• Food Science and Biotechnology
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• 제16권6호
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• pp.1064-1068
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• 2007

We evaluated the effect of soybean dongchunghacho [SD, cultivated dongchunghacho fungus (Paecilomyces tenuipes) on soybeans] on dimethylhydrazine (DMH)-induced DNA damage and oxidative stress in male F344 rats. The animals were divided into 3 groups and fed a casein-based high-fat, low fiber diet without (DMH group) or with 13%(w/w) of soybean (DMH+S group), or SD (DMH+SD group). One week after beginning the diets, rats were treated weekly with DMH (30 mg/kg, s.c.) for 6 weeks; dietary treatments were continued for the entire experiment and endpoints measured at 9 weeks after the first DMH injection. SD supplementation reduced DMH-induced DNA damage in colon cells and reduced plasma lipid peroxidation. Thus, SD may have therapeutic potential for early-stage colon carcinogenesis.

• Archives of Plastic Surgery
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• 제34권1호
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• pp.13-17
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• 2007

Purpose: To understand the pathogenesis of the disease that presents abnormally proliferated vascular endothelial cells, a model of DMH(1,2-dimethylhydrazine)-induced abnormal proliferation of HUVECs(Human Umbilical Vein Endothelial Cells) was made. We indirectly determined that Protein Kinase C(PKC) restricts the cellular proliferation and inhibits the manifestation of growth factor by using several inhibiting substances of the transmitter through our previous studies. Thereupon, we attempted to observe direct enzymatic activities of PKC and its correlation with the abnormal proliferation of vascular endothelial cells. Methods: $10^5$ HUVECs cells were applied to 6 individual well plates in three different groups; A control group cultured without treatment, a group concentrated with $0.75{\times}10^{-8}M$ DMH only, and a group treated with DMH & $5{\times}10^{-9}M$ Calphostin C, inhibitor of PKC. In analyzing the formation of intracellular PKC enzyme, protein separation was performed, and separated protein was quantitatively measured. PKC enzyme reaction was analyzed through Protein Kinase C Assay System (Promega, USA), and the results were analyzed according to Beer's law. Results: Enzymatic activity of PKC presented the highest in all reaction time of a group concentrated only with DMH, and the lowest in the control group. The group treated with DMH and the inhibitor revealed statistically lower enzymatic activity than group only with DMH in all reaction time, although higher than the control group. Conclusion: From the enzymatic aspect, most active and immediate reaction of the PKC was observed in the group concentrated with DMH only. The group treated with DMH & PKC inhibitor showed meaningful decrease. Accordingly, PKC holds a significant role in DMH-induced abnormal proliferation of vascular endothelial cells.

• Archives of Plastic Surgery
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• 제33권1호
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• pp.5-12
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• 2006

Protein tyrosine kinase(PTK), protein kinase C(PKC), oxidase, as a mediator, take a significant role in signal transduction pathway of angiogenesis. The authors utilized the inhibitors, targeting the formation of three co-enzyme in signal transduction pathway in order to quantify the suppression of abnormal vascular endothelial cell proliferation induced by DMH, to compare the level suppression in each up-regulated growth factors, CTGF, CYR61, $ITG{\beta}1$, FHL2, and to identify the relationship between abnormal cell proliferation and signal transduction pathway. Five groups were established; Control group, Group of DMH, Group of DMH-mixed Herbimycin, inhibitor of protein tyrosine kinase, Group of DMH-mixed Calphostin C, inhibitor of protein kinase C, Group Of Dmh-Mixed 10U Catalase, Inhibitor Of oxidase. The rise of vascular endothelial cell was compared by MTT assay, and four growth factors were analysed with RT-PCR method, at pre-administration, 4, 8, 12, and 24 hours after administration. In comparison of abnormal proliferation of vascular endothelial cell induced by DMH, suppression was noticed in Herbimycin and Calphostin C group, and Calphostin C group revealed higher suppression effect. Nevertheless, Catalase group did not have any suppression. In manifestation of four growth factors, Herbimycin and Calphostin C group presented similar manifestation with control group, except in $ITG{\beta}$. Catalse group had similar manifestation with DMH group in all four growth factors. Abnormal proliferation of vascular endothelial cell induced by DMH have a direct relationship with PTK and PKC, more specifically to PKC. Oxidase was confirmed not to have any relevance.

