• BMB Reports
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• 제35권6호
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• pp.623-628
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• 2002

The Th1 vs. Th2 balance is critical for the maintenance of immune homeostasis. Therefore, the genes that are selectively-regulated by the Th1 and Th2 cytokines are likely to play an important role in the Th1 and Th2 immune responses. In order to search for and identify the novel target genes that are differentially regulated by the Th1/Th2 cytokines, the human PBMC mRNAs differentially expressed upon the stimulation with IL-4 or IL-12, were screened by employing the differential display-polymerase chain reaction. Among a number of clones selected, DC21 was identified as a novel target gene that is regulated by IL-4 and IL-12. The DC21 gene expression was up-regulated either by IL-4 or IL-12, yet counter-regulated by co-treatment with IL-4 and IL-12. DC21 is a dendritic cell protein with an unknown function. The sequence analysis and conserved-domain search revealed that it has two AU-rich motifs in the 3'UTR, which is a target site for the regulation of mRNA stability by cytokines, and that it belongs to the N-acetyltransferase family. The induction of DC21 by IL-12 peaked around 8-12 h, and lasted until 24 h. LY294002 and SB203580 significantly suppressed the IL-12-induced DC21 gene expression, which implies that PI3K and p38/JNK are involved in the IL-12 signal transduction pathway that leads to the DC21 expression. Furthermore, tissue blot data indicated that DC21 is highly expressed in tissues with specialized-resident macrophages, such as the lung, liver, kidney, and placenta. Together, these data suggest a possible role for DC21 in the differentiation and maturation of dendritic cells regulated by IL-4 and IL-12.

• Parasites, Hosts and Diseases
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• 제44권3호
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• pp.187-196
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• 2006

The mammalian trematode Paragonimus westermani is a typical digenetic parasite, which can cause paragonimiasis in humans. Host tissues and blood cells are important sources of nutrients for development, growth and reproduction of P. westermani. In this study, a cDNA clone encoding a 47 kDa hemoglobinase of P. westermani was characterized by sequencing analysis, and its localization was investigated immunohistochemically. The phylogenetic tree prepared based on the hemoglobinase gene showed high homology with hemoglobinases of Fasciola hepatica and Schistosoma spp. Moreover, recombinant P. westermani hemoglobinase degradaded human hemoglobin at acidic pH (from 3.0 to 5.5) and its activity was almost completely inhibited by E-64, a cysteine proteinase inhibitor. Immunohistochemical studies showed that P. westermani hemoglobinase was localized in the epithelium of the adult worm intestine implying that the protein has a specific function. These observations suggest that hemoglobinase may act as a digestive enzyme for acquisition of nutrients from host hemoglobin. Further investigations may provide insights into hemoglobin catabolism in P. westermani.

• Biomolecules & Therapeutics
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• 제8권1호
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• pp.84-92
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• 2000

This Study was conducted to assess the single dose toxicity of DA-125, a new anthracycline anti-cancer agent, in rats and mice. The Drug was administered once intravenously to both sexes of rats and mice. Then followed a 14-day period of observation. The $LD_{50}$ Values (95% confidence limit) were estimated to be 60.9 mg/kg (57.5~64.3 mg/kg) for male rats and 60.2 mg/kg (56.2~64.5 mg/kg) for female rats, and 85.8 mg/kg (81.0~90.9 mg/kg) for male mice and 84.5 mg/kg (78.2~91.9 mg/kg) for female mice. Both sexes of rats and mice given the drug revealed the clinical sign of decreased locomotor activity, emaciation, hair loss, red-dish brown urine, salivation, and watery diarrhea. In addition, body weight from the next day to the 7th day tended to be decreased slightly in rats and mice treated with DA-125. Death occurred from the next day after administration to the 12th day. Macroscopically, congestion of gastrointestinal organ, lung, and adrenal glands were found in both sexes on the dead rats and mice. Histopathological examination of dead rats manifested atrophy of spleen, hypoplasia of bone marrow, hypcplasia and necrosis of lymphocyte in thymus, atrophy of villi in small intestine (duodenum, jejunum, and ileum), hyperplasia of granular epithelium in small intestine, degeneration of germinal epithelium in testis, defer oration of tubular epithelium in kidney, and vacuolation and myolysis of myocardium in heart. Histopathological examination of dead mice revealed hypoplasia of spleen and mesenteric lymph node, local necrosis of liver, atrophy of villi in small intestine, hyperplasia of glandular epithelium in small and large intestine, degeneration of tubular in kidney, degeneration of germinal cells in testis, and slight vacuolar degeneration of myocardium in heart.

