• 한국환경성돌연변이발암원학회지
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• 제26권3호
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• pp.77-85
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• 2006

2,3,7,8-Tetrachlorodibenzo-$\rho$-dioxin(TCDD) displays high toxicity in animals and has been implicated in human carcinogenesis. Although TCDD is recognized as potent carcinogens, relatively little is known about their role in the tumor promotion and carcinogenesis. It is known that TCDD can increase of cancer risk from various types of tissue by a mechanism possibly involving the aryl hydrocarbon receptor (AhR) activation. In this study, effects of TCDD on cellular proliferation of normal human skin and lung fibroblasts, Detroit551 and WI38 cells were investigated. In addition, to enhance our understanding of TCDD-mediated carcinogenesis, we have investigated process in which expression of Erk1/2, cyclinD1, oncogene such as Ha-ras and c-myc, and their cognate signaling pathway. TCDD that are potent activators of AhR-mediated activity was found to induce significant increase of cytochrome P4501A1 mRNA expression, suggesting a presence of functional AhR. These results support that CYP1A1 enzyme may be involved in the generation of TCDD-induced toxicity. Moreover mitogen-activated protein kinases (MARKs) phosphorylation and cyclin D1 overexpression are induced by TCDD, which corresponded with the progression of cellular proliferation. However, TCDD did not affected Ha-ras and c-myc mRNA expression. Taken together, it seems that TCDD are could be a part of cellular proliferation in non-tumorigenic normal human cells such as Detroit551 and WI38 cells through the upregulation of MAPKs signaling pathway regulating growth of cell population. Therefore, AhR-activating TCDD could potentially contribute to tumor promotion and Detroit551 and WI38 cells have been used as a detection system of tumorigenic effects of TCDD.

• 한국식품과학회지
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• 제48권4호
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• pp.378-383
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• 2016

본 연구에서는 퉁퉁마디 추출물의 용매 분획을 통해 얻은 Fr.H, Fr.E, Fr.EA, Fr.B, 및 Fr.W, 분획의 인간 단핵구 THP-1 세포에 대한 면역조절 활성과 정상 장관계 세포 및 장관계 암세포를 이용하여 면역세포와 장관상피 세포의 상호작용에 미치는 영향을 조사하였다. THP-1 세포는 PMA에 의해 분화가 진행되었으며 분화된 THP-1 세포는 LPS에 의해 활성화되어 COX-2 단백질 발현이 유도 되었다. 퉁퉁마디 분획은 분화된 THP-1 세포에서 COX-2, iNOS, 및 $cPLA_2$ 발현에는 영향을 미치지 않았으나, 분획 중 Fr.E는 LPS에 의해 유도된 COX-2의 발현을 유의적으로 증가시켰다. 분화된 THP-1에서 퉁퉁마디 분획을 처리하여 얻은 배양액은 INT-407 정상 장관계 세포의 성장을 촉진한 반면, HT-29 대장암 세포에는 영향을 미치지 않거나 성장 억제 활성을 나타내었다. THP-1에 LPS를 처리한 배양액은 HT-29 세포의 COX-2 발현을 유도하였으며 이러한 LPS의 효과는 Fr.E의 처리에 의해 억제되었다. 본 연구에서는 면역세포와 장관계 세포 간의 상호작용에 미치는 퉁퉁마디 분획의 영향을 조사하여 이를 통한 면역조절 활성을 나타낼 수 있음을 보였으며, 면역조절 기능성 소재로서의 퉁퉁마디의 이용성 확대를 위한 기본 정보를 제공하고자 하였다.