• 한국식품영양과학회지
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• 제38권7호
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• pp.839-845
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• 2009

오만둥이는 우리나라의 전통적인 수산식품으로써 찜 또는 찌개류로 조리하여 널리 이용하여 왔다. 본 연구에서는 오만둥이의 기능성 소재로서의 기능적 특성을 파악하기 위하여 오만둥이 추출물의 항산화 활성 및 항유전독성 활성을 in vitro 방법으로 측정하였다. 또한 대장암에 대한 예방효과를 알아보기 위하여 DMH로 대장암을 유발한 SD 쥐를 이용하여 오만둥이를 경구투여한 후 DNA 손상 및 ACF 형성에 미치는 영향을 알아보았다. 그 결과 총항산화능은 모든 추출물에서 대조구에 비해 유의적으로 높은 활성을 나타내었다. 동결건조 한 추출물에서는 메탄올, 에탄올(0.225, 0.219 mM) > 물(0.179 mM) > 아세톤(0.150 mM) 순으로 나타났으며, 신선한 오만둥이에서는 메탄올 추출물(0.215 mM)이 가장 높은 항산화력이 있는 것으로 나타났다. Comet assay에서는 모든 추출물이 $H_2O_2$에 의한 산화적 스트레스에 대항한 DNA 손상억제력을 향상시키는 것으로 나타났으며 특히 동결건조 한 오만둥이에서 메탄올 추출물의 억제력이 가장 높은 것으로 나타났다. 백혈구의 DNA 손상정도는 대조군에 비해 DMH 투여군에서 유의적으로 손상정도가 증가한 반면, DMH+S. placata군에서는 DMH를 주입한 군에 비하여 손상정도가 유의적으로 감소하였다. 또한 ACF의 생성수치가 DMH군에 비하여 DMH+S. placata군에서 유의적으로 감소하는 결과를 나타내었다. 이상의 결과로 미루어 볼 때 오만둥이는 in vitro 뿐만 아니라 대장암을 유발한 쥐에서도 항산화 및 항암효과에 긍정적인 영향을 미치는 것으로 나타나 오만둥이가 대장암을 예방하기 위한 기능성식품 소재로서 가능성을 보여 주었다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.73-80
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• 2016

Colorectal cancer is a very prevalent diagnosed cancer. The current study was performed in order to examine the role of BRAE (Basella rubra aqueous extract) in regulating aberrant crypt foci (ACF) formation, cell proliferation and inhibition of apoptosis in a colon carcinogenesis model in male Wistar rats. Rats were randomly allocated into six groups. Group I served as control, and group II acted as a drug control administered BRAE (250mg/kg b.w.) orally for 30 weeks. Rats in group III-VI were given subcutaneous injections of DMH (25mg/kg b.w. weekly) for 15 weeks to initiate colon carcinogenesis. Those in group IV and VI were administered BRAE along with DMH injections. Rats in group V were administered with BRAE after cessation of DMH injection. After 30 weeks of experimental period colons were obtained from experimental groups and analyzed for ACF incidence, argyrophilic nucleolar organizing region-associated proteins (AgNOR) count, histopathological and immunohistochemical changes. Only in DMH exposed groups were ACF and AgNOR numbers increased. Administration of BRAE appreciably decreased the numbers of ACF and AgNOR in BRAE treated groups. Histopathological findings revealed a high level of dysplastic changes with decreased number of goblet cells found only in only DMH injected rats. Administration of BRAE in treated group rats reversed these changes. Expression markers for cell proliferation (PCNA and Ki67) were elevated in DMH treated rats, but reduced with BRAE treatement. This expression was reversed with apoptosis markers (p53 and Caspase-3). Thus the results results of the present study were found to be significant and confirmed the potential efficacy of BRAE against colon carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5331-5339
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• 2013

