• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4161-4168
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• 2015

Colorectal cancer (CRC) is a worldwide health problem, being the third most commonly detected cancer in males and the second in females. Rising CRC incidence trends are mainly regarded as a part of the rapid 'Westernization' of life-style and are associated with calorically excessive high-fat/low-fibre diet, consumption of refined products, lack of physical activity, and obesity. Most recent epidemiological and clinical investigations have consistently evidenced a significant relationship between obesity-driven inflammation in particular steps of colorectal cancer development, including initiation, promotion, progression, and metastasis. Inflammation in obesity occurs by several mechanisms. Roles of imbalanced metabolism (MetS), distinct immune cells, cytokines, and other immune mediators have been suggested in the inflammatory processes. Critical mechanisms are accounted to proinflammatory cytokines (e.g. IL-1, IL-6, IL-8) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$). These molecules are secreted by macrophages and are considered as major agents in the transition between acute and chronic inflammation and inflammation-related CRC. The second factor promoting the CRC development in obese individuals is altered adipokine concentrations (leptin and adiponectin). The role of leptin and adiponectin in cancer cell proliferation, invasion, and metastasis is attributable to the activation of several signal transduction pathways (JAK/STAT, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase (PI3K), mTOR, and 5'AMPK signaling pathways) and multiple dysregulation (COX-2 downregulation, mRNA expression).

• 대한한방종양학회지
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• 제9권1호
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• pp.53-63
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• 2003

This study was analyzed the effects of blood-activating and stasis-eliminating herbs on anti-tumor and hematogenic metastasis. The metastasis and recurrence of tumor was the basis of yudok(yudu) on remained tumor cell and stagnation of blood, thermotoxo, phlegm, asthenia of healthy enerngy, stagnation of vital energy. Malignant tumor is caused by carcinogen and go through the progress of initiation, promotion, progression, it is closely related with Eohyul$(y{\grave{u}}xi {\breve{e}})$. Symptoms of blood stasis disease are purplish tongue, mass, fixed stabbing pain, ecchymosis of nail, hypodermic petechia, dermal thesaurismosis, melena, ecchymoma, disturbance of circulation. Effects on the therapy of activating blood circulation and congestion are anti-tumor, anti-coagulation, anti-hemolysis, anti-solution, anti-inflammation, anti-infection, control of blood circulations, control of connective tissue metabolism and control of immunity. They can directly kill the cancer cells entering the blood circulation, inhibit the formation of tumor embody and reduce the blood hyperviscosity. It is suggested that these herbs can be used to prevent and treat blood metastasis of cancer under the guidance of syndrome differentiation.

• Journal of Ginseng Research
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• 제46권2호
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• pp.266-274
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• 2022

Colon cancer, the third most frequent occurred cancer, has high mortality and extremely poor prognosis. Ginsenoside, the active components of traditional Chinese herbal medicine Panax ginseng, exerts antitumor effect in various cancers, including colon cancer. However, the detailed molecular mechanism of Ginsenoside in the tumor suppression have not been fully elucidated. Here, we chose the representative ginsenoside Rg3 and reported for the first time that Rg3 induces mitophagy in human colon cancer cells, which is responsible for its anticancer effect. Rg3 treatment leads to mitochondria damage and the formation of mitophagosome; when autophagy is inhibited, the clearance of damaged mitochondria can be reversed. Next, our results showed that Rg3 treatment activates the PINK1-Parkin signaling pathway and recruits Parkin and ubiquitin proteins to mitochondria to induce mitophagy. GO analysis of Parkin targets showed that Parkin interacts with a large number of mitochondrial proteins and regulates the molecular function of mitochondria. The cellular energy metabolism enzyme GAPDH is validated as a novel substrate of Parkin, which is ubiquitinated by Parkin. Moreover, GAPDH participates in the Rg3-induced mitophagy and regulates the translocation of Parkin to mitochondria. Functionally, Rg3 exerts the inhibitory effect through regulating the nonglycolytic activity of GAPDH, which could be associated with the cellular oxidative stress. Thus, our results revealed GAPDH ubiquitination by Parkin as a crucial mechanism for mitophagy induction that contributes to the tumor-suppressive function of ginsenoside, which could be a novel treatment strategy for colon cancer.