• Clinical and Experimental Pediatrics
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• 제45권3호
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• pp.354-361
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• 2002

목 적: 본 연구에서는 in vitro 및 in vivo에서 HSV-TK 유전자 치료의 bystander 효과 및 기전을 관찰하고, 싸이토카인 유전자의 병합 치료가 bystander 효과를 증폭시킬 수 있는지 조사하여 그 결과를 향후 신경모세포종 치료에 적용하고자 본 연구를 시행하였다. 방 법: A/J 마우스 신경모세포종 모델에서, neuro-2a/TK 세포와 unmodified neuro-2a세포를 여러 비율로 혼합하여 접종한 후 GCV를 투여하여 종양의 크기 변화 및 생존 유무를 관찰하였다. 마우스 신경모 세포종에서 bystander 효과의 기전을 알아보기 위해 neuro-2a/TK 세포를 주입한 마우스의 조직을 절개하여 connexin 43, CD4+ 및 CD8+ 세포 침윤을 관찰 하였다. 10% 및 25% HSV-TK 투여 군에서 neuro-2a/IL-2 세포의 투여가 bystander 효과를 증폭시키는 지 조사하였다. 결 과 : 1) in vitro 및 in vivo에서 bystander 효과는 뚜렷하게 관찰되었다. 2) 마우스 신경모세포종의 면역 조직 화학 염색 검사에서 connexin 43 발현은 관찰되지 않았으나 많은 수의 CD4+ 및 CD8+ T 세포의 침윤이 관찰되었다. 3) 10% 및 25% HSV-TK 투여군의 마우스에서 neuro-2a/IL-2 세포의 투여는 대조군과 비교하여 종양의 성장을 더 억제 시켰다. 결 론: In vitro 및 in vivo에서 HSV-TK/GCV 유전자 치료의 bystander 효과는 뚜렷하였으며, 그 기전으로 면역 세포가 중요한 역할을 할 것으로 추측된다. 그리고 bystander 효과는 IL-2 투여에 의해 증폭됨을 확인하였다. 이는 향후 신경모세포종의 수술 후 잔존암 치료에 HSV-TK/GCV 유전자 치료가 이용 가능할 것으로 생각된다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제26권6호
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• pp.581-590
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• 2000

Alterations in the cellular genome affecting the expression or function of genes controlling cell growth and differentiation are considered to be the main cause of cancer. Over 30 oncogenes can be activated by insertional mutagenesis, single point mutations, chromosomal translocations and gene amplification. The ras oncogenes have been detected in $15{\sim}20%$ of human tumors that include some of the most common forms of human neoplasia and are known to acquire their transforming properties by single point mutations in two domains of their coding sequences, most commonly in codons 12 and 61. The ras gene family consists of three functional genes, N-ras, K-ras and H-ras which encode highly similar proteins of 188 or 189 amino acid residues generically known as P21. ras proteins have been shown to bind GTP and GTP, and possess intrinsic GTPase activity. Experimental study was performed to observe the mutational change of the ras gene family and apply the results to the clinical activity. 36 Golden Syrian Hamster each weighing $60{\sim}80g$ were used and painted with 0.5% DMBA by 3 times weekly on the right buccal cheek(experimental side) for 6, 8, 10, 12, 14 and 16 weeks. Left buccal cheek (control side) was treated with mineral oil as the same manner of the right side. The hamsters were sacrificed on the 6, 8, 10, 12, 14 & 16 weeks. Normal and tumor tissues from paraffin block were completely dissected by microdissection and DNA from both tissue were isolated by proteinase K/phenol/chloroform extraction. Segments of the K-ras and H-ras gene were amplified by PCR using the oligonucleotide primers corresponding to the homologous region (codon 12 and 61) of the hamster gene, and then confirmational change of ras genes was observed by SSCP and autosequencing analysis. The results were as follows : 1. Malignant lesion could be found in the experimental side from the experimental six weeks. 2. One hamster among six showed point mutation of the H-ras codon 12($G{\rightarrow}A$ transition) at the experimental 10 and 14 weeks. 3. One of six at 6 weeks, two of six at 8 weeks and one of six at 12 weeks revealed the confirmational change of the H-ras codon 61($A{\rightarrow}T$ transversion). 4. The incidence of point mutation of H-ras codon 12 and 61 were 5.5%(2 of 36) and 11%(4 of 36) respectively. 5. Point mutation of the K-ras could not be seen during the whole experimental period. Form the above results, these findings strongly support the concept that H-ras oncogenes may have the influence of the DMBA induced carcinoma of hamster buccal pouch.