Colorectal cancer is one of the leading causes of cancer death, both in men and women. This study investigated the effects of Amorphophallus campanulatus tuber methanolic extract (ACME) on aberrant crypt foci (ACF) formation, colonic cell proliferation, lipid peroxidative damage and the antioxidant status in a long term preclinical model of 1, 2-dimethylhydrazine (DMH) induced colon carcinogenesis in rats. Male Wistar rats were divided into six groups, viz., group I rats served as controls; group II rats treated as drug controls receiving 250 mg/kg body weight of ACME orally; group III rats received DMH (20 mg/kg body weight) subcutaneously once a week for the first 15 weeks; groups IV, V and VI rats received ACME along with DMH during the initiation, post-initiation stages and the entire period of the study, respectively. All the rats were sacrificed at the end of 30 weeks and the intestinal and colonic tissues from different groups were subjected to biochemical and histological studies. Administration of DMH resulted in significant ($p{\leq}0.05$) intestinal and colonic lipid peroxidation (MDA) and reduction of antioxidants such as catalase, glutathione peroxidase, glutathione reductase, glutathione-Stransferase and reduced glutathione. Whereas the supplementation of ACME significantly ($p{\leq}0.05$) improved the intestinal and colonic MDA and reduced glutathione levels and the activities of antioxidant enzymes in DMH intoxicated rats. ACME administration also significantly suppressed the formation and multiplicity of ACF. In addition, the DMH administered rats showed amplified expression of PCNA in the colon and decreased expression of this proliferative marker was clearly noted with initiation, post-initiation and entire period of ACME treatment regimens. These results indicate that ACME could exert a significant chemopreventive effect on colon carcinogenesis induced by DMH.

• Archives of Plastic Surgery
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• 제34권6호
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• pp.679-684
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• 2007

Purpose: DMH(1,2-dimethylhydrazine) has been known to induce vascular neoplasm such as malignant endothelioma in animal experiment, through induction of abnormal proliferation of HUVECs. In our previous studies, 11 types of PKC isoenzymes were determined by RT-PCR and the expression of $PKC{\alpha}$, and ${\mu}$ was more prominent than other PKC isoenzymes in the DMH-treated group. However, this result was not based on objective assessment. In this study, we further evaluated the role of $PKC{\alpha}$ on the DMH-induced abnormal proliferation of HUVECs by two different methods to identify its presence with high relevance in objective view. $PKC{\mu}$ will be investigated in further study. Methods: The study was conducted with the cultured HUVECs group(control) and the $0.75{\times}10^{-9}M$ DMH-treated group. After processing protein extraction in 0 and 24 hour, extracted protein was treated of quantitative test through BCA protein assay. In the western blot analysis, electrophoresis was performed in the order of gel preparation, sample preparation, and gel running. Electrotransfer to nitrocellulose membrane and reaction with antibody were done. Detection of $PKC{\alpha}$ was achieved through "Gel Image Analysis System". In the fluorescence immunocytochemical analysis, the grading of radiance of the intracellular $PKC{\alpha}$ particles was detected with confocal microscope after treating with primary and fluorescent secondary antibody in 0 and 24 hours. Results: The Western blot analysis showed increased $PKC{\alpha}$ expression from the specimen obtained in 24 hour of the DMH treatment group when compared to those in control group. Under confocal fluorescence microscope, the emitting radiance in the DMH treated group was brighter at 24 hours as well. Conclusion: We believe that $PKC{\alpha}$ plays a role in DMH-induced abnormal proliferation of the vascular endothelium, which may provide insights in understanding the vascular neoplasm.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4393-4402
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• 2012

