• Journal of Digestive Cancer Research
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• 제4권2호
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• pp.64-76
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• 2016

The step-wise process of colorectal carcinogenesis from aberrant crypt foci, adenoma to adenocarcinoma, is relatively suitable for chemopreventive intervention. Accumulated evidences have revealed that maintaining an undifferentiated state (stemness), inflammation, and oxidative stress play important roles in this colon carcinogenesis process. However, appropriate molecular targets that are applicable to chemopreventive intervention regarding those three factors are still unclear. In this review, we summarized appropriate molecular targets by identification and validation of the prospective targets from a comprehensive overview of data that showed colon cancer preventive effects in clinical trials, epidemiological studies and basic research. We first selected a study that used aspirin, statins and metformin from FDA approved drugs, and epigallocatechin-gallate and curcumin from natural compounds as potential chemopreventive agents against colon cancer because these agents are considered to be promising chemopreventive agents. Experimental and observational data revealed that there are common target molecules in these potential chemopreventive agents: T-cell factor/lymphoid enhancer factor (TCF/LEF), nuclear factor-&B (NF-κB) and nuclear factor-erythroid 2-related factor 2(NRF2). Moreover, these targets, TCF/LEF, NF-κB and NRF2, have been also indicated to suppress maintenance of the undifferentiated state, inflammation and oxidative stress, respectively. In the near future, novel promising candidate agents for colon cancer chemoprevention could be identified by integral evaluation of their effects on these three transcriptional activities.

• 지식경영연구
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• 제21권3호
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• pp.105-121
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• 2020

신약 개발과 관련하여 글로벌 판매망이 구축되지 않은 국내 바이오텍에게 가장 필요한 것은 신약의 기술이전과 관련된 의사 결정이다. 각 임상 단계별 성공 확률이 다르고, 어느 임상 단계에서 기술이전 계약을 하느냐에 따라서 총 계약금액과 로열티가 달라지게 된다. 이런 기술이전 계약의 특징과 바이오텍의 취약한 재무 구조 등으로 인하여, 바이오텍이 빅파마에게 기술 이전을 하는 시기를 정하는 것은 매우 중요한 의사 결정 문제가 된다. 이 연구에서는 '신약의 기술이전 최적시기 결정 문제'라는 연구모형을 제시하고, 의사결정트리 방법론으로 결과를 도출하였다. 사례 연구로, first-in-class 신약을 대상으로 FDA 글로벌 임상을 진행하고 있는 국내 바이오텍에 적용해 보았다. 타겟 질환의 시장 크기와 예상 시장 침투율은 알려져 있다고 가정하였을 때, 임상 1상이나 2상 이후에 기술이전을 하는 것이 이익을 최대화할 수 있는 대안임을 알 수 있었다. 본 연구는 제약 분야 문제에 경영과학 방법론을 사용할 수 있는 개념적인 틀을 제시하여 신약 기술이전에 대한 지식 및 연구의 기반이 될 수 있을 것으로 기대된다.

• 셀메드
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• 제5권4호
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• pp.22.1-22.7
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• 2015

Depression is an important medical problem in today's world. Despite its high prevalence, treatment of depression remains problematic, as its cause is still not fully understood. Of the ways recommended to tackle this problem is implementing the potentials of various medical schools. A medical school which has played an important role in the history of medicine in the world is Persian medicine. This study was intended to identify non-pharmacological interventions for depression in the most reliable references on Persian medicine, classify these interventions and compare them with the latest medical findings. The study was set to review the most reliable references on Persian medicine. In addition, relevant keywords were used to search the PubMed and Scopus databases. In Persian medicine sources, melancholia is categorized into three main types. One type is regarded as cerebral melancholia, which resembles modern psychiatry's depression closely. Therefore, some key points put forth by Persian medicine scholars regarding melancholia can be used to answer questions concerning depressive disorders and their etiology and treatment. Although recent studies have confirmed most approaches offered by Persian medicine physicians in ancient Persia, it is imperative to design and conduct clinical trial studies according to these approaches.

• 약학회지
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• 제49권4호
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• pp.306-311
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• 2005

Semisulospira libertine (SL) has been used as a folk medicine for quenching a thirst, hepatic fever and inflammation in oriental countries. Although SL has been anecdotally ascertained to ameliorate the hepatic diseases, there are no sufficient experimental evidences. The purpose of this study was to examine the effect of Bitam-S, in which SL is a main component, on non-alcoholic fatty liver disease manifested in C57BL/6J ob/ob mice. At 6 week old, the ob/ob mice were randomly divided into four groups; control and three treatment groups. The control mice was to receive a regular diet, and the treatment groups were fed a regular diet with either 250mg/kg, 500mg/kg of Bitam-S (BS250 and BS500) or 300mg/kg of metformin (MT300) for a 8-week period. Bitam-S exerted beneficial effects on lipid homeostasis in ob/ob mice that are not necessarily due to its ability to decrease food intake but its specific effects on hepatic lipogenesis related genes (SREBP1a, FAS and SCD-1). The combined effects of Bitam-S to reduce body weight and lipogenic gene expressions, and reduce the deposition of triglyceride in the liver are indicative of a marked improvement in obesity-related non-alcoholic fatty liver disease. Taken together, Bitam-S has potential as a treatment agent for non-alcoholic fatty liver disease and deserves clinical trial in the near future.

