A. Rhizogenes, and C. Rhizoma extracts were higher than A. Rhizoma Alba, H. Herba. DPPH radical scavenging activity, ROS activity and NO production of S. Radix, C. Rhizoma extracts were lower than L. Flos, A. Rhizoma, and H. Herba. Conclusions: Metformin and S. Radix, C. Rhizoma, A. Rhizoma Alba, and L. Flos extracts combination groups showed synergistic effect on adipocyte differentiation inhibition and antioxidative activity.

• The Korean Journal of Physiology and Pharmacology
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• 제17권5호
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• pp.455-461
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• 2013

Retinoids regulate not only various cell functions including proliferation and differentiation but also glucose and lipid metabolism. After we observed a marked up-regulation of cellular retinol-binding protein-I (CRBP-I) in the liver of hepatitis B virus x antigen (HBx)-transgenic (HBx Tg) mice which are prone to hepatocellular carcinoma (HCC) and fatty liver, we aimed to evaluate retinoid pathway, including genes for the retinoid physiology, CRBP-I protein expression, and retinoid levels, in the liver of HBx Tg mice. We also assessed the effect of chronic metformin treatment on HCC development in the mice. Many genes involved in hepatic retinoid physiology, including CRBP-I, were altered and the tissue levels of retinol and all-trans retinoic acid (ATRA) were elevated in the liver of HBx Tg mice compared to those of wild type (WT) control mice. CRBP-I protein expression in liver, but not in white adipose tissue, of HBx Tg mice was significantly elevated compared to WT control mice while CRBP-I protein expressions in the liver and WAT of high-fat fed obese and db/db mice were comparable to WT control mice. Chronic treatment of HBx Tg mice with metformin did not affect the incidence of HCC, but slightly increased hepatic CRBP-I level. In conclusion, hepatic CRBP-I level was markedly up-regulated in HCC-prone HBx Tg mice and neither hepatic CRBP-I nor the development of HCC was suppressed by metformin treatment.

• 한국산학기술학회논문지
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• 제16권11호
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• pp.7549-7554
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• 2015

본 이 연구의 목적은 부유 기술을 이용하여 제형이 위에 더 오래도록 머무르면서 약물을 지속적으로 방출하는 이중정을 개발하는 것이다. 실험방법으로는 메트포르민을 주 약물로 선정하였는데, 그 이유는 메트포르민은 주로 소장 상부에서만 흡수되는 좁은 흡수 영역 대를 가지고 있는 점, 용해도가 매우 높아 약물 방출을 조절하는 것이 쉽지 않은 점 등 때문이다. 정제의 부유를 위한 가스를 생성하는 부분과 약물의 방출을 조절하는 부분의 간섭을 최소화하기 위해 이중정 타정 기를 사용해 이중정으로 제조하였으며, 정제의 모양, 질량 및 경도를 측정하였고, 부유정의 중요한 요소인 부유 촉발시간과 부유유지 시간을 평가하였다. 또, 약물의 방출 조절을 평가하기 위해 용출시험을 시행하였으며, 그 결과를 시판되고 있는 메트포르민 서방성 제제인 Glucopharge XR$^{(R)}$과 비교평가 하였다. 그 결과, 부유 촉발제인 $NaHCO_3$ 및 약물 방출 조절제인 hydroxypropyl methylcellulose (HPMC)의 사용량에 따라 13초의 부유 촉발시간, 10시간 이상의 부유 유지시간 및 시판 제제와 매우 유사한 약물 방출 거동을 확인할 수 있었다 ($f_2$: 89.6). 결론적으로 메트포르민을 함유한 위 체류 이중정을 성공적으로 개발할 수 있었으며, 그로 인해 메트포르민의 치료효과도 극대화 할 수 있을 것으로 예상된다.

• 대한임상약리학회:학술대회논문집
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• 대한임상약리학회 2006년도 제15차 추계학술대회
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• pp.96-96
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• 2006

• 대한임상약리학회:학술대회논문집
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• 대한임상약리학회 2006년도 제15차 추계학술대회
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• pp.71-71
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• 2006

• Translational and Clinical Pharmacology
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• 제26권3호
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• pp.143-143
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• 2018

• Bulletin of the Korean Chemical Society
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• 제33권11호
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• pp.3640-3644
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• 2012

An efficient synthetic method for direct Henry reaction catalyzed by a biguanide; namely metformin, as an organosuper-base, between a variety of aromatic and aliphatic aldehydes and nitromethane under neat conditions has been developed. Convenient procedure for removal of the catalyst, chemoselective acquiring of ${\beta}$-nitroalcohols as predominant products, as far as possible short reaction time with excellent conversions are advantages of the developed protocol.

• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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• pp.5143-5148
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• 2012

Objective: The aim was to investigate indicators related to DNA damage and cancer pathogenesis in Type II diabetes cases with breast cancer. It was planned to evaluate the relationship between these markers with oral antidiabetic drugs. Research Design and Methods: Fourty patients and 10 healthy individuals were included in the study. HIF-$1{\alpha}$ and 8-OHdG are examined in blood samples taken from these individuals with an ELISA Kit. Statistical analysis of data was performed with 95% confidence using Windows package program SPSS 15.0. Results: HIF-$1{\alpha}$ parameters were found to be meaningfully higher in the patient group than the controls in both pretreatment and posttreatment periods (p<0.05). No significant differences in terms of 8-OHdG between patients and controls. However, posttreatment serum HIF-$1{\alpha}$ ve 8-OHdG levels was found lower than pretreatment levels in patients receiving metformin, but not with pioglitazone. Conversely, serum 8-OHdG levels decreased significantly in these patients. When patients were evaluated according to the treatment groups (pioglitazone vs. metfformin) no significant differences in terms of serum HIF-$1{\alpha}$ and 8-OHdG levels between treatment groups. Conclusions: HIF-$1{\alpha}$ levels decreased significantly in the patient group receiving metformin. However, there was no significant difference in terms of HIF-$1{\alpha}$ levels in the patients receiving pioglitazone.