Colon cancer is the third most common malignant neoplasm in the world and it remains an important cause of death, especially in western countries. The toxic environmental pollutant, 1, 2-dimethylhydrazine (DMH), is also a colon-specific carcinogen. Tannic acid (TA) is reported to be effective against various types of chemically induced toxicity and also carcinogenesis. In the present study, we evaluated the chemopreventive efficacy of TA against DMH induced colon toxicity in a rat model. Efficacy of TA against the colon toxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities, lipid peroxidation, histopathological changes and expression of early molecular markers of inflammation and tumor promotion. DMH treatment induced oxidative stress enzymes (p<0.001) and an early inflammatory and tumor promotion response in the colons of Wistar rats. TA treatment prevented deteriorative effects induced by DMH through a protective mechanism that involved reduction of oxidative stress as well as COX-2, i-NOS, PCNA protein expression levels and TNF-${\alpha}$ (p<0.001) release. It could be concluded from our results that TA markedly protects against chemically induced colon toxicity and acts plausibly by virtue of its antioxidant, anti-inflammatory and antiproliferative activities.

• Food Science and Biotechnology
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• 제15권6호
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• pp.980-985
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• 2006

The goal of this study was to investigate the effects of a newly developed functional food containing Bacillus polyfermenticus (BP) and other physiologically active materials on the antioxidant system and the process of colon carcinogenesis in male F344 rats. Following a one-week adaptation period, the rats were divided into 3 groups and fed either a high-fat, low-fiber diet (control and DMH groups), or a high-fat, low-fiber diet supplemented with B. polyfermenticus ($3.1{\times}10^8\;CFU/day$) and other physiologically active materials (chitosan, chicory, ${\alpha}$-tocopherol, and flavonoids) (DMH+BP group). One week after the initiation of the diets, 2 groups of rats were subjected to six weeks of treatment with 1,2-dimethylhydrazine (DMH, 180 mg/kg BW, s.c.). The dietary treatments remained consistent throughout the entire experimental period. Nine weeks after the initial DMH injection, the rats supplemented with B. polyfermenticus had significantly lower numbers of aberrant crypt foci than those in the DMH group. Injections with DMH resulted in significantly higher leukocytic DNA damage and plasma lipid peroxidation levels, as well as in a lower plasma total antioxidant potential. These effects were reversed following supplementation with B. polyfermenticus and other physiological materials. Our results indicate that a functional food containing B. polyfermenticus exerts a protective effect on the antioxidant system and on the process of colon carcinogenesis, thereby suppressing the development of preneoplastic lesions.

• 의학교육논단
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• 제22권3호
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• pp.173-188
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• 2020

Medical humanities education (MHE) is as essential as basic medical sciences and clinical medicine education. Despite the importance of MHE, MHE curriculum development (CD) has proven to be challenging. This critical review examines the MHE CD at one medical school. The critical review methodology was developed based on Kern's six step CD model to systematically examine the CD of "Doctoring and Medical Humanities (DMH)" at the Yonsei University College of Medicine. Five review questions were developed related to (1) necessity, (2) direction and purpose, (3) design, (4) operation, and (5) evaluation of CD based on Kern's model. The review showed that the process of DMH CD mapped to components of Kern's model. The DMH curriculum content selected was closely related to medical practice and aimed to combine the acquisition of understanding and skills by designing a student-participatory curriculum based on clinical cases. Assessment methods that emphasized students' reflections were actively introduced in the evaluation section. Since the regular committee for DMH continued the work of the special ad hoc committees for DMH CD, the CD was effectively completed. However, the planning and evaluation functions and responsibilities of the DMH committee need to be strengthened. Despite the apparent limitations, the fact that students showed a high satisfaction rate and preferred small group discussions based on clinical cases has significant implications in the instructional design of MHE, where changes in self-awareness and attitude are more important than the acquisition of information. It is necessary to systematically review and study students' reflection results produced by the changed assessment methods and to develop assessment indicators for MHE that reflect the achievements of the MHE competencies of students.