• Archives of Pharmacal Research
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• 제26권4호
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• pp.286-293
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• 2003

Several polyphenolic compounds and complex mixtures were isolated from brown algae species. The 1,1-diphenyl-2-picryhydarzyl (DPPH) radical scavenging activity and ferric reducing antioxidant power (FRAP) of these compounds were evaluated to determine their physiological usefulness as antioxidants for vascular protection. The antioxidative protection of low-density lipoprotein (LDL) was also evaluated and compared with that of catechin, because the generation of oxidized LDL is one of the most active and specific risk factors contributing to atherogenesis. Oral administration to rats of a commercially available sample ($VNP^{TM}$) containing 30% of these polyphenolic compounds and 70% dietary fiber revealed that the serum reducing capacity measured in terms of FRAP value was significantly elevated 30 min after the treatment, but declined rather quickly thereafter, indicating the good oral absorption of the compounds and their fast binding to the lumenal surface of the blood vessels. An eight-week, human, clinical trial (n=31) of $VNP^{TM}$ showed significant improvement in erectile function measured by IIEF (international index of erectile function) score. These results collectively demonstrated the usefulness of these polyphenolic compounds as fundamental chemopreventive agents against vascular risk factors originating from oxidative stress.

• Biomolecules & Therapeutics
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• 제19권1호
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• pp.126-133
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• 2011

The fruit of Actinidia arguta (AA) has been used mainly for the treatment of skin diseases, diuresis, diabetes mellitus and osteoporosis in Korean traditional medicine. It is known that AA (hardy kiwi) fruit extract has an effect on 2-chloro-1,3,5-trinitrobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice. Mode of action for it is associated with the modulation of biphasic Th1/Th2 cytokines. Furthermore, DA9102 containing AA is a herbal medicine currently under phase II clinical trial for atopic dermatitis in Korea. However, no active principles of AA on the decrease of Th2 cytokines including IL-4 and IL-10 have been identified. In this study, bioactivity-guided fractionation of an alcohol extract from the dried fruits of AA using ELISA assay for IL-4 production led to the isolation of $\alpha$-linolenic acid (I), linoleic acid (II), ethyl linolenate (III), ethyl linoleate (IV) and ethyl stearate (V) as the major active components. These compounds showed the down-regulatory effects of IL-4 production in A23187-stimulated RBL-2H3 cells without cytotoxicity.

• 의학교육논단
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• 제12권1호
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• pp.23-31
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• 2010

Medical humanities has become a third area of medical education following basic and clinical medicine. Also, in the national evaluation of medical schools, medical humanities education is an important factor. However, there are many difficulties in teaching medical humanities in medical schools. First, it is still an unfamiliar education area to medical schools and professors. Second, still, there is no consensus on the definition and contents of this education. Third, it is usually very difficult to find professors who have interest and the ability to teach medical humanities. Fourth, even medical students do not understand why they should study medical humanities and sometimes do not eagerly participate in class. This paper suggests some solutions for these problems. First, medical humanities need to be divided into sections according to how easily the contents can be accepted by existing medical education system and apply these sections in the introduction of this education gradually and in stage. One example of the division can be as follows: Group 1) medical ethics and medical law which can be most easily accepted. Group 2) medical communication skills which can be relatively easily accepted. Group 3) medical history and medical professionalism which is relatively difficult to accept, and Group 4) medical philosophy, medicine and music, medicine and literature, medicine and art, medicine and religion, etc. which is the most difficult to accept. In this paper, four things are suggested. Second, divide the contents into mendatory courses and elective courses. Third, allocate the contents throughout the four years from the first year though the fourth year according to the spiral curriculum model. This paper reports some new ideas and methods for medical humanities education. First, to stimulate students' participation, several methods were applied in a large size lecture and student projects. Second, the emphasis of writing in class and evaluation were discussed. Third, the provision of hands on experience is more emphasized than lectures. Fourth, inviting some doctors who work in non-medical areas such as journalism, pharmaceutical industry, etc is suggested. Trial and error is inevitable in this education, but it is essential in molding a good doctor, so medical professors who are interested or in charge of this medical humanities education need to share their ideas and experiences.