• 대한한방내과학회지
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• 제33권2호
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• pp.126-144
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• 2012

Background : Peripheral nerves more rapidly recover than central nerves. However, it has been known that the degree of reaction of axons of peripheral nerves is affected by distinctive characteristics of axons and environmental factors near the axons. Taxol is a widely used medicine as for ovarian, breast, lung and gastric cancer. However it causes patients difficulties under treatment due to its toxic and side effects, which include persistent pain. Objectives : This study reviewed how SJT extract in vitro and in vivo affects nerve tissues of a sciatic nerve damaged by Taxol. It also studied how SJT extract in vivo affects axons of the sciatic nerve after the sciatic nerve was damaged by pressing. Methods : After vehicle, Taxol, and Taxol plus SJT were treated respectively for tissue of the sciatic nerve in vitro and then tissues were observed using Neurofilament 200, Hoechst, ${\beta}$-tubulin, $S100{\beta}$, caspase-3 and anti-cdc2. SJT was also oral medicated by injecting Taxol into the sciatic nerve of in vivo rats. Tissues of the sciatic nerve and axons of DRG sensory nerves were then observed using Neurofilament 200, Hoechst, ${\beta}$-tubulin, $S100{\beta}$, caspase-3 and p-Erk1/2. After inflicting pressing damage to the sciatic nerve of in vivo rats, tissues of the sciatic nerve and DRG sensory nerve were observed using Neurofilament 200, Hoechst, $S100{\beta}$, caspase-3, anti-cdc2, phospho-vimentin, ${\beta}1$-integrin, Dil reverse tracking and p-Erk1/2. Results : The group of in vitro Taxol plus SJT treatment had meaningful effects after sciatic nerve tissue was damaged by Taxol. The group of in vivo SJT treatment had effects of regenerating Schwann cells and axons which were damaged by Taxol treatment. The group of in vivo SJT had effects of regenerating axons in damaged areas after the sciatic nerve was damaged by pressing, and also had variations of distribution in Schwann cells at DRG sensory nerves and axons. Conclusions : This study confirmed that SJT treatment is effective for growth of axons in the sciatic nerve tissues and improvement of Schwann cells after axons of the sciatic nerve tissues was damaged. After tissues of sciatic nerve was damaged by pressing in vivo, SJT treatment had effects on promoting regeneration of axon in the damaged area and reactional capabilities in axons of DRG sensory nerves.

• 한국식품영양과학회지
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• 제34권10호
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• pp.1509-1513
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• 2005

새로운 기능성 식품 소재를 개발하기 위하여 대두박으로 부터 HP-20 수지를 이용하여 식용조사포닌을 분리한 후 이들에 대한 항암 및 면역 활성을 조사하였다. 분리한 식용사포닌은 1,000 ${\mu}g/mL$의 농도에서 A-549, MCF-7 및 SW480과 같은 암세포주의 성장을 강하게 억제하였으며, 폐암세포주에 1000 ${\mu}g/mL$의 농도를 사포닌을 첨가였을 때 세포의 형태가 심하게 변화되었다. 사포닌은 생쥐의 비장으로부터 분리한 면역세포에 대하여 1 ${\mu}g/mL$의 농도까지 는 대조구에 비하여 그 증식을 유도하였으나 그 농도이상에서는 오히려 감소하는 경향을 보였다. 또한 대식세포주인 RAW 264.7에 사포닌의 처리 시 농도 의존적으로 NO의 함량이 높게 생성되었다.