• Molecular & Cellular Toxicology
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• 제5권1호
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• pp.83-87
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• 2009

In this study, we assessed the stability and toxicological safety of Angelica gigas Nakai (A. gigas Nakai) extract, which is comprised of decursin and decursinol angelate (D/DA). D/DA was tested for mutagenicity using Ames Salmonella tester strains (TA102, TA1535, and TA1537) with or without metabolic activation (S9 mix). No increase in the number of revertants was observed in response to any of the doses tested (1.25, 12.5, 125, and $1,250{\mu}/mLg$). In addition, a chromosome aberration test was conducted in the Chinese hamster lung (CHL) cell line. To accomplish this, cells were treated with D/DA (3.28, 13.12, 52.46, and $209.84{\mu}g/mL$) or with Mitomycin C ($0.1{\mu}/mLg$) as a positive control in the case of no metabolic activation or benzo(a)pyrene ($20{\mu}g/mL$) in the case of metabolic activation. No significant increase in chromosome aberrations was observed in response to treatment with any of these concentrations, regardless of activation of the metabolic system. According to these results, we concluded that D/DA did not induce bacterial reverse mutation or clastogenicity in vitro in the range of concentrations evaluated in these experiments.

• 생약학회지
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• 제34권4호통권135호
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• pp.308-313
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• 2003

A bioassay-guided fractionation of the stem bark extract of Eucommia ulmoides Oliver (Eucommiaceae) led to the isolation of three iridoid constituents, genipin (1), geniposide (3), geniposidic acid (4) as well as $({\pm})-guaiacylglycerol$ (2) and fatty acid mixtures as active ingredients of the extract responsible for the antitumoral property. The EtOAc soluble part and BuOH soluble part of the extract demonstrated a potent inhibition on the proliferation of cultured human tumor cells such as A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system) and HCT-15 (colon) in vitro, whereas the remaining water soluble part exhibited a poor inhibition. The intensive investigation of the EtOAc soluble part and BuOH soluble part of the extract yielded genipin, guaiacylglycerol, geniposide, geniposidic acid and large amounts of fatty acid mixtures as active components.

• Natural Product Sciences
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• 제25권4호
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• pp.311-316
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• 2019

Artocarpus heterophyllus has been used as traditional medicine. This plant is one of the sources of flavonoid. Flavonoid compounds possessed a wide range of biological properties including anticancer. This study was performed to investigate the cytotoxic effect of flavonoids from A. heterophyllus on H460 and MCF-7 cell lines. The interaction of flavonoids and cisplatin against tested cancer cells was also evaluated. MTT assay was used to determine the cytotoxic effect of flavonoid. Isobologram analysis was selected to evaluate the synergistic effect between flavonoid and cisplatin, their interaction was then confirmed using AO/PI staining method. Amongst of flavonoid compounds, artocarpin exhibited strong cytotoxic effect on both MCF-7 and H460 cell lines with IC₅₀ values of 12.53 ㎍/mL (28.73 μM) and 9.77 ㎍/mL (22.40 μM), respectively. This compound enhanced anticancer activity of cisplatin against H460 and MCF-7. The combination produced a synergistic effect on H460 and MCF-7 cell lines with a combination index (CI) values of 0.2 and 0.18, respectively. The AO/PI stained demonstrated that the combination of artocarpin and cisplatin caused morphological changes that indicated apoptosis. Moreover, artocarpanone also significantly increased cytotoxic effect of cisplatin compared to its single concentration with CI below than 1. This result suggested the potency of flavonoid named artocarpin to enhance the anticancer activity of cisplatin on H460 and MCF-7 cell lines.

• Asian Pacific Journal of Cancer Prevention
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• 제14권7호
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• pp.4279-4282
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• 2013

Background: The activation and inactivation of receptor tyrosine kinases are tightly regulated to ensure faithful replication of cells. After having transduced extracellular growth activating signals, activated EGFR is subjected to downregulation either by clathrin mediated endocytosis or c-Cbl mediated proteasome degradation depending on the ligand concentration. c-Cbl is an ubiquitin ligase which requires a phosphorylated tyrosine residue at position 1045 in the cytoplasmic domain of EGFR to interact and add ubiquitin molecules. While activating mutations in exons 19 and 21 have been associated with the development of several cancers, the status of mutations at tyrosine 1045 coding exon 27 of EGFR remain to be investigated. Consistently, defective phosphorylation at 1045 has been associated with sustained phosphorylation of EGFR in non-small lung carcinomas. Hence in the present study we investigated the genetic status of the tyrosine 1045 coding site within exon 27 of EGFR gene to explore for possible occurrence of mutations in this region, especially since no studies have addressed this issue so far. Materials and Methods: Tumor chromosomal DNA isolated from thirty five surgically excised oral squamous cell carcinoma tissues was subjected to PCR amplification with intronic primers flanking the tyrosine 1045 coding exon 27 of EGFR gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Sequence analysis identified no mutations in the tyrosine 1045 codon of EGFR in any of the thirty five samples that were analyzed. Conclusions: The lack of identification of mutation in the tyrosine 1045 codon of EGFR suggests that mutations in this region may be relatively rare in oral squamous cell carcinomas. To the best of our knowledge, this study is the first to have explored the genetic status of exon 27 of EGFR in oral squamous cell carcinoma tissue samples.