• 생명과학회지
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• 제28권7호
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• pp.874-883
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• 2018

전 세계적인 인구 고령화 현상으로 인하여 골다공증은 주요한 질병으로 대두되고 있다. 골다공증은 뼈의 질량과 강도가 감소하여 골절의 위험이 증가하는 질환으로 조골세포의 골 형성 및 파골세포의 골 흡수의 불균형으로 인해 발생하는 질환이다. 조골세포에 의한 골 형성은 BMP, RUNX2, $Wnt/{\beta}-catenin$ 경로 등을 통하여 활성화 되며, 파골세포에 의한 골 흡수는 RANKL과 RANK의 결합에 의해서 시작된다. 폐경기 여성은 호르몬 불균형에 의해 여러 질병의 위험에 처해 있으며, 폐경기 여성의 약 30%에서 관찰되는 골다공증은 폐경기 여성에게서 발생되는 가장 흔한 대사성 질환이기도 하다. Estrogen이 부족할 때 파골세포의 골 흡수가 촉진되므로, 특히 폐경 여성에서 골다공증의 발생위험이 증가하게 된다. 호르몬대체요법은 폐경기 증후군의 증상을 경감시키거나 치료하기 위해 널리 사용되어 왔으나, 호르몬 치료를 장기간 실시할 경우 유방암, 난소암, 자궁암 등의 부작용 위험성이 매우 높은 것으로 알려져 있다. 따라서 최근 들어 여러 부작용을 보완하기 위해 폐경기 증후군 증상에 대처할 수 있는 estrogen과 유사한 활성을 지닌 식물성 estrogen인 phytoestrogen에 대한 연구가 활발히 진행되고 있다. 따라서, 본 총설에서는 조골세포 및 파골세포의 분화 기전에 대한 선행연구를 알아보고 골 대사에서의 estrogen의 역할 및 phytoestrogen과 관련한 연구들에 대해서도 살펴보았다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4347-4351
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• 2015

Background: Previous studies showed that genetic polymorphisms of glutathione S-transferase P1 (GSTP1) were involved in glutathione metabolism and genetic polymorphisms of ribonucleotide reductase (RRM1) were correlated with DNA synthesis. Here we explored the effects of these polymorphisms on the chemosensitivity and clinical outcome in Chinese non-small cell lung cancer (NSCLC) patients treated with gemcitabine-cisplatin regimens. Materials and Methods: DNA sequencing was used to evaluate genetic polymorphisms of GSTP1 Ile105Val and RRM1 C37A-T524C in 47 NSCLC patients treated with gemcitabine-cisplatin regimens. Clinical response was evaluated according to RECIST criteria after 2 cycles of chemotherapy and toxicity was assessed by 1979 WHO criteria (acute and subacute toxicity graduation criteria in chemotherapeutic agents). Results: There was no statistical significance between sensitive and non-sensitive groups regarding the genotype frequency distribution of GSTP1 Ile105Val polymorphism (p>0.05). But for RRM1 C37A-T524C genotype, sensitive group had higher proportion of high effective genotype than non-sensitive group (p=0.009). And according to the joint detection of GSTP1 Ile105Val and RRM1 C37A-T524C polymorphisms, the proportion of type A (A/A + high effective genotype) was significantly higher in sensitive group than in non-sensitive group (p=0.009). Toxicity showed no correlation with the genotypes between two groups (p>0.05). Conclusions: Compared with single detection of genetic polymorphisms of GSTP1 Ile105Val or RRM1 C37A-T524C, joint detection of both may be more helpful for patients with NSCLC to receive gemcitabine-cisplatin regimens as the first-line chemotherapy. Especially, genetic polymorphism of RRM1 is more likely to be used as an important biomarker to predict the response and toxicity of gemcitabine-cisplatin combination chemotherapy in NSCLC.