• 대한임상검사과학회지
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• 제36권2호
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• pp.178-184
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• 2004

This research focuses on the overall evaluation of tumor protein (p53) and cell growth marker (Ki-67) in their functions as carcinogenic factors in both a HPV-infected group and in a HPV-noninfected group with the precancerous dysplasia of uterine cervix. Histological grades were determined by the H&E staining and the expression level of p53 and Ki-67 were tested by the immunohistochemistry method. The results were as follows. Among the total of 66 cases, p53 (+) was observed in 19 cases (29.0%) from the mild grade group, 22 cases (33.0%) from the moderate grade group, and 19 cases (29.0%) from the severe grade group. The values correlate with the increase of dysplasia intensity in HPV-noninfected group and showed significant correlation (p<0.05), but there were no significant difference from the HPV-infected group. Among a total of 66 cases, the mitotic index of Ki-67 (+) were observed in 19 cases (29.0%) from the mild grade group, 22 cases (33.0%) from the moderate grade group, and 19 cases (29.0%) from the severe grade group. The values were significantly different against dysplasia intensity (p<0.05), but showed no significant difference from HPV infection. After cross comparing the statistical parameters of p53 and ki-67 in their significance, p53 was shown to be statistically significant with Ki-67 while there was no statistically significant difference with Ki-67 (p<0.05). Taken together, tumor protein (p53) and an index of Ki-67 observed in cervical dysplasia and in HPV related dysplasia of cervix uterine did not have any notable significance with HPV infection. The incidence rate of p53, however, had some significant correlation with dysplasia while Ki-67 had no particular statistical significance. As a result, p53 and Ki-67 can be considered as effective diagnostic markers in predicting the disease progression of dysplasia to cervical cancer.

• 한국식품저장유통학회지
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• 제8권4호
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• pp.481-487
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• 2001

본 연구에서는 다양한 기능성을 가지는 저령을 80% methanol로 추출한 후 그 농축액을 ehyl acetate와 water로 순차 분획하고, 각 분획물을 이용하여 인간유래 위암세포인 SNU668의 생장 저해 효과와 항산화 효과 및 각종 위장질환의 원인균으로 보고된 H. pylori에 대한 항균활성을 조사하였다. 인간유래의 위암세포인 SNU668에 대한 저해 효과는 methanol fraction 1 mg/$m\ell$의 농도에서 가장 강한 암세포 저해 활성을 보였고, water fraction 1 mg/$m\ell$의 농도에서는 43.9%의 저해 활성을 보였다. 그러나 ethyl acetate fraction에서는 23.7%로 비교적 낮은 저해율을 보였다. 반면에, 성인 남성의 정상 임파구는 분획종류에 관계없이 모두 90% 이상의 높은 생존율을 보였다. 한편, 저령 추출물의 항산화 효과는 생존을 75.2%를 보인 methanol 추출물이 43.7%의 생존율을 보인 water 분획물 보다 높았고, ethyl acetate 분획물은 항산화 효과 역시 가장 낮게 나타났다. H. pylori에 대한 저령의 항균활성은 1mg/disk의 농도에서 80% methanol 추출물 및 모든 분획물에서 H. priori에 대해 항균활성을 나타냈으며, 그중 water 분획물이 12mm의 inhibition zone을 형성하여 가장 우수한 항균활성을 보였다. Methanol 추출물과 ethyl acetate 분획물은 각각 11 및 9.5 mm의 inhibition zone을 형성하였다. H. pylori로부터 분리된 urease의 활성은 urea broth에서의흡광도와 pH의 변화를 조사한 결과, 23$^{\circ}C$에서 반응 1시간 동안 560 nm에서의 흡광도가 0에서 0.93까지 증가하였으며, pH는 7.0으로부터 8.1까지의 증가를 보였다. H.pylori로부터 분리된 urease의 활성은 80% methanol 추출물과 모든 분획물에 의해 억제되었으며, 각 분획물의 억제능은 항균실험 결과와 유사한 유형으로서 역시 10mg/$m\ell$의 농도에서 1시간 후 55%의 억제를 보인 water분획물의 억제능이 가장 우수했다.