• 대한기관식도과학회지
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• 제15권2호
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• pp.75-80
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• 2009

기관지내 평활근종은 기관지의 폐쇄정도에 따라 호흡곤란, 기침, 천명 등의 다양한 증세를 동반하며 그 증상이나 폐쇄정도가 경미할 경우 흉부 X-선 검사에서는 이상소견이 관찰되지 않을수도 있다. 따라서 폐렴이나 천식 등의 치료를 하다가 뒤늦게 발견되는 경우가 있는데 이 경우 반복적인 폐쇄성 폐렴과 폐농양, 기관지 확장증 등의 비가역적인 폐손상이 유발되며, 이는 전폐 절제술 등의 치료를 요하기도 한다. 따라서 무엇보다도 기관지내 평활근종의 치료 목표는, 증상에 따른 기관지내 병변의 의심과 기관지경에 의한 정확한 조기 진단과 보존적 수술, 내시경적 치료에 의해 비가역적인 폐손상을 방지하고 폐기능을 최대한 유지하는 것이다. 본 증례는 항생제 치료에 반응하지 않는 지속적인 폐렴으로 전원되어 온 환자에서 기관지경시행 후 기관지내 평활근종을 진단한 경우로, 이와 같은 경우 기관지내 병변의 가능성에 대해 반드시 고려하고 조기에 기관지경을 시행하여 정확한 진단을 하는 것이 무엇보다 중요하다고 하겠다.

• 혜화의학회지
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• 제19권2호
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• pp.145-151
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• 2011

Backgrounds: Multidisciplinary approaches including surgery, chemotherapy, and radiation therapy are currently being performed to target various cancers in Western Medicine. However, some cancers still remain difficult to battle, which has long attracted many scientists for the discovery of new agents to fight cancers. Ginseng is one of the herbs used in Oriental Medicine including Korea, China and Japan. We have further investigated ginseng for its anticancer effect. Objective: This is a comprehensive review summary of anticancer effect of ginseng and ginsenoids as a possible agent for future cancer treatment. Methods: Data were retrieved from two web sites; www.pubmed.com and www.riss.kr, and authorized texts concerning anticancer effects of ginseng. From collected data, information on anticancer effect of ginseng was thoroughly sorted, restructured, then assessed. Results: Panax Ginseng C.A. Meyer belongs to Araliaceae Panax family, a perennial prairie plant with its root known as Ginseng Radix. Ginseng induces anticancer effect through cell cycle arrest, acceleration of apoptosis, anti-angiogenesis, and suppression of metastasis. Anticancer effect of ginseng may be due to single compound or multi-compound actions. Many studies report involvement of immune mechanisms of cytokines, Natural Killer (NK) cells, macrophages and some antibodies in enhancing anticancer effect of ginseng. In near future, possibility of applying these mechanisms into clinical trials is convinced. There were some important findings on saponin in ginsenoids in reviewing for this article; First, eradication of metastatic tumors were influenced by macrophage activation. Second, suppression of malignant melanoma cell metastasis to lung were induced by macrophage and NK cell activation in spleen with red ginseng acidic polysaccharide (RGAP). Third, final metabolites of M1, M4 had exerted anticancer effect of ginseng. Conclusion: Unknown anticancer mechanisms of ginseng have been studied for many years up until now. Ginseng is comprised of multiple bio-chemical compounds that create complex pharmaceutical interactions. Therefore, for its proper usage and safe prescription, studies on different types of ginseng and patients' susceptibility to ginseng according to their constitution and stages of the disease should be further pursued. More efforts are needed to understand the anticancer mechanisms of ginseng as well.

• 한국식품저장유통학회지
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• 제13권4호
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• pp.495-500
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• 2006

항산화물에 의한 천식 억제 효과를 확인하기 위하여 항산화정도를 알아볼 수 있는 DPPH, FRAP, hydroxyl radical 소거활성 실험을 high throughput-compatible chemical assay로 디자인하여 해바라기씨 추출물에 적용하여 보았다. 해바라기씨 추출물의 용매에 따른 항산화 효과 중 $H_2O_2$에 의한 산화스트레스에 의한 세포사멸을 DW추출물에서 강한 억제능력을 보였다. 이를 이용하여 마우스를 이용한 천식 동물모델에 적용하여 탁월한 천식 억제효과를 $CD4^+$세포, IL-4와 IL-13의 발현정도를 통해 알수 있었다. 해바라기씨 추출물은 천식에 탁월한 효과가 있는 것으로 in vitro 및 in vivo 실험으로 증명하였다.