• Tuberculosis and Respiratory Diseases
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• 제45권4호
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• pp.760-765
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• 1998

연구배경: 암세포에서 포도당의 유입이 증가되어 있다는 사실이 오래 전부터 알려져 왔고 이런 현상을 이용하여 FDG-PET 영상이 암의 진단에 이용되고 있다. 그러나, 암세포에서 포도당 유입이 증가하는 기전에 대해서는 모르고 있다. 최근, 여러 연구에서 소화기계의 악성종양과 두경부종양에서 포도당 운반체의 mRNA 의 존재가 증명되었고, 포도당 운반체가 암세포에서의 포도당 유입 증가와 관련이 있을 가능성을 시사하였다. 폐암에서도 포도당대사가 항진되어 있다. 저자등은 폐암에서의 포도당 유입이 증가하는 기전에 대해 알아 보기 위하여 사람 폐암세포주에서 포도당 mRNA의 발현여부를 확인하였다. 방 법: 15종의 사람 폐암 세포주와 불멸화시킨 기관지 상피세포주에서 total RNA를 추출하였다. $20{\mu}g$의 total RNA를 전기영동시킨후, 포도당 운반체 1형과 3 형에 대한 cDNA를 probe로 Northern blot analysis를 시행하였다. 결 과: 14종의 사람 폐암 세포주중에서 13종에서 포도당 운반체 1형의 mRNA 발현을 확인하였고, 14종의 사람 폐암 세포주중에서 10종에서 포도당 운반체 3형의 mRNA 발현을 확인하였다. 불멸화시킨 기관지 상피세포주의 포도당 운반체 1형의 mRNA 발현을 확인할 수 있었고 3형의 mRNA 발현은 확인할 수 없었다. 결 론: 폐암에서 포도당 대사의 증가는 포도당 운반체 1형과 3형의 발현과 관련이 있을 것으로 사료된다.

• Biomolecules & Therapeutics
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• 제23권3호
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• pp.296-300
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• 2015

${\beta}$-Lapachone has drawn increasing attention as an anti-inflammatory and anti-cancer drug. However, its oral bioavailability has not been yet assessed, which might be useful to develop efficient dosage forms possibly required for non-clinical and clinical studies and future market. The aim of the present study was thus to investigate pharmacokinetic properties of ${\beta}$-lapachone as well as its first-pass metabolism in the liver, and small and large intestines after oral administration to measure the absolute bioavailability in rats. A sensitive HPLC method was developed to evaluate levels of ${\beta}$-lapachone in plasma and organ homogenates. The drug degradation profiles were examined in plasma to assess the stability of the drug and in liver and intestinal homogenates to evaluate first-pass metabolism. Pharmacokinetic profiles were obtained after oral and intravenous administration of ${\beta}$-lapachone at doses of 40 mg/kg and 1.5 mg/kg, respectively. The measured oral bioavailability of ${\beta}$-lapachone was 15.5%. The considerable degradation of ${\beta}$-lapachone was seen in the organ homogenates but the drug was quite stable in plasma. In conclusion, we suggest that the fairly low oral bioavailability of ${\beta}$-lapachone may be resulted from the first-pass metabolic degradation of ${\beta}$-lapachone in the liver, small and large intestinal tracts and its low aqueous solubility.

• Fisheries and Aquatic Sciences
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• 제23권9호
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• pp.24.1-24.9
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• 2020

Brown alga (Ishige okamurae; IO) dietary supplements have been reported to possess anti-diabetic properties. However, the effects of IO supplements have not been evaluated on glucose metabolism in the pancreas and skeletal muscle. C57BL/6 N male mice (age, 7 weeks) were arranged in five groups: a chow diet with 0.9% saline (NFD/saline group), high-fat diet (HFD) with 0.9% saline (HFD/saline group). high-fat diet with 25 mg/kg IO extract (HFD/25/IOE). high-fat diet with 50 mg/kg IO extract (HFD/50/IOE), and high-fat diet with 75 mg/kg IO extract (HFD/75/IOE). After 4 weeks, the plasma, pancreas, and skeletal muscle samples were collected for biochemical analyses. IOE significantly ameliorated glucose tolerance impairment and fasting and 2 h blood glucose level in HFD mice. IOE also stimulated the protein expressions of the glucose transporters (GLUTs) including GLUT2 and GLUT4 and those of their related transcription factors in the pancreases and skeletal muscles of HFD mice, enhanced glucose metabolism, and regulated blood glucose level. Our results suggest Ishige okamurae extract may reduce blood glucose levels by improving glucose metabolism in the pancreas and skeletal muscle in HFD-induced diabetes.