• Archives of Pharmacal Research
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• 제28권10호
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• pp.1196-1202
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• 2005

Omeprazole (OMP) is a proton pump inhibitor used as an oral treatment for acid-related gastrointestinal disorders. In the liver, it is primarily metabolized by cytochrome P-450 (CYP450) isoenzymes such as CYP2C19 and CYP3A4. 5-Hyroxyomeprazole (5-OHOMP) and omeprazole sulfone (OMP-SFN) are the two major metabolites of OMP in human. Cimetidine (CMT) inhibits the breakdown of drugs metabolized by CYP450 and reduces, the clearance of coad-ministered drug resulted from both the CMT binding to CYP450 and the decreased hepatic blood flow due to CMT. Phenobarbital (PB) induces drug metabolism in laboratory animals and human. PB induction mainly involves mammalian CYP forms in gene families 2B and 3A. PB has been widely used as a prototype inducer for biochemical investigations of drug metabolism and the enzymes catalyzing this metabolism, as well as for genetic, pharmacological, and toxicological investigations. In order to investigate the influence of CMT and PB on the metabolite kinetics of OMP, we intravenously administered OMP (30 mg/kg) to rats intraperitoneally pretreated with normal saline (5 mL/kg), CMT (100 mg/kg) or PB (75 mg/kg) once a day for four days, and compared the pharmacokinetic parameters of OMP. The systemic clearance ($CL_{t}$) of OMP was significantly (p<0.05) decreased in CMT-pretreated rats and significantly (p<0.05) increased in PB-pretreated rats. These results indicate that CMT inhibits the OMP metabolism due to both decreased hepatic blood flow and inhibited enzyme activity of CYP2C19 and 3A4 and that PB increases the OMP metabolism due to stimulation of the liver blood flow and/or bile flow, due not to induction of the enzyme activity of CYP3A4.

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book II
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• pp.201-212
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• 2003

The heartwood extract of Artocarpus lakoocha Roxb., which contains a potent tyrosinase inhibitor oxyresveratrol, was evaluated for its melanin-reducing efficacy in both guinea pigs and human volunteers. After 4 week-daily application of the extract dissolved in propylene glycol to the back of guinea pigs, significant reduction in melanin content was detected, with the effect greater than 3% kojic acid and solvent propylene glycol (P < 0.05). The extract was subsequently tested in female volunteers (3 groups of 20 subjects) using a parallel clinical trial with self-control. The first group received the A. lakoocha solution in propylene glycol whereas the second and the third group respectively received 0.25% licorice extract and 3% kojic acid in the same solvent. The subject in each group twice daily applied the test solution on one arm whereas the remaining arm was applied with only propylene glycol (self-control) for 12 weeks. The A. lakoocha extract was found to be the most effective agent, giving the shortest onset of significant whitening after only 4 weeks of application (P < 0.05), followed by 3% kojic acid (8 weeks) and 0.25% licorice extract (10 weeks). The whitening effect also increased with time, with the highest extent observed with A. lakoocha at week 12. The in vitro antityrosinase activity of A. lakoocha extract decreased with time upon storage at room temperature but could be stabilized by a combination of several antioxidants. In conclusion, the heartwood extract of A. lakoocha appeared to have promising potential for use as an effective and economical skin-whitening agent.

• Physical Therapy Rehabilitation Science
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• 제7권2호
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• pp.61-66
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• 2018

Objective: Patellofemoral pain syndrome (PFPS) is a condition that is characterized by patellar discomfort or pain that is aggravated during certain activities such as ascending/descending stairs. The Patellofemoral Disability Index (PDI) was developed to assess the effect of pain on functional activities in individuals with PFPS. The objectives of the current study were to determine the internal consistency, test-retest reliability, and validity of this index. Design: Cross-sectional study. Methods: Forty-one subjects who had PFPS with a mean age of $28.8{\pm}5.0years$ and a mean body mass index of $25.6{\pm}4.7kg/m^2$ participated in the study. All subjects were concurrently enrolled in a clinical trial for which they were instructed to complete hamstring-resistance exercises for 4 weeks. Over the course of the intervention, they completed both the PDI and the Oswestry Disability Index (ODI) at baseline after two weeks, and after four weeks. Pearson correlation coefficient was used to assess the criterion validity. Cronbach's ${\alpha}$ was used to examine the internal consistency. Intraclass correlation coefficients with 95% confidence interval were computed to examine test-retest reliability. Results: Subjects' responses within both the PDI and the ODI yielded Pearson correlation coefficient values that were positive and highly significant (range, 0.73-0.97; p<0.001). There was a high level of internal consistency (Cronbach's ${\alpha}{\geq}0.8$), with the exception of stair climbing (Cronbach's ${\alpha}=0.65$). Intraclass correlation ranged from 0.87 to 0.92, indicating high levels of test-retest reliability. Conclusions: The PDI is a valid, reliable, and feasible method of assessing pain and functional ability in patients with PFPS.