• Journal of Ginseng Research
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• 제3권1호
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• pp.66-93
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• 1979

Panax ginseng C. A. Meyer, which has been known for more than EWO years. occupies a Particular prince in folk medicine as so called tonic remedy. The pharmacolgical investigations of ginseng, based on the scientific concepts and methodology, have been performed by many researchers through the past 50∼60 years at different parts of the world. The pharmacological action of Panax ginseng compiled from the numerous reports can be summarized as follows: 1. On central nervous system, the effect of Panax ginseng is timulatory in smaller doses and somewhat depressive in larger doses. From the psychopharmacological aspect, ginseng seems to increase the mental efficiency of man. 2. Ginseng has the effect tending to Protect organism from various physical and chemical stresses. 3. The growth and basal metabolic rates of experimental animals are stimulated by ginseng. Ginseng also prolongs the survival time of animals under adverse influences. 4. Increasing the physical and mental efficiency, ginseng postpones the onset of fatigue and increases the working capacities. 5. In the case of the intravenous administration of ginseng, a transitory and slight hypotensive effect is observed. These hypotensive effects seems to include that of a direct action and actions related to the release of histamine and/or serotonin by ginseng. 6. It is Presumed that ginseng lowers the elevated bleed ingar and cholesterol level. 7. Ginseng tends to increase the gastrointestinal motizity and tone 8. It is presumed that ginseng Promotes the iron metabolism and activates the hematopoietic factors. 9. Ginseng tends to stimulate the biosynthesis of nucleic acid and release of histamine and serotonin. 10. The toxicity end adverse reactions of ginseng appear to be nothing that warrants apprehension. 11. Anticancer erects of ginseng seem to be due to indirect action rather than direct action on cancer cell, by improving the host condition 12. Recent clinical trials of ginseng harts obtained sent good results, but Present trial is still limited in its range, so it is necessary to broaden the scope of trial covering many kinds of organs and diseases. From the above, although it appears that substantial advancements have been achieved in the studies on the Pharmacological actions of Panax ginseng there are many discrepancies noticed in the reported data. Furthermore the precise mechanisms of actions of ginseng are sometimes obscure, even unknown in other actions as the students stand now. The main reasons for this are considered to be that even though saponin has been identified at one of the active substances of ginseng, other components have not fully been identified and that the experimental approaches of the investigations varied with different researchers. Thus a thorough analysis of the chemical components and newer standardized concepts and metohds appear to be the pre-requisites for further study of the pharmacolgical effects and mechaisms of Panax ginseng.

• 한국식품과학회지
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• 제37권5호
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• pp.741-745
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• 2005

농산가공 부산물인 펙틴을 이용하여 기능성 펙틴 올리고머를 제조할 시 감마선 조사를 이용하는 기초 자료를 마련하고자 펙틴 용액(2%, 0.05N HCl, citrate, 증류수)을 0, 2.5, 5, 10, 20, 30 및 50kGy로 감마선 조사한 후 이화학적 특성과 생리활성을 확인하였다. 펙틴 용액의 점도는 조사선량 10kGy까지 급격히 감소하였고 그 이후의 선량에서는 조사선량별 유의적인 차이가 없었다(p>0.05). 분자량은 조사선량이 증가하면서 30-40kDa의 당과 단당류가 증가하였다. 펙틴 용액의 전자공여능을 측정해본 결과 모든 선량에서 증류수 처리 펙틴 용액이 가장 높은 값을 나타내었고, 펙틴 용액 농도별 전자공여능은 모든 선량에서 유의적으로 증가하였다(p>0.05). 펙틴 용액의 ${\beta}-carotene$ bleaching assay 결과 전자공여능의 결과와 같이 조사선량이 증가할수록 높은 ${\beta}-carotene$ 유지력을 나타내었으며 항산화지수(Al)도 선량이 증가함에 따라 증가하였다(p<0.05). 펙틴 용액의 5개 암세포주에 대한 생장 억제 효과는 조사 선량이 증가할수록 증가하였고 이 중 인체 유래 피부암 세포주인 G361의 생장억제 효과가 모든 처리구에서 가장 높았다. 본 실험 겉과 방사선 조사를 이용한 펙틴 용액의 저분자화를 확인할 수 있었고 생리활성이 증가하는 것으로 보아 방사선 조사가 기능성 펙틴 올리고머 제조기술에 효과적으로 사용될 수 있을 것으로 판단된다.