• Journal of Microbiology and Biotechnology
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• 제31권7호
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• pp.1011-1021
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• 2021

The root bark of Ulmus davidiana var. japonica (Japanese elm) is used in Korea and other East Asian countries as a traditional herbal remedy to treat a variety of inflammatory diseases and ailments such as edema, gastric cancer and mastitis. For this study, we investigated the lipid metabolism and anti-obesity efficacy of ethyl alcohol extract of Ulmus davidiana var. japonica root bark (UDE). First, HPLC was performed to quantify the level of (+)-catechin, the active ingredient of UDE. In the following experiments, cultured 3T3-L1 pre-adipocytes and high-fat diet (HFD)-fed murine model were studied for anti-obesity efficacy by testing the lipid metabolism effects of UDE and (+)-catechin. In the test using 3T3-L1 pre-adipocytes, treatment with UDE inhibited adipocyte differentiation and significantly reduced the production of adipogenic genes and transcription factors PPARγ, C/EBPα and SREBP-1c. HFD-fed, obese mice were administered with UDE (200 mg/kg per day) and (+)-catechin (30 mg/kg per day) by oral gavage for 4 weeks. Weight gain, epididymal and abdominal adipose tissue mass were significantly reduced, and a change in adipocyte size was observed in the UDE and (+)-catechin treatment groups compared to the untreated control group (^***p < 0.001). Significantly lower total cholesterol and triglyceride levels were detected in UDE-treated HFD mice compared to the control, revealing the efficacy of UDE. In addition, it was found that lipid accumulation in hepatocytes was also significantly reduced after administration of UDE. These results suggest that UDE has significant anti-obesity and lipid metabolism effects through inhibition of adipocyte differentiation and adipogenesis.

• 대한핵의학회지
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• 제24권2호
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• pp.222-228
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• 1990

The development of histomorphometric and histodynamic investigations has permitted the description of a specific and complex osteopathy in hyperthyroidism. The increased bone turnover rate in hyperthyroid patients may be accompanied by a considerable bone loss. These features are associated with both inclosed osteoclastic bone resorption and increased osteoblastric bone formation, with an accelerated calcification rate. Conventional biochemical markers of bone metabolism, i.e. serum calcium and alkaline phosphatase and urinary hydroxyproline and calcium are normal in most patients with hyperthyroidism. However, the correlation between serum BGP and serum concentration of thyroid hormon suggests that serum BGP may be a sensitive marker of increased bone formation due to the hypersecretion of thyroid hormones. Any increase in bone turnover, whether focal or diffuse, will result in an increase in $^{99m}Tc-methylenediphosphonate$ uptake (MDP). The measurement of this uptake in hyperthyroid patients by bone provides a sensitive and objective means of quantifying skeletal metabolism. Using a standard shadow-shield whole-body monitor and radioimmunoassay kit, we have measured whole-body retention of $^{99m}Tc-MDP$ up to 24hr and concentration of serum Osteocalcin in 20 patients with hyperthyroidism and in 42 normals. The results were as follows; 1) The average of serum Osteocalcin level in 42 patients with normals was $9.90{\pm}4.87(ng/ml)$ and in 20 patients with hyperthyroidism was $19.54{\pm}5.7(ng/ml)$. Both the averages of serum Osteocalcin and 24hr $^{99m}Tc-MDP$ uptakes in hyperthyroid patients were higher than those in normals. 2) $^{99m}Tc-MDP$ uptakes in skeletal system increased in proportion to normal ageing after 40 yrs old in 42 patients with normals. The average of $^{99m}Tc-MDP$ uptakes in hyperthyroid patients were higher than those in normals without related ageing. 3) A significant relationships between the $^{99m}Tc-MDP$ uptakes and serum Osteocalcin level were peformed (r=0.55, $y=17.58+6.7\times$). From the above results we concluded that the measurement of serum Osteocalcin and 24hr $^{99m}Tc-MDP$ uptakes can be used for evaluation of bone turnover as a specific marker in hyperthyroid patients.